Dose-Intense Chemotherapy and Stem Cell Rescue in the Treatment of Inflammatory Breast Carcinoma
Phase: PHASE2
Conditions: Breast Cancer
Sponsor: City of Hope Medical Center

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CI T Y O F H O P E N A TI O N A L M E DI C A L C E N T E R 
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D E P A R T M E N T O F M E DI C A L O N C O L O G Y  A N D T H E R A P E U TI C S R E S E A R C H 
TI T L E:   
D ose-I nte nse C he m ot hera p y a n d Ste m Cell Resc ue i n t he Treat me nt of I nfla m mat or y Breast 
Carci n o ma 
CI T Y O F H O P E P R O T O C O L N U M B E R/ V E R SI O N: 
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D A T E( S)/ O F A M E N D M E N T( S)/ R E VI SI O N( S): 
 
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SI T E:  
Breast 
HI S T O L O G Y:  
I nfla m mat or y 
S T A G E (If a p plic a ble):  
Sta ge III B 
M O D A LI T Y:  
Tra ns pla nt 
T Y P E:  
P hase II 
P RI N CI P A L I N V E S TI G A T O R:  
J oa n ne M orti mer, M. D. 
P A R TI CI P A TI N G C LI NI CI A N S: 
Me dical 
O nc ol o g y: 
Mi haela Cristea, 
M. D., 
Warre n C h o w, 
M. D., 
Maria n na K ocz y was, 
M. D., Ste p he n K oe hler, 
M. D., L ucille Le o n g, 
M. D., Dea n Li m, M. D., R o bert M or ga n, M. D., Ge or ge S o ml o, M. D., 
Na ya na V ora, M. D., Jeffre y Weitzel, M. D., Y u n Ye n, M. D. 
P A R TI CI P A TI N G I N S TI T U TI O N S:   
Cit y of H o pe Nati o nal Me dical Ce nter 
 
Cit y of H o pe G o o d Sa marita n H os pital, P h oe ni x, A Z 

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A P P E N DI C E S 
 
A  Perf or ma nce Stat us Scale 
B  T o xicit y Gra di n g 
C  A d verse E ve nt Re p orti n g Material 
 
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S C H E M A 
 
Strat u m 1 
  
D o x  
D o x  
D o x  
Ta x  
Ta x  
S ur ger y  
Ta x  
P B S C H  A C T  
Mel/ Cis
Wee k  
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3  
5  
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Strat u m 2 
 
 
 
 
 
 
 
 
 
 
 
 
Wee k    
  
  
  
  
  
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D o x:  
D o x or u bici n 
Ta x:  
Ta x ol 
A C T:  
D o x or u bici n/ C ycl o p h os p ha mi de/ Ta x ol 
Mel/ Cis:  Mel p hala n/ Cis plati n 
P B S C H:  Peri p heral Bl o o d Ste m Cell Har ves 
 

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1. 0 
O B J E C TI V E S  
1. 1.  
Pri mar y O bjecti ves 
1. 1. 1.  T o assess t he feasi bilit y of ne oa dj u va nt d ose-i nte nse se q ue ntial 
c he m ot hera p y f oll o we d b y s ur gical resecti o n, a dj u va nt t hera p y a n d 
ta n de m c ycles of hi g h- d ose c he m ot hera p y a n d ste m cell resc ue f or 
patie nts wit h i nfla m mat or y sta ge III B breast carci n o ma. 
1. 1. 2.  T o assess t he cli nical a n d pat h ol o gical re missi o n rate (c o m plete [ C R], 
partial [ P R], a n d o verall [ O R]) f oll o wi n g ne oa dj u va nt d ose-i nte nsi ve 
se q ue ntial c he m ot hera p y i n patie nts wit h i nfla m mat or y sta ge III B breast 
ca ncer. 
1. 1. 3.  T o assess rela pse-free a n d o verall s ur vi val of patie nts wit h i nfla m mat or y 
sta ge III B breast carci n o ma treate d wit h ne oa dj u va nt d ose-i nte nse 
se q ue ntial c he m ot hera p y f oll o we d b y s ur gical resecti o n, a dj u va nt t hera p y 
a n d ta n de m c ycles of hi g h- d ose c he m ot hera p y a n d ste m cell resc ue. 
1. 2.  
Sec o n dar y O bjecti ves 
1. 2. 1.  T o perf or m bi oc he mical, i m m u n o hist oc he mical a n d m olec ular a nal ysis of 
pri mar y breast t u m ors pri or t o ne oa dj u va nt c he m ot hera p y a n d at t he ti me 
of defi niti ve mastect o m y. 
1. 2. 2.  T o assess t hr o u g h a q uesti o n naire a n d i nter vie w pr ocess t he p ote ntial 
c orrelati o ns bet wee n a g gressi ve cli nical prese ntati o n (i.e., i nfla m mat or y 
feat ures) a n d here ditar y bac k gr o u n d. 
2. 0 
B A C K G R O U N D  
A p pr o xi matel y 1 8 0, 0 0 0 ne w cases of breast ca ncer are dia g n ose d eac h year.  O ne t o t hree 
perce nt of ne wl y detecte d cases will prese nt wit h i nfla m mat or y disease.  T he dia g n osis of 
i nfla m mat or y breast carci n o ma is base d o n t he prese nce of cli nical feat ures s uc h as 
er yt he ma a n d e de ma [ pea u d’ ora n ge], or t hic ke ni n g of t he s ki n wit h o ut a pal pa ble mass 
de vel o pi n g o ver a relati vel y s h ort ti me peri o d.  T he pat h ol o gical fi n di n gs res p o nsi ble f or 
t he prese nti n g cli nical c haracteristics i ncl u de der mal l y m p hatic i n vasi o n.  Pri or t o t he 
i ntr o d ucti o n of s yste mic t hera p y, 5- year s ur vi val rates of patie nts wit h i nfla m mat or y 
carci n o ma treate d wit h s ur gical a n d/ or ra di ot hera pe utic mea ns were u n der 5 %.  T he 
i ncl usi o n of s yste mic c he m ot hera p y first as a dj u va nt a n d m ore rece ntl y i n t he 
ne oa dj u va nt setti n g see ms t o ha ve c ha n ge d t he nat ural hist or y of t his disease.  
D o x or u bici n-c o ntai ni n g ne oa dj u va nt re gi me ns are ca pa ble of i n d uci n g cli nical res p o nse 
i n a p pr o xi matel y 8 0 % of patie nts, alt h o u g h c o m plete re missi o ns d oc u me nte d at t he ti me 
of mastect o m y occ ur i n less t ha n 1 5 % of patie nts.  W hile patie nts res p o n di n g t o 
ne oa dj u va nt c he m ot hera p y te n d t o ha ve better l ocal c o ntr ol rates t ha n t heir n o n-
res p o n di n g c o u nter parts, o ver 9 0 % of patie nts ca n be re n dere d disease free wit h t he 
c o m bi nati o n of c he m ot hera p y, s ur ger y a n d ra diati o n t hera p y.  Des pite a n i nitial res p o nse 
t o t hera p y, o verall s ur vi val rates are 4 0- 7 0 % at 3 years a n d, at best 5 0 %, at 5 years fr o m 
t he ti me of dia g n osis.1 

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Precli nical data s u g gest t hat se veral dr u gs acti ve a gai nst breast ca ncer s uc h as 
c ycl o p h os p ha mi de, cis plati n, mel p hala n, t hi o te pa, B C N U, d o x or u bici n a n d p ossi bl y ot her 
classes of c he m ot hera pe utic a ge nts de m o nstrate stee p d ose-res p o nse c ur ves i n vitr o.  F or 
sta n dar d d ose c he m ot hera pe utic re gi me ns, a c orrelati o n has bee n esta blis he d bet wee n t he 
act ual d ose recei ve d a n d t hera pe utic o utc o me.  M o derate decreases i n d o x or u bici n d ose 
a n d/ or sta n dar d a d mi nistrati o n of c ycl o p h os p ha mi de, d o x or u bici n a n d 5- F U ( C A F) res ult 
i n decrease d rela pse-free a n d o verall s ur vi val c o m pare d t o sta n dar d treat me nt sc he d ules.3 
We perf or me d a retr os pecti ve re vie w of 5 8 patie nts treate d at t he C O H si nce 1 9 8 5 f or 
i nfla m mat or y sta ge III B disease.  We ha ve o bser ve d t hree- a n d fi ve- year rela pse-free 
s ur vi val rates of 2 9 % a n d 1 7 % a n d o verall s ur vi val rates of 4 3 % a n d 3 1 %, res pecti vel y 
( C urci o, et al., u n p u blis he d data).  I n c o ntrast, we ha ve rece ntl y re p orte d o ur i nstit uti o nal 
e x perie nce i n 2 2 patie nts wit h i nfla m mat or y breast ca ncer w h o u n der we nt i n d ucti o n 
c he m ot hera p y, s ur gical resecti o n a n d hi g h- d ose c he m ot hera p y c o ns oli dati o n wit h eit her 
d o x or u bici n or cis plati n t o get her wit h V P - 1 6 a n d c ycl o p h os p ha mi de ( C A V P or C C V P).  
Patie nts recei ve d l ocal-re gi o nal ra diati o n t hera p y, a n d t h ose wit h rece pt or p ositi ve 
t u m ors were treate d wit h ta m o xife n.  T he 3- year rela pse-free a n d o verall s ur vi vals, 
c o u nti n g fr o m i nitiati o n of hi g h- d ose c he m ot hera p y, were 5 0 % a n d 7 3 %, res pecti vel y. 4  
W hile t hese res ults c o m pare fa v ora bl y t o hist orical c o ntr ols, clearl y t here is a nee d f or 
s u bsta ntial i m pr o ve me nt. 
We ha ve e x pl ore d se veral c o m bi nati o ns at t he Cit y of H o pe c o nsisti n g of 2 c ycles of 
hi g h- d ose c he m ot hera p y f oll o we d b y ste m cell s u p p ort.  F ort y-fi ve patie nts wit h hi g h-
ris k pri mar y or metastatic breast ca ncer ha ve recei ve d 2 c ycles of mel p hala n 2 0- 1 5 0 
m g/ m²/c ycle a n d cis plati n 2 0 0 m g/ m 2/c ycle.  E xce pt f or pr ol o n ge d t hr o m b oc yt o pe nia (at 
t he hi g hest d ose le vel of 2 c ycles of mel p hala n/cis plati n) n o u n us ual t o xicities, a n d m ore 
i m p orta ntl y, n o gra de 3 or 4 t o xicities b y t he N CI a ut ol o g o us b o ne marr o w tra ns pla nt 
criteria were n ote d. 5  We ha ve als o teste d, i n a n o n g oi n g p hase II st u d y f or patie nts wit h 
s oft tiss ue a n d b o ne sarc o mas, a ta n de m c o m bi nati o n c o nsisti n g of d o x or u bici n 1 5 0 
m g/ m 2 a n d if osfa mi de 1 4 g m/ m2 as c ycle 1 a n d mel p hala n 1 5 0 m g/ m² a n d cis plati n 2 0 0 
m g/ m² as c ycle 2.  B ot h treat me nt c ycles were s u p p orte d wit h peri p heral bl o o d ste m 
cells.  T o date, we ha ve n ot e nc o u ntere d a n y si g nifica nt t o xicities ot her t ha n m uc ositis 
si milar i n de gree t o t hat o bser ve d wit h o ur first ge nerati o n hi g h- d ose c o m bi nati o n of 
C A V P ( S o ml o, et. al, u n p u blis he d data). 
I n t he desi g n of effecti ve c he m ot hera pe utic c o m bi nati o ns, se q ue nce of dr u g deli ver y ma y 
als o be i m p orta nt.  A d mi nistrati o n of d o x or u bici n, t he a ge nt wit h t he hi g hest re p orte d 
res p o nse rate, f oll o we d b y C M F f or patie nts wit h sta ge II breast ca ncer, yiel de d a better 
o utc o me t ha n t he sa me 2 treat me nt re gi me ns a d mi nistere d i n a n alter nati n g fas hi o n. 6  I n 
o ur series of 1 1 4 patie nts treate d wit h sta n dar d d ose a dj u va nt c he m ot hera p y f oll o we d b y 
hi g h- d ose c he m ot hera p y c o ns oli dati o n, we ha ve als o o bser ve d better o verall o utc o me i n 
patie nts w h o ha ve recei ve d d o x or u bici n as part of t heir sta n dar d a dj u va nt c he m ot hera p y. 4 
 Base d o n t hese fi n di n gs, o ne ca n p ost ulate t hat a d mi nistrati o n of t he m ost effecti ve 
a ge nts earl y i n t he c o urse of ne oa dj u va nt/a dj u va nt c he m ot hera p y is of t hera pe utic 
si g nifica nce. 
I n rece nt years, paclita xel has e mer ge d as o ne of t he m ost acti ve si n gle a ge nts f or t he 
treat me nt of breast ca ncer wit h res p o nse rates i n t he ra n ge of 5 0 % f or patie nts wit h 
u ntreate d metastatic disease. 7  T his dr u g has bee n i nc or p orate d i nt o o n g oi n g pr os pecti ve, 

