Abstract
2092 Background: D, P & C are 3 active chemotherapeutic agents with different mechanisms of activity. We investigated a weekly D & P with twice daily C regimen in patients (pts) with advanced solid tumors in a phase I study. Methods: Three pts were treated at each dose level (DL) given no dose-limiting toxicity (DLT) was noted. D & P were each given intravenously over 30 min on D1 & D8, and C was given orally BID on D1-D14; the cycle was repeated every 21 days. DL of D, P & C (mg/m2) were: 1) 20, 20, 600; 2) 20, 20; 825; 3) 27, 20; 825; 4) 27, 27; 825; 5) 36, 27; 825; 6) 36, 36; 825. DLT was defined as any treatment-induced grade (G) 4 neutropenia > 1 week, febrile neutropenia, G4 thrombocytopenia, G3 or higher non-hematologic toxicity (diarrhea must be > 1 day; nausea appropriately medicated), and delay in treatment of ≥ 2 weeks. CT scans were performed every 2 cycles. PK studies of D were performed on D1/cycle 1 with C and on D1/cycle 2 without C. D plasma concentrations were measured by an LC-MS/MS assay. Results: Twelve pts are evaluabe for toxicity (7/5 M/F; median age 57; 3 NSCL; 2 pancreatic carcinoma; and 1 each SCLC, gastric, anal, unknown, H & ENT, colon, and esophageal carcinomas; 10 pre-treated). Ten pts are evaluable for response. No DLT was noted at DL1–4 and accrual continues at DL 5. Treatment-related toxicities were G1 or G2 in the first cycle. G2 diarrhea occurred in 4 pts on DL 1–2. G2 stomatitis occurred in 1 pt on DL 2. No G2 or greater hand and foot syndrome was noted. Two patients had a confirmed partial response (gastric 8 months+; pancreatic 6 months+). Seven pts had stable disease (SD) lasting 12 or more weeks, 2 pts unconfirmed SD, and 1 patient (NSCL) progressed. A median of 6 cycles/pt has been administered to date. The mean +/- standard deviation of D clearance was 32 +/- 13.2 L/hr/m2 and 33 +/- 19.2L/hr/m2 on cycle 1 & 2 respectively. Conclusions: DPC is a well-tolerated combination with clinical activity in this phase I study. PK analysis suggests that C does not alter the disposition of D. This combination should be investigated further in efficacy studies once a phase II recommended-dose is identified. Author Disclosure Employment or Leadership Consultant or Advisory Stock Ownership Honoraria Research Funding Expert Testimony Other Remuneration Sanofi Aventis Pharmaceuticals
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