bluuebunny/crossref_metadata_2025 huggingface dataset:
Intermittent androgen deprivation therapy (IADT) for patients with non-metastatic prostate cancer: A retrospective review
Authors: So-Rosillo R. , Small E. J. , Weinberg V.
Published: March 2020

15635

Background: IADT is a therapeutic option frequently utilized in men with progressive non-castrate prostate cancer (PCa) which, compared to continuous ADT, may result in an improvement in quality of life while potentially prolonging time to androgen independence (AI). Methods: The records of 43 consecutive men with non-metastatic progressive non-castrate PCa treated with IADT were analyzed. 21 men had received no prior primary treatment (tx), and 22 had developed recurrent disease after previous local therapy. Therapy for this cohort of patients (pts) consisted of combined androgen blockade for 32 pts and a leutenizing hormone-releasing hormone agonist alone for 11. Pts were allowed to come off androgen deprivation (AD) when (a) PSA became undetectable, (b) after 9 to 12 months (mos) of receiving AD, (c) or per patient request. AD was re-initiated when (a) serum PSA reached 50% or greater of the pre-tx level, (b) at physician discretion, or (c) at patient's request. A tx cycle was defined as the number of months on tx plus the number of months off tx until the reinstitution of AD. Progressive disease and AI were defined by consensus criteria (climbing PSA despite AD). Results: Follow up ranged from 18 to 153 mos (median 68.2 mos) from the start of tx. Pts received from 1 to 10 cycles (median 4), with a median cycle length of 19 mos. The median pre-tx PSA value was 8.9, and the median nadir serum PSA level with ADT was 0.09 and was reached within an average of 6.4 mos (range 2–25) after beginning tx. Pts spent an average of 50.7% of time on hormones and 49.3% off hormones. Eleven pts developed AI progressive disease, with a median time to progression of 47 mos. When examining for potential characteristics that contributed to AI, such as duration of ADT, PSA at start of therapy, nadir PSA, stage, or Gleason score, no consistent patterns of failure emerged. Conclusions: IADT appears to be a viable tx option for men with non-metastatic progressive non-castrate PCa, resulting in prolonged duration of response. However, with a median follow up of nearly 6 years, AI still develops in over a quarter of pts, at a median of 47 months from starting ADT.

No significant financial relationships to disclose.
Efficacy of pegylated liposomal doxorubicin (PLD) and oxaliplatin (Ox) in pre-treated advanced epithelial ovarian cancer (EOC) in relation to BRCA status
Authors: Nicoletto M. O. , Donach M. E. , Borgato L. , Artioli G. , Zovato S. , Barile C. , Bertorelle R. , Cartei G.
Published: March 2020

16006

Background: The mechanism of action of PLD+Ox suggests that and carriers of BRCA mutations might have better survival compared to sporadic ovarian cancer even when pre-treated in advanced EOC. Methods: Inclusion criteria: Performance Status<=2, relapse or progression after 1–3 lines of therapy; <=4 prior antiblastic drugs; life expectancy >3 months; LVEF >50%, informed consent. Treatment consisted of 1 hr infusion of PLD 30–35 mg/m2 on day 1 and 70 mg/m2 of Ox in 2 hrs on day 2 for 8 cycles, then 2 cycles of PLD alone. Clinical response was evaluated by CT scan every 3 cycles. Primary endpoints were overall survival and its correlation with BRCA mutations and p53. Results: From June 2000, 63 pre-treated pts with advanced EOC were enrolled. Median age = 62 yrs, range 41–83, (18pts >70 yrs). 17 had known germline BRCA1/2 mutations (10pts) or family history of ovarian cancer (4pts). In this BRCA/high-risk population 15 pts were evaluable for response with ORR=93.3% (8 CR, 6 PR>50%, 1 SD). 139 courses were administered (median = 10 courses/pt). There was 1 episode of G3 toxicity: mucositis; G1–2 toxicity was gastrointestinal (16 episodes), mucositis (11 episodes), neutropenia (9 episodes). Median LVEF showed no significant changes during treatment. There is no clear correlation between OS and amount of Platinum/Taxol administered previously. p53 was analyzed for expression and mutations. Mutations were sought in exons 5, 6, 7 and 8. 5/6 CR evaluable for p53 showed overexpression. p53 overexpression was seen in 9/11 evaluable pts; of these 4/9 also had p53 mutations. 3/4 of these patients obtained a complete response. Median survival from 1st cycle has not been reached; mean survival is 63.6 months vs 24.7 for sporadic EOC (p<.001). Presently 15/17 are alive. The 5-yr survival after first course of therapy is estimated at 82%. BRCA/high-risk patients in PLD-Ox therapy also fared better than counterparts from an historical population (OS from diagnosis 179.4 vs 141.1 months, p=.005). Conclusions: PLD+Ox is well tolerated and highly effective in BRCA/high-risk patients and in p53 positive/mutated pts in this population. This therapy offers low toxicity providing good quality of life.

No significant financial relationships to disclose.
Validation of CA-125 concentration nadir within the normal range following primary treatment as a predictor of survival for epithelial ovarian cancer (EOC)
Authors: Prat A. , Del Campo J. , Peralta S. , Cedres S. , Perez A. , Gil A. , Martinez-Palones J. , Garcia A. , Baselga J.
Published: March 2020