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ra n d o mize d trials as part of a dj u va nt t hera p y a n d as first-li ne treat me nt f or metastatic 
disease.  T here is als o rece nt i nf or mati o n o n t he feasi bilit y of e m pl o yi n g G- C S F-
s u p p orte d se q ue ntial, d ose-i nte nse a d mi nistrati o n of d o x or u bici n, 8 0- 9 0 m g/ m², 
paclita xel, 2 0 0- 2 5 0 m g/ m², a n d c ycl o p h os p ha mi de, 3. 0 g m/ m² q 1 4 da ys f or 3 c ycles. 8  
A n i nter gr o u p trial was rece ntl y i nitiate d t o test t he feasi bilit y a n d efficac y of 3 
se q ue ntiall y a d mi nistere d c ycles eac h of d o x or u bici n 8 0 m g/ m², paclita xel, 2 0 0 m g/ m², 
a n d c ycl o p h os p ha mi de 3. 0 g m/ m², as o ne ar m of a ra n d o mize d, pr os pecti ve cli nical trial 
f or patie nts wit h sta ge II ( 4- 9 a xillar y l y m p h n o des i n v ol ve d) breast ca ncer.  Paclita xel, 
w he n a d mi nistere d as 9 6- h o ur c o nti n u o us i nf usi o n, de m o nstrate d si g nifica nt acti vit y i n 
patie nts w h o pre vi o usl y faile d treat me nt wit h s h ort ta xa ne e x p os ure. 9  T he feasi bilit y of 
paclita xel d ose escalati o n has bee n teste d b y se veral gr o u ps i ncl u di n g o ne st u d y i n w hic h 
paclita xel was s uccessf ull y a d de d t o hi g h d oses of c ycl o p h os p ha mi de a n d cis plati n. 1 0  I n 
a n o n g oi n g trial, 3 c ycles of ste m cell s u p p orte d hi g h- d ose c he m ot hera p y c o nsisti n g of 
paclita xel (c ycle 1), mel p hala n (c ycle 2) a n d t hi ote pa, car b o plati n a n d c ycl o p h os p ha mi de 
( S T A M P V) ha ve bee n a d mi nistere d t o patie nts wit h metastatic breast ca ncer wit h o ut 
si g nifica nt t o xicities wit h t he Ta x ol d ose still bei n g escalate d be y o n d 7 2 5 m g/ m². 1 1  At 
o ur i nstit uti o n, d o x or u bici n 1 6 5 m g/ m², c ycl o p h os p ha mi de 1 0 0 m g/ k g, a n d paclita xel u p 
t o 4 7 5 m g/ m² has bee n teste d i n a n o n g oi n g p hase I st u d y, s o far wit h o ut a n y u nt o war d 
t o xicit y.1 2  Of n ote, we ha ve f o u n d n o cli nicall y si g nifica nt decrease i n t he left ve ntric ular 
ejecti o n fracti o n i n o ver 1 2 0 patie nts wit h d o x or u bici n e x p os ure of <  1 8 0 m g/ m² treate d 
wit h hi g h- d ose (ra n ge, 1 5 0- 1 6 5 m g/ m² a d mi nistere d as c o nti n u o us i. v. i nf usi o n o ver 9 6 
h o urs) d o x or u bici n-c o ntai ni n g re gi me ns ( C A V P, d o x or u bici n a n d if osfa mi de, or 
d o x or u bici n, paclita xel a n d c ycl o p h os p ha mi de) f oll o we d b y l ocal-re gi o nal ra diati o n. 
I n or der t o safel y u n der g o t he sec o n d c ycle of hi g h- d ose c he m ot hera p y, patie nts u n der g o 
ri g or o us testi n g of t heir or ga n f u ncti o ns b ot h bef ore t he first a n d sec o n d hi g h- d ose 
treat me nt c ycle.  T o di mi nis h t he li keli h o o d of a n y decrease of left ve ntric ular ejecti o n 
fracti o n f oll o wi n g hi g h- d ose d o x or u bici n/ paclita xel/c ycl o p h os p ha mi de, patie nts will 
recei ve a 9 6 h o ur i nf usi o n of t he car di o pr otecti ve a ge nt de xraz o xa ne c o nc o mita nt wit h 
d o x or u bici n.  De xraz o xa ne, w he n a d mi nistere d as s h ort I V i nf usi o n t o get her wit h 
d o x or u bici n or e pir u bici n pr otects a gai nst car di ot o xicit y wit h o ut a n y a d verse effect o n 
s ur vi val.  1 3, 1 4 I n o ur pil ot data d o x or u bici n 1 6 5 m g/ m2 as 9 6- h o ur i nf usi o n a n d 
de xraz o xa ne 5 0 0 m g/ m 2 gi ve as 9 6- h o ur i nf usi o n wit h o ut ste m cell s u p p ort res ulte d i n 
a d verse effects si milar t o o ur e x perie nce wit h a d o x or u bici n a n d c ycl o p h os p ha mi de 
c o m bi nati o n.  Of 1 0 patie nts treate d wit h a variet y of mali g na ncies we o bser ve d o nl y o ne 
case of as y m pt o matic, re versi ble, 1 0 % decrease i n left ve ntric ular ejecti o n fracti o n i n a 
patie nt wit h t h y m o ma wit h pri or ra diati o n t o t he me diasti n u m ( u n p u blis he d data, C h o w et 
al).  We e x pect a 3 0-f ol d differe nce i n dr u g c o nce ntrati o ns ( de xraz o xa ne vers us 
d o x or u bici n) base d o n o ur p har mac o ki netic meas ures w hic h s h o ul d res ult o pti m u m 
car di o pr otecti o n. 
Base d o n t he a b o ve i nf or mati o n, we pla n t o i nitiate a cli nical st u d y t hat will: a d mi nister 
ne oa dj u va nt c he m ot hera p y deli veri n g t he m ost  acti ve dr u g ( d o x or u bici n) first, f oll o we d 
b y paclita xel; pr o vi de a g gressi ve l ocal c o ntr ol wit h m o difie d ra dical mastect o m y; 
a d mi nister paclita xel a n d c ycl o p h os p ha mi de wit h G- C S F s u p p ort a n d c ollect peri p heral 
bl o o d pr o ge nit or ste m cells o n rec o ver y fr o m t he na dir; c o ns oli date wit h ta n de m c ycles 
of hi g h- d ose d o x or u bici n, c ycl o p h os p ha mi de a n d paclita xel f oll o we d b y mel p hala n a n d 
cis plati n wit h G- C S F pri me d ste m cell resc ue; c o m plete l ocal-re gi o nal c o ntr ol wit h 
1/ 6/ 0 0 

I R B # 9 6 1 3 9 
6  
J u ne 1 0, 2 0 0 4 
Ver. 1 5 
ra diati o n t hera p y; a n d pr o vi de ta m o xife n f or 5 years f or patie nts wit h rece pt or p ositi ve 
pri mar y t u m ors. 
We e x pect t hat a si g nifica nt n u m ber of patie nts wit h i nfla m mat or y breast ca ncer will 
ha ve recei ve d part or all of t heir ne oa dj u va nt c he m ot hera p y b y t heir pri mar y o nc ol o gist 
pri or t o e val uati o n at o ur i nstit uti o n.  He nce, we pla n t o assess t he efficac y of 
ne oa dj u va nt c he m ot hera p y as well as t he t otal treat me nt strate g y i n patie nts recei vi n g t he 
e ntire  treat me nt pr o gra m (strat u m 1) a n d will als o e val uate t he p ote ntial be nefit of 
paclita xel a n d c ycl o p h os p ha mi de f oll o we d b y ta n de m c ycles of hi g h- d ose c he m ot hera p y 
i n t h ose patie nts w h o w o ul d be referre d t o t he Cit y of H o pe Nati o nal Me dical Ce nter 
f oll o wi n g ne oa dj u va nt c he m ot hera p y a n d s ur ger y (strat u m 2). 
We ha ve re p orte d o ur fi n di n gs o n t he c orrelati o ns bet wee n m or p h ol o gic a n d m ore 
f u ncti o nal c haracteristics ( gra de, mit otic i n de x, i m m u n o hist oc he mical a nal ysis of p 5 3 
m utati o n, C- er bB- 2 e x pressi o n, rece pt or stat us, Ki- 6 7 p ositi vit y) a n d rela pse-free a n d 
o verall s ur vi val f oll o wi n g hi g h- d ose c he m ot hera p y c o ns oli dati o n i n 9 0 hi g h-ris k breast 
ca ncer patie nts treate d wit h hi g h- d ose c he m ot hera p y a n d ste m cell s u p p ort.  We ha ve 
pr o p ose d t he prese nce of p 5 3 m utati o n, estr o ge n a n d pr o gester o ne rece pt or ne gati vit y, 
a n d i ncrease d pr oliferati o n as a d verse pr o g n ostic feat ures. 1 5  Si nce t he i nitial a nal ysis, 
i m m u n o hist oc he mical stai ni n g f or t he prese nce of p- gl yc o pr otei n a n d M R P has als o bee n 
perf or me d o n t he sa me paraffi n e m be d de d tiss ue s peci me ns.  We pla n t o e x pa n d o n o ur 
past w or k b y e xa mi ni n g t he sa me bi oc he mical mar kers i n fres h tiss ue w he n a vaila ble.  I n 
patie nts wit h i nfla m mat or y carci n o ma, we ha ve a u ni q ue o p p ort u nit y t o l o o k f or mar kers 
of b ot h de n ov o  a n d ac q uire d dr u g resista nce wit h t he a vaila bilit y of bi o ps y tiss ue at t he 
ti me of dia g n osis a n d mastect o m y. 
O nl y a relati vel y s mall perce nta ge ( ~ 5 %) of breast ca ncer patie nts are me m bers of 
fa milies wit h B R C A 1 or B R C A 2 m utati o ns, mar kers ass ociate d wit h here ditar y breast 
ca ncer. 1 6  T here are retr os pecti ve data s u g gesti n g t hat y o u n ger a ge at t he ti me of 
dia g n osis ma y be a ma nifestati o n of a g gressi ve cli nical disease. 1 7  O nset of disease at a 
relati vel y y o u n g a ge is als o o ne of t he p ote ntial hall mar ks of here ditar y cl usteri n g.  We 
ha ve treate d o ver 3 0 0 patie nts wit h hi g h-ris k breast ca ncer ( 4 4 patie nts wit h sta ge III B 
i nfla m mat or y disease) o n o ne of f o ur hi g h-d ose c he m ot hera p y pr ot oc ols.  T he me dia n 
a ge at t he ti me of e nr oll me nt was 4 2 years (ra n ge, 2 5- 6 3).  He nce, as part of t he i nitial 
scree ni n g f or st u d y eli gi bilit y we pla n t o as k patie nts t o partici pate i n a n e val uati o n of 
fa mil y/ here ditar y bac k gr o u n d.  F or t h ose patie nts fitti n g t he pr ofile of here ditar y breast 
ca ncer, a p pr o priate c o u nseli n g, a n d if re q ueste d, fa mil y e val uati o n will be pr o vi de d.  I n 
a d diti o n, b ot h paraffi n e m be d de d a n d fres h tiss ue sa m ples of t he pri mar y t u m or a n d 
bl o o d sa m ples will be teste d f or s urr o gate si g ns of here ditar y disease as t he y bec o me 
a vaila ble. 
3. 0 
D R U G I N F O R M A TI O N  
3. 1.  
C ycl o p h os p ha mi de [ N S C- 2 6 2 7 1]  
3. 1. 1.  M o de of Acti o n:  C ycl o p h os p ha mi de is a wea k al k ylati n g a ge nt.  T he dr u g 
u n der g oes e nz y matic o xi dati o n a n d a d diti o nal m ulti-ste p pr ocesses 
res ulti n g i n e n d- pr o d ucts wit h i ncrease d al k ylati n g pr o perties. 

I R B # 9 6 1 3 9 
7  
J u ne 1 0, 2 0 0 4 
Ver. 1 5 
3. 1. 2.  T o xicities:  Al o pecia, na usea, v o miti n g, st o matitis, diarr hea, s ki n ras h, 
pa nc yt o pe nia, sterilit y, decrease d g o na dal f u ncti o n, he m orr ha gic c ystitis, 
s y n dr o me of i na p pr o priate a nti di uretic h or m o ne secreti o n, i m m u ne 
s u p pressi o n, i nterstitial p ul m o nar y fi br osis, le u ke m o ge nic p ote ntial, a n d at 
e xtre mel y hi g h d oses, m y ocar dial necr osis. 
3. 1. 3.  P har mace utical data:  C ycl o p h os p ha mi de is a vaila ble i n 1 0 0 m g, 2 0 0 m g, 
a n d 5 0 0 m g a m p ules c o ntai ni n g w hite p o w der.  T he dr u g ca n be 
rec o nstit ute d i n n or mal sali ne or 5 % de xtr ose a n d water.  T he dr u g s h o ul d 
be diss ol ve d a n d gi ve n i n a p pr o xi matel y 2 5 0 cc of dil ue nt as ra pi d I V 
i nf usi o n o ver 1 h o ur. 
3. 1. 4.  Sta bilit y.  St ore at r o o m te m perat ure.  D o n ot st ore at te m perat ures a b o ve 
9 0 de grees F. 
3. 1. 5.  C ycl o p h os p ha mi de is c o m merciall y a vaila ble. 
3. 2.  
D o x or u bici n [ N S C 1 2 3 1 2 7]  
3. 2. 1.  Mec ha nis m of acti o n:  D o x or u bici n, a n a nt hrac ycli ne deri vati ve, is k n o w n 
t o e n ga ge i n o xi dati o n-re d ucti o n reacti o ns, ge nerati n g free ra dicals a n d t o 
i ntercalate wit h D N A t h us pre ve nti n g D N A a n d R N A s y nt hesis.  I n 
a d diti o n, t he dr u g ca n ca use alterati o ns i n me m bra ne a n d t o p ois o merase II 
f u ncti o n. 
3. 2. 2.  T o xicit y:  Al o pecia, na usea, v o miti n g, m uc ositis, p hle bitis at t he site of 
i njecti o n, tiss ue necr osis at t he site of e xtra vasati o n are all fre q ue ntl y 
re p orte d si de effects.  Se vere car di o m y o pat h y occ urs pre d o mi na ntl y at 
hi g her c u m ulati ve d oses, i n e xcess of 5 5 0 m g/ m 2.  Ac ute car diac 
t o xicities, n ot pre dicta ble base d o n prece di n g me dical e val uati o n, ha ve 
als o bee n descri be d.  M yel os u p pressi o n, pre d o mi na ntl y le u k o pe nia a n d 
gra n ul oc yt o pe nia, occ urs a b o ut 2 wee ks p ost i njecti o n.  A ne mia a n d 
t hr o m b oc yt o pe nia occ ur t o a s u bsta ntiall y lesser de gree.  Sec o n dar y 
he mat ol o gical mali g na nc y a n d d ys plasia ha d bee n re p orte d i n patie nts 
f oll o wi n g c he m ot hera p y wit h d o x or u bici n-c o ntai ni n g c o m bi nati o n wit h a n 
i nci de nce of < 0. 2 5 %. 
3. 2. 3.  P har mace utical data:  D o x or u bici n is s u p plie d i n 1 0 a n d 5 0 m g vials as a 
re d- ora n ge, freeze- drie d p o w der wit h u p t o 2 years of st ora ge a bilit y.  
Rec o nstit uti o n ca n be d o ne i n n or mal sali ne or sterile water.  I n t his st u d y, 
patie nts eit her will recei ve t he dail y d ose o ver 2 4 h o urs, rec o nstit ute d i n 
o ne liter of De xtr ose c o ntai ni n g fl ui d, or if p orta ble p u m ps are feasi ble, 
t he dail y d ose of d o x or u bici n will be rec o nstit ute d i n 2 0 cc of 5 % de xtr ose 
a n d t he deli ver y s yste m will be c ha n ge d e ver y 2 4 h o urs. 
3. 2. 4.  Sta bilit y:  D o x or u bici n is c he micall y sta ble f or 2 4 h o urs at r o o m 
te m perat ure a n d f or 4 8 h o urs u n der refri gerati o n.  Rec o nstit ute d s ol uti o n 
s h o ul d be use d wit hi n 8 h o urs.  Preser vati ves s h o ul d n ot be use d wit h 
dil ue nts d ue t o t he p ote ntial t o w orse n t he effects of e xtra vasati o n. 

