The purpose of the phase I trial is to evaluate potential antitumor effects of the combination of phenylbutyrate and tretinoin as well as safety in prostate cancer patients and those with acute promyelocytic leukemia, neuroblastoma, non-small cell lung cancer, and squamous cell carcinoma of the head and neck. The trial will evaluate the in vivo activity of phenylbutyrate as an inhibitor of histone deacetylase and also evaluate the potential pharmacokinetic interactions between these two agents. The investigators participating in this study from Memorial Sloan-Kettering Cancer Center in New York will accrue a total of 15 patients who will receive tretinoin as a single agent orally twice a day for at least 7 days, then in combination with phenylbutyrate for 21 days. Phenylbutyrate is administered via IV over 60-90 minutes twice a day, shortly after each tretinoin dose, beginning on day 8 and continuing for 21 days. The first course of treatment is followed by 3 weeks of rest.
Additional courses follow depending on results achieved.
Tretinoin was originally approved by the FDA as a topical agent in 1971, and tretinoin capsules were approved in November, 1995. As an antineoplastic agent, tretinoin, like other retinoids, induces cancer cells to mature, thereby eliminating abnormal proliferation. Prostate cancer patients eligible for this study must have failed conventional therapy have no other curative therapy available. Three weeks must have passed since prior cytotoxic chemotherapy or prior radiation for patients to be eligible to begin this study. AHCC is an immune-reinforcing compound extracted from cultured mushrooms.