Cisplatin and vinorelbine in advanced and/or metastatic adenocarcinoma of the endometrium: A new highly active chemotherapeutic regimen

Purpose: To date the systemic treatment of recurrent and/or metastatic aden ocarcinoma of the endometrium (EAC), using both chemotherapy and hormonothe rapy (HT), is far from satisfactory. The significant activity of vinorelbin e (VNR), a relatively new semisynthetic vinca alkaloid, demonstrated in adv anced breast cancer, bronchial adenocarcinoma, and in head and neck cancer, prompted us to carry out a phase II trial employing the combination of cis platin and VNR in a pluri-institutional series of patients with recurrent a nd/or metastatic EAC. Patients and methods: Thirty-five patients affected by recurrent and/or met astatic EAC have been treated with CDDP 80 mg/m(2) on day 1 plus VNR 25 mg/ m(2) i.v. bolus on days 1 + 8. This cycle was repeated every 21 days. After three cycles patients were restaged for objective response. Analysis of re sponse rate and duration, overall survival, and toxicity pattern were the m ain aims of the study. Results: Twenty out of thirty-five patients achieved a major objective resp onse for an overall response rate of 57% (95% confidence limits (CL): 39%-7 4%). Four patients had a complete response (11%; 95% CL: 3%-27%) with a med ian progression-free survival (PFS) of eight hundred fourteen days, while s ixteen patients had a partial response (46%; 95% CL: 29%-63%) with a median PFS of one hundred eighty-four days. Six patients had stable disease and n ine progressed. All patients who achieved a clinical complete response had only a single site of disease at entry, but no association was noted betwee n number of involved sites and likehood of achieving PR. Median overall sur vival was 240 days, while that of patients with complete and partial respon se was 855 and 300 days, respectively. Treatment was quite well tolerated w ith few cases of grade 3-4 myelosuppression. Alopecia was virtually absent and neurotoxicity was mild. One patient complained of an acute pain syndrom e at the tumor site. Conclusions: The CDDP + VNR regimen is quite active against recurrent and/o r metastatic endometrial adenocarcinoma, at least in terms of objective res ponse rate which is among the highest ever reported in medical literature. However, duration of objective response and median overall survival are in the disappointing range reported for other regimens. In our opinion the CDD P plus VNR regimen is good enough to be compared to the anthracycline-based regimens and may represent the basis for future development of newer activ e polychemotherapeutic schedules.