A phase III trial of ifosfamide with or without cisplatin in carcinosarcoma of the uterus: A gynecologic oncology group study

Objective. The aims of this study were to substantiate the previously repor ted activity of ifosfamide in patients with advanced, persistent, or recurr ent carcinosarcoma (mixed mesodermal sarcoma) of the uterus, and to determi ne whether the addition of cisplatin results in an improved response or sur vival. Secondarily, we sought to determine the toxicity of ifosfamide-cispl atin in this patient population. Methods. Patients were randomized to receive ifosfamide (1.5 g/m(2)/day) ti mes 5 days every 3 weeks for eight courses with mesna uroprotection, with o r without cisplatin (20 mg/m(2)/day) times 5 days. No patient had received previous chemotherapy. Results. Of 224 patients entered on this study, 30 were ineligible for a va riety of reasons, leaving 194 evaluable patients. Early in the study, the d ose of the combination regimen was reduced by 20% (1 day) because of toxici ty. The investigational arms were balanced for age, grade, and Gynecologic Oncology Group performance status. Percentages of adverse effects reported in 191 patients receiving chemotherapy included (ifosfamide/cisplatin-ifosf amide) grade 3 or 4 granulocytopenia (36/60), grade 3 or 4 anemia (8/17), g rade 3 or 4 central nervous system toxicity (19/14), and grade 3 or 4 perip heral neuropathy (1/12). Treatment may have contributed to the deaths of 6 patients treated with full doses of ifosfamide and cisplatin for 5 days. Th e proportion of patients responding to ifosfamide alone versus ifosfamide-c isplatin therapy was (0.36 versus 0.54) overall, 0.47 versus 0.61 for pelvi c, 0.21 versus 0.54 for lung, and 0.33 versus 0.40 for "other" metastatic s ites of measurable disease. The relative odds ratio of response adjusted fo r measurable sites of disease was 1.82 (P = 0.03, one-tailed test; 95% lowe r confidence limit, 1.06). Progression-free survival (PFS) and survival dat a suggest that the combination offers a slight prolongation of PFS (relativ e risk, 0.73; 95% upper confidence limit, 0.94; P = 0.02, one-tailed test), but no significant survival benefit (relative risk, 0.80, 95% upper confid ence limit, 1.03; P = 0.071, one-tailed test). Conclusion. The addition of cisplatin to ifosfamide appears to offer a smal l improvement in progression-free survival over ifosfamide alone in the man agement of advanced carcinosarcoma of the uterus; the added toxicity may no t justify the use of this combination. (C) 2000 Academic Press.