Capecitabine in Postoperative Radiochemotherapy for Gastric Adenocarcinoma

Abstract

Background: More than 50% of new gastric cancer patients are diagnosed with unresectable disease. In 50-80% of patients who underwent radical resection, locoregional recurrence is observed. It has been proved that postoperative radiochemotherapy with 5-fluorouracil and leucovorin significantly improves the treatment outcome. The treatment with oral fluoropyrimidines, such as capecitabine, appears to be more comfortable for patients, because there is no need for any invasive procedures. Methods: In the period from October 2006 to December 2009, 95 patients (64 males, 31 females; aged 26-78 years, mean age 58.9 years) were treated for adenocarcinoma of non-cardial gastric cancer with postoperative chemoradiation with capecitabine. All patients had locally and/or regionally advanced disease, stages Ib-IIIc. Distal subtotal resection of the stomach was performed in 46.3%, total resection in 50.5% and multivisceral resection in 3.2% of patients. Radical (R0) resection was performed in 95.8% of patients and 4.2% of patients underwent non-radical (R1) surgery. In 44.2% patients, the tumor was staged as pT3 or pT4, and 77.9% patients had N+ disease. Chemotherapy included peroral capecitabine in the dose of 1250 mg/m 2 bid on days 1-14 followed by a one week break. During irradiation patients took capecitabine in the dose of 825 mg/m 2 bid. After radiotherapy was completed the patients received three more cycles of capecitabine in the dose of 1250 mg/m 2 bid on days 1-14 with a one week break between each cycle. 3-D conformal radiotherapy at a daily dose of 1.8 Gy and total irradiation dose of 45 Gy was delivered on linear accelerator with 15MV photon beams for 5 days per week. The main endpoints of this study were loco-regional control, disease-free survival, disease-specific survival and overall survival. The rates of acute side-effects were also estimated. Results: Seventy-six percent of patients completed the treatment according to the protocol. In 4% of the patients the total irradiation dose was lower than intended and 24% of patients did not receive all cycles of chemotherapy. No death occurred due to the therapy. Acute toxicity, such as nausea and vomiting, stomatitis, diarrhea, hand-foot syndrome and infections of grade 3 or 4 occurred in 5.3%, 1.1%, 2.1%, 7.4% and 19% of patients, respectively. Despite intensive nutritional support during the treatment the weight loss was observed in 58.4% of patients. The median follow-up time for all 95 patients was 4 years (range: 0.4-6.3 years), whereas in survivors it was 4.8 years (range: 3.4-6.3 years). On the close-out date, 63% patients were still alive, all of them without any signs of the disease. Thirty percent of patients died from gastric carcinoma, 5% died from other causes and in 2% the cause of death could not be determined. After adjuvant radiochemotherapy, recurrence was observed in 31.6% of patients: local and/or regional recurrence in 4.2% of patients and systemic disease alone in 27.4% of patients. The 5 years LRC, DFS, DSS and OS were 93.1%, 67%, 68.6%, and 62.2%, respectively. Conclusion: Postoperative radiochemotherapy with capecitabine is feasible, with low toxicity and the results of such treatment are good.