Platinum-sensitive Epithelial Ovarian Cancer Research Articles

A cost–effectiveness analysis of chemotherapy for patients with recurrent platinum-sensitive epithelial ovarian cancer☆

The majority of patients with advanced epithelial ovarian cancer (EOC) will experience a recurrence after primary chemotherapy and receive second-line chemotherapy. Patients who have a disease-free interval >6 months (platinum-sensitive) will often receive multiple chemotherapy regimens. Therefore, our goal was to assess the effectiveness and medical costs of chemotherapy for platinum-sensitive patients with advanced EOC. A decision analysis model compared several chemotherapeutic strategies in a hypothetical cohort of 10,000 platinum-sensitive EOC patients with recurrent disease: (a) best supportive care (BSC); (b) second-line monotherapy; (c) second-line combination therapy; (d) third-line chemotherapy after disease progression on second-line monotherapy or combination therapy; (e) fourth-line chemotherapy after disease progression on second- and third-line chemotherapy. BSC and second-line therapies were cost-effective strategies. The cost-effectiveness ratios ranged from $2896 for second-line monotherapy to $4914 for fourth-line previous monotherapy. Compared to BSC, second-line monotherapy gained an additional 8 months of overall survival (OS) with a favorable incremental cost-effectiveness ratio (ICER) of $24,228 per life year saved (LYS). The ICER for second-line combination therapy compared to second-line monotherapy was also favorable ($46,068 per LYS). Although third- and fourth-line chemotherapy provided small improvements in OS, they were dominated by other strategies or had an unfavorable ICER (>$50,000 per LYS). Second-line chemotherapy is cost-effective for patients with platinum-sensitive recurrent EOC. Due to minimal improvements in overall survival, third- and fourth-line chemotherapy are not cost-effective strategies.

Guidelines and selection criteria for secondary cytoreductive surgery in patients with recurrent, platinum‐sensitive epithelial ovarian carcinoma

The benefit of cytoreductive surgery for patients with recurrent epithelial ovarian cancer has not been defined clearly. The objective of this study was to identify prognostic factors for survival in patients who underwent secondary cytoreduction for recurrent, platinum-sensitive epithelial ovarian cancer and to establish generally applicable guidelines and selection criteria. The authors reviewed all patients who underwent secondary cytoreduction for recurrent epithelial ovarian cancer from 1987 to 2001. Potential prognostic factors were evaluated in univariate and multivariate analyses. In total, 157 patients underwent secondary cytoreduction, and 153 of those patients were evaluable. After secondary cytoreduction, the median follow-up was 36.9 months (range, 0.2-125.6 months), and the median survival was 41.7 months (95% confidence interval, 36.0-47.2 months). For patients who had a disease-free interval prior to recurrence of between 6 months and 12 months, the median survival was 30 months compared with 39 months for patients who had a disease-free interval between 13 months and 30 months and 51 months for patients who had a disease-free interval >30 months (P = .005). For patients who had a single site of recurrence, the median survival was 60 months compared with 42 months for patients who had multiple sites of recurrence and 28 months for patients who had carcinomatosis (P <.001). The median survival for patients who had residual disease that measured < or =0.5 cm was 56 months compared with 27 months for patients who had residual disease that measured >0.5 cm (P <.001). On multivariate analysis, disease-free interval (P = .004), the number of recurrence sites (P = .01), and residual disease (P <.001) were significant prognostic factors. In the authors' analysis of secondary cytoreduction for recurrent epithelial ovarian cancer, a significant survival benefit was demonstrated for residual disease that measured < or = 0.5 cm. The disease-free interval and the number of recurrence sites should be used as selection criteria for offering secondary cytoreduction.

Phase 2 study of weekly triplet regimen of docetaxel, carboplatin and gemcitabine in recurrent platinum-sensitive epithelial ovarian cancer

