A PHASE I STUDY OF IRINOTECAN (CPT-11) WITH PHARMACOKINETIC MODULATION BY CYCLOSPORINE A AND PHENOBARBITAL

Fecha de inicio: 1 de junio de 1996

DISEASE CHARACTERISTICS: Malignant solid tumor or lymphoma refractory to standard therapy or for which no therapy of proven benefit exists No leukemia Measurable or evaluable disease PATIENT CHARACTERISTICS: Age: 18 and over Performance status: Karnofsky 70-100% Life expectancy: At least 3 months WBC at least 3,500/mm3 Absolute neutrophil count at least 1,500/mm3 Platelet count at least 100,000/mm3 Hemoglobin at least 9 g/dL Bilirubin no greater than 1.5 mg/dL AST/ALT less than twice normal (unless due to disease) PT and PTT normal Creatinine no greater than 1.5 mg/dL Creatinine clearance at least 60 mL/min No history of congestive heart failure requiring medical therapy No clinically significant or life threatening cardiac arrhythmia No history of significant pulmonary disease or lymphangitic lung disease No hypersensitivity to cyclosporine or cremophore No history of manifest or latent porphyria or hypersensitivity to barbiturates (for parts of study using phenobarbital) No history of inflammatory bowel disease requiring therapy No chronic diarrhea syndrome or paralytic ileus No medical or psychiatric condition that precludes informed consent Not pregnant Effective contraception required of fertile women PRIOR CONCURRENT THERAPY: At least 4 weeks since prior biologic therapy At least 2 weeks since prior colony stimulating factors At least 4 weeks since prior chemotherapy (at least 6 weeks since nitrosoureas or mitomycin) No prior bleomycin or irinotecan At least 4 weeks since prior radiotherapy to greater than 25% of bone marrow Minimum time interval between prior therapy and eligibility shortened by 2 weeks when phenobarbital is administered Concurrent use of medications that affect the central nervous or cardiovascular systems (e.g., anticonvulsants, calcium channel blockers, oral contraceptives) must be approved by the Principal Investigator