OBJECTIVES:To assess the efficacy and toxicity of paclitaxel and carboplatin (PC) compared to bleomycin, etoposide, and cisplatin (BEP) for treatment of newly diagnosed Stage IIA-IV or recurrent chemotherapy-naive ovarian sex cord-stromal tumors (SCST). METHODS:This phase II noninferiority trial randomly assigned patients to receive PC (6 cycles P 175 mg/m2 and C AUC = 6 IV every 3 weeks), or BEP (4 cycles B 20 units/m2 IV push day 1, E 75 mg/m2 IV days 1-5, and cisplatin 20 mg/m2 IV days 1-5 every 3 weeks). The primary endpoint was progression- free survival (PFS). This trial is registered with ClinicalTrials.gov, NCT01042522. RESULTS:At the interim analysis, 63 patients (31 PC and 32 B.P. had accrued between Feb 8, 2010 and Apr 30, 2020. Median age was 48 years. 87% had granulosa cell tumors. 37% had measurable disease. The DSMB closed accrual early for futility of PC arm. The futility analysis was supported by an estimated HR = 1.11 [95% CI: 0.57 to 2.13] which exceeded the pre-determined threshold for non-inferiority (1.10). Median PFS was 27.7 months [11.2 to 41.0] for PC and 19.7 months for BEP [95% CI: 10.4-52.7]. PC patients had fewer grade 3 or higher adverse events (PC 77% vs BEP 90%). CONCLUSIONS:The study met its pre-specified criterion for stopping early for futility and so failed to demonstrate non-inferiority of PC versus BEP in ovarian SCSTs, in a non-inferiority test with a hazard ratio margin of 1.1. Both PC and BEP may be considered in patients with advanced/recurrent SCST.

ObjectivePatients with advanced epithelial ovarian cancer (EOC) alive without progression at a landmark time-point of 10 years from diagnosis are likely cured. We report the proportion of patients with Stage III EOC who were long-term disease-free survivors (LTDFS≥10 years) following either intraperitoneal (IP) or intravenous (IV) chemotherapy as well as the predictors of LTDFS.MethodsData from 3 mature NRG/GOG trials (104, 114, 172) were analyzed and included demographics, clinicopathologic details, route of administration, and survival outcomes of patients living ≥10 years assessed according to the Kaplan-Meier method. Cox regression survival analysis was performed to evaluate independent prognostic predictors of LTDFS.ResultsOf 1174 patients randomized, 10-year overall survival (OS) was 26% (95% CI, 23–28%) and LTDFS ≥10 years was 18% (95% CI, 16–20%). Patients with LTDFS ≥10 years had a median age of 54.6 years (p < 0.001). Younger age (p < 0.001) was the only independent prognostic factor for LTDFS≥10 years on multivariate Cox analysis.ConclusionsApproximately 18% of patients were LTDFS ≥10 years. They form the tail end of the survival curve and are likely cured. Our results provide a comparative benchmark to evaluate the impact of PARP inhibitors in 1st line maintenance trials on survival outcomes.

Objective. The primary objective of the study was to estimate the 12-month progression-free survival (PFS) for carboplatin/paclitaxel + temsirolimus in women with newly diagnosed clear cell ovarian cancer (CCOC), compared to historical controls in this patient population. Methods. Patients with Stage III or IV CCOC were treated with Paclitaxel 175 mg/m2 on Day 1, Carboplatin AUC 6 Day 1, and temsirolimus (CCI-779) 25mg IV Days 1 and 8 every 3 weeks for Cycles 1-6 or disease progression, followed by consolidation therapy with temsirolimus 25mg Days 1, 8, and 15 every 3 weeks cycles 7-17 or until disease progression. Results. Ninety patients were accrued to the study: 45 in the US and Korea (US/Korea) and 45 in Japan. Twenty-two percent received =6 cycles of therapy while 28% completed all 17 cycles of chemotherapy. Median PFS (OS) was 11 (23) months for US/Korea and 12 (26) months for Japan. In the US, none of suboptimally debulked patients had PFS >12 months, and 49% of optimal patients did, compared to 25% and 59% in Japan. Most common grade 3-4 adverse events were neutropenia, leukopenia, anemia, thrombocytopenia, hypertension, hypertriglyceridemia, and oral mucositis. Conclusion. The carboplatin/paclitaxel+ temsirolimus regimenwaswell tolerated. In optimally debulked patients, 54% had a PFS >12 months. This regimen did not statistically significantly increase PFS at 12months compared to historical controls. No statistically significant differences in PFS or OSwere observed between US/Korea vs Japan, or Asians vs non-Asians.

