Osteosarcoma - historical

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The purpose of this page is to provide references to regimens that are obsolete, outdated, or of historical interest only. Is there a regimen missing from this list? See the main osteosarcoma page for current regimens.
Last updated on 2024-07-23:10 regimens on this page
10 variants on this page
 
=Neoadjuvant therapy=
==MA-BCD==
MA-BCD: High-dose Methotrexate, Adriamycin (Doxorubicin), Bleomycin, Cyclophosphamide, Dactinomycin
===Regimen===
Study 	Dates of enrollment	Evidence 	Comparator	Comparative Efficacy
Winkler et al. 1984 (COSS-80)	1979-1982 	Phase 3 (C)	MAP 	Did not meet primary endpoint of CDF rate
Note: The exact schedule is unclear based on limited/conflicting information in the reference. For example, Figure 1 appears to depict high-dose methotrexate starting 2 weeks after adriamycin, but the text says that methotrexate begins after a 3-week rest period. Additionally, the diagram in Figure 1 implies that the later therapies are given 4 times (once, then repeated x 3 cycles), but based on the cumulative doses listed, they are only given for a total of 3 cycles. The optional interferon arm is omitted given lack of benefit seen in the study.
====Chemotherapy====
*Doxorubicin (Adriamycin) as follows:
**Cycles 1, 3, 4: 45 mg/m2 IV bolus once per day on days 1 & 2
**Cycle 2: 45 mg/m2 IV bolus once per day on days 15 & 16 (delayed during cycle 2 until after surgery)
*Methotrexate (MTX) as follows:
**Cycle 1: 12,000 mg/m2 (maximum dose of 20,000 mg) IV over 4 hours once per day on days 22 & 29
**Cycles 2 to 4: 12,000 mg/m2 (maximum dose of 20,000 mg) IV over 4 hours once per day on days 1, 8, 29, 36
**MTX is dissolved at a concentration of 20,000 mg/L in a solution containing 5% glucose
*Bleomycin (Blenoxane) as follows:
**Cycle 1: 12 mg/m2 IV bolus once per day on days 36 & 37
**Cycles 2 to 4: 12 mg/m2 IV bolus once per day on days 43 & 44
*Cyclophosphamide (Cytoxan) as follows:
**Cycle 1: 600 mg/m2 IV bolus once per day on days 36 & 37
**Cycles 2 to 4: 600 mg/m2 IV bolus once per day on days 43 & 44
*Dactinomycin (Cosmegen) as follows:
**Cycle 1: 0.45 mg/m2 IV bolus once per day on days 36 & 37
**Cycles 2 to 4: 0.45 mg/m2 IV bolus once per day on days 43 & 44
====Supportive therapy====
*Leucovorin (Folinic acid) 15 mg/m2 PO every 6 hours x 12 hours once per day, starting 24 hours after the completion of each methotrexate infusion; additional leucovorin used for delayed methotrexate elimination
*Sodium bicarbonate urine alkalinization prior to high-dose methotrexate
*Normal saline 4.5 L/m2 on day 1 after methotrexate; NS 3 L/m2 on day 2, with adjustments made to keep urine pH greater than 7.4
8-week cycle for 4 cycles, with surgery done during cycle 2 before doxorubicin; surgery is done 9 to 18 weeks after the start of chemotherapy
===References===
# COSS-80: Winkler K, Beron G, Kotz R, Salzer-Kuntschik M, Beck J, Beck W, Brandeis W, Ebell W, Erttmann R, Göbel U, Havers W, Henze G, Hinderfeld L, Höcker P, Jobke A, Jürgens H, Kabisch H, Preusser P, Prindull G, Ramach W, Ritter J, Sekera J, Treuner J, Wist G, Landbeck G. Neoadjuvant chemotherapy for osteogenic sarcoma: results of a Cooperative German/Austrian study. J Clin Oncol. 1984 Jun;2(6):617-24. link to original article dosing details in manuscript have been reviewed by our editors EuroPMC
==M-BCD==
M-BCD: High-dose Methotrexate, Bleomycin, Cyclophosphamide, Dactinomycin
===Regimen===
Study 	Dates of enrollment	Evidence 	Comparator	Comparative Efficacy
Winkler et al. 1988 (COSS-82)	1982-1984 	Phase 3 (C)	MAP 	Lower ORR
Note: The exact schedule is unclear based on limited information in the reference, as schedule of doses is primarily extrapolated from Figure 1, which does not contain clear delineations in time.
