A new biweekly schedule of @entity3003 and @entity136 : Phase I feasibility trial in @entity1 with advanced XXXX ( @entity1149 ).

@entity1 @entity137 @entity390 @entity417 @entity882 @entity3003 @entity1149 @entity177 @entity1503 @entity1398 @entity136 @entity2359
UNASSIGNED: 7245 Background: In preclinical trials, @entity3003 (C) followed by @entity136 (G) after 24 hours demonstrates a supra-additive/synergistic effect in term of cell killing. To evaluate the clinical implications of this sequence, we performed a pilot study to explore the maximum tolerated dose (MTD) and dose-limiting @entity137 (DLT) of C and G administered respectively on days 1,2 every 15. METHODS: Eligible criteria were a stage IIIb/IV @entity1149 , age <=  80 years, ECOG Performance Status 1 or 2, adequate marrow, @entity177 . The starting-dose of C-day 1- (AUC = 2.5) was escalated, stepwise AUC =0.5, (three @entity1 entered per dose level) in combination with a fixed dose of G -day 2- (1500 mg/m(2)) until achievement of DLT. A cycle (30 days) consisted of 4 administrations (days 1,2,15,16). DLT was considered any >=  grade 2 myelotoxicity resulting into a treatment delay of >2 consecutive weeks or any grade >2 organ-specific @entity137 . RESULTS: Between March and August 2003, 18 chemo na  ve pts were enrolled and received 52 cycles (median cycles 3, range 1-6) at 6 dose levels: male/female =15/3, median age =70 (range:65-80), ECOG performance status 1/2 =10/8, stage IIIB/IV disease =8/10. Drug-related @entity137 (NCI grading scale) included @entity1398 grade 2/3/4, 2%/6%/19%, @entity417 grade 1/2/3, 52%/11%/2%, @entity882 grade 1/2/3, 15%/6%/2%. All grade @entity1398 and @entity882 lasted <7 days. Other @entity1503 ( @entity390 , fatigue) have been rare and did not exceed grade 1. Severe alterations of electrolytic balance and a grade 3 @entity2359 resulted DLT at the sixth dose level (C: AUC = 5, G: 1500 mg/m(2)). Promising clinical activity has been observed, with four/two partial/minor responses on 13 evaluable @entity1 . CONCLUSIONS: The schedule's manageable @entity137 profile and activity have encouraged an ongoing phase II trial at doses of @entity3003 AUC = 4.5 and @entity136 1500 mg/m(2) including a Quality of Life evaluation (EORTC C-30). No significant financial relationships to disclose.