I R B # 9 6 1 3 9 
8  
J u ne 1 0, 2 0 0 4 
Ver. 1 5 
3. 2. 5.  D o x or u bici n is c o m merciall y a vaila ble. 
3. 3.  
Paclita xel [( Ta x ol ®) N S C # 1 2 5 9 7 3]  
3. 3. 1.  F or m ulati o n:  Sterile s ol uti o n c o ntai ni n g 6 m g/ ml i n a 5 ml (i.e. 3 0 m g) 
a m p ule.  It is f or m ulate d i n Cre m o p h or E L ® ( p ol y o x yet h ylate d cast or oil 
a n d de h y drate d alc o h ol U. S. P.).  I n tact paclita xel vials s h o ul d be st ore d 
at 2- 8°C.  After fi nal dil uti o n, paclita xel s ol uti o ns of 0. 3- 1. 2 m g/ ml are 
sta ble f or 2 7 h o urs. 
3. 3. 2.  T he d ose-li miti n g t o xicit y of paclita xel is ne utr o pe nia.  Ot her k n o w n 
t o xicities i ncl u de m yal gias, art hral gias, fati g ue, na usea, v o miti n g, 
m uc ositis, st o matitis, diarr hea, p har y n gitis, arr h yt h mia, li ver f u ncti o n test 
a b n or malities (ele vate d S G O T, S G P T, bilir u bi n, al kali ne p h os p hatase), 
he patic fail ure, he patic necr osis, st o matitis, t y p hlitis, isc he mic c olitis, 
ne utr o pe nic e nter oc olitis, ra diati o n recall reacti o ns, ve ntric ular 
tac h ycar dia, atrial arr h yt h mia, heart bl oc k, m y ocar dial i nfarcti o n, 
h y p ote nsi o n, h y perte nsi o n ( p ossi bl y relate d t o c o nc o mita nt 
De xa met has o ne), m o o d c ha n ges, he patic e nce p hal o pat h y, e nce p hal o pat h y, 
se ns or y c ha n ges (taste), peri p heral ne ur o pat h y, m yel os u p pressi o n, 
seiz ures, a na p h ylact oi d reacti o ns, urticaria, fl us hi n g, pr urit us, li g ht-
hea de d ness, m y o pat h y, al o pecia, s ki n ras h, a n d visi o n c ha n ges (se nsati o n 
of flas hi n g li g hts, bl urre d visi o n).  L ocal i nfiltrati o n wit h Ta x ol will ca use 
mil d l ocal s y m pt o ms (er yt he ma, i n d urati o n, te n der ness, a n d rarel y, 
ulcerati o n) t hat us uall y res ol ve wit hi n a wee k.  W he n Ta x ol has bee n 
a d mi nistere d wit h G- C S F, t here ha ve bee n re p orts of isc he mic or i nfarcte d 
c ol o n, s o meti mes wit h ot her GI tract i n v ol ve me nt. 
3. 3. 3.  Paclita xel m ust be a d mi nistere d i n glass or p ol y olefi n c o ntai ners.  
Nitr o gl yceri n a d mi nistrati o n sets ( p ol yet h yle ne li ni n g) are als o necessar y 
f or Ta x ol a d mi nistrati o n.  D o n ot use or di nar y P V C t u bi n g.  Ta x ol 
s ol uti o ns s h o ul d be filtere d d uri n g a d mi nistrati o n wit h a 0. 2 2 micr o n i n-
li ne filter (e. g. Mille x- G V, Milli p ore; I V E X- 2, A b b ott). 
3. 3. 4.  Ta x ol is c o m merciall y a vaila ble. 
3. 4.  
G- C S F [( Fil grasti m, Ne u p o ge n ®) N S C # 6 1 4 2 9]  
G- C S F or Fil grasti m is a 1 7 5 a mi n o aci d pr otei n ma n ufact ure d b y rec o m bi na nt 
D N A tec h n ol o g y.  It is pr o d uce d b y E. C oli bacteria c o ntai ni n g t he h u ma n 
gra n ul oc yte c ol o n y sti m ulati n g fact or ge ne. 
3. 4. 1.  I ntact vials m ust be st ore d u n der refri gerati o n at 2- 8 °C.  Pr ol o n ge d 
e x p os ure of G- C S F t o te m perat ures o utsi de t his ra n ge will i nacti vate t he 
dr u g.  Freezi n g G- C S F ma y c o m pr o mise t he bi ol o gical acti vit y of t he 
m olec ule. 
3. 4. 2.  G- C S F vials c o ntai n n o preser vati ves .  Discar d vials left at r o o m 
te m perat ure f or greater t ha n 2 4 h o urs.  St ore o pe ne d vials u n der t he 
refri gerati o n at 2- 8°C. 

I R B # 9 6 1 3 9 
9  
J u ne 1 0, 2 0 0 4 
Ver. 1 5 
3. 4. 3.  Mil d t o se vere b o ne pai n, h y p ote nsi o n, a ne mia, taste per versi o n a n d pai n 
at t he s u bc uta ne o us i njecti o n site are t he m ost n ota ble si de effects. 
3. 4. 4.  A d mi nistrati o n is b y s u bc uta ne o us or I V b ol us i njecti o n. 
3. 4. 5.  S pecial Ha n dli n g:  G- C S F i njecti o n s h o ul d n ot be s ha ke n; tra ns p ortati o n 
i n i nstit uti o nal p ne u matic t u be s yste ms or ot her hi g h s pee d mec ha nical 
de vices is als o n ot a d vise d. 
3. 4. 6.  G- C S F is c o m merciall y a vaila ble. 
3. 5.  
C D D P, Cis plati n [ Cis plati n u m II Dia m mi ne dic hl ori de, N S C 1 1 9 8 7 5]  
3. 5. 1.  M o de of Acti o n:  T he pr o p ose d mai n mec ha nis m of acti o n is i nterfere nce 
wit h D N A f u ncti o n b y cr oss-li n ki n g c o m ple me ntar y stra n ds of D N A. 
3. 5. 2.  T o xicit y:  T he maj or ac ute m or bi dit y is na usea a n d e mesis.  
M yel os u p pressi o n is descri be d a n d see ms t o be d ose de pe n de nt.  Re nal 
t o xicit y is ma nifeste d m ostl y as re versi ble rise of ser u m B U N a n d 
creati ni ne a n d electr ol yte-l osi n g ne p hr o pat h y d ue t o fail ure of uri nar y 
c o nce ntrati o n.  T o xicities ass ociate d wit h lar ge c u m ulati ve d oses of 
C D D P are peri p heral a n d occasi o nal a ut o n o mic ne ur o pat h y, hi g h 
fre q ue nc y heari n g l oss, ata xia, bl urr y visi o n a n d defect i n c ol or visi o n. 
3. 5. 3.  P har mace utical Data:  Eac h 2 0 ml vial ( Brist ol) c o ntai ns 1 0 m g 
C D D P( w hite l y o p hilize d ca ke); 9 0 m g Na C L; 1 0 0 m g ma n nit ol ( U S P); 
a n d H C L f or p H a dj ust me nt.  U p o n rec o nstit uti o n wit h 1 0 ml of sterile 
water ( U S P) eac h ml of t he res ulti n g s ol uti o n will c o ntai n 1 m g of C D D P, 
1 0 m g ma n nit ol, 9 m g Na Cl at a p H of 3. 5 - 4. 5.  At 2 2 _C t he rec o nstit ute d 
s ol uti o n is sta ble f or at least 8 h o urs. A d mi nistrati o n is b y i ntra ve n o us 
i nf usi o n i n 3 % sali ne at 2 5 m g/ h o ur. 
3. 5. 4.  S u p plier:  T his dr u g is c o m merciall y a vaila ble. 
3. 6.  
Al kera n ®, Mel p hala n [ L- P he n ylala ni ne M ustar d, L- Pa m]  
3. 6. 1.  M o de of Acti o n:  I n c o m m o n wit h ot her nitr o ge n m ustar ds, mel p hala n 
reacts wit h D N A t o pr o d uce eit her D N A- D N A or D N A- pr otei ns cr oss-
li n ke d pr o d ucts pr o ba bl y b y bi n di n g at t he N- 7 p ositi o n of g ua ni ne. 
3. 6. 2.  S u p pl y, Rec o nstit uti o n a n d A d mi nistrati o n:  Mel p hala n is c o m merciall y 
a vaila ble b y B urr o u g hs Wellc o me C o m pa n y i n sterile vials c o ntai ni n g 5 0 
m g l y o p hilize d dr u g as t he h y dr oc hl ori de salt.  It is f or m ulate d wit h 2 0 m g 
p o vi d o ne per 5 0 m g vial.  Sterile dil ue nt is s u p plie d w hic h c o ntai ns per 1 0 
ml: s o di u m citrate 0. 2 0 g, pr o p yle ne gl yc ol 6 ml, et ha n ol ( 9 5 %) 0. 5 2 6 ml, 
sterile water q.s. 1 0 ml. Rec o nstit ute d vials ( u n dil ute d s ol uti o ns) are sta ble 
f or 9 0 mi n utes.  Mel p hala n dil ute d i n N S t o 0. 1- 0. 4 5 m g/ ml is sta ble f or 
o nl y 6 0 mi n utes.  Mel p hala n is u nsta ble w he n dil ute d wit h N S t o 2 m g/ ml. 
 T he rate of i nf usi o n s h o ul d be 3 0 mi n utes or less. 
1 2/ 1 0/ 0 2 

I R B # 9 6 1 3 9 
1 0  
J u ne 1 0, 2 0 0 4 
Ver. 1 5 
3. 6. 3.  P har mace utical Data: T he dr u g is s u p plie d i n sterile vials c o ntai ni n g 5 0 
m g l y o p hilize d mel p hala n as t he h y dr oc hl ori de salt.  Al kera n ® f or 
i njecti o n is f or m ulate d wit h 2 0 m g p o vi d o ne per 5 0 m g vial.  Sterile 
dil ue nt is s u p plie d w hic h c o ntai ns per 1 0 ml:  s o di u m citrate 0. 2 0 g, 
pr o p yle ne gl yc ol 6. 0 0 ml, et ha n ol ( 9 5 %) 0. 5 2 6 ml, sterile water q.s. 1 0 ml. 
Al kera n ® s h o ul d be rec o nstit ute d wit h t he dil ue nt t o a fi nal c o nce ntrati o n 
of 5 m g/ ml.  Rec o nstit ute d Al kera n ® s h o ul d be dil ute d o nl y wit h 0. 9 % 
sali ne, t o a c o nce ntrati o n n o greater t ha n 2 m g/ ml.  A d mi nistrati o n of 
rec o nstit ute d Al kera n ® s h o ul d be c o m plete d wit hi n o ne h o ur of 
rec o nstit uti o n.  T he rate of i nf usi o n s h o ul d be 1 0 m g/ mi n or less i n or der 
t o a v oi d h y p ote nsi o n fr o m t he pr o p yle ne gl yc ol i n t he dil ue nt. 
3. 7.  
Mes na ( N S C- 1 1 3 8 9 1)  
3. 7. 1.  M o de of Acti o n 
S o di u m- 2- merca pt o-et ha ne s ulf o nate ( Mes na) is a ur ot helial pr otecta nt.  It 
bi n ds t o acr olei n, t he ur ot o xic meta b olite of c ycl o p h os p ha mi de a n d it als o 
i n hi bits t he brea k d o w n of its 4- h y dr o x y meta b olites.  It is e xcrete d 
e xcl usi vel y i n t he uri ne. 
3. 7. 2.  S u p pl y, rec o nstit uti o n a n d a d mi nistrati o n 
Mes na is a vaila ble fr o m Brist ol- M yer S q ui b b as a 1 0 0 m g/ ml s ol uti o n 
( 4 0 0 m g/ ml a m p ule).  It ma y be a d mi nistere d i ntra ve n o usl y b y b ol us a n d 
/ or c o nti n u o us i nf usi o n. 
3. 7. 3.  T o xicit y 
Na usea a n d v o miti n g are t he o nl y o bser ve d si de effects. 
3. 8.  
De xraz o xa ne (I C R F 1 8 7) 
3. 8. 1.  C he mistr y: 2, 6- Pi perazi ne di o ne, 4, 4'-( 1  met h yl- 1, 2-et ha ne di yl) bis, ( +)-, 
( S)- or De xraz o xa ne (als o k n o w as A D R- 5 2 9), is a w hite t o off- w hite 
p o w der wit h a m olec ular wei g ht of 2 8 6. 3 a n d a melti n g p oi nt of 1 9 3˜ C  t o 
1 9 4˜ C.   T he m olec ular f or m ula of t his c o m p o u n d is C 1 1H 1 6N 4O 4. 
3. 8. 2.  Mec ha nis m of Acti o n: De xraz o xa ne acts i n part b y c helati o n of metals a n d 
di vale nt cati o ns.  T his a ge nt als o i n hi bits D N A s y nt hesis, p ossi bl y b y 
acti n g as a bif u ncti o nal al k ylat or.  I n hi biti o n of t o p ois o merase II has als o 
bee n de m o nstrate d as a n acti o n of De xraz o xa ne. 
3. 8. 3.  T o xic ol o g y: P hase I st u dies perf or me d t o date ha ve re veale d 
m yel os u p pressi o n t o be t he pri mar y t o xicit y, wit h le u k o pe nia m ore 
pr o mi ne nt t ha n t hr o m b oc yt o pe nia.  Re versi ble li ver f u ncti o n 
a b n or malities, m ol d na usea a n d v o miti n g, al o pecia, l o w gra de fe ver, 
malaise, a n d pai n at t he i njecti o n site ha ve als o bee n n ote d.  I ncrease d 
uri nar y cleara nces of metals ha ve bee n f o u n d. 
1/ 6/ 0 0 

