Phase I study of treatment with oral 13-cis-retinoic acid, subcutaneous interferon alfa-2a, cisplatin, and 24-hour infusion 5-fluorouracil/leucovorin

• Published in: Cancer chemotherapy and pharmacology 1997, Vol.39 (3), p.227-232
• Main Authors: FLEMING, G. F, O'BRIEN, S. M, HOFFMAN, P. C, VOKES, E. E, VOGELZANG, N. J, SCHILSKY, R. L, WAGGONER, S. E, RATAIN, M. J
• Format: Article
• Language: English
• Subjects: Administration, Oral; Adult; Aged; Antidotes - administration & dosage; Antineoplastic agents; Antineoplastic Combined Chemotherapy Protocols - administration & dosage; Antineoplastic Combined Chemotherapy Protocols - adverse effects; Antineoplastic Combined Chemotherapy Protocols - therapeutic use; Biological and medical sciences; Chemotherapy; Cisplatin - administration & dosage; Cisplatin - adverse effects; Drug Synergism; Female; Fluorouracil - administration & dosage; Fluorouracil - adverse effects; Humans; Injections, Subcutaneous; Interferon alpha-2; Interferon-alpha - administration & dosage; Interferon-alpha - adverse effects; Isotretinoin - administration & dosage; Isotretinoin - adverse effects; Leucovorin - administration & dosage; Leucovorin - adverse effects; Leukopenia - chemically induced; Male; Medical sciences; Middle Aged; Neoplasms - drug therapy; Pharmacology. Drug treatments; Recombinant Proteins; Remission Induction
• ISSN: 0344-5704; 1432-0843

A combination of oral 13-cis-retinoic acid (cis-RA) and subcutaneous interferon alfa-2a (IFN) has been reported to yield high response rates in patients with squamous cell carcinomas (SCCAs) of the cervix and skin. Cisplatin and 5-fluorouracil with leucovorin (5-FU/LV) are chemotherapeutic agents commonly used for SCCAs. To determine the maximum tolerated doses (MTDs) of cisplatin and 5-FU/LV when combined with IFN and cis-RA, and to define a recommended phase II regimen for testing in cervical cancer and other appropriate tumor types. Phase I cohort design. Cisplatin was administered every 3 weeks. 5-FU and LV were administered together as a weekly 24-h infusion. Cis-RA was given orally twice daily. IFN was initially given subcutaneously at a dose of 3 million units (MU) daily. A total of 31 patients were treated. The IFN dose was reduced to 3 MU three times weekly because of patient intolerance. Cytopenias prevented the administration of weekly 5-FU/LV. Single-agent cisplatin with three times weekly IFN and twice daily cis-RA was tolerable. Four partial responses were observed, in patients with adrenal cancer, bladder cancer, gastric cancer, and adenocarcinoma of unknown primary. The recommended phase II regimen is cisplatin 100 mg/m2 every 3 weeks, IFN 3 MU three times weekly, and cis-RA 1 mg/kg daily. This appears to be more toxic than single-agent cisplatin, but the preliminary activity observed warrants further testing.