Concomitant radiotherapy and paclitaxel for high-risk endometrial cancer: First feasibility study

Objective. Postoperative radiotherapy (RT) is the most used adjuvant treatment in high risk endometrial cancer (HREC), and it appears to reduce the incidence of pelvic relapses but doesn't seem to improve survival. Paclitaxel (P) has shown in vitro and clinical activity against endometrial cancer, and it is also a potent radiosensitizer by blocking dividing cells in G2/M phase. This is the first study that verifies the feasibility of a treatment with concomitant weekly chemotherapy and RT to potentially reduce the incidence of local and distant relapses in order to improve survival in HREC. Patients and Methods. Thirteen patients with HREC have entered the feasibility study at San Raphael Hospital University of Milan. All patients underwent total abdominal hysterectomy, bilateral salpingo-oophorectomy, and surgical staging. Four patients presented stage IC disease, 2 women had IIB stage tumors, 5 patients revealed IIIA stage disease, and 2 had stage IIIC. The patients received P (60 mg./m2) via a continuous 1-h infusion once weekly during the 5 weeks of RT (mean radiation dose of 50.4 Gy). At the end of RT three additional consolidation courses of P (80 mg/m2) were subministered. Eleven patients received only pelvic irradiation; in 2 cases radiotherapy was performed on an extended field. Results. Eleven of the 13 enrolled patients have completed the radiochemotherapy regimen. A total of 100 courses of P were performed. All patients completed the RT. Adverse effects were evaluated. Hematological toxicity was mild: four cycles (4%) were delayed 1 week because of grade 1 neutropenia. No severe thrombocytopenia was identified. No hemotrasfusions were performed. One cycle was delayed for fever. Gastrointestinal adverse effects were observed in 2 patients, in which the cycles were delayed 1 week because of diarrhea. One cycle was delayed 1 week because of dermatitis. One patient developed a subocclusion 8 weeks after the end of the treatment, with medical resolution. No patients developed hypersensitivity reactions. Conclusions. Concomitant P and RT is safe and acceptable treatment in patients with HREC. Prospective clinical studies are necessary to evaluate the benefits of this regimen for the long-term survival rate.