I R B # 9 6 1 3 9 
1 1  
J u ne 1 0, 2 0 0 4 
Ver. 1 5 
3. 8. 4.  P har mace utical Data: De xraz o xa ne is s u p plie d i n vials as a sterile 
l y o p hilize d p o w der f or i njecti o n.  Eac h vial c o ntai ns 5 0 0 m g De xraz o xa ne 
a n d u p o n rec o nstit uti o n wit h 5 0 m L M/ 6 s o di u m lactate f or i njecti o n U S P, 
yiel ds 5 0 m L wit h dra wa ble s ol uti o n c o ntai ni n g 1 0 m g De xraz o xa ne per 
m L.  T he d osa ge f or m is pac ka ge d i n 5 0 cc a m ber vials t hat c o ntai n n o 
preser vati ves.  T he s helf-life of t he u nrec o nstit ute d vial at a m bie nt 
te m perat ure is o ne year.  Base d o n a sta bilit y st u d y perf or me d at t he Cit y 
of H o pe, t he dil ute d De xraz o xa ne at a c o nce ntrati o n of 0. 1 m g/ ml t o 1 
m g/ ml is sta ble f or 2 4 h o urs.  T he pr o d uct is t o be a d mi nistere d via t he 
i ntra ve n o us r o ute, wit h n o s pecial t u bi n g re q uire d.  T he rec o nstit ute d 
s ol uti o n is p h ysicall y c o m pati ble wit h M/ 6 s o di u m lactate, 5 % de xtr ose 
i njecti o n, D. 5 n or mal sali ne, 0. 4 5 % sali ne, a n d D. 5- 0. 4 5 % sali ne.  T he p H 
of t he rec o nstit ute d s ol uti o n is 4. 5 ± 0. 3.  E xtra vasati o n i nj ur y has n ot 
bee n a pr o ble m wit h t he a d mi nistrati o n of t his dr u g. 
3. 8. 5.  S u p plier: T he f or m ulati o n is c o m merciall y a vaila ble. 
4. 0 
P A TI E N T E LI GI BI LI T Y  
4. 1.  
P A TI E N T S M U S T M E E T T H E F O L L O WI N G E LI GI BI LI T Y C RI T E RI A: 
4. 1. 1.  Patie nts m ust ha ve hist ol o gicall y pr o ve n breast ca ncer wit h cli nical 
feat ures of i nfla m mati o n, er yt he ma, pai n or h y perse nsiti vit y, e de ma ( pea u 
d’ ora n ge) or  t hic ke ni n g of t he s ki n, or 
4. 1. 2.  Der mal/e pi der mal i n vasi o n s h o ul d be prese nt i n t he bi o ps y s peci me n. 
4. 1. 3.  Patie nts m ust ha ve sta ge III B disease. 
4. 1. 4.  Patie nts m ust ha ve a perf or ma nce stat us of 8 0 % or greater (see attac he d 
Perf or ma nce Stat us Scale). 
4. 1. 5.  Patie nts wit h a p h ysi ol o gical a ge <  6 0 years are eli gi ble. 
4. 1. 6.  Bilir u bi n <  1. 5 m g/ dl a n d S G O T or S G P T < 2 x t he u p per li mit of n or mal. 
4. 1. 7.  Creati ni ne <  1. 2 m g/ dl a n d creati ni ne cleara nce > 7 0 cc/ m L. 
4. 1. 8.  Ne utr o p hil c o u nt >  1. 5 0 0/µ l, platelet c o u nt > 1 0 0, 0 0 0/˜l. 
4. 1. 9.  Patie nts m ust ha ve a left ve ntric ular ejecti o n fracti o n >  5 5 % o n M U G A 
sca n. 
4. 1. 1 0. Patie nts m ust ha ve a F E V 1 of >  6 0 % pre dicte d, a r o o m air p O2 > 8 5 
m m H g, a r o o m air p C O 2 < 4 3 m m H g, a n d a D L C O > 6 0 % of t he l o wer 
li mit of pre dicte d val ue. 
4. 1. 1 1. Pretreat me nt la b orat or y a n d x-ra y para meters m ust ha ve bee n perf or me d 
wit hi n 4 wee ks pri or t o t he i nitiati o n of t hera p y. 
0 7/ 0 1 
1 1/ 9 8 

I R B # 9 6 1 3 9 
1 2  
J u ne 1 0, 2 0 0 4 
Ver. 1 5 
4. 1. 1 2. All patie nts m ust ha ve si g ne d t he i nf or me d c o nse nt i n acc or da nce wit h 
i nstit uti o nal a n d fe deral g ui deli nes. 
4. 1. 1 3. Patie nts m ust be wit hi n 1 8 m o nt hs fr o m t he ti me of dia g n osis a n d wit hi n 
1 2 m o nt hs of t heir last c he m ot hera p y. 
4. 2.  
P A TI E N T S A R E I N E LI GI B L E I F T H E Y F U L FI L L A N Y T H E F O L L O WI N G 
C RI T E RI A: 
4. 2. 1.  Hist or y of pri or mali g na nt disease i n t he past 5 years, e xce pt f or s q ua m o us 
or basal cell s ki n carci n o ma, a n d sta ge I or i n sit u cer vical carci n o ma. 
4. 2. 2.  Or ga nic C N S d ysf u ncti o n. 
4. 2. 3.  Hist or y of a n y pre vi o us val v ul ar heart disease or arr h yt h mia. 
4. 2. 4.  Pre vi o us hist or y of he m orr ha gic c ystitis. 
4. 2. 5.  C urre nt pre g na nc y. 
4. 2. 6.  Patie nts wit h a k n o w n a n d p ote ntiall y disa bli n g ps yc h os ocial hist or y are 
i neli gi ble. 
4. 2. 7.  Patie nts wit h pri or ra diati o n t o t he left c hest wall are i neli gi ble. 
4. 2. 8.  Patie nts wit h he patitis B A g p ositi vit y or a p ositi ve HI V a nti b o d y are 
i neli gi ble. 
4. 2. 9.  Patie nts w h o are ca n di dates f or treat me nt o n strat u m 1 s h o ul d ha ve 
recei ve d < 1 c ycle of c he m ot hera p y. 
4. 2. 1 0. Patie nts w h o are ca n di dates f or treat me nt o n strat u m 2 m ust ha ve recei ve d 
< 2 4 0 m g/ m 2 d o x or u bici n a n d <7 5 0 m g/ m 2 paclita xel gi ve n as a s h ort 
i nf usi o n or <4 2 0 m g/ m 2 gi ve n as c o nti n u o us i. v. i nf usi o n ( >9 6 h o urs). 
4. 2. 1 1. Patie nts wit h a hist or y of i nfla m mat or y b o wel disease are e xcl u de d. 
5. 0 
P R E T R E A T M E N T E V A L U A TI O N  
5. 1.  
P h ysical e val uati o n a n d b ot h la b orat or y a n d ra di o gra p hic e val uati o n will be 
perf or me d acc or di n g t o t he st u d y cale n dar liste d u n der Secti o n 9.  Patie nts will be 
e val uate d pri or t o ne oa dj u va nt t hera p y a n d pri or t o peri p heral bl o o d ste m cell 
c ollecti o n (strat u m 1)  or if t he y al rea d y u n der we nt m o difie d ra dical mastect o m y, 
pri or t o t he first c ycle of paclita xel o n t his pr ot oc ol (strat u m 2). 
5. 2.  
Pretreat me nt testi n g/re q uire me nts. 
5. 2. 1.  Hist or y a n d p h ysical e xa mi nati o n. 
5. 2. 2.  Ra di o gra p hic e val uati o n as i n dicate d ( C T of c hest, a b d o me n or pel vis, 
M RI of t he hea d a n d b o ne sca n). 
0 9/ 0 1 
7/ 2 8/ 9 9 
4/ 2 9/ 0 2 

I R B # 9 6 1 3 9 
1 3  
J u ne 1 0, 2 0 0 4 
Ver. 1 5 
5. 2. 3.  P ul m o nar y f u ncti o n test, A B G's 
5. 2. 4.  M U G A sca n, E K G 
5. 2. 5.  He patitis a n d HI V pa nel, S M A 1 8, P T, P T T, C B C, differe ntial a n d platelet 
c o u nt. 
5. 2. 6.  T we nt y-f o ur h o ur creati ni ne cleara nce. 
5. 2. 7.  Bilateral b o ne marr o w bi o psies, u nilateral as pirate, c yt o ge netics. 
5. 2. 8.  A B O, R h a n d H L A t y pi n g. 
5. 2. 9.  Uri ne pre g na nc y test f or pre me n o pa usal fe male patie nts 
5. 2. 1 0. D o u ble l u me n ce ntral ve n o us cat heter place me nt, size >  1 2. 0 Fre nc h. 
6. 0 
D E S C RI P TI V E F A C T O R S  
6. 1.  
Stratificati o n 
6. 1. 1.  Patie nts w h o ha ve recei ve d all  p hases of treat me nt i ncl u di n g ne oa dj u va nt 
t hera p y o n t his pr ot oc ol (strat u m 1) vers us t h ose patie nts e nr olle d o n st u d y 
after c o m pleti o n of s ur ger y (strat u m 2). 
6. 2.  
Descri pti ve Fact ors 
6. 2. 1.  Pat h ol o gical C R vers us P R at t he ti me of m o difie d ra dical mastect o m y. 
6. 2. 2.  Estr o ge n a n d/ or Pr o gester o ne rece pt or p ositi ve vers us rece pt or ne gati ve 
pri mar y t u m ors. 
6. 2. 3.  Pat h ol o gical a n d cli nical vers us cli nical o nl y si g ns of i nfla m mat or y 
disease. 
6. 2. 4.  P ost me n o pa usal ( > 1 2 m o nt hs si nce last  peri o d [ wit h o ut h ysterect o m y] or  
   pri or bilateral o o p h orect o m y]) vers us pre- a n d peri me n o pa usal patie nts 
7. 0 
T R E A T M E N T P L A N  
I deal b o d y wei g ht will be use d w he n calc ulati n g d ose f or all c he m ot hera pe utic a ge nts. 
7. 1.  
Patie nt Re gistrati o n 
After all pretreat me nt e val uati o ns ha ve b ee n perf or me d a n d wit hi n f o ur wee ks of 
a ntici pate d ne oa dj u va nt c he m ot hera p y (strat u m 1) or paclita xel t hera p y (strat u m 
2) patie nts ca n be e ntere d o n st u d y.  Eli gi bilit y re q uire me nts m ust be re vie we d b y 
a me m ber of t he De part me nt of Bi ostatistics. 
7. 2.  
Stratificati o n of Treat me nt Sc he ma 
T here will be t w o treat me nt strata.  All patie nts e nr olli n g after <  1 c ycle of pri or 
ne oa dj u va nt c he m ot hera p y will u n der g o all treat me nt p hases ( patie nts alrea d y 

I R B # 9 6 1 3 9 
1 4  
J u ne 1 0, 2 0 0 4 
Ver. 1 5 
treate d wit h 1 c ycle of d o x or u bici n-c o ntai ni n g c he m ot hera p y will recei ve o nl y 2 
c ycles of ne oa dj u va nt d o x or u bici n); patie nt s w h o ha ve recei ve d m ore t ha n 1 c ycle 
of ne oa dj u va nt c he m ot hera p y will e nr oll f oll o wi n g m o difie d ra dical mastect o m y. 
Patie nts w h o ha ve recei ve d m ore t ha n 1 c ycle of ne oa dj u va nt or a dj u va nt 
c he m ot hera p y a n d ha ve u n der g o ne m o difie d ra dical mastect o m y will be e nr olle d 
t o start wit h Paclita xel 1 4 0 m g/ m² I V o ver 9 6 h o urs as pri mi n g, a n d will c o nti n ue 
o n pr ot oc ol wit h ste m cell har vest a n d t he n ta n de m c ycles of hi g h- d ose 
c he m ot hera p y. 
Ne oa dj u va nt C he m ot hera p y  
D o x or u bici n   
7 5 m g/ m² I V o ver 9 6 h o urs ; Da ys 1- 4,  
 
1 5- 1 9, 2 9- 3 2 
Paclita xel  
1 4 0 m g/ m² I V o ver 9 6 h o urs; Da ys 4 3- 4 7, 5 7- 6 0 
G- C S F 
5 µ g/ k g sc, da ys 5- 1 0, 2 0- 2 5, 3 3- 3 8, 4 8- 5 5 
 
a n d 6 1- 6 8 
a d mi nistrati o n ma y c o nti n ue be y o n d t he da ys liste d 
if t he a bs ol ute gra n ul oc yte c o u nt is < 1 0 0 0/µ l 
Ofl o xaci n  
4 0 0 m g p o, BI D o n da ys 4 8- 5 5 a n d 6 1- 6 8 
M o difie d Ra dical Mastect o m y   
Bet wee n Da ys 7 0 a n d 8 0 after i nitiati o n of 
  
  
  
  
  
c he m ot hera p y 
Paclita xel  
1 4 0 m g/ m 2, I V o ver 9 6 h o urs; Da ys 1 0 0- 1 0 4 
G- C S F 
5 µ / k g, sc, Da ys 1 0 5- 1 1 0 
G- C S F 
1 0 µ / k g, sc, Da ys 1 1 1- 1 1 6 
Har vesti n g a n d Cr y o preser vati o n of Ste m Cells  
P B S C c ollecti o n  
Da ys 1 1 3- 1 1 6 
A t otal of >  1 4 x 1 08 m o n o n uclear cells/ k g wit h a C D 3 4+  cell c o nte nt of > 6 x 
1 0 6/ k g will be pr oc ure d. 
I n case of tec h nical pr o ble ms, or ti me, or ge o gra p hical c o nstrai nts, a ut ol o g o us 
b o ne marr o w ca n be c ollecte d as a n a dj u nct, i nstea d of peri p heral ste m cells 
f oll o wi n g t he t hir d c ycle of paclita xel.  T he peri p heral ste m cells a n d a ut ol o g o us 
b o ne marr o w will be pr ocesse d a n d cr y o preser ve d acc or di n g t o sta n dar d 
pr oce d ures at t he C O H ste m cell a p heresis a n d c yr o preser vati o n facilities. 
Hi g h- D ose C he m ot hera p y  
C ycle 1 – D o x or u bici n, C ycl o p h os p ha mi de a n d Ta x ol ( A C T)  
0 2/ 9 8 
0 7/ 0 1 

I R B # 9 6 1 3 9 
1 5  
J u ne 1 0, 2 0 0 4 
Ver. 1 5 
D a y – 7 
A d missi o n, c hec k la b orat or y a n d x-ra y data, hist or y a n d 
p h ysical. 
 
Start oral ofl o xaci n 4 0 0 m g bi d. 
 
