Sequences of Taxol and Cisplatin: A Phase I and Pharmacologic Study

摘要: Untreated and minimally pretreated solid tumor patients received alternating sequences of taxol cisplatin. Sequential dose escalation each agent using doses 110 or 135 mg/m2 cisplatin 50 75 resulted in four dosage permutations that induced grades 3 4 neutropenia 72% to 84% 50% 53% courses, respectively. Neutropenia was brief, hospitalization for fever required 13% 24% courses. However, further 170 200 grade 79% 82% At the highest taxol-cisplatin level (200 mg/m2), mean neutrophil count nadir 98/microL, 64% The sequence before taxol, which has less antitumor activity vitro, more profound than alternate sequence. Pharmacologic studies indicated this difference probably due 25% lower clearance rates when preceded taxol. Although neurotoxicity initially thought be a potentially serious effect combination, mild modest occurred only 27% patients. Adverse effects also included myalgias, alopecia, vomiting, diarrhea, bradycardia, asymptomatic ventricular tachycardia. Objective responses were noted melanoma, as well non-small-cell lung, ovarian, breast, head neck, colon, pancreatic carcinomas. Based on these results, at mg/m2, respectively, is recommended phase II/III trials, with if treatment tolerated.