====Chemotherapy====
*Methotrexate (MTX) 12,000 mg/m2 (maximum dose of 20,000 mg) IV over 4 hours once per day on days 15 & 22
**MTX is dissolved at a concentration of 20,000 mg/L in a solution containing 5% glucose
*Bleomycin (Blenoxane) 15 mg/m2 IV bolus once per day on days 1 & 2
*Cyclophosphamide (Cytoxan) 600 mg/m2 IV bolus once per day on days 1 & 2
*Dactinomycin (Cosmegen) 0.6 mg/m2 IV bolus once per day on days 1 & 2
====Supportive therapy====
*Leucovorin (Folinic acid) 15 mg/m2 PO every 6 hours x 12 hours once per day on days 16 & 23, starting 24 hours after the completion of methotrexate infusion; additional leucovorin used for delayed methotrexate elimination
*Sodium bicarbonate urine alkalinization prior to high-dose methotrexate
*Normal saline 4.5 L/m2 on day 1 after methotrexate; NS 3 L/m2 on day 2, with adjustments made to keep urine pH greater than 7.4
35-day cycle for 2 cycles
====Subsequent treatment====
*Surgery, then risk-adapted treatment:
**COSS-82, patients who had a good response: Adjuvant M-BCD
**COSS-82, patients who had a poor response: Adjuvant AP
===References===
# COSS-82: Winkler K, Beron G, Delling G, Heise U, Kabisch H, Purfürst C, Berger J, Ritter J, Jürgens H, Gerein V, Graf N, Russe W, Gruemayer ER, Ertelt W, Kotz R, Preuzzer P, Prindull G, Brandeis W, Landbeck G. Neoadjuvant chemotherapy of osteosarcoma: results of a randomized cooperative trial (COSS-82) with salvage chemotherapy based on histological tumor response. J Clin Oncol. 1988 Feb;6(2):329-37. link to original article dosing details in manuscript have been reviewed by our editors EuroPMC
=Adjuvant therapy=
==Doxorubicin monotherapy==
===Regimen===
Study 	Dates of enrollment	Evidence
Cortes et al. 1974	Not reported 	Non-randomized
====Preceding treatment====
*Surgery
====Chemotherapy====
*Doxorubicin (Adriamycin) 30 mg/m2 IV once per day on days 1 to 3
4- to 6-week cycle for 6 cycles
===References===
# Cortes EP, Holland JF, Wang JJ, Sinks LF, Blom J, Senn H, Bank A, Glidewell O. Amputation and adriamycin in primary osteosarcoma. N Engl J Med. 1974 Nov 7;291(19):998-1000. link to original article dosing details in abstract have been reviewed by our editors EuroPMC
==IP-BCD==
IP-BCD: Ifosfamide, Platinol (Cisplatin), Bleomycin, Cyclophosphamide, Dactinomycin
===Regimen===
Study 	Dates of enrollment	Evidence
Winkler et al. 1988 (COSS-82)	1982-1984 	Non-randomized part of phase 3 RCT
====Preceding treatment====
*Neoadjuvant MAP, then surgery, with poor response
====Chemotherapy====
*Ifosfamide (Ifex) 2000 mg/m2 IV over 23.5 hours once per day on days 1 to 5, given second, with mesna
*Cisplatin (Platinol) 20 mg/m2 IV over 30 minutes once per day on days 1 to 5, given first
*Bleomycin (Blenoxane) 15 mg/m2 IV bolus once per day on days 22 & 23
*Cyclophosphamide (Cytoxan) 600 mg/m2 IV bolus once per day on days 22 & 23
*Dactinomycin (Cosmegen) 0.6 mg/m2 IV bolus once per day on days 22 & 23
====Supportive therapy====
