Effectiveness of third-line chemotherapy in recurrent ovarian cancer patients

Objective: Despite recent advances in the treatment of recurrent ovarian cancer, little evidence exists describing the benefit of thirdline chemotherapy. The present authors previously reported that the treatment-free interval (TFI) after second-line chemotherapy may predict a survival benefit of third-line chemotherapy, however the length of TFI was uncertain due to limited cases. In this study, the authors evaluated the length of TFI, which is correlated with the effectiveness of third-line chemotherapy and a prognostic factor of thirdline chemotherapy. Materials and Methods: The authors reviewed the medical records of 85 women with recurrent ovarian cancer who received third-line chemotherapy after a paclitaxel/carboplatin (PC) regimen as first-line chemotherapy. Results: The response rate [complete response (CR) + partial response (PR)] and clinical benefit rate [(CBR): CR + PR + stable disease (SD)] during the TFI after second-line chemotherapy for 0–3 months, 3–6 months, and 6–12 months and ≥ 12 months were 9.8%, 0%, 0%, 43.8% and 15.7%, 50%, 66.7%, and 93.8%, respectively. The median overall survival (OS) from the onset of third-line chemotherapy was longer for TFI ≥3 months than for TFI 0–3 months (795 days vs. 281 days, p < 0.001). Finally, according to univariate (HR = 0.256; p < 0.001) and multivariate (HR = 0.264; p < 0.001) analyses, TFI was the independent significant prognostic factor for OS. Conclusions: TFI less than three months after second-line chemotherapy may predict little survival benefit of third-line chemotherapy.

Epithelial ovarian cancer; Recurrent ovarian cancer; Third-line chemotherapy.

[1] Siegel R., Naishadham D., Jemal A.: “Cancer statistics, 2012”. CA Cancer J. Clin., 2012, 62, 10.

[2] Chiyoda T., Tsuda H., Nomura H., Kataoka F., Tominaga E., Suzuki A., et al.: “Effects of third-line chemotherapy for women with recurrent ovarian cancer who received platinum/taxane regimens as first-line chemotherap”:. Eur. J. Gynaecol. Oncol., 2010, 31, 364.

[3] McGuire W.P., Hoskins W.J., Brady M.F., Kucera P.R., Partridge E.E., Look K.Y., et al.: “Cyclophosphamide and cisplatin compared with paclitaxel and cisplatin in patients with stage III and stage IV ovarian cancer”. N. Engl. J. Med., 1996, 334, 1.

[4] Markman M., Rothman R., Hakes T., Reichman B., Hoskins W., Rubin S., et al.: “Second-line platinum therapy in patients with ovarian cancer previously treated with cisplatin”. J. Clin. Oncol., 1991, 9, 389.

[5] Pujade-Lauraine E., Wagner U., Aavall-Lundqvist E., Gebski V., Heywood M., Vasey P.A., et al.: “Pegylated liposomal Doxorubicin and Carboplatin compared with Paclitaxel and Carboplatin for patients with platinum-sensitive ovarian cancer in late relapse”. J. Clin. Oncol., 2010, 28, 3323.

[6] Sehouli J.W.M., Wimberger P., Chekerov R., Belau A., Mahner S., Kurzeder C., et al.: “Topotecan plus carboplatin versus standard therapy with paclitaxel plus carboplatin (PC) or gemcitabin plus carboplatin (GC) or carboplatin plus pegylated doxorubicin (PLDC): A randomized phase III trial of the NOGGO-AGO-Germany-AGO Austria and GEICO-GCIG intergroup study (HECTOR)”. J. Clin. Oncol., 2012, 30, suppl; abstr 5031.

[7] Pujade-Lauraine E.: “How to approach patients in relapse”. Ann. Oncol., 2012, 23, x128.

[8] Hanker L.C., Loibl S., Burchardi N., Pfisterer J., Meier W., Pujade- Lauraine E., et al.: “The impact of second to sixth line therapy on survival of relapsed ovarian cancer after primary taxane/platinum-based therapy”. Ann Oncol., 2012, 23, 2605. Epub 2012 Aug 21.

[9] Griffiths R.W., Zee Y.K., Evans S., Mitchell C.L., Kumaran G.C., Welch R.S., et al.: “Outcomes after multiple lines of chemotherapy for platinum-resistant epithelial cancers of the ovary, peritoneum, and fallopian tube”. Int. J. Gynecol. Cancer, 2011, 21, 58.

[10] Hoskins P.J., Le N.: “Identifying patients unlikely to benefit from further chemotherapy: a descriptive study of outcome at each relapse in ovarian cancer”. Gynecol. Oncol., 2005, 97, 862.