A PHASE I CLINICAL AND PHARMACOLOGIC EVALUATION OF PHENYLBUTYRATE IN PATIENTS WITH REFRACTORY SOLID TUMORS: STUDY OF CONTINUOUS EXPOSURE ORAL PHENYLBUTYRATE ON A THREE TIMES DAILY SCHEDULE

Fecha de inicio: 1 de febrero de 1997

DISEASE CHARACTERISTICS: Histologically or cytologically confirmed solid tumor or lymphoma that is progressive or refractory to conventional therapy or for which no effective therapy is known Priority given to hormone-refractory prostate cancer and melanoma No untreated CNS metastases Head CT not required in the absence of clinical signs or symptoms but recommended for metastatic melanoma PATIENT CHARACTERISTICS: Age: 18 and over Performance status: ECOG 0-2 Life expectancy: At least 3 months WBC greater than 2,000/mm3 OR absolute neutrophil count greater than 1,500/mm3 Platelet count greater than 100,000/mm3 Hemoglobin greater than 9 g/dL Bilirubin less than 1.5 mg/dL AST/ALT less than 1.5 times normal Creatinine less than 2.0 mg/dL Obstructive uropathy allowed if relieved by nephrostomy or other appropriate device Left ventricular ejection fraction greater than 40% by MUGA or normal by echocardiogram No history of congestive heart failure No uncontrolled hypertension (diastolic greater than 110 mm Hg) Forced expiratory volume (1 second) greater than 1.5 L/min No active infection, including HIV or viral hepatitis No active seizure disorder No clinical evidence of increased intracranial pressure No baseline dementia (mini-mental exam less than 23) No autoimmune disease, including systemic lupus erythematosus, scleroderma, or other connective tissue illness No nonmalignant medical or psychiatric problem of sufficient severity to limit full compliance with study or to pose undue risk Not pregnant or nursing Adequate contraception required of fertile patients for 2 weeks prior to, during, and for 3 months after study Normal gastrointestinal function with ability to tolerate large intake of oral volume required for phenylbutyrate administration Patients with persistent nausea or moderate to severe anorexia may not be good candidates for study PRIOR CONCURRENT THERAPY: Fully recovered from all prior therapy Prior suramin allowed if serum suramin level less than 50 micrograms/mL at entry At least 28 days since chemotherapy No prior phenylacetate, phenylbutyrate, or antineoplaston therapy The following may be continued during study: Luteinizing hormone-releasing hormone agonist with evidence of tumor progression (e.g., rising prostate-specific antigen, new lesions on bone scan) despite therapy Adrenal steroid replacement (if needed) Dexamethasone or other steroids At least 4-6 weeks since flutamide with evidence of PSA progression required (if possible) At least 28 days since radiotherapy At least 28 days since major surgery