(ChemotherapyAdvisor) – An adjuvant chemotherapy regimen of doxorubicin, ifosfamide, and cisplatin is associated with improved disease-free survival (DFS), but not overall survival (OS), among patients undergoing radiotherapy for uterine sarcomas — but the regimen is highly toxic, according to data from a randomized phase 3 multicenter clinical trial, reported in the Annals of Oncology.

The “adjuvant chemotherapy statistically increases the 3-year DFS in patients with uterine sarcomas,” reported lead author Patricia Pautier, MD, of the Department of Medical Oncology’s Gyencologic Unit at the Gustave-Roussy Institute in Villejuif Cedex, France, and coauthors.

The phase 3 multicenter SARCGYN study (NCT00162721) enrolled 81 patients younger than age 66 years at diagnosis with uterine sarcoma, randomized to receive either radiotherapy alone (RT; 45 Gy in 1.8-Gy fractions over 5 weeks; n=39 patients) or 4 cycles of adjuvant API polychemotherapy (doxorubicin+cisplatin+ ifosfamide) + G-CSF (Granulocyte colony-stimulating factor), every 3 weeks, followed by pelvic RT.

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Adjuvant polychemotherapy (API)-arm patients received 4 cycles of doxorubicin (50mg/m2 on day 1), ifosfamide (3g/m2 on days 1 & 2), cisplatin (75 mg/m2 on day 3).

“After a median follow-up of 4.3 years, 41/81 patients recurred, 15 in arm A [API] and 26 in Arm B [RT only],” the authors reported. “The 3-year DFS rate was 55% in API-arm patients and 41% in RT-only-arm patients (P=0.048). However, OS was not statistically-significantly different between the two arms (81% API vs 69% RT-only; P=0.4, n.s.),” the authors noted.

API toxicity was frequent and serious. API was associated with two (5%) patient deaths from septic shock following the fourth cycle. The two toxic deaths among API-arm patients likely played a role in the disappointing OS findings, the authors noted.

Grade 3 to 4 toxicities were common among API-arm patients, including anemia (58% of patients), neutropenia (58%), febrile neutropenia (24%), thrombocytopenia (76%), and Grade 3 renal toxicity (1%).

Along with previous randomized trials, the study “shows that addition of 4 cycles of API chemotherapy prior to adjuvant pelvic RT increases slightly the DFS,” the authors concluded. A less-toxic chemotherapeutic regimen “could be less effective,” they cautioned.

SARCGYN enrolled patients with uterine sarcomas, including 19 patients with carcinosarcomas, in addition to patients with leiomyosarcomas and high-grade stromal sarcomas, the authors reported. The study did not meet its enrollment accrual goals.