A phase I trial of oblimersen sodium in combination with cisplatin and 5-fluorouracil in patients with advanced esophageal, gastroesophageal junction, and gastric carcinoma

Am J Clin Oncol. 2010 Feb;33(1):61-5. doi: 10.1097/COC.0b013e3181a31ad0.

Abstract

Purpose: To determine the maximum tolerated dose of oblimersen, an antisense oligonucleotide 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/m2/d) plus intravenous cisplatin (100 or 75 mg/m2 over 2 hours). The recommended phase II dose of oblimersen was 5 mg/kg/d in combination with 5-FU (750 mg/m2/d for 4 days) and cisplatin (75 mg/m). The most common grade 3 to 4 adverse events that occurred in at least 10% of patients at all dose 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.

Publication types

  • Clinical Trial, Phase I
  • Research Support, N.I.H., Extramural

MeSH terms

  • Adult
  • Aged
  • Antineoplastic Combined Chemotherapy Protocols / therapeutic use*
  • Cisplatin / administration & dosage
  • Drug Therapy, Combination
  • Esophageal Neoplasms / drug therapy*
  • Esophageal Neoplasms / pathology
  • Esophagogastric Junction / drug effects*
  • Esophagogastric Junction / pathology
  • Female
  • Fluorouracil / administration & dosage
  • Humans
  • Male
  • Maximum Tolerated Dose
  • Middle Aged
  • Neoplasm Staging
  • Oligonucleotides, Antisense / therapeutic use*
  • Pilot Projects
  • Prognosis
  • Stomach Neoplasms / drug therapy*
  • Stomach Neoplasms / pathology
  • Survival Rate
  • Thionucleotides / therapeutic use*
  • Treatment Outcome

Substances

  • Oligonucleotides, Antisense
  • Thionucleotides
  • oblimersen
  • Cisplatin
  • Fluorouracil