the therapeutic index better with paclitaxel plus carboplatin than with paclitaxel plus cisplatin in initial treatment of advanced ovarian cancer?

ABSTRACT

Retrospective analysis and comparison of the side effects, efficacy and feasibility of cisplatin and carboplatin each in combination with paclitaxel as front-line therapy in advanced epithelial ovarian cancer. Between January 2001 and January 2006, 39 patients with advanced epithelial ovarian cancer were allocated to receive paclitaxel 175mg/m[2] intravenously as a 3-hour infusion followed by either cisplatin 75mg/m[2] or carboplalin [area under the plasma concentration-time curve of 5] both on day [1]. The schedule was repeated every 3 weeks for at least six cycles to the majority of the patients. The primary endpoint was the proportion of patients without progression at 2 years. Secondary endpoints included toxicity, tolerability, response to treatment, and overall and progression-free survival time. Kaplan-Meier method estimated overall and time to disease progression. Log rank test compared survival curves with p value patients were analyzed. Prognostic factors were almost similar in the two treatment groups. Both regimens could be delivered in an optimal dose and without significant delay. Paclitaxel-carboplatin [TC] produced less nausea and vomiting, as well as less renal complications with borderline significance [p=0.08], also less peripheral neurotoxicity but without significance [p=0.25], while more anaemia, granulocytopenia and thrombocytopenia, however these differences were not statistically significant [all p=NS]. Elevated level of CA[125] >230 had 92.3% sensitivity and 100% specificity [p=<0.001] and tumor size at start of chemotherapy had 96.3% sensitivity and 100% specificity [p<0.001]. The 2-years progression-free survival [PFS] of all patients was 39.4% and the median time to disease progression was 23.3 months. While the median overall survival time of all patients was 37.5 months and the 2-years overall survival [OAS] was 62.9%. The 2-years PFS and OAS were 35.2% and 44.4%, respectively, for TC arm compared with 44.4% and 83.3%, respectively, for paclitaxel-cisplatin [TP] arm. The relative risk [RR] of progression for patients with incomplete response was 6.9 [95%- CI, 2.052 to 23.11] and the RR of death for TC arm was 6.3 [95% CI, 1.7 to 9.0]. The small number of patients entered onto the study caused wide CI around the hazards ratio for RR of death with delayed treatment [hazards ratio, 4.0; 95% CI, 1.7 to 23.3] and did not allow conclusions about efficacy. Age >60 [p=0.05], stage IIIB, IIIC and IV disease [p=0.02], and delayed treatment [0.001] had statistically significant adverse effect on the OAS, while response to chemotherapy [p=0.03] had statistically significant effect on prolonging the OAS. Presence of residual disease >1cm had borderline significance [p=0.06] on the OAS. However elevated level of CA[125] >230, tumor grade, pathological subtype, Karnofsky performance status [KPS] had no statistically significant effect on the OAS [all p=NS]. Univariate analysis of factors that might affect PFS showed that patients with a residual tumor of less than 1cm before chemotherapy [p=0.0003], KPS [p=0.0268], FIGO stage II or IIIa [p=0.0018], had statistically significant longer PFS while CA125 >230 [p=0.0012] and incomplete response [p=0.002] had a significant adverse impact on PFS. In patients with advanced ovarian cancer, a chemotherapy regimen consisting of TC results in less toxicity, is easier to administer, and has similar median time to disease progression [23.3 months], when compared with TP regimen, however a longer follow-up is required for a definitive statement on survival