A phase II evaluation of mifepristone in the treatment of recurrent or persistent epithelial ovarian, fallopian or primary peritoneal cancer: a gynecologic oncology group study.

OBJECTIVE: To evaluate the effectiveness and toxicity of mifepristone in patients with ovarian, peritoneal and fallopian tube cancers. METHODS: Patients with confirmed epithelial ovarian, peritoneal and fallopian tube cancers which were persistent or recurred in less then 1 year after primary chemotherapy were entered into this study. Patients were given mifepristone 200 mg by mouth daily for a 28 day cycle. The medication was stopped for unacceptable toxicity or tumor progression. RESULTS: Twenty-four patients were entered into the study. Twenty-two patients were evaluable for response. Only one patient had a partial response for a response rate of only 4.5% (90% confidence interval: 0.2%, 19.8%). CONCLUSION: Mifepristone has not proven to be an effective agent in the treatment of patients with recurrent or persistent ovarian, peritoneal and fallopian tube cancers.

Phase III study of cisplatin with or without paclitaxel in stage IVB, recurrent, or persistent squamous cell carcinoma of the cervix: a gynecologic oncology group study.

PURPOSE: To determine whether cisplatin plus paclitaxel (C+P) improved response rate, progression-free survival (PFS), or survival compared with cisplatin alone in patients with stage IVB, recurrent, or persistent squamous cell carcinoma of the cervix. PATIENTS AND METHODS Eligible: patients with measurable disease, performance status (PS) 0 to 2, and adequate hematologic, hepatic, and renal function received either cisplatin 50 mg/m2 or C+P (cisplatin 50 mg/m2 plus paclitaxel 135 mg/m2) every 3 weeks for six cycles. Tumor measurements and quality-of-life (QOL) assessments were obtained before each treatment cycle. RESULTS: Of 280 patients entered, 6% were ineligible. Among 264 eligible patients, 134 received cisplatin and 130 received C+P. Groups were well matched with respect to age, ethnicity, PS, tumor grade, disease site, and number of cycles received. The majority of all patients had prior radiation therapy (cisplatin, 92%; C+P, 91%). Objective responses occurred in 19% (6% complete plus 13% partial) of patients receiving cisplatin versus 36% (15% complete plus 21% partial) receiving C+P (P = .002). The median PFS was 2.8 and 4.8 months, respectively, for cisplatin versus C+P (P < .001). There was no difference in median survival (8.8 months v 9.7 months). Grade 3 to 4 anemia and neutropenia were more common in the combination arm. There was no significant difference in QOL scores, although a disproportionate number of patients (cisplatin, n = 50; C+P, n = 33) dropped out of the QOL component, presumably because of increasing disease, deteriorating health status, or early death. CONCLUSION C+P is superior to cisplatin alone with respect to response rate and PFS with sustained QOL.

Phase II evaluation of oxaliplatin in previously treated squamous cell carcinoma of the cervix: a gynecologic oncology group study.

OBJECTIVE: A phase II study was conducted to determine the efficacy of oxaliplatin therapy in patients with previously treated squamous cell carcinoma of the cervix. METHODS: Eligible patients were to have measurable disease and not more than one prior chemotherapy regimen that could include carboplatin or cisplatin but not oxaliplatin. Oxaliplatin 130 mg/m(2) was administered intravenously over 2 h. This treatment was repeated every 21 days until progression of disease or adverse effects prohibited further therapy. RESULTS: Twenty-eight patients were entered onto this study, of whom 24 were evaluable for toxicity and 22 were evaluable for response; 23/24 evaluable patients had had prior platinum. There were two (8.3%) responses. One patient achieved a complete response which lasted 2.2 months, and a second patient attained a partial response which lasted 3.2 months. Nine (37.5%) patients had stable disease with a median duration of 7.6+ (3.1-21.2) months. The most frequently reported drug-related toxicities consisted of anemia, nausea and vomiting, and neurotoxicity. Three (12.5%) patients had a grade 3 allergic response that was infusion-related and was largely resolved by increasing infusion time. CONCLUSIONS: Oxaliplatin has limited activity in patients with persistent or recurrent squamous cell carcinoma of the cervix at the dose and schedule tested.

Activity of paclitaxel as second-line chemotherapy in endometrial carcinoma: a Gynecologic Oncology Group study.

OBJECTIVE: To estimate the antitumor activity of paclitaxel (Taxol) in patients with persistent or recurrent endometrial carcinoma who have failed prior chemotherapy. To determine the nature and degree of toxicity of paclitaxel in this group of patients. METHODS: Paclitaxel was administered as a 3-h infusion at an initial dose of 200 mg/m(2) every 21 days or 175 mg/m(2) for patients with prior pelvic radiation therapy. Dose modifications were based on nadir toxicity, both hematologic and nonhematologic, and were accomplished by dose level adjustments. The dose levels were 200, 175, 135, and 110 mg/m(2). Patients were evaluable for response after receiving one dose of paclitaxel and living 3 weeks. They were evaluable for toxicity after receiving any paclitaxel. RESULTS: Of the 44 patients evaluable for response, three patients (6.8%) achieved a complete response and nine patients (20.5%) had a partial response for an overall response rate of 27.3%. The 95% confidence interval for the true response rate was 15-42.8%. The median number of courses of paclitaxel to response was 2 (range: 1-4) and the median response duration was 4.2 months. The median overall survival was 10.3 months. Of 48 patients evaluable for toxicity, 28 experienced at least one episode of grade 3 or 4 neutropenia, with one treatment-related death. There were four patients who developed grade 3 neurotoxicity in this group of previously treated patients, most of whom had received cisplatin-containing chemotherapy. There was virtually no cardiac toxicity and only 3 of 48 patients experienced grade 3 or 4 gastrointestinal symptoms. CONCLUSIONS: Paclitaxel is an active agent in the treatment of endometrial cancer in patients who have had prior chemotherapy.

Goserelin acetate as treatment for recurrent endometrial carcinoma: a Gynecologic Oncology Group study.

This Gynecologic Oncology Group (GOG) study was designed to estimate the activity of goserelin acetate as treatment for advanced and recurrent endometrial carcinoma. Forty evaluable patients received monthly treatment with goserelin acetate at a dose of 3.6 mg, given subcutaneously. Standard GOG response and adverse effects criteria were used. The median age of patients was 71 years. Seventy-one percent of patients had received prior radiation therapy; 18% of patients were reported to have received prior progestational therapy for endometrial cancer. One patient had received prior chemotherapy. There were two complete responses (5%) and three partial responses (7%). One response occurred in a patient who previously did not respond to progestin therapy after having achieved a response. The overall response rate was 11% (95% CI: 4-27%). Median progression-free survival was 1.9 months and median overall survival was 7.3 months. No severe or life-threatening toxicities occurred because of goserelin. Deep venous thrombosis developed in two patients. This study confirmed the limited activity of goserelin acetate in endometrial carcinoma, with only one response in a patient previously treated with hormonal therapy. The activity is insufficient to warrant further study of the single agent at this time. Elucidation of the mechanism of action of this drug may allow more effective use in conjunction with other agents in the future.