*Mesna (Mesnex) 2000 mg/m2 IV over 23.5 hours once per day on days 1 to 5, given second, with ifosfamide, then 2000 mg/m2/day IV continuous infusion over 48 hours, started on day 6 (total dose: 14,000 mg/m2)
*Mannitol given with cisplatin; no further details provided
35-day cycle for 3 cycles
===References===
# COSS-82: Winkler K, Beron G, Delling G, Heise U, Kabisch H, Purfürst C, Berger J, Ritter J, Jürgens H, Gerein V, Graf N, Russe W, Gruemayer ER, Ertelt W, Kotz R, Preuzzer P, Prindull G, Brandeis W, Landbeck G. Neoadjuvant chemotherapy of osteosarcoma: results of a randomized cooperative trial (COSS-82) with salvage chemotherapy based on histological tumor response. J Clin Oncol. 1988 Feb;6(2):329-37. link to original article dosing details in manuscript have been reviewed by our editors EuroPMC
==MA-BCD/AP==
MA-BCD/AP: High-dose Methotrexate, Adriamycin (Doxorubicin), Bleomycin, Cyclophosphamide, Dactinomycin alternating with Adriamycin (Doxorubicin) & Platinol (Cisplatin)
===Regimen===
Study 	Dates of enrollment	Evidence 	Comparator 	Comparative Efficacy
Link et al. 1986	1982-1984 	Phase 3 (E-esc)	No further treatment	Longer RFS
Note: Routes were not specified in the text, but are assumed to be intravenous here.
====Preceding treatment====
*Surgery
====Chemotherapy, MA-BCD portion====
*Methotrexate (MTX) as follows:
**Week 4: 12,000 mg/m2 IV over 4 hours once on day 1
**Weeks 5, 6, 7, 11, 12, 15, 16, 29, 30, 44, 45: Dose titrated to achieve a peak serum drug level of 1000 μt
*Doxorubicin (Adriamycin) as follows:
**Weeks 8 & 17: 30 mg/m2 IV once per day on days 1 to 3
*Bleomycin (Blenoxane) as follows:
**Weeks 2, 13, 26, 39, 42: 15 mg/m2 IV once per day on days 1 & 2
*Cyclophosphamide (Cytoxan) as follows:
**Weeks 2, 13, 26, 39, 42: 600 mg/m2 IV once per day on days 1 & 2
*Dactinomycin (Cosmegen) as follows:
**Weeks 2, 13, 26, 39, 42: 0.6 mg/m2 IV once per day on days 1 & 2
====Chemotherapy, AP portion====
*Doxorubicin (Adriamycin) as follows:
**Weeks 20, 23, 33, 36: 50 mg/m2 IV once on day 1
*Cisplatin (Platinol) as follows:
**Weeks 20, 23, 33, 36: 100 mg/m2 IV once on day 1
45-week course
===References===
# Link MP, Goorin AM, Miser AW, Green AA, Pratt CB, Belasco JB, Pritchard J, Malpas JS, Baker AR, Kirkpatrick JA, Ayala AG, Shuster JJ, Abelson HT, Simone JV, Vietti TJ. The effect of adjuvant chemotherapy on relapse-free survival in patients with osteosarcoma of the extremity. N Engl J Med. 1986 Jun 19;314(25):1600-6. link to original article dosing details in manuscript have been reviewed by our editors EuroPMC
==M-BCD==
M-BCD: High-dose Methotrexate, Bleomycin, Cyclophosphamide, Dactinomycin
===Regimen===
Study 	Dates of enrollment	Evidence 	Comparator 	Comparative Efficacy
Eilber et al. 1987 	1981-1984 	Randomized (E-esc) 	Observation	Seems to have longer OS
Winkler et al. 1988 (COSS-82)	1982-1984 	Non-randomized part of phase 3 RCT	 	
Note: The exact schedule is unclear based on limited information in the references; schedule of doses is primarily extrapolated from Figure 1 of Winkler et al. 1988, which does not contain clear delineations in time.
