Phase I study of @entity901 , full-dose @entity136 , and concurrent @entity1161 in XXXX .

@entity901 @entity1 @entity788 @entity137 @entity548 @entity1161 @entity136
PURPOSE: To determine a biweekly dose of @entity901 for combination with full-dose @entity136 and concurrent @entity1161 ( @entity1161 ) in @entity788 . @entity1 AND METHODS: @entity1 with previously untreated @entity788 received @entity136 days 1, 8, and 15, and @entity901 days 1 and 15, repeated at 28-day intervals. @entity1161 (27 Gy in 1.8-Gy fractions) was administered during cycle 1. Dose escalation was guided using the time-to-event continuous reassessment method. Dose levels 1 to 4 included @entity136 1 g/m2 intravenously (IV) during 30 minutes and @entity901 40, 55, 70, or 85 mg/m2 IV during 90 minutes, respectively; for dose levels 5 and 6, @entity901 dose remained 85 mg/m2 but infusion time for @entity136 1 g/m2 was increased to 65 or 100 minutes, respectively. The trial objective was to determine the dose level associated with dose-limiting @entity137 (DLT) through cycle 2 in < or = 20% of @entity1 . RESULTS: Forty-four @entity1 were enrolled (median age, 64 years; 27 @entity1 , 17 @entity1 ) with resectable (n = 12), unresectable (n = 29), and metastatic (n = 3) @entity788 . Ten DLTs occurred in nine @entity1 , including grade 4 platelets (n = 4), decline in performance status (n = 2), @entity548 (n = 2), and @entity137 (n = 2). The estimated probability of DLT for dose level 3 was .21 (90% posterior probability interval [PI], .12 to .33); for dose level 4, the estimated probability was .24 (90% PI, .14 to .36). CONCLUSION: The addition of @entity901 85 mg/m2 days 1 and 15 to full-dose @entity136 and @entity1161 was well tolerated. On the basis of these results, a multi-institutional neoadjuvant phase II study in resectable @entity788 is planned.
