Clinical Cancer Research, Vol 2, Issue 10 1693-1697, Copyright © 1996 by American Association for Cancer Research

ARTICLES

Modulation of platinum sensitivity and resistance by cyclosporin A in refractory ovarian and fallopian tube cancer patients: a phase II study

SK Chambers, CA Davis, PE Schwartz, EI Kohorn and JT Chambers
Department of Obstetrics and Gynecology, Comprehensive Cancer Center Clinical Research Office, Yale University School of Medicine, New Haven, Connecticut 06520-8063, USA.

Our objective was to assess the activity of cyclosporin A (CsA) used as a chemomodulator of carboplatin in refractory ovarian and fallopian tube cancer patients. Fifty-one patients (47 epithelial ovarian, 1 ovarian mixed mesodermal tumor, and 3 fallopian tube carcinomas) were enrolled in a prospective Phase II trial of CsA and carboplatin. CsA was infused as a loading dose of 10 mg/kg over 5 h, followed by carboplatin infused over 30 min at an AUC of 6 mg/ml x min, then a 24-h continuous infusion of 11.6 mg/kg CsA. The patients received this protocol as second- to sixth-line therapy and had received between 1 and 3 prior platinum-based regimens. Eight patients received more than six cycles every 28 days, 34 patients received three to six cycles; and 9 patients received only one or two cycles. Thirty-eight patients were evaluable for objective response, and in an additional nine patients, CA-125 was the only marker of response. Four patients had no marker of disease. Of evaluable patients, 74% were platinum resistant. There were nine objective responses (one complete and eight partial responses) for an overall response rate in evaluable patients of 24%, with a median duration of response of 7 months (range, 3-38+ months). No responses were seen in patients who had received only one or two cycles of therapy. Among the strictly defined platinum-resistant patients, there was an overall 14% response rate, including one partial response seen after five prior regimens of chemotherapy including paclitaxel, and one ongoing complete response for 38+ months. Among the rest of the patients (those who were potentially platinum sensitive), there was an overall 50+ response rate; four of five responses were seen in patients with a platinum-free interval of <24 months, with only one response seen in a patient with a platinum-free interval of >24 months. Of evaluable patients, 34% had stable disease for a duration of 3-19 months. The most common grade 3 or 4 toxicity, thrombocytopenia, was seen in 22% of the patients. Hypertension, which responded to medications, was seen in 18% of the patients during the CsA infusion. We concluded that this CsA/carboplatin regimen is active in potentially platinum-sensitive patients and compares well with the expected response rate of 30% in patients with a platinum-free interval <24 months who are retreated with platinum. Moreover, this regimen had modest but real activity in platinum-resistant patients.

This article has been cited by other articles:

				M. Qadir, K. L. O'Loughlin, S. M. Fricke, N. A. Williamson, W. R. Greco, H. Minderman, and M. R. Baer Cyclosporin A Is a Broad-Spectrum Multidrug Resistance Modulator Clin. Cancer Res., March 15, 2005; 11(6): 2320 - 2326. [Abstract] [Full Text] [PDF]