Oral Capecitabine May Simplify Chemoradiotherapy for Rectal Cancer

HOUSTON-Concomitant boost radiotherapy plus capecitabine(Drug information on capecitabine) (Xeloda) produces pathologic response rates comparable to those of continuous infusion fluorouracil(Drug information on fluorouracil) (5- FU) for patients with locally advanced colorectal cancer (abstract 3593). Results from a phase II study also show that capecitabine is well tolerated and avoids the discomfort and potential complications associated with continuous infusion 5-FU, like infection and phlebitis. Edward H. Lin, MD, and colleagues at the University of Texas M. D. Anderson Cancer Center in Houston, enrolled 54 patients in the study. All patients had rectal carcinoma > T3 or N1(+) and normal renal, hepatic, and hematologic function. The Eastern Cooperative Oncology Group performance status ranged between 0 and 2. The median age was 58 years (range 36-76 years). As part of the rationale for the study, the investigators noted that using 5- FU as a radiation sensitizer for rectal cancer produces pathologic complete remissions of 8% to 30% and that capecitabine, an oral fluoropyrimidine, is converted to 5-FU in tumor tissue, enabling chronic dosing that mimics continuous infusion 5-FU. "Oral capecitabine simplifies chemoradiation," the investigators concluded, "avoiding the unwanted risks and inconvenience associated with IV 5- FU." Combined Response of 90% Oral capecitabine (825 mg/m² twice daily) was administered for 35 continuous days during radiation therapy with concomitant radiation boosts of 45 Gy x 25 to the pelvis and 52.5 Gy x 30 fractions to the primary tumor and perirectal nodes. Following surgery, eligible patients received four cycles of capecitabine (1,250 mg/m² twice daily) for 14 days every 3 weeks. Pathological complete response, the primary endpoint of the study, was reached in 9 of 52 patients (17%). "It is interesting to note that the response in patients with microscopic residual disease (15%) was almost as high as the pCR rate," the investigators noted. Sphincter preservation was achieved in 17 of 29 patients (59%) with tumors that were ≤ 6 cm from the anal verge. Only one patient had progressive disease. The combined clinical and pathological response rate was 90% (see Table 1). "Results from the current study appear similar to historical data from trials using the conventional radiotherapy technique," the investigators concluded. Mostly Mild to Moderate Adverse Events Most treatment-related adverse events during preoperative chemoradiotherapy were grade 1. Common grade 1/2 clinical toxicities included diarrhea, radiation dermatitis, fatigue, and hand-foot syndrome. Radiation dermatitis, hand-foot syndrome, and diarrhea also occurred as grade 3 clinical toxicities. The only grade 4 adverse event was diarrhea, which was reported in 2% of patients and led to early patient withdrawal. No treatment- related deaths occurred. Lymphopenia, uncomplicated by infection, was the most common hematologic toxicity, with grade 2 lymphopenia occurring in 27% of patients and grade 3 lymphopenia, in 52% of patients. Neutropenia and anemia were rare. There were no grade 4 toxicities. As permitted by protocol, 31% of patients received adjuvant FOLFOX (5-FU, leucovorin, oxaliplatin(Drug information on oxaliplatin) [Eloxatin]) therapy, at the clinician's discretion.