Final results of a phase I study of adjuvant chemoradiation for gastric adenocarcinoma with infusional 5-fluorouracil and bi-weekly cisplatin

Abstract

15671 Background: This phase I study assessed the maximum tolerated dose (MTD) of 2-weekly cisplatin, infusional 5-FU and concurrent conformal radiotherapy (RT) for resected gastric cancer. Methods: Thirty four patients with resected stage IB to IV(M0) gastric adenocarcinoma were prescribed 12 weeks of infusional 5FU 200 mg/m2/day with RT 45Gy in 25 fractions starting at day 16. Cisplatin dose escalation occurred after a minimum of 3 patients without dose limiting toxicity (DLT) per cohort. DLT was defined as ≥ grade 3 toxicity requiring treatment or hospitalization; hematologic or biochemical changes not requiring treatment were not considered DLT. MTD was the highest dose level where no more than 1 of 6 patients had DLT. If 1 patient had DLT another 3 were treated at the same dose level. If ≥2 had DLT in any cohort that level exceeded MTD and the previous dose level was expanded to 6 patients. Results: Median age was 56 years (range 31–77); M:F 53:47%. Median follow up was 2.5 years (0.3–5). There were no grade 5 events. Five patients experienced DLT (see table). Cohort 5 had 2 patients with DLT exceeding MTD; cohort 4 was defined as the MTD. Acute toxicity included skin, weight loss, fatigue, anorexia, nausea, dehydration, hand-foot syndrome, sepsis, hyponatremia and hematological events. Eleven patients did not complete prescribed 5FU (cohort 1[1], 2[3], 3[3], 4[1], 5[3]) among whom the mean duration of 5FU received was 7 weeks (0.5–11). Of these 11 patients, 4 did not complete cisplatin (cohort 2[1], 5[3]); 3 did not complete RT on study receiving 0, 0 and 36Gy. One patient had late grade 3 toxicity: weight-loss and G-tube dependence. Nine patients relapsed of whom 6 died; 3-year overall and relapse free survival were 86% and 71% with median survival not reached. Conclusion: MTD occurred in cohort 4 with no DLT in this cohort. A phase II study is accruing patients using 12 weeks of infusional 5FU 200 mg/m2/day and 4 cycles cisplatin 40 mg/m2 2-weekly with RT 45Gy in 25 fractions starting at day 16. Acute and dose limiting toxicity in each cohort Cohort Cisplatin mg/m2 Cycles of cisplatin N Number of patients with toxicity Type of non hematological grade 3 toxicity+ All grade 1/2 Non-hematological grade 3 Hematological grade 3/4 1 0 0 6 6 1* 1 Sepsis* Hyponatremia 2 20 4 10 9 1* 0 Fatigue* 3 30 4 7 7 1* 4 Vomiting with dehyration* Stomatitis 4 40 4 6 6 2 0 Hyponatraemia not requiring treatment 5 40 5 5 5 2* 3 Anorexia* Dehyradtion* + Note that several patients experienced multiple non-hematologic and/or dose limiting toxicities; * Dose limiting toxicity No significant financial relationships to disclose.