16007

Background: Recent studies suggest that the CA-125 nadir within the normal range after surgery and chemotherapy treatment is a predictor of survival (Crawford, ASCO 2004; Crawford, Ann Oncol 2005) and relapse (Markman, J Clin Oncol 2006). In order to validate these previous findings, we have conducted a retrospective analysis of patients (pts) treated in our institution for EOC. Methods: Between March 1, 1997, and October 30, 2005, all pts treated for EOC at Vall d'Hebron University Hospital were identified from the tumor registry database and screened retrospectively for their standard prognostic factors (age at diagnosis (=65 vs. >65), stage (III-IV vs. IC-II), and suboptimal vs. optimal cytorreduction). Inclusion criteria: an elevated CA-125 at time of diagnosis (>35 U/mL); primary treatment (PT) that consisted in surgery and intravenous carboplatin/paclitaxel for a maximum of 6–9 cycles; complete clinical and radiological response to initial treatment with normalization of CA-125 (=35 U/mL); and disease status at the time of last follow-up. Standard Kaplan-Meier methods were used to plot the progression-free survival (PFS) of members of each of the nadir groups. The relative contribution of the different potential correlates of prognosis was assessed by the Cox proportional hazards method. Results: 123 pts were identified: 64 Group A (=10 U/mL), 42 Group B (11–20 U/mL), 17 Group C (21–35 U/mL). Median age: 56. Stage IC 25%, II 13%, III 52%, IV 10%. Median follow-up 39.2 months (m). Median PFS was 69.7 m, 27.7 m, and 15.8 m for A, B and C, respectively (p< .0001, log-rank test). The Cox model showed a highly-significant impact on PFS in relation to CA-125 nadir levels, residual tumor after surgery and stage. Hazard ratios (HR) for PFS (95% CI) of B vs. A, C vs. B, and C vs. A were 1.98 (p= .034), 2.35 (p= .02), and 4.67 (p< .001), respectively. HR for PFS (95% CI) of suboptimal vs. optimal cytorreduction and stage III-IV vs. IC-II were 1.84 (p= .058) and 3.2 (p= .002), respectively. Conclusions: The CA-125 nadir in the normal range following PT for EOC is a reproducible predictor of PFS in stage IC-IV. Prospective studies of maintenance-consolidation therapies or different approaches in selected pts based on CA-125 nadir seem warranted.

No significant financial relationships to disclose.
Serum YKL-40 levels are usuful diagnostic tumor markers for adenocarcinoma of the uterine cervix
Authors: Mitsuhashi A. , Usui H. , Matsui H. , Tate S. , Unno Y. , Hirashiki K. , Shozu M.
Published: March 2020

16008

Background: YKL-40 is secreted by cancer cells, macrophages, and neutrophils. It may be a growth factor, play a role in angiogenesis, or prevent apoptosis. The current study examined serum YKL-40 levels in patients with adenocarcinoma of the cervix to determine if it is a serum marker. Methods: The serum YKL-40 level was assayed by enzyme-linked immunosorbent assay in 24 patients with benign gynecologic disease, in 104 patients with squamous cell carcinonma , in 37 patietns with adenocarcinoma, and in 45 healthy controls, Serum squamous cell carcinoma antigen (SCC) and CA125 and CA19–9 values were obtained. Results: The serum YKL-40 level was higher in patients with cervical carcinoma than in the healthy controls (p<0.0001). YKL-40 concentrations increased significantly in patients with squamous cell carcinoma and in those with adenocarcinoma (vs. normal control: p<0.0001 and p<0.0001, respectively). Judging from the receiver operating curves (ROC), the serum YKL-40 was more sensitive than other serum markers at identifying adenocarcinoma. In squamous cell carcinoma, this ability of serum YKL-40 was equal to that of SCC. YKL-40 was elevated in 68.4% of patients with stage I adenocarcinoma. The pretherapeutic serum level of YKL-40 correlated significantly with the International Federation of Gynecology and Obstetrics advanced stage in patients with adenocarcinoma of the cervix. Furthermore, the pretherapeutic serum level of YKL-40 correlated with disease persistence or recurrence. Conclusions: The serum YKL-40 level has potential usefulness as a diagnostic marker of adenocarcinoma of the cervix.

[Table: see text]

No significant financial relationships to disclose.
Safety and efficacy of pegfilgrastim administration on the same day as myelosuppressive chemotherapy (CT) in women with ovarian or primary peritoneal cancer
Authors: Schuman S. I. , Lambrou N. , Robson K. , Glück S. , Myriounis N. , Pearson J. , Alvarez E. , Crisp M. P. , Twiggs L. B. , Lucci J. A.
Published: March 2020

16009

Background: According to prescribing information, pegfilgrastim should not be administered within 14 days prior to, or within 24 hours after, the administration of cytotoxic CT. However, little data exist to support this recommendation. The purpose of the current study is to determine the safety and efficacy of administering pegfilgrastim on the same day as myelosuppressive CT in patients with ovarian or primary peritoneal carcinoma. Methods: A retrospective review was conducted of all ovarian and primary peritoneal cancer patients that received prophylactic pegfilgrastim on the same day as CT from May 2003 to June 2006. Results: Forty-six patients (mean age: 57, range: 21–82) were treated for the following malignancies: 35 (76%) epithelial ovarian, 6 (13%) primary peritoneal, and 5 (11.0%) ovarian germ cell or stromal cell carcinoma. Twenty-six patients (56%) had primary cancers and 20 (44 %) had recurrent disease. All patients met the ASCO or NCCN recommendations of using colony-stimulating factors for prophylaxis against febrile neutropenia (FN) (Risk of FN > 20%). A total of 269 cycles of CT were administered including 125 cycles (46.5%) docetaxel + carboplatin, 39 cycles (14.5%) gemcitabine + platinum, 30 cycles (11.1%) intravenous paclitaxel + carboplatin, 28 cycles (10.4%) liposomal doxorubicin, 19 cycles (7.1%) paclitaxel + intraperitoneal platinum, 6 cycles (2.2%) docetaxel, 6 cycles (2.2%) liposomal doxorubicin + cisplatin, 5 cycles (2%) bleomycin + etoposide + cisplatin, 4 cycles (1.5%) topotecan, 3 cycles (1.1%) of paclitaxel, 2 cycles (0.7%) vincristine + actinomycin-D + cyclophosphamide, and 2 cycles (0.7%) docetaxel + gemcitabine. All patients received pegfilgrastim within one hour of the completion of CT administration. Grade 1 or 2 neutropenia developed in 10 cycles (3.7%) out of the 269 cycles, mean absolute neutrophil count = 4926 (range, 1293 -24300). No patients had FN episodes, hospitalizations or antibiotic use secondary to neutropenia, or dose-reductions and CT delays due to neutropenia. Conclusions: Administration of pegfilgrastim on the same day as CT in ovarian and primary peritoneal cancer patients is more convenient to the patient and appears safe and effective.

