A Phase I Trial of Oblimersen Sodium in Combination With Cisplatin and 5-Fluorouracil in Patients With Advanced Esophageal, Gastroesophageal Junction, and Gastric Carcinoma

Purpose: To determine the maximum tolerated dose of oblimersen, an antisense oligonucleolide directed to the Bcl-2 mRNA, in combination with cisplatin and 5-flourouracil in patients with advanced gastric and esophageal carcinoma. Methods: patients were treated with escalating doses of oblimersen administered by continuous intravenous infusion (CIVI) days 1 to 7, CIVI 5-fluorouracil (5-FU) days 4 to 7, and cisplatin on day 4 every 3 weeks. Results: Fifteen patients received a total of 49 Courses of oblimersen at doses of 3, 5, or 7 mg/kg/d given as a 7 day CIVI in combination with 4 or 5 day CIVI of 5-FU (1000 or 750 mg/m(2)/d) plus intravenous cisplatin (100 or 75 mg/m(2) over 2 hours). The recommended phase II dose of oblimersen was 5 mg/kg/d in combination with 5-FU (750 mg/m(2)/d for 4 days) and cisplatin (75 mg/m(2)). The most common grade 3 to 4 adverse events that occurred in at least 10% of patients at all (lose levels included neutropenia (33%), hypokalemia (27%), infection (20%), and mucositis, fatigue, dizziness, thrombosis, and dehydration (in 13%) for each category). Conclusion: The combination of oblimersen with 5-FU and cisplatin chemotherapy is feasible in patients with advanced upper gastrointestinal cancer, with antitumor activity observed in gastric carcinoma.