5150 Background: To investigate the efficacy and toxicity of a triplet regimen of weekly Docetaxel, Carboplatin, and Gemcitabine in recurrent Platinum-sensitive epithelial ovarian cancer. Methods: 24 patients with recurrent Platinum-sensitive epithelial ovarian cancer were treated with a novel triplet regimen of weekly Docetaxel (25mg/m2) and weekly Carboplatin (AUC:2) and weekly Gemcitabine (600 mg/m2). Patients were evaluated for response by clinical,imaging and biochemical (CA 125) methods. Restin criteria was used for CA 125 response. Patients were treated from 2000 to 2003. The mean Platinum-free interval was 18.2 months with a range of 8 - 48 months. Patients were eligible if they had relapsed more than 6 months after their primary treatments. Patients were evaluated for response after 8 cycles of treatment. CA 125 level was elevated above 175 in all 24 patients. Results: We obtained complete remission in 10 pts (41%). The CR was evidenced by the normalization of CA 125 level and normal imaging studies and physical exm. Partial remission was shown in 7 pts (25%). the remaining 7 pts met the criteria for stable disease. No patient progressed under treatment. Our response rate i.e: CR + PR was therefore 66%. Toxicities included: grade 3 neutropenia in 8% (2/24), grade 1 neurotoxicity in 8%(2/24) and grade 3 anemia in 4%(1/24). The median progression-free survival was 14.8 months with a range of 3 - 27 months. Conclusions: To our knowledge, this is the first study of its kind to date. Our 41% CR rate is impressive in this population of heavily pretreated patients. The results we have achieved in this study are promising and this novel weekly triplet (G.C.D) deserves to be considered in the primary treatment of epithelial ovarian cancer. No significant financial relationships to disclose.

Phase 2 study of weekly triplet regimen of docetaxel, carboplatin and gemcitabine in recurrent platinum-sensitive epithelial ovarian cancer

5150 Background: To investigate the efficacy and toxicity of a triplet regimen of weekly Docetaxel, Carboplatin, and Gemcitabine in recurrent Platinum-sensitive epithelial ovarian cancer. Methods: 24 patients with recurrent Platinum-sensitive epithelial ovarian cancer were treated with a novel triplet regimen of weekly Docetaxel (25mg/m2) and weekly Carboplatin (AUC:2) and weekly Gemcitabine (600 mg/m2). Patients were evaluated for response by clinical,imaging and biochemical (CA 125) methods. Restin criteria was used for CA 125 response. Patients were treated from 2000 to 2003. The mean Platinum-free interval was 18.2 months with a range of 8 - 48 months. Patients were eligible if they had relapsed more than 6 months after their primary treatments. Patients were evaluated for response after 8 cycles of treatment. CA 125 level was elevated above 175 in all 24 patients. Results: We obtained complete remission in 10 pts (41%). The CR was evidenced by the normalization of CA 125 level and normal imaging studies and physical exm. Partial remission was shown in 7 pts (25%). the remaining 7 pts met the criteria for stable disease. No patient progressed under treatment. Our response rate i.e: CR + PR was therefore 66%. Toxicities included: grade 3 neutropenia in 8% (2/24), grade 1 neurotoxicity in 8%(2/24) and grade 3 anemia in 4%(1/24). The median progression-free survival was 14.8 months with a range of 3 - 27 months. Conclusions: To our knowledge, this is the first study of its kind to date. Our 41% CR rate is impressive in this population of heavily pretreated patients. The results we have achieved in this study are promising and this novel weekly triplet (G.C.D) deserves to be considered in the primary treatment of epithelial ovarian cancer. No significant financial relationships to disclose.

Second-line chemotherapy with gemcitabine and carboplatin in paclitaxel-pretreated, platinum-sensitive ovarian cancer patients: A Hellenic Cooperative Oncology Group Study

Objective. Patients with epithelial ovarian cancer (EOC) who relapse more than 6 months following completion of platinum-based primary chemotherapy are considered platinum-sensitive, and can be effectively retreated with cisplatin or carboplatin. The nucleoside analogue gemcitabine has proven activity in both platinum-sensitive and platinum-resistant disease. We conducted a phase II study using the combination of carboplatin and gemcitabine for the treatment of patients with relapsed platinum-sensitive and paclitaxel-pretreated EOC. Methods. Forty-three patients were treated with gemcitabine 1000 mg/m 2, intravenously, over 30 min on days 1 and 8, and carboplatin at AUC 5 on day 1. Courses were administered every 3 weeks on an outpatient basis. Results. Among 37 patients with measurable or evaluable disease, 15 (40.5%) achieved an objective response including 10 complete and 5 partial responses. The median overall survival was 24.5 months, and the median time to progression for all patients was 9 months. The treatment was well tolerated without toxic deaths; the most common toxicities were Grade 3 or 4 neutropenia, anemia, and thrombocytopenia that occurred in 69%, 26%, and 24% of patients, respectively. Conclusions. The combination of carboplatin and gemcitabine is a well-tolerated outpatient regimen with activity in patients with relapsed platinum-sensitive and paclitaxel-pretreated EOC. However, a randomized prospective study is justified to define whether the addition of gemcitabine to single-agent carboplatin results in improved efficacy in this subset of patients.