No significant financial relationships to disclose.
Phase I/II study to evaluate the optimum dose of pegylated-interferon (PEG INTRON) in patients with platinum-resistant ovarian cancer
Authors: Soliman P. T. , Gano J. B. , Levenback C. F. , Kavanagh J. , Gershenson D. M. , Wolf J. K.
Published: March 2020

16010

Background: Intraperitoneal interferon therapy has been shown to have response rates as high as 45% in patients with recurrent ovarian cancer. Continued exposure has also been associated with the effectiveness of interferon treatment. The purpose of this study was evaluate the optimum dose and toxicity profile of PEG INTRON given subcutaneously (SC) on a weekly schedule to women with platinum-resistant ovarian cancer. Methods: Women with platinum-resistant ovarian, peritoneal, or fallopian tube cancer were eligible. Those whose tumors tested positive for IL-8, bFGF, or VEGF were randomized to three PEG INTRON treatment doses, 1.0, 1.25, or 1.5 micrograms/kg/wk SC for a total of 4 weekly injections per cycle. Re-evaluation for tumor response by imaging, physical exam and CA-125 was performed every 2 -3 cycles (8 - 12 weeks). Up to 12 cycles of treatment was allowed. Treatment was continued until progression of disease or unacceptable toxicity. Results: Thirty patients were enrolled, only 17 received treatment; 11 tested negative, 1 refused testing, 1 tested positive but refused treatment. Median age was 56 years (35–73). Of those treated, 94% (16/17) had a performance status of 0. All were heavily pretreated (3–8 prior chemo regimens). One patient received 9 cycles (1.25 micrograms/kg, total dose = 80 mcg) with stable disease. In the remaining 16 patients, 14 (75%) were taken off study due to disease progression; 3 after completing 2 treatment cycles and 11 after <2 treatment cycles. Four patients (24%) discontinued treatment because of toxicity. Two episodes of grade 4 fatigue were reported. Other grade 3 toxicities included visual changes, pain, anemia, neutropenia, depression, myalgia, and nausea/vomiting. Conclusions: There were no clinical responses to weekly PEG INTRON in this patient population. In addition, the regimen was difficult to tolerate. Further investigation into the dose and delivery of PEG INTRON is needed to determine the safety and efficacy of interferon treatment in patients with reuccurent ovarian cancer.

No significant financial relationships to disclose.
A phase II randomized, double-blind, placebo-controlled trial of clinical activity and safety of Å6 in patients with asymptomatic CA 125 progression of epithelial ovarian, fallopian tube, or primary peritoneal cancer
Authors: Ghamande S. , Silverman M. , Gold M. , Huh W. , Behbakht K. , Ball G. , Cuasay L. , Brunner N.
Published: March 2020

16014

Background: Patients (pts) with epithelial ovarian cancer (EOC) often relapse and rising CA 125 levels predate clinical or radiological appearance of tumor. High tumor and serum levels of urokinase plasminogen activator (uPA) in EOC correlate to adverse outcomes. Å6 is a novel peptide derived from human uPA that down-regulates the uPA system and has anti-angiogenic and anti-metastatic activity in animals. Methods: Pts with EOC, fallopian tube, or primary peritoneal cancer in clinical remission after first line chemotherapy had to have 2 consecutive rises of CA 125 levels above normal with no disease on physical examination or imaging studies. Pts were randomized to receive daily subcutaneous injections of placebo, 150 mg Å6, or 300 mg Å6 until disease progression. The primary objectives were to assess safety and clinical activity of Å6 by the effect on the onset of disease progression. Results: 48 pts were planned for the study. The trial ended early with 24 patients {12 pts (50%) placebo, 8 pts (33%) low dose Å6, 4 pts (17%) high dose Å6} randomized, treated and followed for up to 9 months. Despite early study termination and small sample size, A6 therapy was associated with a statistically significant progression free survival (PFS) (log rank p value=0.01) with a median PFS of 100 days (95% CI 64,168) compared to 49 days (95% CI 29,67) in pts who received the placebo. The treatments were well tolerated with one serious adverse event (transient nausea and dyspnea ) possibly related to study drug. Treatment was not associated with CA 125 response (Fisher exact test p value= 0.44). Conclusions: Å6 therapy increases PFS of patients with EOC and asymptomatic progression of CA 125. This therapy is novel, safe, feasible and deserves further investigation

[Table: see text]
Prognostic value of change in CA 125 levels after the first cycle of induction chemotherapy for epithelial ovarian cancers: Results of a multicentric French study
Authors: Riedinger J. , Basuyau J. , Eche N. , Bonnetain F. , Pichon M. F. , Fargeot P.
Published: March 2020

16017

Background: CA 125 assays enable treatment-response monitoring in ovarian cancer. Patients and Methods: This multicentric study was performed to assess the predictive value with regard to pathologic complete response at surgical second look and the prognostic value of the serum CA 125 change (=rease [D], 50%, 25%, < 25%ase) after one or two courses of induction chemotherapy (CT) with platinum salts and cyclophosphamide Of the 494 stage IIc - IV patients who were treated at the French Cancer Centres of Dijon, Bordeaux, Toulouse, Rouen, Reims, Nantes, Angers, Saint Cloud, 397 (80.4%d and 382 (77.3%om cancer. Median (range) follow up time was 34 months (3 - 215 months). Among them, 194 patients had a surgical second look. Results: The CA 125 change after the first, the second and the two first CT courses and CA 125 concentration (> or =-1) before the third CT cycle had an univariate prognostic value for overall survival (OS) (p < 0.0001 for both). In Cox models, CA 125 change after the first CT course (p < 0.0001), residual tumour (p = CA 125 concentration before the second CT course (p =and patients’ age (p =were independent prognostic factors for OS. A normal CA 125 before each of the two first CT courses or a CA 125 decrease higher than 50%e first CT course with a CA 125 =-1 before the second CT course identify patients with good prognosis. Both criteria retained a significant value in predicting second-look findings by univariate and multivariate analysis (p < 0.0001). Conclusion: Among well-established prognostic factors in ovarian cancers, the CA 125 change after the first CT course was independent prognostic factors for both achievement of pathological complete response and OS.