====Preceding treatment====
*Neoadjuvant M-BCD, then surgery, with good response
====Chemotherapy====
*Methotrexate (MTX) 12,000 mg/m2 (maximum dose of 20,000 mg) IV over 4 hours once per day on days 15 & 22
**MTX is dissolved at a concentration of 20,000 mg/L in a solution containing 5% glucose
*Bleomycin (Blenoxane) 15 mg/m2 IV bolus once per day on days 1 & 2
*Cyclophosphamide (Cytoxan) 600 mg/m2 IV bolus once per day on days 1 & 2
*Dactinomycin (Cosmegen) 0.6 mg/m2 IV bolus once per day on days 1 & 2
====Supportive therapy====
*Leucovorin (Folinic acid) 15 mg/m2 PO every 6 hours x 12 hours once per day on days 16 & 23, starting 24 hours after the completion of methotrexate infusion; additional leucovorin used for delayed methotrexate elimination
*Sodium bicarbonate urine alkalinization prior to high-dose methotrexate
*Normal saline 4.5 L/m2 on day 1 after methotrexate; NS 3 L/m2 on day 2, with adjustments made to keep urine pH greater than 7.4
35-day cycle for 2 cycles
===References===
# Eilber F, Giuliano A, Eckardt J, Patterson K, Moseley S, Goodnight J. Adjuvant chemotherapy for osteosarcoma: a randomized prospective trial. J Clin Oncol. 1987 Jan;5(1):21-6. link to original article EuroPMC
## Update: Bernthal NM, Federman N, Eilber FR, Nelson SD, Eckardt JJ, Eilber FC, Tap WD. Long-term results (>25 years) of a randomized, prospective clinical trial evaluating chemotherapy in patients with high-grade, operable osteosarcoma. Cancer. 2012 Dec 1;118(23):5888-93. Epub 2012 May 30. link to original article EuroPMC
# COSS-82: Winkler K, Beron G, Delling G, Heise U, Kabisch H, Purfürst C, Berger J, Ritter J, Jürgens H, Gerein V, Graf N, Russe W, Gruemayer ER, Ertelt W, Kotz R, Preuzzer P, Prindull G, Brandeis W, Landbeck G. Neoadjuvant chemotherapy of osteosarcoma: results of a randomized cooperative trial (COSS-82) with salvage chemotherapy based on histological tumor response. J Clin Oncol. 1988 Feb;6(2):329-37. link to original article dosing details in manuscript have been reviewed by our editors EuroPMC
==Methotrexate & Vincristine==
===Regimen===
Study 	Dates of enrollment 	Evidence
Jaffe et al. 1974	1972-06 to not reported	Non-randomized
====Preceding treatment====
*Surgery
====Chemotherapy====
*Methotrexate (MTX) 1500 mg/m2 IV over 6 hours once on day 1
*Vincristine (Oncovin) 2 mg/m2 IV once on day 1, given 30 minutes prior to methotrexate
====Supportive therapy====
*Leucovorin (Folinic acid)
14-day cycle until therapeutic goal achieved, then 21-day cycle for up to 33 cycles (2 years total)
===References===
# Jaffe N, Frei E 3rd, Traggis D, Bishop Y. Adjuvant methotrexate and citrovorum-factor treatment of osteogenic sarcoma. N Engl J Med. 1974 Nov 7;291(19):994-7. link to original article dosing details in manuscript have been reviewed by our editors EuroPMC
=Relapsed, refractory, or metastatic=
==Doxorubicin monotherapy==
===Regimen===
Study 	Dates of enrollment	Evidence
Cortes et al. 1972	Not reported 	Non-randomized, fewer than 20 pts
====Chemotherapy====
*Doxorubicin (Adriamycin) 17.5 to 35 mg/m2 IV once per day on days 1 to 3 or 1 to 4
1-month cycles
===References===
# Cortes EP, Holland JF, Wang JJ, Sinks LF. Doxorubicin in disseminated osteosarcoma. JAMA. 1972 Sep 4;221(10):1132-8. link to original article dosing details in abstract have been reviewed by our editors EuroPMC
==MAPifn [COG AOST0331]==
Study 	Dates of enrollment 	Evidence
Marina et al. 2019 (EURAMOS-1 poor response)	2005-04-14 to 2011-06-30	Non-randomized part of phase 3 RCT
Note: Induction is received by all patients and consists of 2 cycles of MAP. The remainder of this protocol is for good responders.