Objective. To assess quality of life (QOL) in patients who developed lower-extremity lymphedema (LLE) after radical gynecologic cancer surgery on prospective clinical trial GOG 244. Methods. The prospective, national, cooperative group trial GOG-0244 determined the incidence of LLE and risk factors for LLE development, as well as associated impacts on QOL, in newly diagnosed patients undergoing surgery for endometrial, cervical, or vulvar cancer from 6/4/2012-11/17/2014. Patient-reported outcome (PRO) measures of QOL (by the Functional Assessment of Cancer Therapy [FACT)), body image, sexual and vaginal function, limb function, and cancer distress were recorded at baseline (within 14 days before surgery), and at 6, 12, 18, and 24 months after surgery. Assessments of LLE symptoms and disability were completed at the time of lower limb volume measurement. A linear mixed model was applied to examine the association of PROs/QOL with a Gynecologic Cancer Lymphedema Questionnaire (GCLQ) total score incremental change >= 4 (indicative of increased LLE symptoms) from baseline, a formal diagnosis of LLE (per the GCLQ), and limb volume change (LVC) >= 10%. Results. In 768 evaluable patients, those with a GCLQ score change >= 4 from baseline had significantly worse QOL (p < 0.001), body image (p < 0.001), sexual and vaginal function (p < 0.001), limb function (p < 0.001), and cancer distress (p < 0.001). There were no significant differences in sexual activity rates between those with and without LLE symptoms. Conclusions. LLE is significantly detrimental to QOL, daily function, and body image. Clinical intervention trials to prevent and manage this chronic condition after gynecologic cancer surgery are needed. (C) 2020 Elsevier Inc. All rights reserved.

OBJECTIVE:Preclinical data suggest elesclomol increases oxidative stress and enhances sensitivity to cytotoxic agents. The objective of this prospective multicenter phase 2 trial was to estimate the activity of IV elesclomol plus weekly paclitaxel in patients with platinum-resistant recurrent ovarian, tubal or peritoneal cancer through the frequency of objective tumor responses (ORR). METHODS:Patients with measurable disease, acceptable organ function, performance status ≤ 2, and one prior platinum containing regimen were eligible. A two-stage design was utilized with a target sample size of 22 and 30 subjects, respectively. Prior Gynecologic Oncology Group studies within the same population involving single agent taxanes showed an ORR of approximately (20%) and served as a historical control for direct comparison. The present study was designed to determine if the regimen had an ORR of ≥40% with 90% power. RESULTS:Fifty-eight patients were enrolled, of whom 2 received no study treatment and were inevaluable. The median number of cycles was 3 (268 total cycles, range 1-18). The number of patients responding was 11 (19.6%; 90% CI 11.4% to 30.4%) with one complete response. The median progression-free survival and overall survival was 3.6 months and 13.3 months, respectively. The median ORR duration was 9.2 months. Percentages of subjects with grade 3 toxicity included: Neutropenia 9%; anemia 5%; metabolic 5%; nausea 4%; infection 4%; neurologic (mostly neuropathy) 4%; and vascular (mostly thromboembolism) 4%. There were no grade 4 toxicities reported. CONCLUSIONS:This combination was well tolerated but is unworthy of further investigation based on the proportion responding [ClinicalTrials.gov Identifier: NCT00888615].

