Clinical pharmacology of carboplatin administered in combination with paclitaxel.

摘要: The clinical pharmacology of carboplatin (C) administered with paclitaxel (Taxol; Bristol-Myers Squibb Company, Princeton, NJ) (P) was investigated in two phase I studies undertaken 83 previously untreated patients either non-small cell lung cancer or ovarian cancer. Carboplatin over 30 minutes and 3 hours. Both agents were given every 4 weeks. Non-small randomized to administration sequences, followed by (C-->P) the reverse (P-->C). Each patient received alternate sequence during second subsequent courses. Ovarian uniformly before carboplatin. Platinum concentrations plasma ultrafiltrate measured via flameless atomic absorption spectrometry, 122 concentration-time curves obtained. For patients, mean area under curve (AUC) per 300 mg/m2 3.52 mg/mL x min (range, 1.94 5.83) for C-->P 3.62 1.91 5.01) P-->C. No sequence-dependent effect observed (P > .5). AUC 3.83 2.72 6.10), showing no difference when compared data derived from = .13). In addition, not influenced increasing doses 100 250 mg/m2. Neutropenia principal toxicity, anemia frequent. However, there a striking lack thrombocytopenia. Modeling relationship between decrease platelets revealed 50% at (AUC50) 6.3 min. This contrasts historical documenting AUC50 4.0 Our findings suggest that is considerable interaction both drugs cellular level, least an additive on main hematologic toxicity (ie, neutropenia). There also protective exerted carboplatin-related thrombocytopenia). clear this combination suggests it possible reduce dose interval Studies are progress test hypothesis investigate underlying pharmacologic interactions.