No significant financial relationships to disclose.
Clinical outcome and risk factors for recurrence in borderline ovarian tumors
Authors: Yokoyama Y. , Mizunuma H. , Yaegashi N. , Tanaka T. , Kurachi H. , Sato A. , Tase T. , Sugiyama T.
Published: March 2020

16020

Background: We investigated the long-term prognosis of borderline ovarian tumors and determined risk factors for recurrence. Methods: One hundred and twenty one borderline ovarian tumors treated between 1994 and 2003 at the participating institutions in the Tohoku Gynecologic Cancer Unit were retrospectively investigated for clinical stage, histopathological subtype, surgical technique, postoperative chemotherapy, the presence or absence of recurrence, and prognosis. Results: The median follow-up period was 57 months (1–126 months). One hundred and nine cases (90.6%) were at clinical stage I. The histopathological subtypes consisted of 91 cases of mucinous tumor (75.2%), 27 cases of serous tumor (22.3%), and 3 cases of endometrioid tumor. Conservative surgery was used in 53 cases (43.8%), radical surgery in 68 cases (56.2%), a staging laparotomy in 43 cases (35.5%), and postoperative adjuvant therapy in 30 cases (24.8%). Recurrence was found in 8 cases, but no tumor-related deaths were reported. Although no significant difference in disease free survival rate was seen between different clinical stages, the difference in disease free survival rate between serous and non-serous (mucinous and endometrioid) types was significant (p<0.05). The 10-year disease free survival rate was 89.1% for the radical surgery group, and 57.4% for the conservative surgery group- this difference was significant (p<0.05). In the conservative surgery group, cystectomy and serous tumor were independent risk factors for recurrence. Although recurrence was observed, the long-term prognosis of borderline ovarian tumor was favorable, without tumor-related deaths. Conclusion: Considering the favorable prognosis, conservative surgery can be chosen as far as the patient has a non-serous tumor and receive adnexectomy. However, in cases of serous type and/or receiving cystectomy special care should be given as relative risk rates of recurrence elevate by 2 to 4 folds.

No significant financial relationships to disclose.
Pregancy after bilateral dysgerminoma treated with conservative surgery and BEP chemotherapy
Authors: Shami N. , Shaila A. , Shaharyar A. , Asif S.
Published: March 2020

16039

Background: Pregnancy after treatment of germ cell tumours of ovary is common. However patients with bilateral dysgerminoma treated with unilateral oophorectomy, wedge biopsy of opposite ovary, and conservation of uterus face difficulty in conception. This study was conducted with the objective to evaluate the fertility status of ovarian dysgerminoma patients treated with conservative surgery and BEP chemotherapy. Methods: Patients of bilateral dysgerminoma who underwent conservative surgery and chemotherapy with cisplatin 20 mg / m2 and etoposide 100 mg / m2 day 1 to 5 and bleomycin 30 mg on day 1, 8 and 15 of three weekly cycles were eligible. A normal AFP and beta HCG at baseline was required. Post treatment CT scans of abdomen and pelvis were obtained. Patients were regularly followed on monthly basis. Pregnancy was allowed 2 years after completion of last cycle of chemotherapy. Results: From January 1998 to December 2003, 11 patients were enrolled. Medain age was 16 years (range 13–18). All patients had complete disappearance of disease after treatment. Treatment related amenorrhea did not last beyond one year. During a median follow up of 5 years, all patients conceived and a total of 14 pregnancies were completed successfully.Three patients required use of clomiphene citrate for ovulation induction. No patient was treated with gonadotrophins. Six patients underwent lower segment caesarean section for obstetric indications and seven delivered vaginally. All babies were healthy without the signs of birth abnormalities or retardation. Conclusions: With conservative surgery and BEP chemotherapy for treatment of bilateral dysgerminoma the fertility is retained with good pregnancy outcome, when conception occurs at least two years after the last dose of chemotherapy.

No significant financial relationships to disclose.
Relation between vascular endothelial growth factor receptor (VEGFR) in tumor sample and response rate in patients with cervical cancer treated with chemo-radiotherapy
Authors: Richardet E. , Richardet M. , Mascheroni M. B. , Lingua A. , Gómez Storniolo P. , Celiz P. , Bella S. , Guidi A. , Ferraris G. , Kaen L. , De la Colina M.
Published: March 2020

16040

Background: The vascular endothelial growth factor (VEGF) and their receptors play a fundamental role in the regulation of the angiogenesis and linfoangiogenesis. This study examined the relation between levels of expression of the VEGFR with the rate of response in patients (pts) with cervical cancer treated with chemo-radiotherapy-brachytherapy with cisplatinum. Methods: Clinical records of 30 women with their pathology were analyzed. The expression of the VEGFR was evaluated by inmunohistochemestry (IHQ-) by a pathologists committee and It was classified in 4 categories according percentage of tumor cells cytoplasm marked: 0 = 0% / 1=< 25% / 2=<26%-50% and 3 = > 50%. In order to correlate the VEGFR expression with response rate, patients were classified in 2 groups: lower level of expression (VEGFR 0–1), and high level of expression (VEGFR 2–3). In a second analysis we discriminated those with VEGFR expression 3 ant the rest of the group. The evaluation of the tumor response was made by clinical examination and magnetic nuclear resonance (RNM). We used Fisher exact test for statistical analysis Results: Median age: 47 years (r: 27 - 69). Pts with VEGFR 0 =2 (6.66%) pt with 1,2,3 VEGFR =28 (93.33%)(p:<0,001) . Objective respnse rate (OR) in pts with low expression of VEGFR was 90.9%, OR rate for pts with high levels of expression VEGFR was 56.97% (p: 0,52). The OR rate for pts with VEGFR 3 OR was 28.57% and for pats with VEGFR 0,1,2 was 69.56% (p:0,035) Conclusions: We observed that 93.33% of pts expresed VEGFR. OR rate was higher among pts. with lower expression compared with pts. of higher level of expression. These results, although in a small group of patients, stimulate investigation of anti angiogenic therapies in cervical cancer.

