TAEJON, Korea—In a study from Korea of patients with locally advanced rectal cancer, preoperative capecitabine(Drug information on capecitabine) (Xeloda) with leucovorin given concurrently with radiotherapy resulted in primary tumor downstaging and nodal downstaging, reported Jun-Sang Kim, MD, of Chungnam National University, Taejon, and colleagues.
In a separate study, German scientists evaluating concurrent capecitabine/radiotherapy in rectal cancer found the approach feasible and well tolerated with promising preliminary efficacy results.
Both researchers noted that oral chemotherapy with capecitabine mimics the pharmacokinetics of continuous fluoro-uracil (5-FU) infusion as a radiation sensitizer. Continuous infusion 5-FU has been shown to cause tumor downstaging when given preoperatively in locally advanced rectal cancer patients and to improve resectability.
The Korean study enrolled 45 patients. The whole pelvis radiotherapy dose was 45 Gy given in 25 fractions over 5 weeks, followed by a boost dose of 5.4 Gy in three fractions to the primary tumor. Chemotherapy, administered concurrently, consisted of two 14-day cycles of capecitabine 825 mg/m2 twice daily and leucovorin 10 mg/m2 twice daily. Each cycle was followed by a 7-day rest period. Surgery was performed 6 weeks after the completion of chemoradiation.
Of 38 patients who underwent definitive surgery, primary tumor downstaging occurred in 63% and nodal downstaging in 90%, for an overall downstaging rate of 84%. The pathologic complete response rate was 31%.
Among 21 patients with distal tumors (located initially 5 cm or less from the anal verge), 18 underwent surgery. Of these, 13 (72%) received sphincter-preserving surgery (Int J Radiation Oncology Biol Phys 34:403-408, 2002).
Grade 3 toxicities included hand-foot syndrome (7%), fatigue (4%), diarrhea (4%), and radiation dermatitis (2%). There were no grade 3-4 hematologic toxicities.
