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Intensified neoadjuvant chemoradiotherapy (CRT) with capecitabine and irinotecan in patients with locally advanced rectal cancer (LARC): A phase I/II study.

3693 Background: This study aimed to determine the maximum tolerated dose (MTD) of capecitabine when given with irinotecan and concurrent radiation as intensified neoadjuvant therapy for LARC.


METHODS
We treated 10 women and 13 men (14 uT3, 9 uT4, 22 uN+) with a median age of 64 years (range, 48-75). Mean tumor length was 7 cm (range, 3-13). Treatment consisted of conventionally fractionated radiation (1.8 Gy/fx to a total 50.4 Gy) with a local boost of 5.4 Gy depending on the intestinal volume in the radiation field. Concurrent irinotecan 40 mg/m2 was given weekly x6. Capecitabine was given daily throughout treatment (d1-43) at dose levels of 1000, 1300, 1500, and 1650 mg/m2. Patients proceeded to surgery after 4-6 weeks, and postoperative maintenance chemotherapy was given according to the recommendations of the German Cancer Association.


RESULTS
DLT occurred at a capecitabine dose level of 1650 mg/m2, with two grade 4 diarrhea and one hand-foot syndrome. There was one sudden cardiac death on day 5 (not related to irinotecan), and another death due to pneumonia six weeks after completion of CRT. The predominant toxicity of CRT was diarrhea (7 grade 3, 2 grade 4). Hematologic toxicity was moderate. Thus far, 12 patients have proceeded to surgery, with one laparotomy being discontinued because of peritoneal spread. R0 resection was possible in 10/11 patients (91%), and 9/11 (82%) had downstaging of their disease by at least one T category. 2/11 patients (18%) had a pCR, 2/11 had only microscopic residues, and the remainder (7/11, 64%) had a PR.


CONCLUSIONS
The phase II dose of neoadjuvant capecitabine is 1500 mg/m2 daily in combination with weekly doses of irinotecan 40 mg/m2 and concurrent radiation. No significant financial relationships to disclose.