[Table: see text]
Computer simulation of pharmacokinetic analysis of 161,051 drugs after intraperitoneal (IP) or intravenous (IV) administrations
Authors: Miyagi Y. , Fujiwara K. , Nagao S. , Kigawa J. , Miyake K. , Oda T. , Miyagi Y.
Published: March 2020

16042

Background: Recent clinical studies for ovarian cancer have demonstrated the survival benefit of intraperitoneal (IP) administration of anti-cancer drugs, such as platinum agents, or paclitaxel. It is of great interest to investigate whether IP administration of other cytotoxic agents are more effective compared with intravenous (IV) administration. In this study we investigated the pharmacological advantage of IP administration using anti-cancer drugs, of which cytocidal effect is determined by the value of the area under the time concentration curve (AUC), by using computer simulation model. Methods: The 3-compartment pharmacokinetic computer model was used and 161,051 sets of the rate constants were substituted into the model. Because one set of the rate constants determines a pharmacokinetic behavior of one drug, it was considered to simulate over 160,000 drugs in this study. The constants were referred to ones of carboplatin. The simulations were made after 210 mg/body of the drugs were administered. The values of the AUC in the serum and in the IP cavity after IP or IV administration were calculated for each set, and then, these two administration methods were compared. Results: The values of the AUC in the serum by IP vs IV administration were 6.675 ± 21.603 (mean±SD); [0.08 - 106.155 (range)] vs 6.663 ± 21.541; [0.183 - 105.726]. The values of the AUC in the cavity after IP vs IV administration were 128.799 ± 344.491; [0.342 - 2288.48] vs 90.700 ± 283.946; [0.002 - 2259.32]. The ratios of AUC in the serum after IP or IV administrations were 0.995 ± 0.023; [0.401 - 1.020]. 147,201 sets (91.4%) were between 0.99 and 1.01. On the other hand, the ratios in the IP cavity were 25.327 ± 86.515; [1.003 - 548.976]. All the IP/IV ratios in the cavity were more than 1. Conclusions: The simulated probability clearly indicated that IP administration is not a local but a systemic chemotherapy for most drugs. All of the chemotherapeutic agents should be investigated for IP administration as well as conventional IV administration in clinical research protocol, especially in phase I/II study to clarify the effects and toxicities.

No significant financial relationships to disclose.
Platinum and taxane intraperitoneal chemotherapy after secondary cytoreductive surgery for recurrent ovarian carcinoma
Authors: Seamon L. G. , Seward S. , Richardson D. , Fowler J. M. , Cohn D. E.
Published: March 2020

16043

Background: Intraperitoneal chemotherapy (IP) after primary optimal debulking for advanced stage epithelial ovarian carcinoma improves survival. The objective of this research is to describe our experience with IP taxane and platinum chemotherapy after optimal secondary cytoreductive surgery in patients with platinum-sensitive recurrent ovarian cancer. Methods: We retrospectively reviewed charts from January 2006 to January 2007 and identified approximately 30 patients who received IP chemotherapy for optimally debulked advanced ovarian carcinoma. Of these patients, 8 were treated at first recurrence with cytoreductive surgery followed by second-line IP chemotherapy with intravenous docetaxel (70 mg/m2) and IP cisplatin (75–85 mg/m2) on day 1 and IP paclitaxel (60 mg/m2) on day 8, every 21 days. Results: The median disease free interval from completion of initial chemotherapy to recurrence was 19 months. All patients who underwent secondary cytoreductive surgery were considered optimally debulked (less than 1 cm residual disease), with 6 patients having no residual disease. One patient required rectal resection and another patient had ileocecal resection without a protective ostomy. All patients had insertion of an intraperitoneal venous access device for infusion of IP chemotherapy at the time of cytoreduction. While four patients have completed all 6 cycles of IP chemotherapy, one patient completed only 3 cycles due to catheter related toxicity requiring removal of the port (abdominal pain). This patient did not undergo concurrent bowel surgery. In addition, two patients have completed 3 cycles and two patients are currently scheduled to begin IP chemotherapy. Only two patients experienced grade 3 or 4 neutropenia. No other grade 3 or 4 toxicities were identified. A median of 5 cycles (range 2–5 cycles) was required to achieve a CA125 nadir. Complete clinical response was obtained in all patients at a median follow up of 9 months (range 4–10 months). Conclusions: In optimally debulked, platinum-sensitive patients following secondary cytoreductive surgery for recurrent ovarian cancer, intraperitoneal taxane and platinum chemotherapy is feasible with acceptable toxicity and provides another option for treatment.