===Induction===
====Chemotherapy====
*Cisplatin (Platinol) 60 mg/m2 IV over 4 hours once on day 1
*Doxorubicin (Adriamycin) 37.5 mg/m2/day IV continuous infusion, started on day 1 (total dose per cycle: 75 mg/m2)
*Methotrexate (MTX) 12,000 mg/m2 (maximum dose of 20,000 mg) IV over 4 hours once on day 1 of weeks 4, 5, 9, and 10. 
====Supportive therapy====
*Leucovorin (Folinic acid) 15 mg/m2 PO or IV every 6 hours beginning 24 hours after the beginning of the methotrexate infusion and continuing until the serum methotrexate level is less than 0.1 μM.
35-day cycle for 2 cycles
===Consolidation, Cycles 3-4 (Weeks 12 to 21)===
====Chemotherapy====
*Cisplatin (Platinol) 60 mg/m2 IV infusion over 4 hours, started on day 1 of weeks 12 and 17
*Doxorubicin (Adriamycin) 37.5 mg/m2/day IV continuous infusion, started on day 1 (total dose per cycle: 75 mg/m2)
*Methotrexate (MTX) 12,000 mg/m2 (maximum dose of 20,000 mg) IV over 4 hours once on day 1 of weeks 15, 16, 20, and 21. 
====Supportive therapy====
*Leucovorin (Folinic acid) 15 mg/m2 PO or IV every 6 hours beginning 24 hours after the beginning of the methotrexate infusion and continuing until the serum methotrexate level is less than 0.1 μM.
35-day cycle for 2 cycles
===Consolidation, Cycles 5-6 (Weeks 22 to 31)===
====Chemotherapy====
*Doxorubicin (Adriamycin) 37.5 mg/m2/day IV continuous infusion, started on day 1 (total dose per cycle: 75 mg/m2)
*Methotrexate (MTX) 12,000 mg/m2 (maximum dose of 20,000 mg) IV over 4 hours once on day 1 of weeks 24, 25, 28, and 29
====Supportive therapy====
*Leucovorin (Folinic acid) 15 mg/m2 PO or IV every 6 hours beginning 24 hours after the beginning of the methotrexate infusion and continuing until the serum methotrexate level is less than 0.1 μM.
35-day cycle for 2 cycles
===Maintenance, Weeks 32-104===
Note: Peginterferon alfa-2b dose is increased only if the starting dose is well tolerated.
