Postoperative chemoradiotherapy in gastric cancer--a phase I-II study of radiotherapy with dose escalation of weekly cisplatin and daily capecitabine chemotherapy.

BACKGROUND: Postoperative chemoradiotherapy with concurrent 5-fluorouracil improves gastric cancer outcome. We previously demonstrated that chemoradiotherapy with a more intensified--and therefore potentially more effective--schedule with daily cisplatin and oral capecitabine is feasible. Because such an intensive schedule requires an extensive logistic infrastructure which is not available in every hospital, we additionally investigated the tolerability of this combined regimen with weekly instead of daily cisplatin in a dose-escalation study. PATIENTS AND METHODS: After R0 or R1 resection, treatment initiated with capecitabine 1000 mg/m(2) b.i.d. for 2 weeks and 1-week rest. Subsequently, patients received capecitabine (575-650 mg/m(2) orally b.i.d., 5 days/week) and cisplatin (20-25 mg/m(2) i.v., once weekly) according to a predefined dose-escalation schedule concurrent with radiation. Radiotherapy was given to a fixed total dose of 45 Gy in 25 fractions.
RESULTS: Thirty-one patients were eligible and started treatment. During chemoradiotherapy, seven patients developed 10 items of grade III and one episode of grade IV (mainly hematological) toxicity (National Cancer Institute-Common Toxicity Criteria version 3.0). The maximum tolerable dose was determined to be for cisplatin 20 mg/m(2) i.v. weekly and for capecitabine 575 mg/m(2) b.i.d. orally.
CONCLUSIONS: This phase I-II study demonstrated that postoperative chemoradiotherapy with weekly cisplatin and daily capecitabine is feasible in gastric cancer at the defined dose level. This schedule is currently being tested as the experimental arm in a phase III multicenter study (CRITICS: chemoradiotherapy after induction chemotherapy in cancer of the stomach; Clinicaltrials.gov NCT 00407186).