No significant financial relationships to disclose.
Activation of MMP-2 by endometrial cancer cells in vitro is enhanced by LPA
Authors: Boyd L. R. , Ariztia E. V. , Fishman D. A.
Published: March 2020

16047

Background: Matrix metalloproteinases (MMPs) are responsible for the breakdown of extracellular matrix components, and are important in the metastatic phenotype. HEC-1A is an endometrial cancer cell line, derived from a moderately-differentiated tumor. These cells do not produce MMP-2, an important mediator of invasive behavior. We sought to: evaluate if HEC-1A cells have the capacity to activate proMMP-2 if given the proenzyme exogenously; and determine if the addition of lysophosphatidic acid (LPA), a known activator of MMPs in other cancers, would further enhance this conversion. Methods: HEC-1A cells were maintained per known protocols. Conditioned media from HT1080 chondrosarcoma cells, a source of proMMP-2, was added to HEC-1A cells. Cells were also treated with 0.1, 1.0 and 10uM LPA. Conditioned media from the cells was analyzed for the presence of MMP-2 and its proenzyme utilizing gelatin zymography. Cellular invasion through collagen matrix was quantified using a modified Boyden chamber assay. Migration was evaluated using a wound healing assay with quantification of wound closure at 48 hours. Proliferation was assessed following cell culture for 48 hours using an MTS tetrazolium salt/phenazine methosulfate assay. Results: HEC-1A cells activated exogenous proMMP-2 to MMP-2, as confirmed by gelatin zymography. This occurred in both the presence and absence of LPA. Invasion of HEC-1A cells treated with proMMP-2 was significantly increased as compared to controls (p < .001). LPA increased invasion in cells with and without exogenous proMMP-2, with the most invasive cells being those treated with both LPA and exogenous proMMP-2. The addition of both exogenous MMP-2 and LPA significantly increased cellular migration as quantified using the wound healing assay (p < .001). Cellular proliferation was significantly increased with LPA vs. controls. The addition of proMMP-2 did not lead to a significant difference in proliferation. Conclusions: HEC-1A cells can convert exogenous proMMP-2 to its active form, and in doing so exhibit a more invasive phenotype. LPA serves to further increase these behaviors. This may reflect the tumor microenvironment, with endometrial cancer cells responding to bioactive lipids and proenzymes secreted by the surrounding stroma.

No significant financial relationships to disclose.
A phase I study combining high-dose (HD) topotecan (TPC) plus cyclophosphamide (CPM) with blood stem cells support in poor prognosis ovarian carcinoma (OC): The ITOV 01bis protocol
Authors: Lotz J. , Pautier P. , Selle F. , Fabbro M. , Viens P. , Ribrag V. , Lokiec F. , Gligorov J. , de Labareyre C. M. , Lhommé C.
Published: March 2020

16061

Background: TPC and CPM-based CT may be proposed as 2nd-line chemotherapy (CT) after taxanes/platinum-compounds in refractory/relapsed OC. We have previously shown that the maximum tolerated dose (MTD) of TPC used as a single agent was 45 mg/m2 in a 5-d administration schema (ITOV 01 protocol - Lotz et al, BMT 2006, 37: 669). Method: We decided herein to combine TPC at a dose ranging from 8 to 10 mg/m2/d x 5d (30’ daily perfusion) to a fixed HD CPM (60 mg/kg/d x 2d) until the MTD of TPC was reached. Three pts were to be treated at each planned dose level (8.0, 8.5, 9.0, 9.5, 10 mg/m2/d). Limiting toxicity was defined as one toxic death (excluding sepsis) or grade (G) 4 non-hematological toxicity. In this event, a further 3 pts were to be recruited at the same dose level. Mobilization to collect 3x106 CD34+/kg BW (6x106 if a 2nd HD course using TPC alone was planned) was performed with CPM + filgrastim. Results: From 09/02 to 05/06, 26 pts (median age, 54, range: 21–64) were included (platinum-refractory/relapse - 15 pts, initial stage FIGO IV - 5 pts, residual disease at 2nd-look - 6 pts). Three pts failed to be collected, one progressed before and one progressed after mobilization, so that 21 pts were able to complete their 1st course. Six received a second cycle of HD TPC. One septicemia-related toxic death occurred at level 8 mg/m2/d. Median durations of G4 neutropenia & thrombocytopenia observed during the first course of HDCT were 10 & 9 d. No patients experienced G4 diarrhea. One pt experienced a G4 cutaneous toxicity at level 8.5 and 2/3 at level 9.5 mg/m2/d. MTD of TPC combined with CPM was consecutively set up at 9.0 mg/.m2/d x 5d. Pharmacokinetic data (Cmax, AUC) will be available. Conclusion: The MTD of TPC combined with CPM was set up at 9 mg/m2/d x 5d, i.e., 45 mg/m2. The forthcoming ITOV 04 protocol will combine HD TPC and Carboplatin (AUC 20) in patients whose relapse occurs between 6 and 12 months after platinum- based first-line CT.

No significant financial relationships to disclose.
Risk factors for febrile neutropenia and the utilization of pegfilgrastim in patients receiving chemotherapy for gynecologic malignancies
Authors: Numnum T. M. , Bryant S. , Williams E. , Kilgore L. , Straughn J. M.
Published: March 2020

16063

Background: Recently published gudelines for the use of granulocyte-colony stimulating factors define risk factors for the development of febrile neutropenia (FN) in patients receiveing chemotherapy. Our objective is to assess the risk factors associated with FN and the utilization of pegfilgrastim (G-CSF) for the prevention of FN in patients receiving chemotherapy for gynecologic malignancies. Methods: A computerized database identified all outpatient chemotherapy encounters over a 4 month period. Risk factors for FN (adapted from guidelines published by ASCO) were determined for each chemotherapy encounter and a risk factor score was calculated (1–17). Each chemotherapy encounter was analyzed to determine if G-CSF was administered and the reason for utilization. Dose delays/modifications were also determined. Statistical comparisons were performed using the χ2 test. Results: 692 chemotherapy encounters were identified in 209 patients. 77 % of patients had a diagnosis of ovarian cancer. The mean risk factor score was 3.9 (range 1–9). The most common risk factors were: female (100%), advanced cancer (81%), prior chemotherapy (54%), and age > 65 yo (46%). 276 of the 692 (40%) encounters utilized G-CSF. 135 patients (49%) received G-CSF as primary prophylaxis for the development of FN; 141 patients (51%) received G-CSF after an episode of Grade 3 or 4 neutropenia. The mean risk factor score was 4.3 in patients receiving primary prophylaxis. After primary prophylaxis, 1 dose delay/modification for neutropenia was experienced versus 14 dose delays/modifications without prophylaxis (p <0.01). There were 12 dose delays/modifications due to thrombocytopenia in patients receiving PP. There was only one episode of FN. 64% of patients receiving primary prophylaxis were treated with a docetaxel-containing regimen and 61% of patients were receiving primary chemotherapy. Conclusions: G-CSF is utilized in 40% of chemotherapy encounters and is commonly associated with docetaxel-containing regimens. Dose delays/modifications are uncommon after primary prophylaxis with G-CSF in patients receiving chemotherapy for gynecologic malignancies.

