STATISTICAL EVALUATION OF TAXOL PHASE II CLINICAL TRIALS IN ADVANCED OVARIAN CANCER

Abstract

Ovarian cancer, when detected early (Stage I or II) is one of the most treatable solid tumors. However, patients diagnosed with this disease generally have Stage III or IV tumors and as a result have the highest fatality rate of all gynecologic cancers. The 5 year fatality rate for ovarian cancer is approximately 70%. Platinum-based compounds have been identified as the most active class of compounds in the treatment of advanced ovarian cancer. Platinum-based compounds, such as cisplatin and carboplatin have demonstrated a 6.1% effectiveness rate in treating patients with relapsed ovarian cancer; therefore, new treatment agents are being investigated. Taxol is a complex diterpene molecule which has demonstrated activity in the treatment of relapsed ovarian cancer. Initial phase II studies have reported a response rate of approximately 30% in patients with platinum-resistant disease treated with taxol. Further studies will investigate the effectiveness of taxol as a first-line method of treatment against both control groups (with no treatment) and groups given other methods of conventional treatment. Trends within the experimental treatment groups were investigated to determine the potential factors contributing to tumor response and systemic toxicity in this group of ovarian cancer patients treated with taxol. The goal of this study was to evaluate three independent variables: dose-response, dose-intensity and blood enzyme levels and their relationship to the dependent variable tumor response, in Phase II clinical trials with taxol in the treatment of advanced ovarian cancer. The results indicate no relationship between taxol dose or dose-intensity and tumor response or blood enzyme levels and toxicity in the range of dose and dose-intensities studied. The clinical significance of both the independent dose-response and the dose-intensity relationship, if supported by further research, could result in lower administered doses of taxol in the clinic. Lower doses may potentially decrease the unpleasant side effects and drug-related toxicity associated with the administration of taxol. Dose-response curves may differ in size and shape for large tumors (>4cm) versus small tumors (<4cm) and for differing tumor types. Therefore, further research should center around patients with smaller residual tumor area and patients with less advanced disease to determine if the same dose-response or dose-intensity response relationship exists outside this group of ovarian tumors and advanced stage disease.