Treatment of recurrent ovarian cancer: a retrospective analysis of women treated with single-agent carboplatin originally treated with carboplatin and paclitaxel: The Memorial Sloan-Kettering Cancer Center experience

Objective There is no standard treatment for recurrent epithelial ovarian cancer (EOC). As there are no curative options, many oncologists choose to treat women who recur with carboplatin, particularly if they are deemed to have platinum-sensitive disease. However, particularly in the era of platinum–taxane treatment as primary therapy, the utility of this treatment has not been established, nor is it clear whether the results of single-agent treatment are equivalent to that of combination therapy. We sought to determine the outcomes for patients with platinum-sensitive EOC who were treated with carboplatin–taxane therapy and received single-agent carboplatin (C) as second chemotherapy. In addition, we sought to compare these results to the outcomes in women who received carboplatin and paclitaxel (C + T) at first relapse. Patients and methods We identified 24 patients using our electronic institutional database with a histologically confirmed diagnosis of ovarian cancer that had a complete response to platinum–paclitaxel chemotherapy, relapsed greater than 6 months after treatment, and received single-agent carboplatin as second-line chemotherapy. We performed a subsequent comparison between a subgroup of this cohort and one that met the same inclusion criteria but received C + T at relapse between January 1998 and December 2000. Results Eighteen patients were evaluable for response, and all were available for analysis of survival end points. For evaluable patients, the overall response rate was 39% (complete, 11%; partial, 28%). Twenty-two percent had stable disease. Six (25%) patients experienced a hypersensitivity reaction, including 1 who required hospitalization. The median overall survival was 22 months. The 2-year overall survival rate was 49%. Stratification by treatment-free interval (TFI) showed a 25% for a TFI between 6 and 12 months and 43% for a TFI > 12 months. When a subgroup of these women (18/24) was compared to a cohort that received C + T (29), the combination was associated with a higher complete and overall response rate, 7 and 36% for C versus 45 and 71% for C + T ( P = 0.02). The overall survival in women who received C was 26 months versus 42 months in the women who received C + T ( P < 0.02). Conclusions Carboplatin as a single agent is effective therapy for recurrent ovarian cancer in women who recur following treatment with carboplatin and paclitaxel, and the treatment-free interval predicts response to single-agent carboplatin. However, our secondary analysis suggests that carboplatin and paclitaxel may produce a higher response rate and a survival benefit compared to C alone. This supports the conclusions of ICON4, which recently reported both overall and progression-free survival benefits with C + T over C in women with platinum-sensitive recurrent disease.

Results of Reinduction Therapy with Paclitaxel and Carboplatin in Recurrent Epithelial Ovarian Cancer

Objective. The purpose of the study was to evaluate the treatment results and toxicity of a retreatment regimen of paclitaxel and carboplatin in patients with ovarian cancer relapse.Methods. A retrospective analysis of 241 consecutive patients with primary epithelial ovarian cancer receiving paclitaxel and a platinum analogue as first-line treatment was performed. Relapse treatment of platinum-sensitive patients consisted of paclitaxel (175 mg/m2) over 3 h followed by carboplatin at an area under the concentration-time curve of 5, repeated every 3 weeks.Results. Forty-three patients with relapse were treated with paclitaxel and carboplatin after a median progression-free interval from the end of first-line chemotherapy of 15.8 months (range 6.0–41.7 months). In patients with evaluable disease the overall response rate was 84% (95% CI: 68.0–93.8%). The progression-free survival and overall survival from start of relapse treatment were a median of 9.7 months (range 1.4–26.9 months) and 13.1 months (range 4.5–35.5 months), respectively. In a multivariate Cox analysis independent prognostic factors for progression-free survival after first relapse were response to relapse treatment (P = 0.002, hazard ratio = 13.9) and time to first recurrence (P = 0.016, hazard ratio = 0.167). The planned treatment was accomplished by 67% of patients. Grade 4 neutrocytopenia over 1 week was observed in 9.3% of patients. Grade 1–2 peripheral neuropathy was reported in 30% of patients. Only 1 patient had her paclitaxel dose attenuated because of grade 4 neuropathy.Conclusion. Retreatment with paclitaxel and carboplatin in patients with platinum-sensitive epithelial ovarian cancer relapse yielded a high response rate and encouraging progression-free survival and overall survival. Paclitaxel–carboplatin reinduction therapy is generally well tolerated and the toxicity is manageable.