Purpose. Bevacizumab (BV) monotherapy leads to compensatory upregulation of multiple signaling pathways, resulting in mTOR activation. We evaluated combining BV and everolimus (EV), an mTOR kinase inhibitor, to circumvent BV-resistance in women with recurrent or persistent ovarian, fallopian tube or primary peritoneal cancer (DC). Patients and methods. Eligible OC patients had measurable (RECISTI.1) or detectable disease, 1-3 prior regimens, performance status (PS) 0-2, and no prior m-TOR inhibitor. All patients received BV 10 mg/kg IV every 2wks. Patients were randomized (1:1) to oral EV (10 mg daily) or placebo stratified by platinum-free interval (PFI), measurable disease and prior BV. Primary endpoint was progression-free survival (PFS); secondary endpoints included safety and response. Results. 150 patients were randomized to BV with (n = 75) and without (n = 75) EV. Arms were well-balanced for age (median 63: range 28-92), PS (0: 73%, 1-2: 27%), prior regimens (1: 37%, 2: 47%, 3:16%), prior BV (11%), PR (<6mos: 65%) and measurable disease (81%). The BV + EV vs BV median PFS was 5.9 vs 4.5 months (hazard ratio [HR] 0.95 (95% CI, 0.66-1.37, p = 0.39)). Median OS was 16.6 vs 17.3 months (HR 1.16 (95% CI, 0.72-1.87, p = 0.55). Objective measurable responses were higher with BV + EV (22% vs 12%). Study removal due to toxicity was higher with BV + EV (29% vs 12%). Toxicity (>= grade 3) from BV + EV were "other GI (mucositis)" (23 vs 1%) and "metabolic/nutrition" (19 vs. 7%); common >= grade 2 toxicities with BV + EV were cytopenia, nausea, fatigue and rash. Conclusion. The combination regimen (BV + EV) did not significantly reduce the hazard of progression or death relative to BV and was associated with higher rates of adverse events and study discontinuation when compared to BV alone. (C) 2018 Elsevier Inc. All rights reserved.

ObjectivePreclinical data suggest elesclomol increases oxidative stress and enhances sensitivity to cytotoxic agents. The objective of this prospective multicenter phase 2 trial was to estimate the activity of IV elesclomol plus weekly paclitaxel in patients with platinum-resistant recurrent ovarian, tubal or peritoneal cancer through the frequency of objective tumor responses (ORR).MethodsPatients with measurable disease, acceptable organ function, performance status ≤ 2, and one prior platinum containing regimen were eligible. A two-stage design was utilized with a target sample size of 22 and 30 subjects, respectively. Prior Gynecologic Oncology Group studies within the same population involving single agent taxanes showed an ORR of approximately (20%) and served as a historical control for direct comparison. The present study was designed to determine if the regimen had an ORR of ≥40% with 90 …

5556 Background: ~25% of patients with stage III OC are reported to be alive ≥ 10 years after diagnosis in registry studies1. Some have long term disease-free survival (LTDFS) without recurrence and others have recurrent active disease but the proportions of each is unclear. We propose to determine the proportion, characteristics, and predictors of long term survival in patients with stage III ovarian cancer (OC) enrolled in clinical trials who are ≥ 10 years LTDFS . Methods: Data from 3 NRG/GOG trials (104, 114, and 172) which enrolled patients to intraperitoneal (IP) vs. intravenous (IV) chemotherapy were analysed. Demographics and clinic-pathologic characteristics of patients living ≥ 10 years were tabulated. Using a landmark approach at 10 years, Cox regression survival analysis was performed to evaluate independent prognostic factors that predict LTDFS. Results: Of 1,229 stage III OC patients, 18.8% (232/1229) were alive ≥ 10 years. Of these, 13.7% (n = 168) had LTDFS ≥ 10 years and 5.2% (n = 64) had recurrent disease. Compared to the overall study group, the LTDFS ≥10 years patient had a median age of 54.8 vs. 57.2 years (p < 0.001), gross residual disease after primary surgery 42.3% vs. 45.8% (p = 0.027); serous cell type 62.5% vs. 68.4%; endometrioid 14.3% vs. 9.4% (p = 0.035), well differentiated cancers 12.5% vs. 8.5% (p < 0.001), respectively. Of the LTDFS patients, 45.2% were treated with IP and 54.8% with IV chemotherapy (p = 0.3). Age (HR = 1.077; 95% CI = 1.03–1.12; p < 0.001) was the only independent prognostic factor for LTDFS ≥10 years on multivariate Cox analysis. Conclusions: Approximately 14% of stage III ovarian cancer patients were in LTDFS at ≥10 years and an additional 5% were alive with recurrent disease. Younger age at diagnosis was the only independent prognostic factor for LTDFS ≥10 years. Further work is needed to understand characteristics and predictors of exceptional responders and whether they could be identified at initial diagnosis. 1 Baldwin et al Obstetrics & Gynecology: 2012: 120; 3: 612–618

