(P007) Safety and Tolerability of Adjuvant Radiation "Sandwiched" Between Carboplatin and Paclitaxel in Women With Uterine Carcinosarcoma

April 15, 2014

We report the initial analysis on the tolerability and toxicity of radiotherapy “sandwiched” with carboplatin and paclitaxel in surgically staged carcinosarcoma.

Merieme Klobocista, MD, Jennifer Heim, MD, Mark H. Einstein, MD, Dennis Y. Kuo, MD, Keyur Mehta, MD, Gary L. Goldberg, MD; Montefiore Medical Center, Albert Einstein College of Medicine

Objective: Carcinosarcoma (CS) is a rare uterine tumor with a poor prognosis and a high recurrence rate, even in early-stage disease. Adjuvant treatment includes radiotherapy (RT), systemic chemotherapy, or both; however, the optimal sequence and agents remain undefined. We report the initial analysis on the tolerability and toxicity of radiotherapy “sandwiched” with carboplatin and paclitaxel in surgically staged CS.

Methods: After institutional review board (IRB) approval, women with surgically staged CS with no evidence of gross residual disease were administered carboplatin (AUC 6) and paclitaxel (175 mg/m2) every 3 weeks for 3 cycles, followed by intensity-modulated radiation therapy (IMRT) and brachytherapy, followed by 3 additional cycles of carboplatin (AUC 5) and paclitaxel (175 mg/m2) every 3 weeks. Toxicities were graded by Common Toxicity Criteria and Adverse Events version 4.0 (CTCAE v4.0). Of note, IMRT was utilized in the planning and treatment delivery. This allowed placing constraints of radiation dose to the bone marrow, bladder, rectum, and bowel with the goal of reducing toxicity in the setting of multimodality therapy.

Results: There are seven patients enrolled thus far, and six patients have completed the protocol. One patient declined further chemotherapy after the first cycle. All patients completed IMRT and brachytherapy. Median age at diagnosis was 70 years (range: 46–78 y); mean BMI was 28.7 kg/m2 (range: 19–38 kg/m2); and five out of seven patients had stage 1A disease. Of the 37 cycles of chemotherapy administered, there were 10 (27%) grade 3/4 neutropenia, 2 (5.4%) anemia, and 4 (10.8%) thrombocytopenia, most of which were self-limiting. There were only one (2.7%) grade 3/4 nonhematologic toxicity and one radiation-related toxicity. Two patients required growth factor support following Cycle 2 and each subsequent cycle. An additional two patients required growth factor support following Cycle 4 and each subsequent cycle.

Conclusions: Carboplatin and paclitaxel “sandwiched” with IMRT and brachytherapy are well tolerated, with the majority of toxicities being grade 1 or 2 and self-limiting. Accrual of patients on this regimen will continue in order to delineate the efficacy of these findings as well as the long-term toxicity of this regimen.