Weekly carboplatin with paclitaxel compared to standard three-weekly treatment in advanced epithelial ovarian carcinoma--a retrospective study.

OBJECTIVE: To retrospectively compare primary treatment with weekly carboplatin/paclitaxel (PC-W) to the standard 3-weekly carboplatin/paclitaxel (PC-3 W) in women with advanced epithelial ovarian cancer, tubal carcinoma and primary peritoneal carcinoma. METHODS: Medical records were assessed for age, stage of disease, tumor histology and grade, BRCA mutation status, and platinum sensitivity. Patients were treated with either paclitaxel (175 mg/m(2)) and carboplatin (AUC 6) every three weeks (PC-3 W; 133 patients), or with weekly paclitaxel (80 mg/m(2)) and weekly carboplatin (AUC 2) on days 1, 8, and 15 every 28 days (PC-W; 267 patients). RESULTS: Patient baseline characteristics were similar in both groups. Median overall survival (OS) was similar for PC-W and PC-3 W (64.5 months vs. 61.5 months), but PC-W had longer median progression-free survival [PFS: 27.4 months (95% CI, 22.7-31.4) vs. 19.5 months (95% CI, 15.6-22.2) for PC-3 W, p = 0.0024] and a longer median platinum-free interval [PFI: 22.1 months (95% CI, 16.0-24.5) vs. 14.2 months (95% CI, 10.7-17.2) for PC-3 W, p = 0.0075]. PC-W showed a significantly higher response rate (86.4% vs. 77.9% for PC-3 W, p = 0.0435). Multivariate analysis including for age at diagnosis, stage of disease, optimal debulking, histology, BRCA status, pretreatment CA-125 and PFI revealed that the PC-W women had lower risk of death (HR = 0.587, 95% CI, 0.402-0.857, p = 0.0058), lower risk of disease progression (HR = 0.494, 95% CI, 0.359-0.680, p < 0.0001), higher 2- and 3-year survival rates, and decreased grade II hair loss, neuropathy and thrombocytopenia compared with the PC-3 W women. CONCLUSION: The PC-W protocol improved PFS and had a similar OS as PC-3W.

The combination of gemcitabine and carboplatin shows similar efficacy in the treatment of platinum-resistant and platinum-sensitive recurrent epithelial ovarian cancer patients.

The aim of this study was to evaluate progression-free survival, overall survival (OS), response rate (RR), and clinical benefit in recurrent ovarian cancer patients treated with gemcitabine and carboplatin and to compare the outcome among platinum-resistant and platinum-sensitive patients. A retrospective study using the medical records of patients diagnosed and treated for recurrent epithelial ovarian cancer, fallopian tube carcinoma, or primary peritoneal carcinoma with gemcitabine and carboplatin from 2005 through 2012 at the Tel Aviv Sourasky Medical Center. The treatment regimen was carboplatin (area under the curve=5) administered on day 1 and gemcitabine 850 mg/m administered on days 1 and 8 in a 21-day cycle. Seventy patients with a median age of 57 years (range: 38-86) were included in the study. Most patients (94.3%) were initially diagnosed with stage III-IV disease and 44.3% had platinum-sensitive disease. Median progression-free survival in platinum-sensitive patients was 6.3 months [95% confidence interval (CI): 4.3-8.3] and 6.3 months (95% CI: 4.6-7.9) in platinum-resistant patients. Median overall survival was 15.8 months (95% CI: 13.6-18.1) in the platinum-sensitive patients and 18.4 months (95% CI: 10.0-27.8) in the platinum-resistant patients. Platinum-sensitive patients had a RR of 43.2% and platinum-resistant patients had a RR of 39.1%. The clinical benefit was 70.5% in platinum-sensitive patients and 65.2% in platinum-resistant patients. Overall treatment had a favorable safety profile. Gemcitabine and carboplatin demonstrate moderate toxicity with similar efficacy in both platinum-sensitive and platinum-resistant epithelial ovarian cancer, suggesting reversal of platinum resistance by gemcitabine.

