Phase I study of gefitinib, oxaliplatin, 5-fluorouracil, and leucovorin (IFOX) in patients with advanced solid malignancies.

Abstract

PURPOSE:

Aphase 1 study of gefitinib in combination with oxaliplatin, 5-fluorouracil and leucovorin (IFOX)was conducted to evaluate the safety and feasibility of this regimen.

PATIENTS AND METHODS:

Patients with advanced solid malignancies were treated with escalating doses of gefitinib (250 mg or 500 mg once daily) in combination with FOLFOX (oxaliplatin, 5-fluorouracil, and leucovorin). The initial dose of oxaliplatin was 70 mg/m2 with sequential dose escalation to 85 mg/m2.

RESULTS:

Sixteen patients received a total of 138 14-day courses of daily gefitinib in combination with FOLFOX. Escalation of gefitinib from 250 mg/d to 500 mg/d with FOLFOX was well-tolerated. In addition, no severe toxicities precluded subsequent dose escalation of oxaliplatin from 70 mg/m2 to 85 mg/m2 at which no dose-limiting toxicity was seen. No further dose escalation was performed as this represented the oxaliplatin dose administered in the standard FOLFOX-4 regimen. The most predominant toxicity was diarrhea, which was well controlled with oral antidiarrheal agents. Four partial remissions occurred in patients with metastatic colorectal cancer.

CONCLUSIONS:

Gefitinib as a 500 mg daily continuous dose was well tolerated in combination with full doses of FOLFOX-4.

• Authors: Cheryl D Cho, George A Fisher, Joanne Halsey, Branimir I Sikic
• Journal: Investigational new drugs (Invest New Drugs) Vol. 24 Issue 2 Pg. 117-23 (Mar 2006) ISSN: 0167-6997 [Print] United States
• PMID: 16683204 (Publication Type: Clinical Trial, Clinical Trial, Phase I, Journal Article, Research Support, N.I.H., Extramural, Research Support, Non-U.S. Gov't)

Chemical References

• Organoplatinum Compounds
• Quinazolines
• Oxaliplatin
• Leucovorin
• Gefitinib
• Fluorouracil

Topics

• Adult
• Antineoplastic Combined Chemotherapy Protocols (administration & dosage, adverse effects, therapeutic use)
• Carcinoma, Non-Small-Cell Lung (drug therapy)
• Colorectal Neoplasms (drug therapy)
• Dose-Response Relationship, Drug
• Female
• Fluorouracil (administration & dosage)
• Gefitinib
• Humans
• Leucovorin (administration & dosage)
• Lung Neoplasms (drug therapy)
• Male
• Middle Aged
• Organoplatinum Compounds (administration & dosage)
• Oxaliplatin
• Quinazolines (administration & dosage, adverse effects)