Pronk L C, Schellens J H, Planting A S, van den Bent M J, Hilkens P H, van der Burg M E, de Boer-Dennert M, Ma J, Blanc C, Harteveld M, Bruno R, Stoter G, Verweij J
Department of Medical Oncology and Neuro-Oncology, Rotterdam Cancer Institute (Daniel den Hoed Kliniek) and University Hospital, the Netherlands.
J Clin Oncol. 1997 Mar;15(3):1071-9. doi: 10.1200/JCO.1997.15.3.1071.
This phase I study was performed to assess the feasibility of the combination of docetaxel and cisplatin and to determine the maximum-tolerated dose (MTD) and the side effects with an emphasis on sequence-dependent side effects.
Patients who were not pretreated with taxanes or cisplatin derivatives and who had received no more than one prior combination chemotherapy regimen or two single-agent regimens were entered. Treatment consisted of docetaxel given as a 1-hour infusion followed by cisplatin as a 3-hour infusion (schedule A), or cisplatin followed by docetaxel (schedule B). Docetaxel doses ranged from 55 to 100 mg/m2 and cisplatin doses from 50 to 100 mg/m2.
Leukocytopenia and granulocytopenia were common (overall, 90%; grade 3 or 4, 87%), short-lasting, and docetaxel dose-dependent. Infections and neutropenic fever occurred in 10% and 4.5% of courses, respectively. Nonhematologic toxicities were mild to moderate and included alopecia, nausea, vomiting, diarrhea, mucositis, neurotoxicity, fluid retention, and skin and nail toxicity. There were no significant differences in pharmacokinetic parameters between schedules A and B. Tumor responses included one complete response (CR) and nine partial responses (PRs).
The dose levels docetaxel 100 mg/m2 plus cisplatin 75 mg/m2 and docetaxel 85 mg/m2 plus cisplatin 100 mg/m2 appeared to be manageable. At these dose levels, the median relative dose-intensity was high and 81% and 88% of all cycles, respectively, could be given at full dose. Schedule A is advocated for further treatment.
开展本I期研究以评估多西他赛与顺铂联合使用的可行性，并确定最大耐受剂量（MTD）及副作用，重点关注顺序依赖性副作用。
纳入未接受过紫杉烷类或顺铂衍生物预处理、既往接受不超过一种联合化疗方案或两种单药化疗方案的患者。治疗方案包括多西他赛静脉输注1小时后顺铂静脉输注3小时（方案A），或顺铂后接多西他赛（方案B）。多西他赛剂量范围为55至100mg/m²，顺铂剂量范围为50至100mg/m²。
白细胞减少和粒细胞减少常见（总体发生率90%；3级或4级发生率87%），持续时间短且与多西他赛剂量相关。感染和中性粒细胞减少性发热分别发生在10%和4.5%的疗程中。非血液学毒性为轻至中度，包括脱发、恶心、呕吐、腹泻、黏膜炎、神经毒性、液体潴留以及皮肤和指甲毒性。方案A和B之间的药代动力学参数无显著差异。肿瘤反应包括1例完全缓解（CR）和9例部分缓解（PR）。
多西他赛100mg/m²加顺铂75mg/m²以及多西他赛85mg/m²加顺铂100mg/m²的剂量水平似乎可耐受。在这些剂量水平下，中位相对剂量强度较高，所有周期分别有81%和88%可给予全剂量。提倡采用方案A进行进一步治疗。
