Randomized phase II trial of gemcitabine and either day 1 or day 8 carboplatin for advanced non-small-cell lung cancer: Is thrombocytopenia predictable?

Aim: Two 21-day gemcitabine–carboplatin schedules were evaluated in patients with advanced non-small cell lung cancer in order to assess the effect of timing of the carboplatin dose on toxicity and efficacy. Methods: Patients were randomized to gemcitabine (1000 mg/m2 on days 1 and 8 of a 21-day cycle) and carboplatin (AUC 5, on day 1) (Carbo d1 arm) or the same gemcitabine schedule with carboplatin given on day 8 (Carbo d8 arm). Twenty patients with Stage IIIB or IV non-small-cell lung cancer were enrolled in each arm. Results: The achieved dose intensities of both gemcitabine and carboplatin were significantly higher in the Carbo d1 arm. The total rates of grade 3 or 4 hematological and non-hematological toxicities (any toxicity, any cycle) were 80% and 65%, respectively, with no significant differences between the two arms. Nine patients in the Carbo d1 arm, but only one patient in the Carbo d8 arm, required a platelet transfusion. There were 10 partial responses (four Carbo d1 arm, six Carbo d8 arm), giving an overall response rate of 25% (95% CI 13–41%). Conclusion: Administration of carboplatin on day 8 of this regimen confers no clear advantage compared with day 1 carboplatin, with similar toxicity but lower dose intensity. A formula for the prediction of thrombocytopenia is proposed. [ABSTRACT FROM AUTHOR]