Phase-II-study of preoperative chemoradiation with capecitabine in rectal cancer

Abstract

3559 Purpose: A recent phase-I-study demonstrated that capecitabine (Xeloda) can safely be combined with pelvic radiotherapy in patients with rectal cancer (Dunst et al, JCO 2002). We conducted a phase-II-study for to confirm safety and efficacy of chemoradiation with Xeoda as preoperative therapy in locally advanced rectal cancers. Patients & methods: 98 patients (median age 65 years, range 34 - 81years) with advanced rectal cancers (cT3–4 or extensive nodal involvement) were recruited from 7 centers in the period from 6/2001 through 11/2003. Therapy consisted of preoperative chemoradiation (50.4Gy in 28 fractions + 5.4Gy boost, Xeloda 825mg/m2 b.i.d. from first to last day of radiotherapy) followed by surgery 6 weeks later. At the time of this analysis (Dec-2003), 58 patients have completed therapy and are evaluable for baseline characteristics and toxicity (N=58) as well as clinical (N=49) and pathological response (N=50). All patients had advanced disease (cT4: 50%, cT3: 48%, cT2: 2%, cN+: 55%). Results: Chemoradiation with Xeloda was well tolerated with no or mild to moderate toxicity in the vast majority of patients. No treatment-related grade 4-toxicity was observed (except a period of hyperglycemia in a patient with diabetes). Main grade 3 toxicities included leuko- and lymphopenia (10%), diarrhea (4%), hypopotassemia (4%) as well as local skin erythema in the radiation fields, bilirubin increase, hypocalcemia and hyponatremia (each in 1 pat.). Clinical response (evaluated 6 weeks after chemoradiation) was observed in 30/49 patients with 28 cPR (57%) and 2 cCR (4%). All patients underwent surgery with 46 R0-resections (92%) and 4 R1-resections (8%). Downstaging of the primary tumor (cT < pT) occurred in 37 pats (74%). A pCR was observed in 2 patients (4%) with 1 additonal case with only pTis in the resection specimen (2%). Conclusions: This phase-II study confirmed that Xeloda is an adequate substitute for continuous infusional 5-FU in preoperative chemoradiation regimens with regard to the favorable toxicity profile and response. Author Disclosure Employment or Leadership Consultant or Advisory Stock Ownership Honoraria Research Funding Expert Testimony Other Remuneration Roche Roche