Phase I study of postoperative radiotherapy combined with capecitabine for gastric cancer.

AIM

To determine the maximum tolerated dose (MTD) and dose-limiting toxicity (DLT) of capecitabine combined with postoperative radiotherapy for gastric cancer.

METHODS

We enrolled patients with any T stage and node-positive gastroesophageal or gastric adenocarcinoma after complete resection with negative margins (R0) or microscopic (R1) or macroscopic (R2) resection. Intensity modulated radiotherapy (IMRT) using a five-to-seven-field, coplanar, sliding window technique was delivered to the tumor bed (T4b), anastomosis site, duodenal stump and regional lymph nodes (LNs) to a total dose of 45 Gy (1.8 Gy/fraction, 5 d/wk). Patients with R1 or R2 resection received 10.8 Gy as a boost. Capecitabine was administered twice daily on every radiotherapy treatment day in a dose-escalation schedule (mg/m²) of 625 (level I, n = 6), 700 (level II, n = 6), 800 (level III, n = 6), 900 (level IV, n = 0) and 1000 (level V, n = 0). DLT was defined as grade 4 leukopenia or neutropenia, grade 3-4 thrombocytopenia or anemia and grade 3-4 non-hematological toxicity.

RESULTS

Between October 2007 and August 2009, 18 patients (12 men, 6 women; median age, 54 years) were enrolled in the study. The median number of positive LNs was 6, and total number of resected LNs was 19. Twelve patients underwent R0 resection (66.7%). Fifteen patients received adjuvant chemotherapy under the leucovorin, fluorouracil and oxaliplatin (FOLFOX4) regimen. Six patients each were enrolled at dose levels I, II and III. Grade 1-3 leukopenia (16 patients, 88.9%), anorexia (15, 83.3%) and nausea (15, 83.3%) were the most common toxicities. Grade 3 anorexia/nausea and grade 4 vomiting occurred in one level-I patient. Grade 3 anorexia and nausea occurred in one level-II patient. One level-III patient developed grade 4 neutropenia, while another developed grade 3 radiation esophagitis. No abnormal liver or renal function examinations were observed. Three patients did not finish chemoradiotherapy because of DLTs and two without DLTs received sequential boosts (total dose, 55.8 Gy).

CONCLUSION

The MTD of capecitabine was 800 mg/m² twice daily concurrent with IMRT for gastric cancer after surgery. The DLTs were anorexia/nausea, vomiting, neutropenia and radiation esophagitis.