A Phase I Pharmacokinetic and Pharmacodynamic Study of 17-Allylamino-17-Demethoxygeldanamycin (17-AAG) (NSC 330507) Via Intravenous Administration in Patients With Advanced Malignancies

Date de début de l'étude : 1 août 1998

DISEASE CHARACTERISTICS: Histologically or cytologically proven malignancies refractory to conventional treatment or for which no standard therapy exists Primary brain tumor or brain metastases allowed if stable symptoms within 2 weeks prior to study and able to give informed consent PATIENT CHARACTERISTICS: Age: 18 to 75 Performance status: WHO 0-2 Life expectancy: At least 3 months Hematopoietic: WBC at least 3,500/mm^3 Platelet count at least 100,000/mm^3 Hemoglobin at least 10.0 g/dL Absolute neutrophil count at least 1,500/mm^3 Hepatic: Bilirubin less than 1.0 mg/dL AST and ALT no greater than 2.5 times upper limit of normal if due to liver metastases No chronic liver disease Renal: Creatinine less than 1.47 mg/dL OR Creatinine clearance greater than 60 mL/min Cardiovascular: No myocardial infarction within the past 6 months No angina requiring treatment within the past 6 months No uncompensated coronary artery disease by electrocardiogram or physical examination No prior transient ischemic attacks, stroke, or peripheral vascular disease LVEF at least 45% Other: Not pregnant or nursing Negative pregnancy test Fertile patients must use effective contraception during and for 4 weeks after study No allergy to egg products No nonmalignant systemic disease that would increase risk No active uncontrolled infection No diabetes mellitus with evidence of severe peripheral vascular disease or diabetic ulcers PRIOR CONCURRENT THERAPY: 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 No other concurrent chemotherapy Endocrine therapy: At least 4 weeks since other prior endocrine therapy and recovered Concurrent corticosteroids for symptom control allowed if no change in dose requirement within 2 weeks prior to study Radiotherapy: At least 4 weeks since prior radiotherapy (except for palliative reasons) and recovered Concurrent radiotherapy allowed for control of bone pain or as indicated Surgery: Not specified Other: No other concurrent investigational treatment No concurrent treatment with drugs interfering with hepatic CYP3A4 metabolism (e.g., grapefruit juice or warfarin)