Chemoradiation with raltitrexed and oxaliplatin in preoperative treatment of stage II-III resectable rectal cancer: Phase I and II studies

PURPOSE: Two separate studies were conducted, the first to evaluate the maximal tolerated dose and the second the efficacy of raltitrexed plus oxaliplatin in conjunction with preoperative chemoradiation in patients with resectable T3 rectal carcinoma. METHODS AND MATERIALS: A total of 48 patients received radiotherapy (50 Gy) administered to the posterior pelvis 5 d/wk for 5 weeks. Combination raltitrexed (3 mg/m(2)) and oxaliplatin (60 to 130 mg/m(2)) was administered on Days 1, 19, and 38. RESULTS: The recommended dose of oxaliplatin is 130 mg/m(2) (maximal tolerated dose not reached). No patients developed Grade 4 acute toxicity. Grade 3 acute toxicity occurred in 9 patients (18.7%). It was hematologic in 1 patient and GI in 1 patient; 7 patients had an asymptomatic increase of transaminase. Surgery was performed in 47 (98%) of 48 patients. Of the 47 patients, 42 underwent sphincter-saving surgery; in 19, the tumor at diagnosis was located <30 mm from the anorectal ring. Chemoradiation in combination with raltitrexed and oxaliplatin produced high rates of tumor response. The overall tumor downstaging rate was 73% for T and N stages. A complete pathologic tumor response (pT0) or microscopic tumor foci (pTmic) was observed in 28 patients. The tumor regression grade (TRG), using the Mandard scoring system, was TRG1 in 16 patients (43.2%), TRG2 in 12 (32.4%), TRG3 in 12 (32.4%), TRG4 in 6 (16.2%), and TRG5 in 1 patient (2.7%). CONCLUSION: Raltitrexed plus oxaliplatin combined with pelvic radiotherapy was effective and well tolerated in patients with resectable T3 rectal carcinoma.