A multicentre phase II study of carboplatin plus pegylated liposomal doxorubicin as first-line chemotherapy for patients with advanced or recurrent endometrial carcinoma: the END-1 study of the MITO (Multicentre Italian Trials in Ovarian Cancer and Gynecologic Malignancies) group

Abstract

Anthracyclines and platinum derivates are active drugs for advanced endometrial carcinoma (AEC), but new schedules with higher efficacy and better tolerability are needed. A phase II study was conducted to describe activity and tolerability of carboplatin (C) þ pegylated liposomal doxorubicin (PLD) in patients with AEC. Patients with chemonaive AEC, PS p2, aged o75 years, with at least one measurable lesion were eligible. Treatment was C (area under curve 5) þ PLD (40 mg m À2 ) on day 1 every 4 weeks, up to six cycles. Forty-two patients were needed in a single-stage design, with at least 13 objective responses to define the treatment active. Forty-two patients were enrolled. Median age was 64 years (31 -74). A total of 64% of patients were recurrent while 36% were advanced. Three complete (7%) and 22 partial responses (52%) were observed, for an overall response rate of 59.5% (95% exact CI: 43.3 -74.3). One death potentially related to treatment was recorded (death at home for unknown reasons after 6th cycle). Other relevant toxicities (% of patients) were grade 3/4 neutropaenia 33%/14%, febrile neutropaenia 5%, grade 3/4 thrombocytopaenia 17%/5%, grade 3/4 anaemia 31%/2%. Skin toxicity was mild: grade 1 14%, grade 2 10%, grade 3 5%. Hair loss: complete 5%, partial 12%. The combination of carboplatin and PLD shows good activity and favourable toxicity as first-line chemotherapy of patients with AEC, deserving further studies in this setting.

Phase 2 Trial of Nonpegylated Doxorubicin (Myocet) as Second-Line Treatment in Advanced or Recurrent Endometrial Cancer

“…Pegylated liposomal doxorubicin had been tested in the treatment of advanced and recurrent endometrial cancer in monotherapy, with response rate ranging from 9.5% to 21%, 5,16 and in combination with carboplatin, with response rate ranging from 44% to 58.5%. 17,18 The drug was well tolerated with an exactable toxicity profile mainly characterized by moderate hand-foot syndrome (grade 3/4).…”

What is the Role of Chemotherapy in Endometrial Cancer?

“…The combination of liposomal doxorubicin + carboplatin has shown equal activity as paclitaxel + carboplatin in ovarian cancer [29]. In recurrent or advanced endometrial cancer, two fairly large phase 2 trials found response rates of 44% and 52% with a favorable toxicity profile [30,31].…”

Endometrial Cancer

“…268 28 endometrial stroma sarcomas). This might be an attractive alternative regimen for women at risk for neurotoxicity.…”