A phase II study of cetuximab, capecitabine and radiotherapy in neoadjuvant treatment of patients with locally advanced resectable rectal cancer.

BACKGROUND: Neoadjuvant chemoradiotherapy (CRT) reduces local tumor recurrence in locally advanced rectal cancer (LARC). This phase II study assessed neoadjuvant cetuximab with capecitabine-based CRT in LARC. METHODS: Patients with stage II/III LARC received capecitabine 1250 mg/m(2) twice daily for 2 weeks followed by intravenous cetuximab 400 mg/m(2) at week 3, then weekly intravenous 250 mg/m(2) cetuximab plus CRT including capecitabine 825 mg/m(2) twice daily (including weekends during radiotherapy) with radiotherapy of 45 Gy (25 x 1.8 Gy), 5 days a week for 5 weeks. Total mesorectal excision was scheduled 4-6 weeks following completion of CRT. The primary endpoint was pathological complete response (pCR). RESULTS: Thirty-seven patients were eligible for safety and efficacy. TMN staging at baseline was: T4N2, 11%; T3N2, 40%; T2N2, 3%; T3N1, 35%; T2N1, 3% and T3N0 8%. The most common adverse events included, grade 1/2 acneiform skin rash (86%), and grade 3 radiodermatitis, (16%), diarrhea (11%) and hypersensitivity (5%). pCR was achieved in 3 patients (8%). Overall-, T- and N-downstaging rates were 73%, 57% and 81% respectively. Total sphincter preservation rate was 76%, and 53% in 17 patients whose tumors were located within 5 cm from the anal verge. Non-fatal perioperative complications occurred in 13 patients (35%) with delayed wound healing occurring in 6 patients (16%). One death was recorded due to sepsis following colonic necrosis. CONCLUSION: Neoadjuvant cetuximab with capecitabine-based CRT is tolerable in patients with resectable LARC. Whilst the pCR rate was similar to recent reports, a high pathological downstaging rate was achieved.

Anal cancer chemoirradiation with curative intent - a single institution experience.

UNLABELLED: Results of radiochemotherapy in 50 patients with squamous cell carcinoma of the anal canal, treated with radical radiochemotherapy between January 2003 and September 2007, at the Institute of Oncology Ljubljana are presented. The treatment schedule consisted of 3-D conformal external beam radiotherapy (45 Gy in 25 fractions), with two cycles of concurrent chemotherapy (5-fluorouracil (5-FU) / Mitomycin C), followed by brachytherapy or external beam boost (15-30 Gy) to the primary tumor. Locoregional control (LRC), disease-free survival (DFS), disease-specific survival (DSS), overall survival (OS) and colostomy-free survival (CFS) rates and the rate of acute and chronic side-effects were estimated. The impact of individual tumor- and therapy-related factors on treatment outcome was assessed.

Treatment was completed according to the protocol in 72% of patients. The median follow-up time of 40 survivors was 22 months (range 1.7-53.2 months). At 2 years, LRC, DFS, DSS, OS and CFS rates were 68%, 67%, 87%, 76% and 85%, respectively. In the multivariate analysis, nodal stage was identified as an independent prognostic factor for LRC, DSS and CFS and application of Mitomycin C for OS. The most frequent acute side-effect of treatment was radiodermatitis (grade 3 in 66% of patients, grade 4 in 2%). Late anal stenosis, chronic ulceration and grade 2-3 incontinence developed in 3 (6 %), 2 (4 %) and 5 (10 %) of colostomy-free survivors, respectively.

Radiotherapy with concurrent 5-FU / Mitomycin C chemotherapy is feasible, with acceptable toxicity. The presented treatment outcome is comparable to other published results.

Results of adjuvant radiochemotherapy for gastric adenocarcinoma in Slovenia.

AIMS: To analyze the results of postoperative concomitant radiochemotherapy with 5-florouracil (5-FU) and leucovorin (LV) in patients with gastric carcinoma treated in a single institution. METHODS: During 2001-2004, 123 patients with the mean age of 60 years, were treated for adenocarcinoma of the stomach, stage Ib-IV, with postoperative concomitant radiochemotherapy. Radical (R0) and non-radical (R1) resection of the tumor was performed in 107 and 16 patients, respectively. Adjuvant treatment consisted of five cycles of five-day chemotherapy with 5-FU (425 mg/m(2)) and LV (20 mg/m(2)) and concomitant radiotherapy with the total dose of 45 Gy. RESULTS: The treatment was completed according to the protocol in 101 patients. Stomatitis, dysphagia, and nausea and vomiting of grade three occurred in 32, 27, and 23 patients, respectively. The median follow-up time of 87 survivors was 30.4 months (range 17.4-58.3 months). At two years, locoregional control (LRC), disease-free survival (DFS), disease-specific survival (DSS) and overall survival (OS) rates were 86%, 65%, 74%, and 73%, respectively. In the multivariate analysis, the initial Hb level was identified as independent prognostic factor for all survival four endpoints, the involvement of whole stomach with cancer for LRC, the total dose of 5-FU per five-day cycle for DFS, and pT stage for DSS. CONCLUSIONS: In operable gastric carcinoma, postoperative concomitant radiochemotherapy with 5-FU and LV is feasible and its toxicity acceptable. Its potential to improve the treatment outcome compared to the surgery alone is yet to be tested in well designed prospective randomized studies.