The addition of paclitaxel in chemoradiotherapy of anal squamous cell carcinoma: a prospective randomized phase 3 trial
AIM: to compare late outcomes and safety of the addition of paclitaxel to chemoradiotherapy for squamous cell anal carcinoma. PATIENTS AND METHODS: a prospective phase 3 randomized trial included patients with histologically verified nonmetastatic anal squamous cell carcinoma. Patients received radiotherapy 52-54 Gy (for T1-T2 tumors) and 56-58 Gy (for T3-T4 tumors) in 2 Gy daily fractions during chemotherapy with mitomycin C (10 mg/m<sup>2</sup> i.v. day 1), capecitabine (625 mg/m<sup>2</sup> 2 times a day orally on days of radiation therapy), paclitaxel (45 mg/m<sup>2</sup> i.v. on days 3,10,17, 24,31) during 2013-2019. In the control group patients received a similar course of RTand chemotherapy with mitomycin C (12 mg/m<sup>2</sup> i.v. day 1), capecitabine (825 mg/m<sup>2</sup> 2 times a day orally on radiotherapy days).The primary endpoint was 3-year disease-free survival (DFS). Secondary endpoints included complication rate (NCI-CTCAE 4.0), complete clinical response rate at 12 weeks and 26 weeks after completion of CRT, and 3-year overall survival (OS). RESULTS: the study and control groups included 72 patients each. The median follow-up was 39.5 months. A complete clinical response at the 26-week follow-up was recorded in 64 (88.9%) patients in the study group and in 54 (75.0%) patients in the control group (p = 0.049). There were no differences in the incidence of complications of grades 3-4 in the two groups (41/72 [56.9%] in the study group versus 19/72 [26.4%] in the control group (p < 0.0001)). Three-year progression-free survival in the study group was 87.1%, in the control group - 64.4% (p = 0.001). Three-year overall survival in the study group was 95.5%, in the control group - 80.0% (p < 0.001). CONCLUSION: CRT with paclitaxel for squamous cell anal carcinoma has acceptable toxicity and may improve late treatment outcomes.