Pilot study of escalating doses of carboplatin and cyclophosphamide in patients with advanced cancer.
In all, 18 patients with histologically proven advanced cancer received 400 mg/m2 carboplatin (CBDCA) plus 800 mg/m2 cyclophosphamide (level 1), and 14 others received 550 mg/m2 CBDCA plus 1100 mg/m2 cyclophosphamide (level 2). A maximum of six cycles was given if a response occurred. The dose-limiting toxicity was myelosuppression, with neutropenia being more marked than thrombocytopenia. At level 2, patients experiencing a febrile-neutropenic event showed a mean 24-h urinary creatinine clearance value of 1.1 ml/s (95% confidence limits 0.8-1.4 ml/s), whereas in those who remained afebrile it was 1.7 ml/s (95% confidence limits, 1.3-2.0 ml/s). This difference was significant (P less than 0.01). Other toxicities were only mild. Creatinine clearance is a predictor of febrile episodes after treatment with high doses of CBDCA and cyclophosphamide. We are now conducting a study using human granulocyte colony-stimulating factor to reduce the incidence of neutropenia with escalating doses of these drugs in an attempt to prevent febrile events.
Basser
R L
RL
Department of Medical Oncology, Royal Melbourne Hospital, Australia.
Green
M D
MD
Sheridan
W P
WP
Fox
R M
RM
D000368:Aged; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use*; D001853:Bone Marrow / Q000187:drug effects; D001854:Bone Marrow Cells; D016190:Carboplatin / Q000008:administration & dosage; D003404:Creatinine / Q000652:urine; D003520:Cyclophosphamide / Q000008:administration & dosage; D004305:Dose-Response Relationship, Drug; D004341:Drug Evaluation; D005260:Female; D006801:Humans; D007668:Kidney / Q000503:physiopathology; D007958:Leukocyte Count / Q000187:drug effects; D008297:Male; D008875:Middle Aged; D009325:Nausea / Q000139:chemically induced; D009369:Neoplasms / Q000188:drug therapy* / Q000503:physiopathology; D009504:Neutrophils / Q000187:drug effects; D010865:Pilot Projects; D014839:Vomiting / Q000139:chemically induced
D003520:Cyclophosphamide; D003404:Creatinine; D016190:Carboplatin