Intraperitoneal Cisplatin and Intravenous Paclitaxel in the Treatment of Epithelial Ovarian Cancer Patients with a Positive Second Look

Objective. The aim of this study was to review the role and safety of intraperitoneal (IP) cisplatin and intravenous (IV) paclitaxel in platinum-sensitive epithelial ovarian cancer patients who were found to have small-volume disease (<1 cm) at the time of their second-look procedure.Methods. In a retrospective review, 32 patients with small-volume disease had an IP Bardport catheter placed at the time of second look at Memorial Sloan-Kettering Cancer Center (1995–1998). Patients received IP cisplatin (75 mg/m2) every 3 weeks and either IV paclitaxel (135 mg/ m2) every 3 weeks or IV paclitaxel (80 mg/m2) weekly for a maximum of five cycles.Results. Twenty-four (75%) of 32 patients received IP cisplatin/IV paclitaxel every 3 weeks and 8 (25%) received IP cisplatin every 3 weeks with weekly IV paclitaxel. Seven (21.9%) of 32 patients required interruption of treatment secondary to neuropathy. Of these, 4 (15.6%) were changed to another IV chemotherapeutic agent, and 3 (9.3%) required discontinuation of IV paclitaxel only. Two (6%) patients required IP port removal secondary to malfunction and were changed to IV therapy and 1 (3%) requested discontinuation of IP therapy secondary to abdominal pain. Median follow-up was 19 months (mean, 20.1 months; range, 6–36 months). Progression of disease after completion of IP therapy was documented by clinical exam, abnormal CT, and/or rising CA-125 levels. The median progression-free interval was 13 months (mean, 15.1 months; range, 2–33 months). Median overall survival was 27 months (mean, 34.2 months; range, 10–42 months). At the time of review, 13 (40.6%) of the 32 patients were alive with disease, 7 (21.9%) were without evidence of disease, and 12 (37.5%) were dead of disease.Conclusion. IP cisplatin in combination with IV paclitaxel appears to be no more effective than other reported regimens as second-line therapy for patients with persistent small-volume disease. Neurotoxicity is dose limiting, and the combination cannot be recommended for the routine care of persistent peritoneal cancers.

Prolonged Disease-Free Survival by Maintenance Chemotherapy among Patients with Recurrent Platinum-Sensitive Ovarian Cancer

Objective.The aim of this study was to determine the potential benefit and complications of prolonged salvage and maintenance chemotherapy among patients with recurrent epithelial ovarian cancer who achieve response to salvage chemotherapy.Methods.Patients with recurrent platinum-sensitive epithelial ovarian cancer who were treated between 1982 and 1996 and achieved complete response to platinum-based salvage chemotherapy were offered prolonged (1 year) monthly salvage followed by maintenance (every 8 weeks) chemotherapy. Patients who accepted such treatment (n= 16) were compared to those who refused and discontinued therapy (n= 11) with regard to overall survival from time of initial diagnosis and overall and disease-free survival from time of recurrence. Chemotherapy-related toxicity in the study group was recorded. Survival curves were constructed according to the Kaplan and Meier method and survival curves were compared using the log-rank test.Results.Patients in the study and control groups were similar with regard to age, stage, histology, grade, performance status, primary cytoreductive surgery, type of primary and salvage chemotherapy, and method of assessment of tumor response. The study group had a significantly longer disease-free interval from date of recurrence than the control group (median: 35.0 versus 6.0 months, respectively,P= 0.001). The study group had longer overall survival from date of recurrence than the control group. However, the difference did not achieve statistical significance (median: 119 versus 90 months, respectively,P= 0.056). There was no significant difference between the study group and the control group as to survival from date of initial diagnosis (median: 157 versus 124 months, respectively,P= 0.28). Chemotherapy-related toxicity was minimal.Conclusions.Prolonged salvage and maintenance chemotherapy is a safe method of treatment that may extend disease-free interval among patients with platinum-sensitive recurrent epithelial ovarian cancer who achieve response to salvage chemotherapy. These preliminary results need to be confirmed by a larger prospective randomized trial.