Phase I study of paclitaxel and carboplatin: implications for trials in head and neck cancer.
An ongoing phase I and pharmacokinetic trial of paclitaxel (Taxol; Bristol-Myers Squibb Company, Princeton, NJ) in combination with carboplatin is evaluating the maximum tolerated dose (MTD) of a 3-hour paclitaxel infusion combined with fixed doses of carboplatin in previously treated and untreated patients with a variety of advanced cancers. A patient's previous treatment status determines the fixed carboplatin dose: target area under the concentration-time curves of 4.0 and 4.5 mg.min/mL in previously treated and untreated patients, respectively. Studies 1 and 2 entered previously treated patients to establish the paclitaxel MTD without and with cytokine support: study 1 established 135 mg/m2 paclitaxel as the MTD without such support. In study 2, granulocyte colony-stimulating factor is administered, and the MTD has not yet been reached with paclitaxel doses of 135 mg/m2 to 230 mg/m2 assessed thus far and 250 mg/m2 now being evaluated. Objective responses have been seen in three of five patients with squamous cell carcinoma of the head and neck and in patients with non-small cell lung cancer and metastatic cancer of unknown primary site as well. Myelosuppression has been the dose-limiting toxicity, although significant nausea and vomiting and myalgia have been documented occasionally. Paclitaxel apparently has nonlinear pharmacokinetics with a beta half-life of 6.7 hours (SD +/- 1.3 hours). Future trials of paclitaxel/carboplatin will address the management of squamous cell carcinoma of the head and neck and non-small cell carcinoma of the lung.
D000230:Adenocarcinoma / Q000188:drug therapy / Q000556:secondary; D000328:Adult; D000368:Aged; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000009:adverse effects / Q000493:pharmacokinetics / Q000627:therapeutic use*; D016190:Carboplatin / Q000008:administration & dosage; D002283:Carcinoma, Bronchogenic / Q000188:drug therapy; D002294:Carcinoma, Squamous Cell / Q000188:drug therapy; D005260:Female; D016179:Granulocyte Colony-Stimulating Factor / Q000008:administration & dosage; D006207:Half-Life; D006258:Head and Neck Neoplasms / Q000188:drug therapy*; D006801:Humans; D008297:Male; D008875:Middle Aged; D017239:Paclitaxel / Q000008:administration & dosage* / Q000009:adverse effects / Q000493:pharmacokinetics
D016179:Granulocyte Colony-Stimulating Factor; D016190:Carboplatin; D017239:Paclitaxel