No significant financial relationships to disclose.
Intraperitoneal therapy for ovarian cancer: Impact on survival and recurrence—The result of multi-institutional studies
Authors: Takeuchi S. , Tsubamoto H. , Adachi S. , Ito K. , Itani Y. , Miyamoto T. , Terai Y. , Kigawa J. , Sugiyama T.
Published: March 2020

16068

Background: For optimal debulked mullerian cancer (MC), the Intraperitoneal (IP) therapy has become the effective modality of chemotherapy to obtain better prognosis. We have reported KCOG9811study: IP CDDP + Paclitaxel (PTX) intravenous (IV) 2 cycles followed by 3 cycles of usual PTX-Carboplatin (abstr.1970, ASCO2002). And we have also reported the feasibility study and satisfactory response rate of the weekly IP-PTX with IV Carboplatin therapy (IP-PIVC, abstr. 5120, ASCO2005). Objectives: We have conducted two types of IP therapy for optimal debulked MC to improve the progression free survival (PFS) and overall survival (OS). Here are the prognosis and recurrent fashion after these IP therapies. Methods: Twenty patients (pts) with optimal debulked ovarian cancer were enrolled for KCOG9811, and eleven pts with optimal debulked MC newly/recurrent diagnosed disease were enrolled for IP-PIVC. The regimen of each therapy consisted of as follows: KCOG9811:50mg/ m2 of CDDP was administered via IP port at operation, after 2 weeks (wks) of operation, PTX was administered at a dose of 175mg/ m2IV for 3hrs on day 1, CDDP was administered at 75mg/ m2IP on day 2, every 3wks for 2 cycles, followed by PTX 175mg/ m2 IV and Carboplatin AUC5 IV on day1 every 3wks for 3 cycles. The IP-PIVC therapy consisted of IP-PTX, on days 1, 8, 15 at a dose of 45 mg/m2 (3pts) and 60 mg/m2(8pts). Carboplatin was administered monthly at a dose of AUC 5 on day 1 only. 2–6 cycles were performed. Results: The mean observation time was 72.6 months (m) and 32.6m for KCOG9811 and IP-PIVC, respectively. As for the median PFS was 1308+ days and 678+ days, and the median OS was 2180+ days and 978+ days, respectively. The five years survival rate showed 59.3% on KCOG9811, and the three years survival rate showed 75.8% on IP-PIVC. As for recurrent fashion, liver metastases and proximal lymphnodes metastases, and retroperitoneal metastases were detected. Few cases recurred Intraperitoneal lesion with small ascites Conclusions: There are some differences in the recurrent fashion of IP treatment from that of IV treatment. IP treatment prevented ascitic recurrence. Further improvement of chemotherapy is necessary for liver metastasis and proximal lymphnodes.

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Morbidity and survival of 32 recurrent ovarian cancer patients treated with aggressive cytoreductive surgery followed by intraperitoneal hyperthermic chemoperfusion
Authors: Richard S. D. , Gusani N. , Zeh H. J. , Colovos C. , Cho S. W. , Bartlett D. L. , Edwards R. P.
Published: March 2020

16078

Background: Cytoreductive surgery followed by intraperitoneal hyperthermic chemoperfusion (CS/IPHC) has shown increased survival for patients with recurrent and persistent GI malignancies with peritoneal dissemination. We present our preliminary experience with CS/IPHC as palliative therapy for recurrent ovarian cancer treated at a single institution. Methods: A retrospective review of CS/IPHC for women with recurrent or persistent epithelial ovarian carcinoma previously treated with platinum/taxane chemotherapy at a single institution from 2002–2006 was performed. Each patient had an attempted optimal surgical debulking (volume of residual disease <1 cm) prior to chemoperfusion. IPHC was performed on all patients for 100 minutes at temperatures between 40–42°C with either mitomycin C (40 mg/m2) or cisplatin (100 mg/m2). Post-surgical complications were evaluated. End points analyzed included morbidity, progression free survival, and over all survival. Results: Thirty-two patients were identified, with optimal cytoreductive surgery obtained in 26 (81.3%). Procedures required for cytoreduction included omentectomy (n=16), splenectomy (n=14), colonic resection (n=14), small bowel resection (n=13), ileostomy (n=9), hepatic resection (n=5), partial gastrectomy (n=5), and diaphragmatic stripping (n=3). Over-all morbidity was 65.6%, with major morbidity of 9.4%. There were three mortalities within sixty days of operation. Common morbidities included neutropenia (n=5), ileus (n=5), pleural effusions (n=4), and sepsis (n=4). Median length of stay was 11 days (6 to 47). Nineteen patients had a documented recurrence with a median progression free survival of 8 months (1 to 22). Median survival was 13 months (1 to 54) for these patients with recurrent end stage ovarian cancer. Conclusions: CS/IPHC is associated with high morbidity, but acceptable mortality. In a subset of patients, survival is improved compared to historical controls for recurrent ovarian cancer. A randomized phase II study is planned based on this data.

