Mitomycin-C/5-fluorouracil/leucovorin and hyperfractionated radiation therapy for rectal carcinoma: a phase II study...

Preoperative chemotherapy followed by surgery and adjuvant chemotherapy is a standard treatment for most patients with rectal cancer. We aimed to determine efficacy and tolerability of preoperative mitomycin, fluorouracil (5-FU), and leucovorin (LV) concurrent with hyperfractionated radiation therapy (RT) followed by surgery and adjuvant chemotherapy.

Patients with clinical stage II/III disease were treated with mitomycin 10 mg/m(2) on day 1, continuous venous infusion 5-FU 600 mg/m(2) per day for 96 hours, and oral LV 25 mg every 6 hours on days 1-5. All patients received concurrent RT in fractions of 150 cGy twice daily beginning on day 1. Unfixed tumors received 3000 cGy, whereas fixed tumors received a dose of 4500 cGy. Patients then underwent resection and postoperative adjuvant chemotherapy with oral LV and continuous venous infusion 5-FU 600 mg/m(2) per day on days 1-5 on a 28-day cycle for 6 cycles. Primary endpoints were to determine the rate of pathologic response and downstaging, long-term locoregional control, progression-free survival, and overall survival.

Between the years 1993 and 2000, 83 patients were enrolled. Eighteen patients (31%) were downstaged. Six patients (7%) had pathologic complete response. Median follow-up was 62 months with a 5-year overall survival of 71%. Local control rate was 96%. Treatment was well tolerated with stomatitis, diarrhea, and radiation proctitis being the most common toxicities.

This regimen is effective in the treatment of rectal carcinoma. The favorable toxicity profile of mitomycin and hyperfractionated RT allows these strategies to be utilized with the newer chemotherapies for this disease.