Combined weekly carboplatin and paclitaxel as primary treatment of advanced epithelial ovarian carcinoma.

OBJECTIVE: To evaluate safety and outcome of weekly carboplatin and paclitaxel as the initial postoperative adjuvant chemotherapy for epithelial ovarian carcinoma (EOC) patients. METHODS: Patients with stage IC-IV epithelial ovarian cancer (EOC) primary peritoneal or tubal carcinoma were enrolled in this phase II study. Intravenous carboplatin (area under the curve 2) and paclitaxel (80 mg/m(2)) were administered on days 1, 8, and 15 of a 28-day cycle for 6-8 cycles. Cytoreductive surgery was performed as primary treatment or after 3 cycles of weekly neoadjuvant chemotherapy, followed postoperatively by an additional 3 cycles of chemotherapy. RESULTS: Sixty-four women (median age 65 years, range 39.9-82.8) were enrolled. Fifty-six of them (87.6%) were diagnosed with stage III-IV disease. Neutropenia was the most common hematological toxicity: 25% of the subjects had grade 3-4 neutropenia, 34.4% were supported by GCSF and 15.6% received epoetin. The majority (89%) of the patients had grade 1 and only 7.8% had grade 2 alopecia. 7.8% had grade 3 fatigue and 14.1% had grade 2 and 3.1% grade 3 neuropathy, none developed grade 4 neuropathy and only 6.3% had some residual neuropathy at >6 months after treatment. With a median follow-up of 31.5 months (range 5.9-57.3), estimated median survival was 52.0 months and median progression-free survival 25.74 (8.4-57.3) months (95% CI, 21.2-30.3). Overall and complete response rates were 92.1% and 64.1% respectively. CONCLUSION: Weekly carboplatin and paclitaxel as the initial chemotherapy for EOC is a feasible and well tolerated regimen and should be further evaluated in a larger phase III study.

Efficacy and toxicity of weekly topotecan in recurrent epithelial ovarian and primary peritoneal cancer.

OBJECTIVES: We assessed the efficacy and toxicity of once-weekly topotecan (Hycamtin; GlaxoSmithKline) for relapsed or persistent epithelial ovarian cancer (EOC) and primary peritoneal carcinoma (PPC). METHODS: Patients with recurrent or persistent EOC and PPC previously treated with > or = 1 course of platinum-based chemotherapy were treated with weekly topotecan 4.0 mg/m2 on days 1, 8, and 15 of a 28-day cycle in this prospective open-label, single-arm, phase II study. RESULTS: The median age of the 63 study patients was 63 years (range, 36-88); patients had been previously exposed to a median of 1 course (range, 1-4) of chemotherapy. A median of 5 courses (range, 1-16) were administered. Median follow-up time was 13. 2 month s (range, 1.5-39.0). The overall response rate (RR) was 23.8%, of which 17.5% (11 patients) represented a complete response and 6.3% (4 patients) a partial response. Patients with platinum-sensitive disease had a RR of 20%, whereas patients with platinum-resistant disease had a RR of 28.6%. Median time to progression was 6.2 months (95% confidence interval: 4.43, 7.97), and median survival from initiation of topotecan therapy was 22.3 months (95% confidence interval: 14.56, 30.04). Hematologic toxicities included grade 3 anemia in 3 (4.8%) patients, grade 3 thrombocytopenia in 3 (4.8%) patients, and grades 3-4 neutropenia in 5 (7.9%) patients. Dose reductions, granulocyte colony-stimulating factor, and erythropoietin support were required by 10 (15.9%), 6 (9.5%), and 16 (25.4%) patients, respectively. The most frequent nonhematologic toxicities were grades 2-3 fatigue in 10 (15.9%) patients and grades 2-3 nausea/vomiting in 3 (4.7%) patients. CONCLUSION: Weekly administration of topotecan 4.0 mg/m2 is active and well tolerated by patients with recurrent or persistent EOC and PPC.