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Objectives While primary treatment for high-grade serous ovarian cancer tends to be uniform – maximal debulking and platinum/taxane adjuvant chemotherapy – there is little standardization of treatment in the recurrent setting beyond the exhaustive use of platinum therapies. Using secondary data from multiple centers participating in the Cancer Genome Atlas study (TCGA), we seek to characterize clinical features, timing and serial response data to provide empirical evidence for treatment expectations in the recurrent setting. Methods We conducted a retrospective survival analysis of TCGA study primary and secondary patient chemotherapy regimens by characterizing the dynamics of 1119 lines of therapy comprising the treatment of 461 high-grade serous ovarian cancer patients. All patients with post-surgical drug therapy information from the TCGA database were included in this study. Results A complete response to adjuvant therapy led to longer overall survival, but did not affect treatment free intervals (TFIs) after relapse of disease. A strong predictor of the TFI on the next treatment regimen was the previous TFI with a decaying effect. The number of previous treatments, of platinum treatments, and the length of time from surgery all have an exponentially decreasing effect on TFI. Re-treatment times appear to cluster at predictable times following surgery. Conclusions While patients experience a consistent reduction in TFI with increasing re-treatment, the initial adjuvant interval is unrelated to later interval lengths. Platinum re-treatment remained an effective option in patients typically thought to be platinum resistant and the timing of monitoring visits may drive overall re-treatment patterns. [ABSTRACT FROM AUTHOR]

Purpose: The aim of the present study was to investigate, in ovarian carcinoma cases, the predictive association between the treatment-free interval (TFI) after an initial paclitaxel plus carboplatin (TC) therapy and the subsequent effectiveness of a second-line taxane-containing chemotherapy. Methods: Patients with a TFI < 6 months from the first-line TC therapy were treated with a combination chemotherapy using docetaxel and irinotecan; patients with a TFI ≥ 6 months were retreated with the same regimen as the initial TC therapy. The clinical data of these patients were retrospectively analyzed for this study. Results: The response rate of those with a TFI equal to 6-12 months was greater than that of those with a TFI < 6 months ( p = 0.014) and less than that of those with a TFI > 12 months ( p = 0.012). The progression-free survival of the cases with TFI equal to 6-12 months was longer than that of those with TFI < 6 months ( p = 0.012) and shorter than that of those with TFI > 12 months ( p = 0.0011). Overall survival of cases with a TFI equal to 6-12 months was longer than that of those with TFI < 6 months ( p = 0.012) and shorter than that of those with TFI > 12 months ( p = 0.0005). Conclusions: The effectiveness of using a second-line taxane-containing chemotherapy was shown to be predictable by the TFI after the first-line taxane-containing chemotherapy, implying that the theory of 'taxane-sensitivity' may be applied for second-line chemotherapy in the same way as that of 'platinum-sensitivity'. [ABSTRACT FROM AUTHOR]

Background Pertuzumab, a humanized monoclonal antibody targeting human epidermal growth factor receptor (HER)-mediated signalling, has shown activity in ovarian cancer in preclinical models and in the clinic. This randomized phase II study evaluated efficacy and safety of pertuzumab in combination with carboplatin-based chemotherapy in patients with platinum-sensitive, recurrent advanced ovarian cancer. Patients and methods Patients were randomized to receive six cycles of chemotherapy (carboplatin and either paclitaxel (Taxol) or gemcitabine) with or without pertuzumab. The primary end point was progression-free survival (PFS) as determined by Response Evaluation Criteria in Solid Tumors and/or by CA 125 measurements. Secondary end points evaluated the response rate, safety profile, duration of response, time to progression and overall survival for both treatment arms. Results A total of 149 patients received either chemotherapy with pertuzumab (arm A, n = 74) or chemotherapy alone (arm B, n = 75). There was no significant difference either in median PFS or in the secondary end points between the two arms. No differences were seen in an exploratory biomarker analysis of HER3 mRNA expression between the two arms. Pertuzumab was well tolerated, with no increase in cardiac adverse events compared with chemotherapy alone. Conclusions The addition of pertuzumab to carboplatin-based chemotherapy did not substantially prolong PFS in unselected patients with platinum-sensitive ovarian cancer. [ABSTRACT FROM PUBLISHER]

Abstract: Objectives: Weekly paclitaxel (WP) has been reported to have significant activity in patients with ovarian and primary peritoneal cancer patients while retaining a favorable toxicity profile. This study assessed the current usage of WP in routine clinical practice in a tertiary cancer center. Methods: We conducted a retrospective audit in 53 patients with recurrent ovarian or primary peritoneal cancer treated with WP (80–100 mg/m2) over a 2-year period (Nov 2003–Nov 2005). Toxicity was assessed using Common Toxicity Criteria, and response was evaluated using radiological and CA-125 criteria. Results: Patients had a median age of 69 (36–86) and previously received a median of 3 treatments (range 1–7). A median of 13 weekly doses of paclitaxel (range 1–39) were given. The response rate was 48% by radiological criteria and 69% by CA-125 assessment. Grade 3 toxicities were fatigue (13% of patients), peripheral neuropathy (11%) and neutropenia (8%) and there were no grade 4 toxicities. The median progression-free survival was 4. 8 months and median survival was 13. 5 months. There was no significant difference in efficacy between those 24 patients previously treated with taxanes (radiol. response 43%/CA-125 response 63%) and those 29 patients who had not received prior taxanes (radiol. response 52%/CA-125 response 76%). There was also no difference in efficacy for patients with platinum-free or treatment-free intervals of less than 6 months compared to 6 months or longer. Conclusions: WP is a well tolerated and active regimen in patients with pre-treated ovarian cancer and its use in recurrent disease is likely to increase. Further studies should aim to assess the importance of the “paclitaxel-free interval” in predicting response in relapsed disease, along similar lines as are now established for platinums. [Copyright &y& Elsevier]

In this article the author examines the effectiveness of combination therapy that incorporates nonplatinum agents in the treatment of women with recurrent ovarian cancer. The author is critical that J. Sehouli and colleagues failed to report the superiority of a nonplatinum doublet based from topotecan compared with single agent. The author also suggests that treatment using a platinum-based combination should remain the established standard of care.

Improvements in ovarian cancer management mean that it may now be a long-term disease for which treatment must be carefully considered. Optimal sequencing of chemotherapy may help to enhance patients'' benefit of therapy and minimize toxicity. The response to retreatment with platinum or a platinum/taxane combination is strongly influenced by the treatment-free interval after initial therapy with a platinum combination. Response rates to platinum retreatment in platinum-resistant patients (relapse within 6 months) are lower than those in platinum-sensitive patients (relapse after 6 months). Increasing the platinum-free interval by using non-platinum-based chemotherapy for treatment after relapse appears to increase the likelihood of response to later rechallenge with platinum. Many alternative agents have been investigated for the treatment of patients with relapsed ovarian cancer, including single-agent topotecan, which has been shown to achieve favorable responses. Topotecan may cause myelosuppression, which is noncumulative but tends to increase in direct correlation with the number of prior chemotherapy courses. Therefore, the best use of topotecan may be early in the course of salvage therapy. The hematologic toxicities associated with topotecan can also be reduced by adjusting the dose and schedule. Prolonged use of topotecan may be feasible and potentially beneficial in some patients. [Copyright &y& Elsevier]