CIRCADIAN-TIMED COMBINATION DOXORUBICIN-CISPLATIN CHEMOTHERAPY FOR ADVANCED ENDOMETRIAL CARCINOMA - A PHASE-II STUDY OF THE GYNECOLOGIC-ONCOLOGY-GROUP

Patients with advanced or recurrent endometrial cancer of any cell type having measurable disease have been entered into this study to determine the effectiveness and toxicity of circadian-timed doxorubicin-cisplatin chemotherapy. This Phase II study involved no randomization with treatment initiated with doxorubicin 60 mg/m2 over 30 minutes at 6:00 a.m., followed by cisplatin 60 mg/m2 over 30 minutes at 6:00 p.m. every 28 days. Treatment was continued for eight cycles or to a maximum tolerable doxorubicin dose of 480 mg/m2 for patients without progression. Thereafter, responders continued on cisplatin alone. A review of 30 evaluable patients showed 6 (20%) complete responses, 12 (40%) partial responses, and 7 (23%) with stable disease. The number of treatment courses ranged from 2 to 14 with a median of 6.5. the median white blood cell nadir for the 27 patients experiencing leukopenia was 1,600/mm3 (range: 300-3,600/mm3). For the 16 patients experiencing thrombocytopenia the median nadir was 48,500/mm3 (range: 8,000-138,000/mm3. There were no treatment-related deaths. Circadian-timed delivery of doxorubicin-cisplatin chemotherapy was reasonably well tolerated and demonstrated notable response rates in patients with advanced or recurrent endometrial carcinoma.