Doxorubicin and cisplatin for advanced endometrial cancer

The combination of doxorubicin and cisplatin increases response rates and progression free survival and produces greater toxicity in patients with advanced endometrial cancer, according to a paper published in Journal of Clinical Oncology.Seventy-five percent of cases of endometrial cancer present as stage I disease and 13% as stage II, and these are curable with surgical resection. Doxorubicin and cisplatin are active agents for treatment of surgically resected stage III and IV disease. This Gynaecologic Oncology Group (GOG) randomised, phase III trial included patients with measurable stage III or stage IV disease, or recurrent endometrial carcinoma after surgery or radiotherapy. Patients were randomised to doxorubicin (60 mg/m2, n=150) or doxorubicin (60 mg/m2) plus cisplatin (50 mg/m2, n= 131), intravenously every 3 weeks. Results showed an overall response rate of 33%. Complete response rate was 19% in the doxorubicin and cisplatin arm and 8% in the doxorubicin alone arm and partial response was 23% and 17% respectively. The complete plus partial response rates were significantly different (p = 0.004).Progression free survival was 5.7 months compared to 3.8 months and the hazard ratio after adjusting for performance status was 0.736 (95% CI, 0.577 - 0.938, p= 0.014). Overall survival was similar in each arm (9 and 9.2 months respectively). Grade III and IV leucopoenia occurred in 62% and 40%, thrombocytopenia in 14% and 2%, anaemia in 22% and 4% and nausea and vomiting in 13% and 3% of patients respectively. All grades of renal toxicity occurred in 10% of patients in the combined arm and none in the single drug arm.The authors concluded that the study showed that the combination of doxorubicin and cisplatin increased response rates and progression free survival but with greater toxicity. The authors noted that this combination has now been used as a control arm in three recent GOG randomised trials. The investigators considered that the magnitude of improvements in response rate were sufficient to justify the toxicity with this combination. They concluded that the study confirmed a role for combination chemotherapy in management of endometrial carcinoma.Reference...