A randomized phase II study of paclitaxel with carboplatin +/- amifostine as first line treatment in advanced ovarian carcinoma.

Author(s): De Vos FY, Bos AM, Schaapveld M, de Swart CA, de Graaf H, van der Zee AG, Boezen HM, de Vries EG, Willemse PH

Affiliation(s): Department of Medical Oncology, University Hospital of Groningen, PO Box 30.001, 9700 RB Groningen, The Netherlands.

Publication date & source: 2005-04, Gynecol Oncol., 97(1):60-7.

Publication type: Clinical Trial; Clinical Trial, Phase II; Multicenter Study; Randomized Controlled Trial

OBJECTIVE: Will amifostine (A) protect against chemotherapy-induced neuro- and myelotoxicity. PATIENTS AND METHODS: Ninety ovarian cancer patients were randomized to receive standard paclitaxel + carboplatin without (PC) or preceded by amifostine 740 mg/m(2) (PC + A). RESULTS: The mean baseline values of hemoglobin, leukocyte, and platelets were slightly lower in the amifostine group, but the mean percentual decrease of these parameters after each treatment cycle showed no difference between both arms. Symptoms of neurotoxicity remained absent in 40% PC vs. 49% PC + A cycles; sensory neurotoxicity grade I occurred in 45% vs. 48% and grade II in 12% PC vs. 2% of PC + A cycles (overall P < 0.001). Nausea grade II was reported in 2% vs. 6% (P = 0.007) and vomiting grade II in 1% of PC vs. 8% PC + A cycles (P < 0.001). Amifostine was temporarily interrupted in five patients due to hypotension, but no dose reductions were indicated. Quality of life questionnaires showed no difference in neurotoxicity scores between both study arms at treatment completion. The median progression-free survival was 16 vs. 22 months (n.s.) for PC and PC + A patients. In a pooled analysis of four randomized studies, amifostine diminished the risk of developing neurotoxicity grade II-III (Odds Ratio 0.3, 95% confidence interval 0.15-0.63, P < 0.05), but had no effect on the risk for bone marrow toxicity. CONCLUSION: Amifostine shows only minor but significant activity in diminishing neurotoxicity without preventing paclitaxel + carboplatin-induced bone marrow toxicity.