Pr o p h ylactic a nti bi otics will be c o nti n ue d dail y, u ntil 
patie nt is re m o ve d fr o m is olati o n, or s yste mic a nti bi otics 
nee d t o be starte d. 
 
Oral a m p h oterici n 1 0 m g/ 5 cc 6 x per da y a n d N ystati n 
va gi nal s u p p osit ories dail y will be gi ve n. 
 
D o x or u bici n 1 6 5 m g/ m 2 c o nti n u o us I V i nf usi o ns will be 
starte d at n o o n , c o nc o mita nt wit h 5 0 0 m g/ m2 of 
de xraz o xa ne as c o nti n u o us i nf usi o n. 
D a ys – 6 
t hr o u g h – 3  C o nti n u o us i nf usi o nal d o x or u bici n a n d de xraz o xa ne f or a 
t otal of 9 6 h o urs. 
D a y – 3  
At 1 5: 0 0 p m:   Mes na ( 4 0 % of c ycl o p h os p ha mi de d ose) I V 
will be starte d a n d will be gi ve n o ver 1 5 mi n utes.  T he 
sa me d ose will be re peate d at 3 h o urs.  T he n Mes na ( 2 4 0 % 
of c ycl o p h os p ha mi de d ose) will be i nf use d o ver 2 1 h o urs. 
 
F oll o wi n g t he a d mi nistrati o n of t he first d ose of Mes na, 
c ycl o p h os p ha mi de 1 0 0 m g/ k g will be gi ve n I V o ver 2 
h o urs i n 5 0 0 cc of D 5/ N S. 
D a y – 2 
F oll o wi n g pre me dicati o n wit h 2 0 m g p o deca dr o n 1 2 a n d 6 
h o urs pri or t o a d mi nistrati o n, a n d 1 h o ur after 2 5 m g of 
Be na dr yl I V a n d 3 0 0 m g of p o Ta ga met, at 1 5: 0 0  a 2 4- 
h o ur c o nti n u o us i nf usi o n of Ta x ol, 7 2 5 m g/ m², will be 
starte d. 
D a y – 1   
start G- C S F 5 µ g/ k g, dail y, I V. 
D a y – 0   
rei nf usi o n of ~ 5 0 % of peri p heral ste m cells. 
G- C S F  
5 µ g/ k g I V, dail y, u ntil A G C > 1 0 0 0/ µ l x 3 da ys 
 
Starti n g as earl y as p ossi ble at 4 t o 6 wee ks fr o m t he first 
da y of c ycle. 
C ycle 2 – Mel p hala n a n d Cis plati n  
D a y – 1 1 
A d missi o n, hist or y a n d cli nical e val uati o n, S M A- 1 8, M g + + , 
 C B C, differe ntial a n d P L T c o u nt, retic ul oc yte c o u nt, 
uri nal ysis, E K G, M U G A sca n, a n d a d diti o nal la b orat or y 
tests as nee de d.  C hest x-ra y a n d a d diti o nal ra di o gra p hic 
tests as necessar y.  Start pr o p h ylactic a nti bi otic: Ofl o xaci n 
1/ 6/ 0 0 
1/ 6/ 0 0 
0 2/ 9 8 

I R B # 9 6 1 3 9 
1 6  
J u ne 1 0, 2 0 0 4 
Ver. 1 5 
4 0 0 m g bi d; a d mi nistrati o n of t he a nti bi otic will  c o nti n ue 
dail y u ntil patie nt re m o ve d fr o m is olati o n, or s yste mic 
a nti bi otics are starte d f or ne utr o pe nic fe vers. Oral 
A m p h oterici n s ol uti o n, 1 0 m g i n 5 cc, will be gi ve n si x 
ti mes dail y.  Patie nts will be gi ve n N ystati n va gi nal 
s u p p osit ories dail y, a n d me nstr uati n g w o me n will recei ve 
n oret hi n dr o ne acetate 1 5 m g orall y o nce a da y. 
 
At 1 1 A M i ntra ve n o us h y drati o n wit h n or mal sali ne at 2 0 0 
cc/ hr will be starte d, a n d e n d after 6 h o urs, I V mel p hala n 
7 5 m g/ m 2 will be i nf use d i n <3 0 mi n utes.  I m me diatel y 
f oll o wi n g t he i nf usi o n of mel p hala n, C D D P 1 0 0 m g/ m2 at a 
rate of 2 5 m g/ hr will be i nf use d i n 3 % sali ne.  Pri or t o 
deli ver y of C D D P, ma n nit ol 2 5 g m, a n d if necessar y, I V 
f ur ose mi de will be gi ve n.  I V h y drati o n will c o nti n ue wit h 
n or mal sali ne a n d sta n dar d electr ol ytes at a rate of 2 0 0 
cc/ h o ur f or a n a d diti o nal 8 h o urs. Ma n nit ol a n d f ur ose mi de 
will be use d as necessar y t o mai ntai n di uresis. A p pr o priate 
a nti na usea me dicati o ns will be gi ve n. 
D a y – 1 0 
t o – 5  
C o nti n ue wit h I V h y drati o n t o mai ntai n e u v ole mia, a n d 
a nti na usea  me dicati o ns as nee de d.  G- C S F 5 
micr o gra ms/ k g/ da y will be gi ve n i ntra ve n o usl y a n d 
disc o nti n ue d o n da y - 6. 
D a y – 4   
Re peat se q ue nce of h y drati o n, mel p hala n a n d C D D P as 
s pecifie d o n da y - 1 1. 
D a y – 3 
t o 0 
C o nti n ue wit h I V h y drati o n a n d a nti na usea me dicati o ns as  
nee de d. 
D a y – 3   
A p pr o xi matel y 1 2. 5 % of t he t otal a m o u nt of ste m cells 
c ollecte d will be rei nf use d.  G- C S F 5 µ g/ k g dail y will be 
gi ve n i ntra ve n o usl y f oll o wi n g rei nf usi o n of ste m cells.  If 
t he n u m ber of   fr oze n ste m cells a vaila ble d oes n ot all o w 
partiti o n i nt o t his ra n ge, t he n a mi ni m u m of o ne ba g will be 
gi ve n.  T he fr oze n peri p herall y har veste d cells will be 
re m o ve d fr o m li q ui d nitr o ge n a n d t ha we d i n a 3 7°C water 
bat h.  Eac h ba g will be ra pi dl y i nf use d, u n dil ute d, t hr o u g h 
sta n dar d I V t u bi n g wit h o ut a filter.  H y dr oc ortis o ne 5 0 m g 
a n d Di p he n h y dra mi ne 2 5 m g will be a d mi nistere d pri or t o 
rei nf usi o n. 
D a y – 0   
T he re mai ni n g 3 7. 5 % of t he t otal a m o u nt of ste m cells 
c ollecte d) will be rei nf use d as a b o ve.  If t here are a n o d d 
n u m ber of t otal fr oze n ste m cell ba gs, t he lar ger n u m ber of 
ba gs will be gi ve n wit h t his c ycle.  A d mi nistrati o n of G-
1 2/ 1 0/ 0 2 
0 2/ 9 8 
0 2/ 9 8 

I R B # 9 6 1 3 9 
1 7  
J u ne 1 0, 2 0 0 4 
Ver. 1 5 
C S F will be disc o nti n ue d f oll o wi n g gra n ul oc yte rec o ver y 
t o > 1 0 0 0/ micr oliter f or 3 c o nsec uti ve da ys. 
Ra diati o n T hera p y  
T o start at 4 t o 7 wee ks fr o m t he be gi n ni n g of c ycle 2. 
Ta m o xife n , 2 0 m g/ da y, wit hi n 2 wee ks of bei n g disc har ge d fr o m h os pital 
f oll o wi n g c ycle 2 ( patie nts wit h E R or P R + t u m ors). 
8. 0 
T O XI CI TI E S A N D D O S E M O DI FI C A TI O N S  
T he N CI C o m m o n T o xicit y Gra di n g will be use d t o assess t o xicities e xce pt f or t he hi g h-
d ose c he m ot hera p y / ste m cell s u p p ort- p hase w he n t o xicities will be gra de d b y t he 
N CI/a ut o B M T T o xicit y Gra di n g. 
8. 1.  
D o x or u bici n 
8. 1. 1.  If o n t he sc he d ule d da y of a d mi nistrati o n t he gra n ul oc yte c o u nt is less 
t ha n 1, 0 0 0/µ l or t he platelet c o u nt is less t ha n 5 0, 0 0 0/µ l, d o x or u bici n will 
be dela ye d.  T he gra n ul oc yte a n d platelet c o u nts will be c hec ke d at least 
bi w a n d d o x or u bici n will be a d mi nistere d w he n t hese mi ni mal le vels are 
ac hie ve d.  If a de q uate bl o o d c o u nts are n ot ac hie ve d b y t hree wee ks fr o m 
t he pri or d o x or u bici n d ose, c o ntact t he Pri nci pal I n vesti gat or. 
8. 1. 2.  T he d osa ge of d o x or u bici n will n ot be re d uce d u nless t he patie nt de vel o ps 
ne utr o pe nic fe ver (a bs ol ute gra n ul oc yte c o u nt bel o w 1, 0 0 0/ µ l at t he ti me 
of a d oc u me nte d te m perat ure of 3 8. 5 °C or greater).  T he s u bse q ue nt d oses 
of d o x or u bici n will be re d uce d b y 2 5 % fr o m t he pre vi o usl y a d mi nistere d 
d ose.  D oses ma y n ot be re-escalate d. 
8. 1. 3.  T he ma xi m u m c u m ulati ve d ose of d o x or u bici n is 2 4 0 m g/ m², pri or t o 
hi g h- d ose c he m ot hera p y.  D o x or u bici n will be disc o nti n ue d a n d a patie nt 
will be ta ke n off st u d y if: c o n gesti ve heart fail ure a p pears, persiste nt 
arr h yt h mia (i ncl u di n g si n us tac h ycar dia wit h n o de m o nstra ble ca use) 
a p pears or heart size i ncreases b y 5 0 % o n P A c hest x-ra y. 
8. 1. 4.  I n case of Gra de 2 or 3 m uc ositis, d ys p ha gia, a n d diarr hea d o x or u bici n 
will be hel d u ntil t o xicit y res ol ves t o Gra de 1 or less at w hic h p oi nt  
c he m ot hera p y will be a d mi nistere d at a f ull d ose.  I n case of gra de 4 
t o xicit y s u bse q ue nt d oses of d o x or u bici n will be re d uce d b y 2 5 % fr o m t he 
pre vi o usl y a d mi nistere d d ose.  D oses ma y n ot be re-escalate d. 
8. 1. 5.  F or bilir u bi n > 1. 5 ti mes t he i nstit uti o nal u p per li mit of n or mal h ol d 
t hera p y; if bilir u bi n re mai ns > 1. 5 ti mes t he i nstit uti o nal u p per li mit of 
n or mal be y o n d o ne wee k, call t he pri nci pal i n vesti gat or t o disc uss t he 
nee d f or a d diti o nal w or k u p a n d f urt her treat me nt. 
8. 2.  
Paclita xel 
7/ 2 8/ 9 9 

I R B # 9 6 1 3 9 
1 8  
J u ne 1 0, 2 0 0 4 
Ver. 1 5 
8. 2. 1.  If o n t he sc he d ule da y of a d mi nistrati o n t he gra n ul oc yte c o u nt is less t ha n 
1, 0 0 0/ µ l or t he platelet c o u nt is less t ha n 5 0, 0 0 0/µ l, Ta x ol will be dela ye d. 
 T he gra n ul oc yte a n d platelet c o u nts will be c hec ke d at least e ver y ot her 
da y, a n d Ta x ol will be a d mi nistere d w he n t hese mi ni mal le vels are 
ac hie ve d.  If a de q uate bl o o d c o u nts are n ot ac hie ve d b y t hree wee ks fr o m 
t he pri or d o x or u bici n d ose, c o ntact t he Pri nci pal I n vesti gat or. 
8. 2. 2.  Wit h t he de vel o p me nt of a peri p heral ne ur o pat h y d oses will be re d uce d b y 
2 0 % (fr o m pre vi o usl y a d mi nistere d d ose) f or Gra de 3 or greater 
ne ur ot o xicit y. 
D oses will si milarl y be re d uce d f or ne utr o pe nic fe ver, or a n y ot her Gra de 
3 t o xicit y attri b uta ble t o a pri or d ose of paclita xel. 
All Gra de 3 or hi g her t o xicit y m ust ha ve res ol ve d t o Gra de 1 or less 
bef ore paclita xel ma y be restarte d. 
8. 3.  
Hi g h- d ose C he m ot hera p y C ycles 
8. 3. 1.  N o d ose m o dificati o ns will be ma de d uri n g t he first c ycle of hi g h- d ose 
c he m ot hera p y wit h d o x or u bici n, c ycl o p h os p ha mi de a n d paclita xel. 
8. 3. 2.  Patie nts s h o ul d meet all sta gi n g a n d f u ncti o nal scree ni n g re q uire me nts 
f oll o wi n g c o m pleti o n of t he first hi g h- d ose c he m ot hera p y c ycle pri or t o 
t he be gi n ni n g of t he sec o n d c ycle of hi g h- d ose c he m ot hera p y. 
8. 3. 3.  Mel p hala n a n d Cis plati n ( Mel/ Cis) 
C he m ot hera p y D osa ge A dj ust me nts 
8. 3. 3. 1 Re nal criteria : 
 
Ser u m Creati ni ne  
Creati ni ne Cleara nce 
( meas ure d or calc ulate d) 
D ose 
( mel p hala n) 
D ose 
( Cis plati n) 
 
< 1. 4 m g/ dl  
> 7 5 cc/ mi n 
1 0 0 %  
1 0 0 % 
 
> 1. 4 < 1. 6 m g/ dl  
< 7 5- 5 0 cc/ mi n 
7 5 % 
7 5 % 
 
> 1. 6 m g/ dl  
< 5 0 cc/ mi n 
0 % 
0 % 
 
8. 3. 3. 2 Ne ur ol o gic criteria : 
 
 
gra de 1 t o xicit y 
1 0 0 %  
7 5 m g/ m 2 
 
 
gra de 2 t o xicit y 
1 0 0 %  
0 
 
Mel/ Cis will be deli vere d at earliest 4 wee ks fr o m da y 1 of 
A C T.  Treat me nt ca n be gi ve n o nce t he ne utr o p hil c o u nt is > 
1 5 0 0/  µl, plt > 1 0 0, 0 0 0/µ l.  A ma xi m u m of 7 wee ks dela y 
will be all o we d f or rec o ver y fr o m treat me nt-relate d 
t o xicities.  A n y patie nt re q uiri n g > 7 wee k dela y ( be y o n d 7 
wee ks fr o m da y 1 A C T) will g o off st u d y. 