No significant financial relationships to disclose.
Neoadjuvant chemotherapy with docetaxel and cisplatin followed by concomitant chemoradiotherapy (CT-RT) in the management of locally advanced laryngeal carcinoma
Authors: Sayed F. S. , Karim A. , Hossain M. , Ahmed D. , Khan M. A. , Momin M. , Sobhan J.
Published: March 2020

16507

Background: Neoadjuvant chemotherapy has been used effectively in the treatment of locally advanced head and neck cancers. We conducted a study to evaluate the efficacy and adverse events associated with neoadjuvant chemotherapy schedule comprising of docetaxel and cisplatin followed by concomitant CT-RT from July 2004 to June 2006. Methods: 25 patients with locally advanced supraglottic laryngeal cancer were enrolled to receive docetaxel 75 mg/m2 and cisplatin 75 mg/m2 every 3 weekly for 3 cycles followed by one cycle of concomitant external beam radiotherapy (6000 cGy) and docetaxel 75 mg/m2+cisplatin 75 mg/m2 on day 7 of radiotherapy. All patients after completion of neoadjuvant chemotherapy were evaluated by CT scan and direct laryngoscopy and biopsy from any residual disease. All patients were followed up every month up to disease progression. Follow-up was done by physical examination and indirect laryngoscopy and by 3 monthly CT scan. Adverse events were treated mostly on outpatient basis. Results: Out of 25 patients, 9 had residual disease after completion of treatment and 2 had a disease relapse within 5 months of disease completion. The remaining 14 patients were disease free from a duration of 6 to14 months follow-up period. Median progress free survival had not been reached. 9 (36%) patients had severe mucositis and neutropenia while receiving concomitant CT-RT. 6 (24%) patients had grade III mucositis and rest 3 (12%) patients had grade II mucositis and all the 9 (36%) patients had grade III neutropenia. All of them were treated with G-CSF and prophylactic antibiotics. All the rest had grade I and grade II mucositis and neutropenia Conclusions: In our experience, neoadjuvant chemotherapy with docetaxel and cisplatin (3 cycles) followed by 1 cycle of concomitant CT-RT may be a good choice in treating locally advanced supraglottic laryngeal cancer. The toxicity profile was also manageable.

No significant financial relationships to disclose.
Impact of post-surgical residual tumor volume on local control in radiotherapy for maxillary sinus cancer
Authors: Elhag A. G. , Elsawy W. H. , Khalifa D. N.
Published: March 2020

16518

Background: The aim was to study the influence of post-surgical gross residual tumor volume on local control of maxillary sinus cancer treated with radiotherapy combined with debulking surgery. Methods: Twenty-five patients with squamous cell carcinoma of the maxillary sinus treated by combined surgery and radiotherapy (50–65 Gy, median 60 Gy). Gross residual tumor volume (GRTV) after surgery was measured on computed tomograms obtained after surgery. Patients were classified according to GRTV as follows: group A, GRTV = 0 (microscopic residual, n = 5); group B, GRTV <10 cm3 (n = 11); group C, 10–40 cm3 (n = 5); and group D, =40 cm3 (n = 4). The relationship between local control and GRTV was analyzed using univariate and multivariate analysis. Results: The 2-year local control rate for all patients was 64%. The differences in local control rates between groups A, B and C were not significant (P > 0.05), but the rate was significantly lower in group D than in the other groups (65% at 2 years vs. 25% at 1 year, P < 0.001). Multivariate analysis showed that GRTV (P = 0.002) and histological differentiation (poorly differentiated histology was favorable, P = 0.035) were independent prognostic factors and that tumor stage and the sequence of treatment were not. Conclusions: Our data suggest that adequate, not complete, debulking associated with the proper dose of radiotherapy can provide satisfactory local control for patients with squamous cell carcinoma of the maxillary sinus.

No significant financial relationships to disclose.
Squamous carcinoma of the skin responding to erlotinib: Three cases
Authors: Read W. L.
Published: March 2020

16519

Background: Systemic therapies for squamous cell carcinoma of the skin (SCCS) include cytotoxic chemotherapy and immunotherapy with retinoids and interferon. Erlotinib is an orally available EGFR inhibitor which is generally well tolerated. This report describes three patients with SCCS in whom erlotinib treatment produced clinical benefit. Methods: Case report. Results: 1. A 40 year old lung transplant recipient with multifocal SCCS was diagnosed with lung metastases by CT scan and bronchoscopy. These lesions progressed during treatment with acitretin and interferon. He began erlotinib at 150 mg daily and one month later CT scan showed his lung metastases to have responded, with the largest lesion decreasing in size by 50%. He continued on erlotinib for his remaining 8 months of life, during which his lung lesions continued to regress. Unfortunately the SCCS on his face progressed while on erlotinib, and ultimately caused his death. 2. A 54 year old with SCCS of the face treated with orbital exenteration and neck dissection followed by chemoradiation for submental recurrence developed a new 2 cm submental mass. He began erlotinib at 150 mg daily with complete resolution of the mass over 1 month. PET scan was negative, and there was doubt as to whether the mass had actually been SCCS. Because of this the patient discontinued erlotinib, and 3 weeks later the mass recurred. It was biopsy confirmed to be SCCS, and erlotinib again produced a clinical CR. Two months later he stopped erlotinib prior to planned surgery, and the tumor again regrew. 3. A 41 year old developed SCCS of the left temple. This lesion repeatedly recurred despite irradiation and resection, ultimately involving the orbit and cranial nerves and causing significant pain. The lesion progressed during chemotherapy with cisplatin and capecitabine. The patient began erlotinib 150 mg daily and experienced a partial response, together with marked improvement in pain and quality of life. He has continued on erlotinib for three months to date. Conclusions: Erlotinib provided excellent palliation for these patients with SCCS who had failed other therapies. The sensitivity of these aggressive SCCS to erlotinib suggests that this drug might be used at earlier points in the treatment of such patients, possibly in combination with radiation.

No significant financial relationships to disclose.