Prolonged Oral Etoposide in Recurrent or Advanced Leiomyosarcoma of the Uterus: A Gynecologic Oncology Group Study

OBJECTIVE: In a previous study by the Gynecologic Oncology Group only modest activity was seen with bolus etoposide in leiomyosarcoma of the uterus (an 11% response rate). To exploit the schedule dependency of etoposide, which favors longer exposure, a Phase II trial of prolonged oral etoposide was conducted in this tumor. METHODS: Eligibility included leiomyosarcoma of the uterus, measurable disease, one prior chemotherapy regimen which did not include etoposide, WBC >/= 3000/microliter, platelet count >/=100, 000/microliter, serum creatinine </=2 mg%, and adequate hepatic function. The starting etoposide dose was 50 mg/m2/day (30-40 mg/m2/day for prior radiotherapy) as a single dose for 21 days, every 28 days. Based on toxicity, a dose escalation to a maximum etoposide dose of 60 mg/m2/day was prescribed. RESULTS: Thirty-six patients were entered on this study; 34 were evaluable for toxicity and 29 were evaluable for response. A median of 2 courses were given (range 1-14). Grade 4 neutropenia occurred in 20.6% and grade 4 thrombocytopenia occurred in 5.8%. One patient developed acute myeloid leukemia 10 months after completing 7 cycles of therapy. Among the patients evaluable for response, 27 had received prior chemotherapy and 6 had received prior radiation therapy. Two partial responses (6.9%) were observed. CONCLUSION: This regimen has minimal activity as second-line chemotherapy in leiomyosarcoma of the uterus. No benefit to the chronic oral schedule is evident.