To determine the toxicity, tolerability, and feasibility of delivering combina tion chemotherapy with subsequent radiation therapy to women with high-risk end ometrial cancer and to evaluate the long-term bowel toxicity of this regimen. T he trial was approved by the Dana Farber/Partners Cancer Care (DF-PCC) Institut ional Review Board (IRB). Patients with stage 3 or stage 4 endometrial cancer or patients with high-risk histology and any stage disease were prospectively ent ered. Complete surgical staging and a normal gated blood pool scan were required prior to entry. Patients were treated with three cycles of paclitaxel (160 mg/m 2), doxorubicin (45 mg/m2) and carboplatin (AUC 5) (TAC) all on day 1 of a 21-d ay schedule as an outpatient with G-CSF support. At the conclusion of chemother apy, patients received radiation therapy (4500 cGy to the whole pelvis) commenci ng within 35 days of the last cycle of chemotherapy. Paraaortic radiation and/or vaginal brachytherapy were allowed at the discretion of the treating radiation oncologist. Twenty patients were entered onto the trial from November 2000 throu gh February 2003. Eighteen patients successfully completed the trial, and two patients came off trial during chemotherapy (both later completed planned radiation therapy). Patients were initially stage 1 (n = 3), stage 3 (n = 14), and stage 4 (n = 3). Papillary serous was the dominant h istology with 13 patients. Chemotherapy was given on average within 32 days of s urgery (range 11-63 days) and radiation was initiated on average within 14 week s of surgery (range 10-18 weeks). Chemotherapy was well tolerated, with 57 tota l cycles delivered of a planned 60 cycles. Two patients required dose modificati on in two cycles (two patients in cycle 3 secondary to hematologic toxicity). No grade 3 or grade 4 neurotoxicity was reported. There were six episodes of grade 3 short-term toxicity with radiation therapy reported in a single patient. Lat e radiotherapy toxicity included bowel obstruction requiring laparotomy in two p atients and grade 3 constipation in one patient. Late radiation toxicity data ar e still being collected as follow-up continues. The TAC chemotherapy regimen is well tolerated and three cycles were delivered successfully with G-CSF support without evidence of the neurotoxicity or cardiac toxicity reported with the cis platin containing TAP regimen. Standard radiation was deliverable following TAC therapy without excessive toxicity. Further study of this regimen with subsequen t radiation therapy is warranted in patients at risk for systemic and regional r ecurrence of their malignancy.
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