title: Phase I study of acivicin and cisplatin in non-small-cell lung cancer. A National Cancer Institute of Canada study.
abstract: Seventeen previously untreated patients with metastatic non-small-cell lung cancer were entered in this phase I trial. Treatment consisted of a combination of acivicin and cisplatin at a starting dose of 12 and 15 mg/m2, respectively, given i.v. during 5 days and repeated every 28 days. A total of 46 cycles was given. Renal function abnormality was the dose-limiting toxicity of cisplatin with a maximum tolerated dose of 12 mg/m2. This toxicity occurred at a dose lower than expected, indicating a possible potentiation of platinum renal toxicity by acivicin. Myelosuppression was the dose-limiting toxicity of acivicin, with a maximum tolerated dose of 12 mg/m2. Other side effects included generalized weakness and gastrointestinal and neurological symptoms. In 15 patients evaluable for response seven progressed, six were stable for a median duration of 13 weeks, and two patients achieved a partial remission lasting 8 and 24 weeks, respectively. The overall response rate was 13%. The recommended phase II dose of both agents in this schedule was 12 mg/m2. The possible enhancement of cisplatin toxicity might have compromised the overall response rate of the combination and further studies using these drugs in this schedule are not recommended.
authors.affiliation: Ottawa Regional Cancer Center, Ontario Cancer Treatment, Ottawa University, Canada.
authors.forename: J A
authors.initials: JA
authors.lastname: Maroun
authors.forename: D J
authors.initials: DJ
authors.lastname: Stewart
authors.forename: S
authors.initials: S
authors.lastname: Verma
authors.forename: W K
authors.initials: WK
authors.lastname: Evans
authors.forename: E
authors.initials: E
authors.lastname: Eisenhauer
mesh_terms: D000328:Adult; D000368:Aged; D000380:Agranulocytosis / Q000139:chemically induced; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000009:adverse effects / Q000627:therapeutic use*; D002170:Canada; D002289:Carcinoma, Non-Small-Cell Lung / Q000188:drug therapy*; D002945:Cisplatin / Q000008:administration & dosage / Q000009:adverse effects; D004334:Drug Administration Schedule; D004341:Drug Evaluation; D005260:Female; D006077:Government Agencies; D006801:Humans; D007555:Isoxazoles / Q000008:administration & dosage / Q000009:adverse effects; D007668:Kidney / Q000187:drug effects; D008175:Lung Neoplasms / Q000188:drug therapy*; D008297:Male; D008875:Middle Aged; D012074:Remission Induction; D013921:Thrombocytopenia / Q000139:chemically induced
chemical_list: D007555:Isoxazoles; C006303:acivicin; D002945:Cisplatin