I R B # 9 6 1 3 9 
1 9  
J u ne 1 0, 2 0 0 4 
Ver. 1 5 
8. 4.  
G- C S F 
G- C S F will be hel d if W B C c o u nts g o be y o n d 2 0, 0 0 0 bet wee n c he m ot hera p y 
c ycles a n d f oll o wi n g hi g h- d osec he m ot hera p y c ycles.  G- C S F will als o be hel d i n 
t he setti n g of ste m cell m o bilizati o n if t he t otal w hite c o u nt reac hes 5 0, 0 0 0 a n d 
t he d ose will be re d uce d t o 5 0 % if t he t otal w hite cell c o u nt i n t he setti n g of ste m 
cell pri mi n g is bet wee n 2 5, 0 0 0 t o 5 0, 0 0 0/ µl. 
8. 5.  
S u p p orti ve care 
8. 5. 1.  All patie nts will ha ve ce ntral i ntra ve n o us cat heters place d. 
8. 5. 2.  L o w bacteria diet a n d pr o p h ylactic ofl o xaci n 4 0 0 m g bi d orall y a n d 
a m p h oterici n 5 m g i. v. a n d ac ycl o vir 2 5 0 m g/ m 2 will be prescri be d. 
8. 5. 3.  I n t he e ve nt of ne utr o pe nic fe ver or d oc u me nte d i nfecti o n, a p pr o priate i. v. 
a nti bi otic treat me nt will be i nitiate d. 
8. 5. 4.  All bl o o d pr o d ucts will be irra diate d.  Bl o o d pr o d uct s u p p ort will be 
pr o vi de d i n a n atte m pt t o mai ntai n t he He mat ocrit a b o ve 2 4 % a n d t he 
platelet c o u nt a b o ve 2 0, 0 0 0 u nless ot her wise i n dicate d. 
8. 5. 5.  Pare nteral n utriti o n will be i nitiate d de pe n di n g o n t he patie nt's nee ds.  T he 
patie nt's cal oric re q uire me nts will be assesse d wit h t he assista nce of t he 
dietar y ser vice. 
8. 5. 6.  P h ysical e xa mi nati o n a n d la b orat or y as well as ra di o gra p hic e val uati o n 
will be perf or me d as o utli ne d i n t he St u d y Para meters secti o n. 
I n e val uati n g t o xicit y, t he N CI C o m m o n T o xicit y Scale will be use d, wit h 
m o dificati o ns a p pr o priate t o t he setti n g of hi g h d ose c he m ot hera p y wit h 
peri p heral bl o o d ste m cell / a ut ol o g o us b o ne marr o w s u p p ort (see attac he d 
T o xicit y Gra di n g Scale).  Si nce ste m cell / b o ne marr o w rei nf usi o n is 
bei n g use d t o alle viate d ose li miti n g he mat ol o gic t o xicit y, he mat o p oietic 
t o xicit y a n d si milarl y, e val uati o n of gastr oi ntesti nal t o xicit y will be base d 
o n g ui deli nes f or st u dies i n v ol vi n g ste m cell, or a ut ol o g o us tra ns pla nt 
criteria a d o pte d fr o m t he N CI a ut ol o g o us b o ne marr o w t o xicit y scale 
( A p pe n di x B). 
8. 5. 7.  A d verse Dr u g Reacti o n ( A D Rs) will be re p orte d as o utli ne d i n A p pe n di x 
C ( Re p orti n g G ui deli nes f or A d verse Dr u g Reacti o ns). 
1 1/ 4/ 9 8 
1 2/ 1 4/ 0 1 

I R B # 9 6 1 3 9 
2 0  
J u ne 1 0, 2 0 0 4 
Ver. 1 5 
9. 0 
S T U D Y P A R A M E T E R S  
9. 1.  
Ne oa dj u va nt C he m ot hera p y a n d S ur ger y 
 
  
D a y 
1 
D a y 
8 
D a y 
* * 
1 5 
D a y 
2 2 
D a y 
2 9 
D a y 
3 6 
D a y 
4 3 
D a y 
5 0 
D a y 
5 7 
D a y 
6 4 
D a y 
7 0- 8 0
R E Q UI R E D S T U DI E S  
Pr e 
St u d y * *  
W k 
1 
W k 
2 
W k 
3 
W k 
4 
W k 
5 
W k 
6 
W k 
7 
W k 
8 
W k 
9 
W k 
1 0 
W k 
1 1- 1 2
Hi st or y a n d P h y si c al 
X  
  
  
X  
  
X  
  
X  
  
X  
  
X 
P el vi c E x a mi n ati o n/ P a p S m e ar  
X *  
 
 
 
 
 
 
 
 
 
 
 
W ei g ht a n d P erf or m a n c e St at u s   
X  
  
  
X  
  
X  
  
X  
  
X  
  
X 
T o xi cit y N ot ati o n 
  
  
  
X  
  
X  
  
X  
  
X  
  
X 
L A B O R A T O R Y 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
C B C/ Diff er e nti al/ Pl at el et s +  
X  
  
X  
X  
X  
X  
X  
X  
X  
X  
X  
X 
Bil at er al b o n e m arr o w bi o p si e s  
  
  
  
  
  
  
  
  
  
  
  
X 
M e a s ur e d cr e ati ni n e cl e ar a n c e  
X  
  
  
  
  
  
  
  
  
  
  
 
H e p atiti s/ HI V 
X  
  
  
  
  
  
  
  
  
  
  
 
S M A 1 8 
X  
  
  
X  
  
X  
  
X  
  
X  
  
X 
Uri n al y si s a n d pr e g n a n c y t e st  
X  
  
  
  
  
  
  
  
  
  
  
 
P F T s/ D L C O/ A B G 
X 
 
 
 
 
 
 
 
 
 
 
 
E R/ P g R a s s a y 
X 
 
 
 
 
 
 
 
 
 
 
X 
P at h ol o g y s u b mi s si o n 
X  
  
  
  
  
  
  
  
  
  
  
X 
M ol e c ul ar P h ar m a c ol o g y St u di e s: 
 Bi o p s y f or > 1 0 m g t u m or ti s s u e  
 
o bt ai n e d pri or t o c h e m ot h er a p y 
f or P C R st u di e s at s ur g er y 
 
 
 
X 
 
 
 
 
 
 
 
 
 
 
 
 
 
X 
X- R A Y S A N D S C A N S  
  
  
  
  
  
  
  
  
  
  
  
 
M a m m o gr a m 
X 
 
 
 
 
 
 
 
 
 
 
 
C h e st x-r a y 
X 
 
 
 
 
 
 
 
 
 
 
 
B o n e s c a n 
X  
  
  
  
  
  
  
  
  
  
  
 
C T c h e st/ a b d/ p el vi s # 
X  
  
  
  
  
  
  
  
  
  
  
 
M U G A 
X 
 
 
 
 
 
 
 
 
 
 
 
E C G 
X 
 
 
 
 
 
 
 
 
 
 
 
T R E A T M E N T 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
S ur g er y 
 
 
 
 
 
 
 
 
 
 
 
 
X 
D o x or u bi ci n 
  
X  
  
X  
  
X  
  
  
  
  
  
 
P a clit a x el 
 
 
 
 
 
 
 
 
X 
 
X 
 
 
*  
A pel vic e xa mi nati o n wit hi n si x m o nt hs pri or t o re gistrati o n is re q uire d prest u d y.  W o me n w h o ha ve ha d 
t heir uter us c o m pletel y re m o ve d are e xe m pt fr o m t he re q uire me nt f or prest u d y pel vic e xa mi nati o ns. 
+  
C B C, differe ntial a n d platelets m ust be perf o r me d wee kl y starti n g Da y 8 d uri n g t hera p y. 
#  
Re peat pel vic C T o nl y if i n dicate d. 
* *  
Patie nts wit h o nl y o ne pri or c ycle of ne oa dj u va nt c he m ot hera p y will ha ve prest u d y testi n g perf or me d a n d 
be gi n treat me nt o n Da y 1 5. 
9. 2.  
Paclita xel a n d P B S C c ollecti o n 
 
R E Q UI R E D S T U DI E S 
  
D a y 
1 0 0 
D a y 
1 0 7 
D a y 
1 1 4 
0 9/ 0 1 
0 9/ 0 1 

I R B # 9 6 1 3 9 
2 1  
J u ne 1 0, 2 0 0 4 
Ver. 1 5 
 
Pr e 
St u d y 
W k 
1 4 
W k 
1 5 
W k 
1 6 
Hi st or y a n d P h y si c al 
  
X  
  
 
W ei g ht a n d P erf or m a n c e St at u s  
  
X  
  
 
T o xi cit y N ot ati o n 
X  
  
  
 
L A B O R A T O R Y 
  
  
  
 
C B C/ Diff er e nti al/ Pl at el et s 
X  
  
X  
 
M e a s ur e d cr e ati ni n e cl e ar a n c e  
X  
  
  
 
S M A 1 8 
X  
  
  
 
P F T s/ D L C O/ A B G 
X  
  
  
 
X- R A Y S A N D S C A N S  
  
  
  
 
C h e st X-r a y 
X  
  
  
 
B o n e S c a n 
X  
  
  
 
B o n e m arr o w bi o p si e s 
X  
  
  
 
C T c h e st/ a b d/ p el vi s # 
X  
  
  
 
Br ai n M RI 
X  
  
  
 
M U G A 
  
  
  
 
E C G 
X  
  
  
 
T R E A T M E N T 
  
  
  
 
P a clit a x el 
  
X  
  
 
C y cl o p h o s p h a mi d e 
  
  
  
 
P B S C C oll e cti o n 
  
  
  
X 
G- C S F 
  
X  
X  
X 
M a m m o gr a m *  
 
 
 
 
 
#  
Pel vic C T o nl y if i n dicate d. 
*  
If t he pri or ma m m o gra m ha d bee n perf or me d m ore t ha n 6 m o nt hs a g o." 
0 9/ 0 1 
0 9/ 0 1 
0 9/ 0 1 
0 9/ 0 1 
0 9/ 0 1 

I R B # 9 6 1 3 9 
2 2  
J u ne 1 0, 2 0 0 4 
Ver. 1 5 
6 / 1 0 / 0 4  
9. 3.  
Hi g h- d ose c he m ot hera p y wit h A C T a n d P B S C 
 
R E Q UI R E D S T U DI E S 
Pr e 
H D C T 
D a y 
- 7 
D a y 
- 6 
D a y 
- 5 
D a y 
- 4 
D a y 
- 3 
D a y 
- 2 
D a y 
- 1 
D a y 
0 
D a y 
7 
D a y 
0 
D a y 
7 
Hi st or y a n d P h y si c al 
X  
  
  
  
  
  
  
  
  
  
  
 
W ei g ht a n d P erf or m a n c e St at u s  
X  
  
  
  
  
  
  
  
  
  
  
 
T o xi cit y N ot ati o n 
  
X  
X  
X  
X  
X  
X  
X  
X  
X  
X  
X 
L A B O R A T O R Y 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
C B C/ Diff er e nti al/ Pl at el et s 
X  
  
X  
X  
X  
X  
X  
X  
X  
X  
X  
X + + 
M e a s ur e d cr e ati ni n e cl e ar a n c e  
  
  
  
  
  
  
  
  
  
  
  
 
S M A 1 8 
X 
 
 
 
 
 
 
 
 
 
 
 
P F T s/ D L C O 
 
 
 
 
 
 
 
 
 
 
 
 
 
X- R A Y S A N D S C A N S 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
C h e st x-r a y 
X 
 
 
 
 
 
 
 
 
 
 
 
E C G 
X 
 
 
 
 
 
 
 
 
 
 
 
1 N er v e C o n d u cti o n T e st 
  A u di o gr a m 
X 
 
 
 
 
 
 
 
 
 
 
 
T R E A T M E N T 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
P B S C 
  
  
  
  
  
  
  
  
X  
  
  
 
G- C S F 
  
  
  
  
  
  
  
X  
X  
X  
X  
X + 
C H E M O T H E R A P Y 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
C y cl o p h o s p h a mi d e 
  
  
  
  
  
X  
  
  
  
  
  
 
D o x or u bi ci n 
  
X  
X  
X  
X  
  
  
  
  
  
  
 
T a x ol 
 
 
 
 
 
 
 
X 
 
 
 
 
 
+  
T hr o u g h A G C > 1 0 0 0/ µ l x 3 da ys 
+ +  Dail y till c o m pleti o n of t hera p y a n d rec o ver y 
1 
A me n de d 3/ 9 8 
9. 4.  
Hi g h- d ose c he m ot hera p y wit h Mel/ Cis a n d P B S C 
 
R E Q UI R E D S T U DI E S 
Pr e 
H D C T 
D a y 
- 1 1 
D a y 
- 1 0 
D a y 
- 9 
D a y 
- 8 
D a y 
- 7 
D a y 
- 6 
D a y 
- 5 
D a y 
- 4 
D a y 
- 3 
D a y 
- 2 
D a y 
- 1 
D a y 
0 
D a y 
7 
Hi st or y a n d P h y si c al 
X  
  
  
  
  
  
  
  
  
  
  
  
  
 
W ei g ht a n d P erf or m a n c e St at u s  
X  
  
  
  
  
  
  
  
  
  
  
  
  
 
T o xi cit y N ot ati o n 
  
X  
X  
X  
X  
X  
X  
X  
  
X  
X  
X  
X  
X 
L A B O R A T O R Y 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
C B C/ Diff er e nti al/ Pl at el et s 
X  
  
X  
X  
X  
X  
X  
X  
X  
X  
X  
X  
X  
X + + 
M e a s ur e d cr e ati ni n e cl e ar a n c e  
X  
  
  
  
  
  
  
  
  
  
  
  
  
 
S M A 1 8 
X 
 
 
 
 
 
 
 
 
 
 
 
 
 
X- R A Y S A N D S C A N S 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
C h e st x-r a y 
X 
 
 
 
 
 
 
 
 
 
 
 
 
 
B o n e S c a n # 
  
  
  
  
  
  
  
  
  
  
  
  
  
 
C T c h e st/ a b d/ p el vi s # 
  
  
  
  
  
  
  
  
  
  
  
  
  
 
M U G A
 
X 
 
 
 
 
 
 
 
 
 
 
 
 
 
E C G  
X 
 
 
 
 
 
 
 
 
 
 
 
 
 
2 N er v e C o n d u cti o n T e st 
X  
  
  
  
  
  
  
  
  
  
  
  
  
 
T R E A T M E N T 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
M el p h al a n 
  
X  
  
  
  
  
  
  
X  
  
  
  
  
 
Ci s pl ati n 
 
X 
 
 
 
 
 
 
X 
 
 
 
 
 
P B S C 
  
  
  
  
  
  
  
  
  
X  
  
  
X  
 
G- C S F 
  
  
X  
X  
X  
X  
  
  
  
  
  
  
  
 
#  
If i n dicate d. 
+ +  Dail y till c o m pleti o n of t hera p y a n d rec o ver y 
2 
A me n de d 3/ 9 8 
0 9/ 0 1 

I R B # 9 6 1 3 9 
2 3  
J u ne 1 0, 2 0 0 4 
Ver. 1 5 
9. 5.  
F oll o w- u p 
 
Da y 3 0 
Fr o m Start of R X 
E ver y 3 M o nt hs  
E ver y 6 M o nt hs 
H & P 
X 
X 
 
C B C, diff, plat 
X 
X 
 
S M A- 7 
X 
X 
 
S M A- 1 2, M g 
X 
X 
 
C X R 
X 
 
X 
M u ga Sca n + E K G 
X 
 
X a 
Ner ve C o n d ucti o n St u dies  
X 
 
X a 
Ma m m o gra m 
 
 
 
  
 a  
Re peat t hereafter at discreti o n of treati n g M D. 
 
