Another investigation targeting platinum-resistant, recurrent, ovarian cancer combined low-dose decitabine with carboplatin.14 Decitabine is a hypomethylating agent that alters DNA methylation to reverse platinum resistance. Among the 17 patients enrolled, 1 had a complete response and 5 had partial responses, for a response rate of 35% (CI, 14–62). The median PFS was 309 days, and PFS was positively correlated (P<0.01) with demethylation of the genes MLH1, RASSF1a, HOXA10, and HOXA11, which are associated with ovarian cancer. The most common grade 3 or 4 AEs were neutropenia (23%), thrombocytopenia (11%), leukopenia (11%), and anemia (11%).

Eribulin mesylate is a tubulin inhibitor whose mechanism differs from that of paclitaxel.15 This agent was tested in recurrent ovarian cancer in a Phase 2 trial with a platinum-resistant cohort and a platinum-sensitive cohort. Each cohort had 37 patients enrolled, who were treated with eribulin mesylate 1.4mg/m2 on Days 1 and 8 every 21 days. Among the 36 evaluable platinum-resistant patients, 2 (5.5%) achieved a partial response and 16 (44%) had stable disease. Among the 37 platinum-sensitive patients, 7 (19%) achieved a partial response, and 21 (57%) had stable disease. The most common grade 3 or 4 AEs were neutropenia and leukopenia in both groups.


Continue Reading

Summary
Antiangiogenesis inhibitors and PARP inhibitors, both approved and in clinical trials, have improved survival rates for ovarian cancer, particularly for recurrent disease. Clinical studies continue efforts to improve survival rates.

References
1.
American Cancer Society. Cancer Facts and Figures 2012. http://www.cancer.org/Research/CancerFactsFigures/index. Accessed April 2, 2012.

2. Perren T.J., Swart A.M., Pfisterer J., et al. A phase 3 trial of bevacizumab in ovarian cancer. N Engl J Med. 2011;365(26):2484-2496.

3. Burger R.A., Brady M.F., Bookman M.A., et al. Incorporation of bevacizumab in the primary treatment of ovarian cancer. N Engl J Med. 2011;365(26):2473-2483.

4. Aghajanian C., Finkler N.J., Rutherford T., et al. OCEANS: a randomized, double-blinded, placebo-controlled phase III trial of chemotherapy with or without bevacizumab (BEV) in patients with platinum-sensitive recurrent epithelial ovarian (EOC), primary peritoneal (PPC), or fallopian tube cancer (FTC) [ASCO 2011 abstract LBA5007]. J Clin Oncol. 2011;29(suppl):LBA5007.

5. del Carmen M.G., Micha J.P., Small L.A., et al. Pegylated liposomal doxorubicin and carboplatin plus bevacizumab in patients with platinum sensitive recurrent ovarian, fallopian tube, or primary peritoneal cancers: results of a phase II study [ASCO 2011 abstract 5061]. J Clin Oncol. 2011;29(suppl):5061.

6. Kohn E.C., Lee J., Annunziata C.M., et al. A phase II study of intermittent sorafenib with bevacizumab in bevacizumab-naive epithelial ovarian cancer (EOC) patients [ASCO 2011 abstract 5019]. J Clin Oncol. 2011;29(suppl):5019.

7. Buckanovich R.J., Berger R., Sella A., et al. Activity of cabozantinib (XL184) in advanced ovarian cancer patients (pts): results from a phase II randomized discontinuation trial (RDT) [ASCO 2011 abstract 5008]. J Clin Oncol. 2011;29(suppl):5008.

8. Coleman R.L., Duska L.R., Ramirez P.T., et al. Phase 1–2 study of docetaxel plus aflibercept in patients with recurrent ovarian, primary peritoneal, or fallopian tube cancer. Lancet Oncol. 2011;12(12):1109-1117.

9. Gelmon K.A., Tischkowitz M., Mackay H., et al. Olaparib in patients with recurrent high-grade serous or poorly differentiated ovarian carcinoma or triple-negative breast cancer: a phase 2, multicentre, open-label, non-randomised study. Lancet Oncol. 2011;12(9):852-861.

10. Ledermann J., Harter P., Gourley C., et al. Olaparib maintenance therapy in platinum-sensitive relapsed ovarian cancer [published online ahead of print March 27, 2012]. N Engl J Med.
doi: 10.1056/NEJMoa1105535.

11. Penson R.T., Whalen C., Lasonde B., et al. A phase II trial of iniparib (BSI-201) in combination with gemcitabine/carboplatin (GC) in patients with platinum-sensitive recurrent ovarian cancer [ASCO 2011 abstract 5004]. J Clin Oncol. 2011;29(suppl):5004.

12. Birrer M.J., Konstantinopoulos P., Penson R.T., et al. A phase II trial of iniparib (BSI-201) in combination with gemcitabine/carboplatin (GC) in patients with platinum-resistant recurrent ovarian cancer [ASCO 2011 abstract 5005]. J Clin Oncol. 2011;29(suppl):5005.

13. Naumann R.W., Coleman R.L., Burger R.A., et al. PRECEDENT: a randomized phase II trial comparing EC145 and pegylated liposomal doxorubicin (PLD) in combination, versus PLD alone, in subjects with platinum-resistant ovarian cancer [ASCO 2011 abstract 5045]. J Clin Oncol. 2011;29(suppl):5045.

14. Matei D., Shen C., Fang F., et al. A phase II study of decitabine and carboplatin in recurrent platinum (Pt)-resistant ovarian cancer (OC) [ASCO 2011 abstract 5011]. J Clin Oncol. 2011;29(suppl):5011.

15. Hensley M.L., Kravetz S., Jia X., et al. Eribulin mesylate (halichondrin B analog E7389) in platinum-resistant and platinum-sensitive ovarian cancer: a 2-cohort, phase 2 study [published online ahead of print Septmber 20, 2011]. Cancer. doi: 10.1002/cncr26569.