Radiochemotherapy with short daily infusion of low-dose oxaliplatin, leucovorin, and 5-FU in T3-T4 unresectable rectal cancer: a phase II IATTGI study.

PURPOSE: Oxaliplatin (OXA)/5-fluorouracil (5-FU) have confirmed their preclinical synergy in advanced colorectal cancer patients. Chemoradiotherapy with 5-FU + leucovorin (LV) is considered the standard treatment in unresectable rectal cancer patients. The objective was to evaluate OXA with 5-FU + LV and concurrent radiotherapy in unresectable rectal cancer patients. TREATMENT: OXA 25 mg/m(2)/day in 30-min infusions, followed by bolus LV 20 mg/m(2)/day and bolus 5-FU 375 mg/m(2)/day. All drugs were given on 4 days during Weeks 1 and 5 of a standard radiotherapy cycle (50.4 Gy). A single OXA dose (50 mg/m(2)) was also given on the third week of radiotherapy. A cycle of OXA with 5-FU + LV was administered 4 weeks after chemoradiotherapy, with surgery planned 4 weeks later. RESULTS: Between March 1998 and April 2000, 22 patients with T3-T4 unresectable rectal cancer were accrued. Patient characteristics included the following: 11 females, 11 males, median age 58 (range: 18-76). Performance status ECOG (PS) 0: 2 patients, PS 1: 7 patients, and PS 2: 13 patients. The following RTOG Grade 3-4 toxicities were reported: diarrhea, 6 patients; cutaneous, 3 patients; neutropenia-leukopenia, 2 patients; and thrombocytopenia, 1 patient; 1 treatment-related death resulted (febrile neutropenia-sepsis after chemoradiotherapy). Only 1 patient had neurosensory Grade 2 (OXA-specific Levi's scale) toxicity. Nine patients had PS worsening during treatment. Five patients had chemoradiotherapy delay (median: 6 days). Of 22 patients, 16 underwent surgery (without serious surgical complications); 12/16 had a complete resection (5/12 had sphincter preservation). Pathologic examination revealed 3/12 complete remissions, 2/12 minimal microscopic residual disease, 2/12 T2N0, 1/12 T3N0, and 4/12 positive nodes; 4/16 had unresectable disease. Median follow-up was 15 months (range: 3.0-43.4 months), median time to progression was 15.7 months (CI 95%, 0, 31.7), and median overall survival was 19.5 months (CI 95%, 18.0, 21). CONCLUSIONS: Outpatient treatment with low-dose, 30-min daily OXA infusion was feasible and very active, with acceptable toxicity.