====Immunotherapy====
*Peginterferon alfa-2b (Sylatron) as follows:
**Cycles 1 to 4: 0.5 mcg/kg (maximum dose of 50 mcg) SC once on day 1
**Cycles 5 to 75: 1 mcg/kg (maximum dose of 100 mcg) SC once on day 1
7-day cycle for 75 cycles
===References===
# EURAMOS-1 poor response: Marina NM, Smeland S, Bielack SS, Bernstein M, Jovic G, Krailo MD, Hook JM, Arndt C, van den Berg H, Brennan B, Brichard B, Brown KL, Butterfass-Bahloul T, Calaminus G, Daldrup-Link HE, Eriksson M, Gebhardt MC, Gelderblom H, Gerss J, Goldsby R, Goorin A, Gorlick R, Grier HE, Hale JP, Hall KS, Hardes J, Hawkins DS, Helmke K, Hogendoorn PC, Isakoff MS, Janeway KA, Jürgens H, Kager L, Kühne T, Lau CC, Leavey PJ, Lessnick SL, Mascarenhas L, Meyers PA, Mottl H, Nathrath M, Papai Z, Randall RL, Reichardt P, Renard M, Safwat AA, Schwartz CL, Stevens MC, Strauss SJ, Teot L, Werner M, Sydes MR, Whelan JS. Comparison of MAPIE versus MAP in patients with a poor response to preoperative chemotherapy for newly diagnosed high-grade osteosarcoma (EURAMOS-1): an open-label, international, randomised controlled trial. Lancet Oncol. 2016 Oct;17(10):1396-1408. Epub 2016 Aug 25. link to original article link to PMC article dosing details in manuscript have been reviewed by our editors EuroPMC NCT00134030
==MAPIE [COG AOST0331]==
Study 	Dates of enrollment 	Evidence 	Comparator	Comparative Efficacy
Marina et al. 2016 (EURAMOS-1 poor response)	2005-04-14 to 2011-06-30	Phase 3 (E-esc)	MAP 	Did not meet primary endpoint of EFS
Note: Induction is received by all patients and consists of 2 cycles of MAP; subsequent treatments in this protocol are for poor responders.
===Induction===
====Chemotherapy====
*Cisplatin (Platinol) 60 mg/m2 IV over 4 hours once on day 1
*Doxorubicin (Adriamycin) 37.5 mg/m2/day IV continuous infusion, started on day 1 (total dose per cycle: 75 mg/m2)
*Methotrexate (MTX) 12,000 mg/m2 (maximum dose of 20,000 mg) IV over 4 hours once on day 1 of weeks 4, 5, 9, and 10. 
====Supportive therapy====
*Leucovorin (Folinic acid) 15 mg/m2 PO or IV every 6 hours beginning 24 hours after the beginning of the methotrexate infusion and continuing until the serum methotrexate level is less than 0.1 μM.
35-day cycle for 2 cycles
===Consolidation, MAPIE Cycles 3 and 7===
====Chemotherapy====
*Cisplatin (Platinol) 60 mg/m2 IV infusion over 4 hours, started on day 1 of weeks 12 and 28
*Doxorubicin (Adriamycin) 37.5 mg/m2/day (total dose is 75 mg/m2 given as a 48 hour infusion) on days 1 to 2 of Weeks 12 and 28.
*Methotrexate (MTX) 12,000 mg/m2 (maximum dose of 20,000 mg) IV over 4 hours once on day 1 of weeks 15 and 31. 
====Supportive therapy====
*Leucovorin (Folinic acid) 15 mg/m2 PO or IV every 6 hours beginning 24 hours after the beginning of the methotrexate infusion and continuing until the serum methotrexate level is less than 0.1 μM.
5-Week Courses
===Consolidation, MAP Cycles 4, 6, and 8===
====Chemotherapy====
*Ifosfamide (Ifex) 2.8 g/m2/dose IV over 4 hours once per day on days 1 through 5 of weeks 16, 24, and 32.
*Etoposide (Vepesid) 100 mg/m2/dose IV over 60 minutes once per day on days 1 through 5 of weeks 16, 24, and 32.
*Methotrexate (MTX) 12,000 mg/m2 (maximum dose of 20,000 mg) IV over 4 hours once on day 1 of weeks 19, 27, and 35. 