1 0. 0 
C RI T E RI A F O R E V A L U A TI O N A N D E N D P OI N T D E FI NI TI O N S  
1 0. 1.  C o m plete Cli nical Res p o nse f oll o wi n g ne oa dj u va nt c he m ot hera p y: Cli nicall y 
u n detecta ble t u m or.  Partial Cli nical Res p o nse f oll o wi n g ne oa dj u va nt 
c he m ot hera p y: Pal pa ble t u m or or si g ns of persiste nt i nfla m mati o n. 
1 0. 2.  C o m plete Pat h ol o gical Res p o nse: Lac k of t u m or i n t he m o difie d ra dical 
mastect o m y s peci me n.  Partial Pat h ol o gical Res p o nse: A n y e vi de nce of resi d ual 
t u m or i n t he m o difie d ra dical mastect o m y s peci me n. 
1 0. 3.  Disease-free S ur vi val: Fr o m date of mastect o m y t o date of rela pse or deat h. 
1 0. 4.  O verall S ur vi val: S ur vi val is meas ure d fr o m t he date mastect o m y t o t he date of 
deat h. 
1 0. 5.  Rela pse: A p peara nce of a n y ne w lesi o ns d uri n g or after pr ot oc ol treat me nt.  
W he ne ver p ossi ble, rela pses s h o ul d be d oc u me nte d hist ol o gicall y. 
1 1. 0 
S T A TI S TI C A L C O N SI D E R A TI O N  
T his is a pil ot st u d y wit h t he g oal of assessi n g t he feasi bilit y a n d efficac y of 
a d mi nisteri n g a c o m plete treat me nt pla n c o nsisti n g of ne oa dj u va nt se q ue ntial 
c he m ot hera p y, m o difie d ra dical mastect o m y, paclita xel, c ycl o p h os p ha mi de a dj u va nt 
t hera p y (f oll o we d b y G- C S F pri me d peri p heral ste m cell c ollecti o n) a n d 2 c ycles of hi g h-
d ose c he m ot hera p y a n d peri p heral bl o o d ste m cell resc ue wit h s u bse q ue nt l ocal-re gi o nal 
ra diati o n treat me nt a n d ta m o xife n f or patie nts wit h rece pt or p ositi ve ne o plas ms.  Base d 
o n  c urre nt referral patter ns t o t he De part me nts of Ge neral a n d O nc ol o gic S ur ger y a n d 
Me dical O nc ol o g y a n d T hera pe utics Researc h, it is e x pecte d t hat a p pr o xi matel y 1 5 
patie nts per year will be accr ue d t o t his st u d y. D uri n g t he first year of t his st u d y we 
esti mate t he rati o of eli gi ble patie nts bet wee n strat u m 1 vers us 2 at 5: 1 0.  O nce t he 
referri n g o nc ol o gists i n t he greater L os A n geles / Ora n ge C o u nt y area bec o me fa miliar 
9 / 0 5 / 0 2

I R B # 9 6 1 3 9 
2 4  
J u ne 1 0, 2 0 0 4 
Ver. 1 5 
wit h t he desi g n we esti mate at least a n e q ualizati o n i n t he n u m ber of patie nts bet wee n t he 
2 strata.   As t he maj orit y of rela pses are e x pecte d t o occ ur wit hi n 3 years, a g oal of 6 0 
patie nts accr ue d i n 8 years will be set.  Patie nts will be a nal yze d f or t o xicit y, disease-free 
a n d o verall s ur vi val a n d t he a bilit y t o deli ver t he treat me nt p hases acc or di n g t o sc he d ule. 
As re p orte d i n Secti o n 2. 0, 3- year rela pse-free s ur vi val i m pr o ve d fr o m 2 9 % t o 5 0 % i n 
t he c urre nt c o h ort of C O H patie nts treate d wit h si n gle c ycle hi g h- d ose c he m ot hera p y 
c o m pare d t o a n hist orical gr o u p of C O H patie nts treate d wit h sta n dar d t hera p y.  Patie nt 
accr ual will be e ve nl y s plit bet wee n t he t w o strata o ver a peri o d of 8 years, he nce, a 
c o m paris o n of strata wit hi n t he st u d y c o ul d detect a n i m pr o ve me nt fr o m 5 0 % t o 8 0 % i n 
3- year rela pse-free s ur vi val (at p =. 0 5 a n d 8 0 % p o wer), w hile a c o m paris o n of all 6 0 
patie nts t o hist orical data c o ul d detect a n  i m pr o ve me nt fr o m 5 0 % t o 7 2 % i n 3- year 
rela pse-free s ur vi val. 
If c o m plete res p o nse rates are near 3 0 % a m o n g t he e x pecte d 3 0 s u bjects u n der g oi n g t he 
e ntire treat me nt at C O H (strat u m 1), t he n t he esti mate d rate w o ul d be acc urate t o wit hi n 
1 7 %, s ufficie nt t o disti n g uis h t he c o m plete res p o nse rate fr o m a hist orical rate of a b o ut 
1 0 %.  T he sa m ple size is t h us s ufficie nt t o esta blis h feasi bilit y at practical referral rates, 
a n d t o detect a mar ke d i m pr o ve me nt i n efficac y. 
We will be utilizi n g t he Di visi o n of Ca ncer Treat me nt's ( D C T)/ Nati o nal Ca ncer 
I nstit ute's ( N CI) C o m m o n T o xicit y Criteria f or e val uati n g t o xicit y of all or ga n s yste ms 
wit h t he e xce pti o n of t he he mat ol o gic s yste m a n d gastr oi ntesti nal s yste m, w here we will 
f oll o w t he g ui deli nes f or st u dies i n v ol vi n g a ut ol o g o us b o ne marr o w tra ns pla ntati o n as 
rec o m me n de d b y t he Ca ncer T hera p y E val uati o n Pr o gra m ( C T E P). 
Criteria f or earl y ter mi nati o n of t his feasi bilit y st u d y i ncl u de > t ha n 2 patie nts wit h 
re gi me n-relate d t o xicit y > gra de 4 arr h yt h mia, C H F, m y ocar dial i nfarcti o n, ta m p o na de or 
> 2 patie nts wit h >  gra de 3 he mat ol o gic or gastr oi ntesti nal t o xicities. 
1 2. 0 
P A T H O L O G Y R E VI E W  
All a vaila ble pat h ol o g y s peci me ns will be re vi e we d b y t he Cit y of H o pe De part me nt of 
Pat h ol o g y t o c o nfir m t he pri mar y dia g n osis.  I n a d diti o n, m or p h ol o gical a n d 
i m m u n o hist oc he mical a nal ysis of bi o ps y a n d mastect o m y s peci me ns will be carrie d o ut 
assessi n g gra de, rece pt or stat us, p 5 3, Ki- 6 7, C- er bB- 2, M D R 1, M R P.   I n a d diti o n, b ot h 
paraffi n e m be d de d a n d fres h tiss ue sa m ples will be teste d f or s urr o gate si g ns of 
here ditar y disease i.e. B R C A 1 a n d 2 as t hese tests bec o me a vaila ble. 
1 3. 0 
R E GI S T R A TI O N G UI D E LI N E S  
O nce all pretreat me nt e val uati o ns ha ve bee n perf or me d, patie nts will be e ntere d o n st u d y 
after re vie w of patie nt eli gi bilit y b y a me m ber of t he De part me nt of Bi ostatistics.  
Patie nts ma y be scree ne d f or re gistrati o n b y calli n g t he Cit y of H o pe De part me nt of 
Bi ostatistics, e xt. 2 4 6 8. 
1 4. 0 
D A T A S U B MI S SI O N S C H E D U L E  
All pri mar y data will be mai ntai ne d b y t he De part me nt of Bi ostatistics, Cit y of H o pe 
Ca ncer Researc h Ce nter.  T hese will i ncl u de eli gi bilit y c hec klist, prest u d y a n d i nitial 
1 2/ 1 0/ 0 2 

I R B # 9 6 1 3 9 
2 5  
J u ne 1 0, 2 0 0 4 
Ver. 1 5 
fl o w s heet, pat h ol o g y re p ort, st u d y s pecific flo w s heets as well as off-st u d y i nf or mati o n. 
1 5. 0 
E T HI C A L A N D R E G U L A T O R Y C O N SI D E R A TI O N S  
T his st u d y is t o be a p pr o ve d b y t he I nstit uti o nal Re vie w B oar d acc or di n g t o Cit y of H o pe 
et hical a n d re g ulat or y g ui deli nes.  All patie nts will ha ve si g ne d a n i nf or me d c o nse nt f or 
partici pati o n i n researc h acti vities, a n d t he y will ha ve bee n gi ve n a c o p y of t he 
E x peri me ntal S u bject's Bill of Ri g hts. 
W he n res ults of a st u d y s uc h as t his are re p orte d i n me dical j o ur nals or at meeti n gs, 
i de ntificati o n of t h ose ta ki n g part will be wit h hel d.  Me dical rec or ds of patie nts will be 
mai ntai ne d i n strictest c o nfi de nce acc or di n g t o c urre nt le gal re q uire me nts.  H o we ver, 
t he y ma y be ma de a vaila ble f or re vie w, as re q uire d b y t he F o o d a n d Dr u g A d mi nistrati o n 
( F D A) or ot her a ut h orize d users o nl y u n der t he g ui deli nes esta blis he d b y t he Fe deral 
Pri vac y Act.  T he Nati o nal Ca ncer I nstit ute or t he F D A ma y re vie w t hese rec or ds. 
1 6. 0 
M O L E C U L A R P H A R M A C O L O G Y  
I n a rece nt e val uati o n of t he e x pressi o n of se veral ge nes i n pri mar y breast ca ncer 
s peci me ns fr o m patie nts wit h hi g h-ris k pri mar y disease treate d wit h b ot h sta n dar d 
c he m ot hera p y a n d hi g h- d ose c he m ot hera p y wit h ste m cell s u p p ort ( S o ml o et al A S C O 
1 9 9 6), e x pressi o n of p 5 3, estr o ge n, a n d pr o gester o ne rece pt or pr otei n were f o u n d t o ha ve 
pr o g n ostic si g nifica nce.  F urt her m ore, i n a rece nt u n p u blis he d e val uati o n of m R N As 
fr o m breast a n d gastric ca ncer s peci me ns b y Da ne n ber g a n d c ollea g ues at t he 
U S C/ N orris C o m pre he nsi ve Ca ncer Ce nter , e x pressi o n of t he D N A re pair ge ne E R C C 1 
was f o u n d t o c orrelate cl osel y wit h rela pse-free s ur vi val i n patie nts treate d wit h 
plati n u m-c o ntai ni n g c he m ot hera p y re gi me ns.  F or t his reas o n, patie nts will be re q ueste d 
t o all o w a bi o ps y of t heir pri mar y t u m or s peci me n t o be perf or me d f or researc h p ur p oses 
i n a d diti o n t o t hat re q uire d f or defi niti ve dia g n osis of i nfla m mat or y breast ca ncer.  A 
s peci me n of > 1 0 m g of tiss ue will be o btai ne d eit her b y m ulti ple p u nc h bi o psies of t he 
s ki n or b y i ncisi o nal bi o ps y u n der l ocal a nest hesia after a p pr o priate c o nse nt has bee n 
o btai ne d.  At least 2 4 h o urs pri or t o c o nse nti n g patie nts f or t his pr oce d ure, Mar y Carr oll, 
R. N. m ust be c o ntacte d at e xte nsi o n 2 9 6 0 i n  t he De part me nt of Me dical O nc ol o g y a n d 
T hera pe utics Researc h s o t hat t he sta n dar d pr oce d ure f or s peci me n ha n dli n g de vel o pe d 
wit h t he C O H Di visi o n of Pat h ol o g y ca n be i m ple me nte d.  All s peci me ns will be di vi de d 
at t he ti me of bi o ps y f or sta n dar d li g ht micr osc o p y t o assess t he e xte nt of t u m or i n t he 
bi o ps y s peci me n a n d t o pre pare sli des f or s u bse q ue nt i m m u n o hist oc he mistr y.  T he 
re mai ni n g material will be q uic k fr oze n a n d t he m R N A pr ocesse d usi n g t he sta n dar dize d 
pr oce d ures i n t he A nal ytical P har mac ol o g y C ore Facilit y of t he C O H Ca ncer Researc h 
Ce nter.  Relati ve q ua ntitati o n R T- P C R will t he n be perf or me d i n Dr. D or os h o w’s 
la b orat or y t o assess t he e x pressi o n of se veral ge nes i ncl u di n g M D R 1, E R C C 1, a n d 
ri b o n ucle oti de re d uctase pri or t o t he i nitiati o n of c he m ot hera p y i n t hese s peci me ns.  
E ver y atte m pt will be ma de t o perf or m assess me nts of ge ne e x pressi o n i n patie nts w h o 
d o n ot res p o n d t o c he m ot hera p y a n d fr o m t he s ur gical s peci me ns o btai ne d at t he e n d of 
t he i n d ucti o n peri o d of treat me nt. 
1 7. 0 
F A MI L Y HI S T O R Y / H E R E DI T A R Y B R E A S T C A N C E R E V A L U A TI O N  
At t he C O H t he me dia n a ge of hi g h-ris k breast ca ncer patie nts -i ncl u di n g t h ose wit h  
i nfla m mat or y carci n o ma- is 4 2 years.  A cli nical feat ure of here ditar y breast ca ncer is 

