Carboplatin plus paclitaxel combination chemotherapy: impact of sequence of drug administration on treatment-induced neutropenia

Abstract

Objective: While the importance of the sequence of administration of cisplatin and paclitaxel on the degree of observed neutropenia has been documented, there is limited information available in the oncology literature to determine whether there exists sequence-dependent toxicity for the combination of carboplatin plus paclitaxel.

Methods: Patients with advanced gynecologic malignancies were randomized to receive either carboplatin (AUC 6), followed by paclitaxel (175 mg/m(2) over 3 h) (C-P), or the same doses of the agents delivered in the opposite sequence (P-C). The primary endpoint was the degree of neutropenia experienced during the initial treatment course.

Results: A total of 40 patients (median age: 63) entered this trial, of whom 27 had complete pretreatment and nadir counts available for course 1 and 24 for both course 1 and course 2. By random chance, patients initially receiving P-C began therapy with a higher baseline ANC than those treated with C-P. During course 1, the P-C population was noted to have a greater reduction, from baseline, in ANC (P = 0.02), but no difference in absolute nadir counts (ignoring the baseline value) (P = 0.64). There was no difference between P-C, followed by C-P, versus C-P, followed by P-C in the severity of neutropenia experienced during course 2 (P = 0.38).

Conclusions: The sequence of carboplatin/paclitaxel administration does not exert a significant influence on the level of observed neutropenia. This finding leads to the suggestion that the sequence of drug delivery can be modified, as necessary, to satisfy unique requirements of individual patients and to establish the optimal drug delivery strategy of an innovative investigational treatment regimen.