Date of Award

January 2016

Document Type

Open Access Thesis

Degree Name

Medical Doctor (MD)

Department

Medicine

First Advisor

Elena Ratner

Abstract

The aim of this study is to report our institutional experience with the use of carboplatin (carbo) and concurrent cyclosporin A (CsA; combined

treatment abbreviated as carbo/CsA) for recurrent epithelial ovarian cancer (EOC) and to assess the efficacy and tolerability of this regimen in treatment of the treatment of EOC. The medical records of patients diagnosed with ovarian cancer and treated with carbo/CsA from 2000 to 2015 at Yale New Haven Hospital were reviewed. Histological classification and staging were determined by the World Health Organization and Ann Arbor systems, respectively. Kaplan-Meier was used to calculate progression free survival (PFS) and overall survival (OS). Objective response was defined by RECIST criteria on computerized tomography (CT) or by a >50% reduction in CA-125. Statistics were run using STATA software. Fifty-four patients were identified carbo/CsA and had adequate documentation for analysis. Patients received a total of 265 cycles of carbo/CsA with a mean of 4.9 cycles per patient (range 1-10). Mean PFS was 7.7 months (SD 5.2), median 5.8 months, with a range of 1 to 25.4 months. OR by CT was observed in 7 patients, objective response by CA-125 was observed in 17 patients. There were a total of 49 patients with adequate data for measure of objective response by either CT or CA-125. By either method, a total of 19 patients exhibited objective response for an overall response rate of 38.8%. The rates of OR were significantly different in patients who were platinum resistant versus platinum sensitive (p= 0.015). Two of fifteen patients (13.3 %) defined as platinum resistant demonstrated objective response while 17 of 34 patients (50.0%) with platinum-sensitive disease experienced objective response. Five patients (9.3%) discontinued therapy due to toxicity. Most common grade III or IV toxicities included anemia (7.4%) and nausea and vomiting (5.6%) with other grade III reactions including hypertension, headache, and pancytopenia, and allergic reaction. Most common low grade toxicities included headache (24%), nausea and vomiting (18.5%), and fatigue (16.7%). Both PFS and OS were significantly higher in patients that demonstrated objective response on carboplatin/CsA than those who did not. There was no significant association of, age at treatment, number of prior chemotherapeutic regimens, histology or disease with likelihood objective response or length of PFS. We find that Carbo/CsA has activity in platinum sensitive patients. It also demonstrates limited but present activity in platinum resistant patients. The regimen was adequately tolerated by patients and revealed a similar side effect profile to prior studies of this regimen.

Comments

This is an Open Access Thesis.

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