Objectives: To evaluate the incidence and risk factors for lymphedema associated with surgery for gynecologic malignancies on GOG study 244. Methods: Women undergoing a lymph node dissection for endometrial, cervical, or vulvar cancer were eligible for enrollment. Leg volume was calculated from measurements at 10-cm intervals starting 10 cm above the bottom of the heel to the inguinal crease. Measurements were obtained preoperatively and postoperatively at 4-6 weeks, and at 3-, 6-, 9-, 12-, 18-, and 24- months. Lymphedema was defined limb volume change (LVC) >= 10% from baseline and categorized as mild: 10-19% LVC; moderate: 20-40% LVC; or severe: >40% LVC. Risk factors associated with lymphedema were also analyzed. Results: Of 1054 women enrolled on study, 140 were inevaluable due to inadequate measurements or eligibility criteria. This left 734 endometrial, 138 cervical, and 42 vulvar patients evaluable for LVC assessment. Median age was 61 years (range, 28-91) in the endometrial, 44 years (range, 25-83) in the cervical, and 58 years (range, 35-88) in the vulvar group. The incidence of LVC >= 10% was 34% (n = 247), 35% (n = 48), and 43% (n = 18), respectively. The peak incidence of lymphedema was at the 4-6 week assessment. Logistic regression analysis showed a decreased risk with advanced age (p = 0.0467). An exploratory analysis in the endometrial cohort showed an increased risk with a node count >8 (p = 0.033). Conclusions: For a gynecologic cancer, LVC decreased with age greater than 65, but increased with a lymph node count greater than 8 in the endometrial cohort. There was no association with radiation or other risk factors. (C) 2019 Elsevier Inc. All rights reserved.

Background. Brivanib is an oral, tyrosine kinase inhibitor against vascular endothelial growth factor (VEGF) and fibroblast growth factor receptor (FGFR). We studied its efficacy and tolerability in persistent or recurrent cervical cancer patients.Methods. Eligible patients had at least one prior cytotoxic regimen for recurrence and with measurable disease. Brivanib 800 mg was administered orally every day (1 cycle = 28 days) until disease progression or prohibitive toxicity. Primary endpoints were progression-free survival (PFS) >6 months and objective tumor response.Results. Of 28 eligible and evaluable women enrolled, 11 (39%) had primary surgery and 25 (89%) had prior radiation. Eighteen (64%) received one prior cytotoxic treatment and 10 (36%) had 2 prior regimens. Twelve (43%) had >2 cycles of brivanib with 4 (14%) receiving >10 cycles (range: 1-20). Seven (25%) patients had PFS >6 months (90% CI: 7.3%-33.9%). Two (7%) (90% CI: 13%-20.8%) patients had partial tumor response with duration of 8 and 22 months and 12 (43%) had stable disease. The median PFS was 3.2 months (90% CI: 2.1-4.4). The median overall survival was 7.9 months (90% CI: 6.1-11.7). More common grade 3 adverse events were hypertension, anemia, hyponatremia, hyperglycemia, elevated liver enzymes, nausea, headache, and colon hemorrhage. Grade 4 adverse events included sepsis and hypertension.Conclusions. Based on early results of this phase II trial, brivanib was well tolerated and demonstrated sufficient activity after first stage but trial was stopped due to lack of drug availability. (C) 2017 Published by Elsevier Inc.

