Combined modality therapy of locally advanced adenocarcinoma of the rectum: Update of a phase I trial of preoperative radiation (RT) with concurrent capecitabine (Cap) and irinotecan (Ir)

13547 Background: We previously reported the combination of preoperative radiation (RT) with concurrent Irinotecan and 5-FU in locally advanced rectal cancer, was well tolerated and had an excellent pathologic complete response rate (CR) of 25%, but with catheter related infections and thromboses as major toxicities (Proc Am Soc Clin Onc 22: 2003). With the potential benefits of capecitabine (Cap) and no need for an implanted catheter, a phase I study was initiated to determine the toxicity and maximum tolerated dose (MTD) of Cap with concurrent Ir and RT. Methods: Eligible patients (pts) had primary or recurrent Stage II or III rectal adenocarcinoma, without a history of prior RT or chemotherapy. The treatment regimen was as follows: external beam RT at 1.8Gy daily M-F, to a total dose of 50.4 or 54 Gy; Ir 50 mg/m2 IV, d 1, 8, 15, 22; dose escalating Cap starting at 825 mg/m2 PO divided in 2 doses, Q 12h. Surgical resection occurred at 6–10 weeks. Dose limiting toxicity is defined as Gr4 heme or non-heme Gr3. Results: A total of 16 pts have enrolled on the study, 10 male and 6 female;the median age was 57 (range 44–77). All are evaluable for toxicity. The Table reviews the maximum toxicities. Grade three diarrhea is the only dose-limiting toxicity to date. There has also been 3 pts with Gr 3 hematologic toxicity. There has been no Gr 4 toxicity. Patients are currently accruing on the 4th dose level of capecitabine. A total of 13 pts have completed the preoperative phase and three are currently on treatment. Eleven pts have had surgical resection. One pt refused surgery due to a biopsy proven CR to chemoradiation. One pt refused surgery and died of disease. Of the 11 pts undergoing surgical resection, there have been 3 pathologic CR. Conclusions: The preoperative combination of capecitabine, irinotecan and radiation in locally advanced rectal cancer pts is feasible and well tolerated. The study continues to accrue, and the MTD has not been achieved. [Table: see text] [Table: see text]