A Phase I Study of the Cyclin-Dependent Kinase (CDK)/Protein Kinase C (PKC) Inhibitor UCN-01 (NSC 638850) in Combination With 5-Fluorouracil in Patients With Advanced Solid Tumors

Date de début de l'étude : 1 juillet 1999

DISEASE CHARACTERISTICS: Histologically confirmed solid tumor that is refractory to standard therapy or for which no standard therapy exists Measurable or evaluable disease No CNS metastasis or primary CNS malignancy PATIENT CHARACTERISTICS: Age: 18 and over Performance status: Karnofsky 60-100% Life expectancy: Not specified Hematopoietic: WBC greater than 3,500/mm^3 Absolute neutrophil count at least 1,500/mm^3 Platelet count at least 100,000/mm^3 Hepatic: Bilirubin no greater than 1.5 mg/dL SGOT and SGPT no greater than 2.5 times upper limit of normal Renal: Creatinine no greater than 1.5 mg/dL OR Creatinine clearance greater than 60 mL/min Cardiovascular: No history of coronary artery disease documented by prior myocardial infarction, angiography, or coronary-artery bypass grafting No cardiac arrhythmias or congestive heart failure within the past 6 months Stable atrial fibrillation on standard treatment allowed at discretion of investigator Pulmonary: DLCO at least 60% of predicted Other: Not pregnant or nursing Negative pregnancy test Fertile patients must use effective contraception during and for 2 months after study No active serious or uncontrolled infection HIV negative No diabetes No other medical condition that would preclude study PRIOR CONCURRENT THERAPY: See Disease Characteristics Biologic therapy: At least 4 weeks since prior immunotherapy and recovered Chemotherapy: At least 4 weeks since prior chemotherapy (6 weeks for nitrosoureas and mitomycin) and recovered Prior fluorouracil allowed Endocrine therapy: Not specified Radiotherapy: No prior mediastinal radiotherapy At least 4 weeks since prior radiotherapy and recovered Surgery: Not specified Other: No concurrent anticonvulsant medications