5015 Background: Antiangiogenesis therapy has led to antitumor effects both preclinically and clinically. Vandetanib (V) is an oral tyrosine kinase inhibitor of VEGFR-2/3, EGFR and RET. These targets are of interest in OC care, as targeting has shown anti-tumor efficacy, particularly in combination with taxanes. We explored the efficacy, safety, and toxicity of docetaxel (D) and V in women with recurrent OC. Methods: Women with resistant, refractory, or progressive/persistent OC were eligible for this randomized phase II study provided they had not received D or V for recurrent disease. Patients were allowed to receive other anti-VEGF targeted agents for primary therapy (stratification variable). Up to 3 additional cytotoxic regimens for recurrence were allowed. Patients were allocated 1:1 to D(75 mg/m2, I.V.)+V (100 mg daily, p.o.) or D(75 mg/m2). Patients receiving single agent D were allowed to crossover to V upon progression (D-V). The primary endpoint was PFS. Other objectives were: OS, objective response (ORR), and frequency/severity of adverse events. The study was designed with 84% power to detect a 1.55 PFS hazard ratio using a one-sided P of 0.1. Results: 131 patients were enrolled; 5 were excluded (1 ineligible, 4 eligible but untreated). 9% had received prior anti-angiogenic therapy. 61 patients on D+V were assessable for toxicity; 19 (31%) had treatment-related G4 events, primarily hematologic. Similarly, 17 (26%) of 65 patients receiving D alone had G4 events, primarily hematologic. 34 (52%) patients crossed over to V; no G4 events were recorded among 32 evaluable patients. G3 diarrhea was observed in 14% of D+V patients; 5% D-V patients. G3 acneiform rash occurred in 2% and 0%, respectively. The median PFS estimates were 3.0 mos (D+V) vs 3.5 (D-V); HR (PFS): 0.98 (80% CI:0.75-1.27). For OS, the median estimates were 14 mos (D+V) vs 12 mos (D-V); HR (OS):0.84 (80% CI:0.56-1.28). ORR was 14% and 17%, respectively. Crossover V response was 4% (1/27 measurable patients). Conclusions: D+V was well tolerated in this population however, did not prolong PFS with respect to D.

5546 Background: BV monotherapy leads to compensatory upregulation of multiple signaling pathways, resulting in persistent mTOR activation, which if blocked, may circumvent resistance to anti-VEGF therapy.We evaluated the efficacy and tolerability of combining BV and oral everolimus (EV), an mTOR kinase inhibitor, in women with EOC/FTC/PPC. Methods: Eligible pts had persistent or recurrent EOC/FTC/PPC, measurable (RECIST 1.1) or detectable (CA125 ≥ 2x upper limit normal), 1-3 prior regimens, performance status (PS) 0-2, and no prior m-TOR inhibitor. All pts received BV 10 mg/kg IV every 2wks in 4wk cycles. Pts were randomized (1:1) to oral EV (10 mg daily) or placebo with stratification for platinum-free interval (PFI), measurable disease and prior BV. Primary endpoint was progression-free survival (PFS); secondary endpoints included safety and response evaluated every 8wks. Results: 150 evaluable pts were randomized to BV with (n=75) and without (n=75) EV. Arms were well-balanced for age (median 63: range 28-92), PS (0: 73%, 1-2: 27%), prior regimens (1: 37%, 2: 47%, 3: 16%), prior BV (11%), PFI (<6mos: 65%) and measurable disease (81%). The BV+EV vs BV median PFS was 5.9 vs 4.5 mos, respectively (hazard for progression 0.95 (95% CI, 0.66-1.37, p=0.39); pts with PFI>6mos had HR 0.615 (95% CI 0.33~1.15, p=NS). Median OS was 16.6 vs 17.3 mos (hazard of death 1.16 (95% CI, 0.72~1.87, p=NS). Among pts with measureable disease, objective responses were higher with BV+EV (19% vs 9%). Study removal due to toxicity was high with BV+EV (29%) compared to BV alone (12%). Toxicity (≥g3) most significantly associated with addition of EV were “other GI” (17 vs 1pts) and “metabolic/nutrition” (14 vs. 5pt). Most common toxicities ( ≥g2) were anemia (24 vs 6pt), neutropenia (20 vs 1pts), oral mucositis (22 vs 0pts), nausea (24 vs 9pts), fatigue (24 vs 15pts), and hypertension (20 vs. 21pts). Conclusions: The combination regimen (BV+EV) is active in this population but did not significantly reduce the hazard of progression or death and was associated with higher rates of study discontinuation for tolerability when compared to BV alone.

Objectives. Vascular endothelial growth factors (VEGF) and their receptors have a critical role in stimulating the growth of ovarian cancer cells. Motesanib is a small molecule inhibitor of multiple receptor tyrosine kinases including VEGF receptors 1-3, as well as c-KIT and platelet-derived growth factor which are related to the VEGF family.Patients and methods. Twenty-two eligible patients with recurrent ovarian, fallopian tube or primary peritoneal carcinoma were treated with an oral daily dose of 125 mg of motesanib. Peripheral blood was analyzed for circulating tumor cells (CTC) and circulating endothelial cells/circulating endothelial progenitors (CEC/CEP), VEGF levels and cell-free circulating DNA (cfDNA).Results. The study was abruptly halted after four patients developed posterior reversible encephalopathy syndrome. One patient had a partial response and seven patients had stable disease at the time they were removed from study treatment. Twelve of the 22 patients (50%) had indeterminate responses at trial closure. Early closure without clinical efficacy data precludes meaningful correlative studies.Conclusions. The serious central nervous system toxicity observed in patients with recurrent ovarian cancer precluded full examination of this agent in this population. There were no clear cut explanations for the high incidence of this known class effect in the study population compared with patients with other cancers. (C) 2013 Elsevier Inc. All rights reserved.