====Supportive therapy====
*Mesna (Mesnex) 2.8 g/m2/24 hours IV continuous infusion over 24 hours on days 1 through 5 of weeks 16, 24, and 32.
*Leucovorin (Folinic acid) 15 mg/m2 PO or IV every 6 hours beginning 24 hours after the beginning of the methotrexate infusion and continuing until the serum methotrexate level is less than 0.1 μM.
5-Week Courses
===Consolidation, MAP Cycle 5===
====Chemotherapy====
*Doxorubicin (Adriamycin) 37.5 mg/m2/day (total dose is 75 mg/m2 given as a 48 hour infusion) on days 1 to 2 of Week 20.
*Ifosfamide (Ifex) 3 g/m2/dose IV over 4 hours once per day on days 1, 2, and 3 of weeks 20.
*Methotrexate (MTX) 12,000 mg/m2 (maximum dose of 20,000 mg) IV over 4 hours once on day 1 of weeks 23. 
====Supportive therapy====
*Mesna (Mesnex) 3 g/m2/24 hours IV continuous infusion over 24 hours on days 1, 2, and 3 of weeks 20.
*Leucovorin (Folinic acid) 15 mg/m2 PO or IV every 6 hours beginning 24 hours after the beginning of the methotrexate infusion and continuing until the serum methotrexate level is less than 0.1 μM.
5-Week Courses
===Consolidation, MAP Cycle 9 (weeks 36 to 40)===
====Chemotherapy====
*Doxorubicin (Adriamycin) 37.5 mg/m2/day IV continuous infusion, started on day 1 (total dose per cycle: 75 mg/m2)
*Ifosfamide (Ifex) 3 g/m2/dose IV over 4 hours once per day on days 1, 2, and 3 of weeks 36.
*Methotrexate (MTX) 12,000 mg/m2 (maximum dose of 20,000 mg) IV over 4 hours once on day 1 of weeks 39 and 40. 
====Supportive therapy====
*Mesna (Mesnex) 3 g/m2/24 hours IV continuous infusion over 24 hours on days 1, 2, and 3 of weeks 36.
*Leucovorin (Folinic acid) 15 mg/m2 PO or IV every 6 hours beginning 24 hours after the beginning of the methotrexate infusion and continuing until the serum methotrexate level is less than 0.1 μM.
5-Week Courses
===References===
# EURAMOS-1 poor response: Marina NM, Smeland S, Bielack SS, Bernstein M, Jovic G, Krailo MD, Hook JM, Arndt C, van den Berg H, Brennan B, Brichard B, Brown KL, Butterfass-Bahloul T, Calaminus G, Daldrup-Link HE, Eriksson M, Gebhardt MC, Gelderblom H, Gerss J, Goldsby R, Goorin A, Gorlick R, Grier HE, Hale JP, Hall KS, Hardes J, Hawkins DS, Helmke K, Hogendoorn PC, Isakoff MS, Janeway KA, Jürgens H, Kager L, Kühne T, Lau CC, Leavey PJ, Lessnick SL, Mascarenhas L, Meyers PA, Mottl H, Nathrath M, Papai Z, Randall RL, Reichardt P, Renard M, Safwat AA, Schwartz CL, Stevens MC, Strauss SJ, Teot L, Werner M, Sydes MR, Whelan JS. Comparison of MAPIE versus MAP in patients with a poor response to preoperative chemotherapy for newly diagnosed high-grade osteosarcoma (EURAMOS-1): an open-label, international, randomised controlled trial. Lancet Oncol. 2016 Oct;17(10):1396-1408. Epub 2016 Aug 25. link to original article link to PMC article dosing details in manuscript have been reviewed by our editors EuroPMC NCT00134030
Category:Osteosarcoma regimens
Category:Historical regimens
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Category:Bone sarcomas
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