I R B # 9 6 1 3 9 
2 6  
J u ne 1 0, 2 0 0 4 
Ver. 1 5 
earlier a ge at t he ti me of dia g n osis.  A u ni q ue o p p ort u nit y is prese nte d at o ur i nstit uti o n 
t o st u d y a si g nifica nt n u m ber of y o u n g breast ca ncer patie nts prese nti n g wit h hi g h-ris k 
breast ca ncer.  We pla n t o i ncl u de t his gr o u p of patie nts wit h i nfla m mat or y breast ca ncer 
i n o ur o n g oi n g pr ojects o n ca ncer ge netics..  Patie nts a n d fa mil y me m bers will be as ke d 
t o si g ne d c o nse nt f or m 2 i n or der t o c o nstr uct a n e xte n de d pe di gree i ncl u di n g fa mil y 
hist or y of ca ncer.  Ris k Fact or a n d Fa mil y Hist or y Q uesti o n naires will be prese nte d t o 
t he partici pa nts ( T hese q uesti o n naires are i ncl u de d i n a se parate pr ot oc ol a n d a ut h ore d b y 
Dr. Weitzel,  Direct or of Cli nical Ca ncer Ge netics ).   I n a d diti o n, t u m or sa m ples b ot h 
pri or t o a n d after ne oa dj u va nt c he m ot hera p y a n d bl o o d sa m ples of patie nts a n d 
a p pr o priate fa mil y me m bers will be o btai ne d t o searc h f or ger m li ne a n d s o matic 
m utati o ns of alrea d y k n o w n ge netic mar kers, t u m or s u p press or ge nes a n d  hit hert o 
u ni de ntifie d ge nes/ mar kers. 
Patie nts will be e nr olle d o n t he treat me nt pr ot oc ol re gar dless of t heir a gree me nt t o 
partici pate i n t he fa mil y s ur ve y / m olec ular ge netics e val uati o n. 
1 8. 0 
MI N O RI TI E S A N D W O M E N  
T he Cit y of H o pe has a pla n i n place t o i ncrease mi n orit y recr uit me nt t o o ur st u dies i n 
c o m plia nce wit h t he Nati o nal I nstit ute of Healt h p olic y f or recr uit me nt of w o me n a n d 
mi n orities. 
T he ta ble bel o w s h o ws t he distri b uti o n b y se x a n d race of t he patie nts accr ue d t o 
t hera pe utic cli nical st u dies at Cit y of H o pe f or t he past fi ve years wit h t he sa me pri mar y 
site of disease tar gete d f or t his pr ot oc ol ( breast).  O ur g oal is t o mai ntai n o ur hi g h accr ual 
of w o me n w hile c o nti n ui n g t o i ncrease t he accr ual of mi n orit y s u bjects. 
Accr ual b y Site, 1 9 8 9 – 1 9 9 4 
 
B y Se x 
B y Et h nicit y 
Site  
T otal  Fe male  
Male  
W hite  
His pa nic  
Blac k  
Asia n  
Ot her 
Breast  
1 0 6 0  1 0 5 9 ( 1 0 0 %)  1 ( 0 %) 8 0 1 ( 7 6 %) 1 1 0 ( 1 0 %)  3 6 ( 3 %)  7 0 ( 7 %)  4 3 ( 4 %) 
 
Base d o n o ur t y pical accr ual, t he ta ble bel o w reflects o ur g oal f or t he accr ual of w o me n 
a n d mi n orities o n t his researc h pr ot oc ol. 
Accr ual G oal f or W o me n a n d Mi n orities 
 
B y Se x 
B y Et h nicit y 
Site  
Accr ual 
G oal 
Fe male  
Male  
W hite  
His pa nic  
Blac k  
Asia n  
Ot her 
Breast  4 2  
4 2 ( 1 0 0 %)  
0 ( 0 %) 2 5 ( 6 0 %)  7 ( 1 7 %)  
3 ( 6. 5 %)  4 ( 1 0 %)  3 ( 6. 5 %) 
 

I R B # 9 6 1 3 9 
2 7  
J u ne 1 0, 2 0 0 4 
Ver. 1 5 
1 9. 0 
BI B LI O G R A P H Y  
1.  
H ort o ba g yi G N, Si n gletar y S E, Mc Neese N M .  Treat me nt of l ocall y a d va nce d a n d 
i nfla m mat or y breast ca ncer.  I n Diseases of t he Breast, (Ja y Harris, Marc Li p p ma n, 
M o nica M orr o w, a n d Sa m uel Hell ma n, e ds), Li p pi nc ott- Ra ve n P u blis hers, P hila del p hia, 
P A, p p 5 8 5- 5 9 9, 1 9 9 6. 
2.  
Peters W P.  A ut ol o g o us b o ne marr o w tra ns pla ntati o n f or breast ca ncer.  I n B o ne Marr o w 
Tra ns pla ntati o n, ( Ste p he n F or ma n, Karl Bl u me E. D o n nall T h o mas, e ds), Blac k well 
Scie ntific P u blicati o ns, B ost o n, Massac h usetts, p p 7 8 9- 8 0 2, 1 9 9 4. 
3.  
W o o d W C, B u d ma n D R, H orz u n A H, C o o per M R, Y o u n ger J, Hart R D, M o ore A, 
Ellert o n J A, N ort o n L, Ferree C R, Ball o w A C, Frei III E, He n ders o n I C.  D ose a n d d ose 
i nte nsit y of a dj u va nt c he m ot hera p y f or sta ge II, n o de- p ositi ve breast carci n o ma.  N E n gl 
J Me d 3 3 0: 1 2 5 3- 1 2 5 9, 1 9 9 4. 
4.  
S o ml o G, D or os h o w J H, F or ma n SJ, Mar y o n T, Lee J, C h o w W, Ha masa ki V, Le o n g L, 
M or ga n Jr. R, Mar g oli n K, Rasc h k o J, S hi bata S, Tetef M, Ye n Y, Si m ps o n J, M oli na A. 
Hi g h- d ose c he m ot hera p y a n d ste m cell resc ue i n t he treat me nt of hi g h-ris k breast ca ncer: 
pr o g n ostic i n dicat ors a n d pr o gressi o n-free a n d o verall s ur vi val.  Ma n uscri pt s u b mitte d. 
5.  
S o ml o G, D or os h o w J H, A h n C, C h o w W, Ha masa ki V, Le o n g L, Mar g oli n K, M or ga n 
R, Rasc h k o J, S hi bata S, O' D o n nell M, S mit h E, Tetef M, F or ma n S, Ye n Y, M oli na A, 
S nieci ns ki, 1. D o u ble c ycle hi g h- d ose mel p hala n ( M E L) a n d cis plati n ( C D D P) wit h 
peri p heral ste m cell resc ue ( P S C R) i n patie nts wit h breast ca ncer ( B C) a n d ot her 
mali g na ncies.  Pr oc A m S oc Cli n O nc ol 1 5: 3 5 2, 1 9 9 6. 
6.  
B o na d o n na G, Za m betti M, Vala g ussa P. Se q ue ntial or alter nati n g d o x or u bici n a n d C M F 
re gi me ns i n breast ca ncer wit h m ore t ha n t hree p ositi ve n o des.  Te n- year res ults.  J A M A 
2 7 3: 5 4 2- 5 4 7, 1 9 9 5. 
7.  
Reic h ma n B S, Sei d ma n A D, Cr o w n J P A, et al.  Paclita xel a n d rec o m bi na nt h u ma n 
gra n ul oc yte c ol o n y-sti m ulati n g fact or as i nitial c he m ot hera p y f or metastatic breast 
ca ncer.  J Cli n O nc ol 1 1: 9 4 3- 1 9 5 1, 1 9 9 3. 
8.  
H u dis C, Sei d ma n A, Ra ptis G, Basel ga J, Fe n nell y D, T he o d o ul o u M, Gile ws ki T, 
C urrie V, M o y na ha n M, S ur b o ne A, S klari n N, R o bles M, Ricci o L, Ya o T-J, U hle n h o p p 
M, N ort o n L. Se q ue ntial (se q) d ose- de nse ( D D) d o x or u bici n ( A) - > paclita xel ( T) - > 
c ycl o p h os p ha mi de 0 is less t o xic t ha n A - > c o nc urre nt ( C o n) T + C as a dj u va nt t hera p y 
i n resecte d n o de p ositi ve ( +) breast ca ncer ( N P B C).  Pr oc A m S oc Cli n O nc ol 1 5: 1 1 9, 
1 9 9 6. 
9.  
Sei d ma n A D, Hac h ha user D, G oll u b M, E del ma n B, Ya o T-J, H u dis C A, Fra ncis P, 
Fe n nell y D, Gile ws ki T A, Ma y na ha n M E, C urrie V, Basel ga J, T o n g W, O’ D o na g h ue M, 
Sal va g gi o R, A u g uste L, S pri g gs D, N ort o n L.  Ni net y-si x- h o ur paclita xel i nf usi o n after 
pr o gressi o n d uri n g s h ort ta xa ne e x p os ure: A p hase II p har mac o ki netic a n d 
p har mac o d y na mic st u d y i n metastatic breast ca ncer.  J Cli n O nc ol 1 4: 1 8 7 7- 1 8 8 4, 1 9 9 6. 
1 0.  
Ste m mer S M, Ca g n o ni PJ, S h pall EJ, Bear ma n SI , Matt hes S, D uft o n C, Da y T, Taffs S, 
Ha mi L, Marti nez C, P ur d y M H, Arr o n J, J o nes R B.  Hi g h- d ose paclita xel, 

I R B # 9 6 1 3 9 
2 8  
J u ne 1 0, 2 0 0 4 
Ver. 1 5 
c ycl o p h os p ha mi de, a n d cis plati n wit h a ut ol o g o us he mat o p oietic pr o ge nit or-cell s u p p ort.  
A p hase I trial.  J Cli n O nc ol 1 4: 1 4 6 3- 1 4 7 2, 1 9 9 6. 
1 1.  
Va h dat L T, Bal mece da C, Pa pa d o p o ul os K P, Garrett TJ, Mc G o ver n T, A nt ma n K H, 
Hes d orffer C S.  Ta n de m hi g h d ose c he m ot hera p y ( H D C) wit h escalati n g paclita xel ( P), 
mel p hala n ( M) a n d c ycl o p h os p ha mi de ( C), t hi ote pa, a n d car b o plati n ( C T C B) wit h 
peri p heral bl o o d pr o ge nit or ( P B P) s u p p ort i n res p o n di n g metastatic breast ca ncer.  
A S B M T, p 3 7, 1 9 9 6, 2 n d A n n ua Meeti n g, Sa n Die g o, C A. 
1 2.  
S o ml o G, D or os h o w J H, S y n ol d T, C h o w W, Ha masa ki V, Le o n g L, Mar g oli n K, 
M or ga n R, Rasc h k o J, F or ma n SJ, S hi bata S, Tetef M, Ye n Y. Hi g h- d ose A dria m yci n ( A), 
c ycl o p h os p ha mi de ( C) a n d paclita xel ( T) f or patie nts ( P T S) wit h hi g h-ris k a n d 
res p o nsi ve sta ge I V breast ca ncer ( B C). A S B M T, p 9 0, 1 9 9 6, 2 n d A n n ual Meeti n g, Sa n 
Die g o, C A. 
1 3.  
S wai n S, W hale F, Ger ber M, Wies ber g S, Y or k M, S picer D, J o nes S, Wa dler S, Desai 
A, V o gel C, S pe yer J, Mittel ma n A, Re d d y S, Pe n der gra d d K, Velz- Garcia E, E wer M, 
Bia nc hi ne J, Ga ms.  Car di o pr otecti o n w it h de xraz o xa ne f or d o x or u bici n-c o ntai ni n g 
c he m ot hera p y i n a d va nce d breast ca ncer.  J Cli n O nc ol 1 5: 1 3 1 8- 1 3 4 0, 1 9 9 7 
1 4.  
L o pez M, Vici P, Di La ur o L, C o nti F, Pa oletti G, Ferrair o ni A, Sci ut o R, Gia narelli D, 
Mai ni C.  Ra n d o mize d pr os pecti ve cli nical trial of hi g h- d ose e pir u bici n a n d de xraz o xa ne 
i n patie nts wit h a d va nce d breast ca ncer a n d s oft tiss ue carci n o mas.  J Cli n O nc ol 1 6: 8 6-
9 2, 1 9 9 8 
1 5.  
S o ml o G, Si m ps o n J, D or os h o w J, F or ma n S, Nila n d J, Le o n g L, M or ga n R, Rasc h k o J, 
Lee J, Mar g oli n K, Ha masa ki V, S hi bata S, C h o w W, Tetef M, M oli na A, Battif ora H. 
I m m u n o hist oc he mical (I H) e x pressi o n of P5 3, estr o ge n ( E R) a n d pr o gester o ne ( P R) 
rece pt ors a n d MI B 1 as well as i ncrease d mit otic i n de x ( MI) are pre dict ors of o utc o me 
after hi g h- d ose c he m ot hera p y ( H D C T) a n d ste m cell resc ue ( S C R) f or hi g h-ris k breast 
ca ncer ( H R B C) patie nts ( P T S).  Pr oc A m S oc Cli n O nc ol 1 5: 1 2 6, 1 9 9 6. 
1 6.  
We ber B L, Gar ber J E.  Fa milial breast ca ncer.  I n Diseases of t he Breast, (Ja y Harris, 
Marc Li p p ma n, M o nica M orr o w, a n d Sa m uel Hell ma n, e ds), Li p pi nc ott- Ra ve n 
P u blis hers, P hila del p hia, P A, p p 1 6 8- 1 8 5, 1 9 9 6. 
1 7.  
Al bai n K S, Allre d D C, Clar k G M.  I nteracti o ns bet wee n ver y y o u n g a ge a n d pr o g n ostic 
fact ors f or disease-free s ur vi val ( D F S) i n t he prese nce or a bse nce of a dj u va nt breast 
ca ncer t hera p y.  Pr oc A m S oc Cli n O nc ol 1 5: 1 0 7, 1 9 9 6.