BACKGROUND:The potent ribonucleotide reductase (RNR) inhibitor 3-aminopyridine-2-carboxyaldehyde-thiosemicarbazone (3-AP) was tested as a chemosensitizer for restored cisplatin-mediated cytotoxicity in platinum-resistant ovarian cancer.METHODS:Preclinical in vitro platinum-resistant ovarian cancer cell survival, RNR activity, and DNA damage assays were done after cisplatin or cisplatin plus 3-AP treatments. Six women with platinum-resistant ovarian cancer underwent four-day 3-AP (96 mg/m(2), day one to four) and cisplatin (25 mg/m(2), day two and three) infusions every 21 days until disease progression or adverse effects prohibited further therapy. Pre-therapy ovarian cancer tissues were analyzed by immunohistochemistry for RNR subunit expression as an indicator of cisplatin plus 3-AP treatment response.RESULTS:3-AP preceding cisplatin exposure in platinum-resistant ovarian cancer cells was not as effective as sequencing cisplatin plus 3-AP together in cell survival assays. Platinum-mediated DNA damage (i.e., γH2AX foci) resolved quickly after cisplatin-alone or 3-AP preceding cisplatin exposure, but persisted after a cisplatin plus 3-AP sequence. On trial, 25 four-day overlapping 3-AP and cisplatin cycles were administered to six women (median 4.2 cycles per patient). 3-AP-related methemoglobinemia (range seven to 10%) occurred in two (33%) of six women, halting trial accrual.CONCLUSIONS:When sequenced cisplatin plus 3-AP, RNR inhibition restored platinum-sensitivity in platinum-resistant ovarian cancers. 3-AP (96 mg/m(2)) infusions produced modest methemoglobinemia, the expected consequence of ribonucleotide reductase inhibitors disrupting collateral proteins containing iron.TRIAL REGISTRY:ClinicalTrials.gov NCT00081276.

Background. Metastatic and recurrent, platinum resistant cervix cancer has an extremely poor prognosis. The Gynecologic Oncology Group has studied >20 cytotoxic drugs or drug combinations in the second-line, phase II setting of advanced, drug resistant cervix cancer.Methods. Nanoparticle, albumin-bound paclitaxel (nab-paclitaxel) was administered at 125 mg/m(2) IV over 30 minutes on days 1,8 and 15 of each 28 day cycle to 37 women with metastatic or recurrent cervix cancer that had progressed or relapsed following first-line cytotoxic drug treatment. A flexible, 2-stage accrual design that allowed stopping early for lack of treatment activity was utilized. Because of slow patient accrual, the second stage was not completed.Results. Of 37 patients enrolled, 2 were ineligible due to no prior cytotoxic chemotherapy, which left 35 eligible patients evaluable for response and tolerability. All of the eligible patients had 1 prior chemotherapy regimen and 27 of them had prior radiation therapy with concomitant cisplatin. The median number of nab-paclitaxel cycles were 4 (range 1-15). Ten (28.6%; Cl 14.6%-46.3%) of the 35 patients had a partial response and another 15 patients (42.9%) had stable disease. The median progression-free and overall survival were 5.0 and 9.4 months, respectively. The only NCI CTCAE grade 4 event was neutropenia in 2 patients (5.7%) which resolved following dose reduction. Grade 3 neurotoxicity was reported in 1 (2.9%) patient and resolved to grade 2 following dose discontinuation.Conclusions. Nab-paclitaxel has considerable activity and moderate toxicity in the treatment of drug resistant, metastatic and recurrent cervix cancer. (C) 2012 Elsevier Inc. All rights reserved.

OBJECTIVES:To evaluate the activity and toxicity of fulvestrant in advanced, recurrent, or persistent endometrial carcinoma.METHODS:Eligible patients with advanced, recurrent or persistent endometrial carcinoma not amenable to curative therapy were treated with fulvestrant at a dose of 250 mg by IM injection every 4 weeks for at least 8 weeks. Therapy was continued until evidence of progressive disease, or adverse effects prohibited further therapy. Response was assessed in patients with at least one target lesion as defined by Response Evaluation Criteria in Solid Tumors (RECIST) v1.0. Immunohistochemical analysis of tumor tissue (histology or cytology) for estrogen and progesterone receptors was required from the metastatic or recurrent site.RESULTS:Sixty-seven patients were enrolled in this study. Upon review, 14 patients were excluded. In the 22 estrogen receptor (ER) negative patients, no patients demonstrated either a complete or partial response, and 4 (18%) demonstrated stable disease (as best response). In the 31 ER positive patients, 1 (3%), 4 (13%) and 9 (29%) patients demonstrated a complete, partial response, and stable disease (as best response), respectively. The median progression free survival and overall survival in the ER negative patients were 2 and 3 months and in the ER positive patients 10 and 26 months. Treatment was well tolerated, and no patient discontinued therapy due to toxicity.CONCLUSIONS:Fulvestrant has minimal activity in advanced, recurrent, or persistent endometrial carcinoma.

Objective. This study aims to estimate the activity of docetaxel 60 mg/m(2) IV over 1 h followed by trabectedin 1.1 mg/m(2) over 3 h with filgrastim, pegfilgrastim, or sargramostim every 3 weeks (one cycle).Methods. Patients with recurrent and measurable disease, acceptable organ function, PS and prior regimens were eligible. A two-stage design was utilized with a target sample size of 35 subjects per stage. Another Gynecologic Oncology Group study within the same protocol queue involving a single agent taxane showed a response rate (RR) of (16%) (90% CI 8.6-28.5%) and served as a hitorical control for direct comparison. The present study was designed to determine if the current regimen had an RR of >= 36% with 90% power.Results. Seventy-one patients were eligible and evaluable (prior regimens: 1=28%, 2=52%, 3=20%). The median number of cycles' was 6 (438 total cycles, range 1-22). The number of patients responding was 21 (30%; 90% CI 21-40%). The odds ratio for responding was 2.2 (90% 1-sided CI 1.07-Infinity). The median progression-free survival and overall survival were 4.5 montlis and 16.9 months, respectively. The median response duration was 6.2 months. Numbers of subjects with grade 3/4 toxicity included neutropenia 7/14; constitutional 8/0; GI (excluding nausea/vomiting) 11/0: metabolic 9/1; pain 6/0. There were no treatment-related deaths nor cases of liver failure.Conclusions. This combination was well tolerated and appears more active than the historical control of single agent taxane therapy in those with recurrent ovarian and peritoneal cancer after failing multiple lines of chemotherapy. Further study is warranted. (C) 2010 Elsevier Inc. All rights reserved.

OBJECTIVE:To estimate the anti-tumor activity of pemetrexed in patients with advanced or recurrent carcinoma of the cervix that failed on higher priority treatment protocols and to determine the nature and degree of toxicity.METHODS:A multicenter Phase II trial was conducted by the Gynecologic Oncology Group (GOG). Patients must have had advanced or recurrent measurable carcinoma of the cervix, and failed one prior chemotherapy regimen. Pemetrexed at a dose of 900 mg/m(2) was to be administered as an IV infusion over 10 min every 21 days.RESULTS:From July 6, 2004 to April 3, 2006, twenty-nine patients were entered by ten member institutions of the GOG. Two patients did not receive treatment and thus were inevaluable. A total of 128 cycles were administered with 37% of patients receiving six or more cycles. The treatment was well tolerated overall. More serious toxicities (grade 3 and 4) included anemia in 41%, leukopenia in 30%, neutropenia in 26%, and infection in 26%. No treatment related deaths were reported. Four patients (15%) had partial responses with a median response duration of 4.4 months. The response rate for non-radiated or radiated disease sites was 25% and 7% respectively. Sixteen patients (59%) had stable disease and seven (26%) patients had increasing disease. Median progression free survival (PFS) was 3.1 months and overall survival (OS) was 7.4 months.CONCLUSION:Pemetrexed at this dose and schedule showed moderate activity against advanced or recurrent cervical cancer that has failed prior chemotherapy. Data from other tumor sites has suggested synergy between pemetrexed and cisplatin and should be considered for further study.