Antwerp University Hospital, Department of Medical Oncology, Wilrijkstraat 10, 2650 Edegem, Belgium.
Anticancer Res. 2009 Dec;29(12):5137-42.
Docetaxel, ifosfamide and cisplatin have all shown activity in squamous cell carcinoma of the head and neck (SCCHN). The optimal combination of the three drugs is, however, unknown. Considering the favorable results of taxane-containing triplets as induction chemotherapy in locally advanced (LA) SCCHN, DIP (docetaxel, ifosfamide, cisplatin) was studied in this setting as part of a phase I dose- and sequence-exploring study.
D (60 or 75 mg/m(2)) was given by 60-min infusion on day 1, I (1000 mg/m(2)/day), with mesna until 12 hours after I, by 24-h infusion days 1-5, and P (50 or 75 mg/m(2)) by 24-h infusion on days 1 or 5. The cycles were repeated every 21 days. Toxicities according to the National Cancer Institute Common Toxicity Criteria version 2 (NCI-CTC2) were evaluated weekly and response was evaluated every 2 cycles according to the World Health Organization (WHO) criteria. Thereafter, radiotherapy (RT, cumulative dose 70 Gy) or chemoradiation (CRT), both with conventional fractionation, were planned.
Twenty-two patients (18 male, 4 female; age 41-66 years, performance status 0-1, 2 T4N0, 3 T3N2, 11 T4N2, 3 T unknown N3, 1 T1N3 and 2 T4N3) received a median of 4 DIP cycles (range 1-5). Grade 4 neutropenia occurred in 18 patients, grade 3 and 4 thrombocytopenia in 5 and 1 patients, respectively, and grade 3 anemia in 5 patients. Gastrointestinal and mucosal toxicities were generally mild/moderate. Vascular complications (probably not DIP-related) precluded local treatment in two patients. Moreover, one patient died on day 13 of the first DIP (neutropenic sepsis and myocardial infarction). The remaining patients received RT (n=2) or CRT (n=17; 16 of these with gemcitabine). The response to 2 x DIP was 95% (1 complete response, 19 partial responses, 1 stable disease); the complete response rate increased to 42% after 4 x DIP. No dose or sequence effect was evident. The minimum follow-up of the surviving patients was 51 months, with median relapse-free survival of 13.8 months and median overall survival of 18.8 months. Only four patients relapsed at distant sites.
DIP is highly active in previously untreated LA SCCHN, however, toxicity of DIP in this population is substantial.
多西紫杉醇、异环磷酰胺和顺铂在头颈部鳞状细胞癌（SCCHN）中均显示出活性。然而，这三种药物的最佳组合尚不清楚。考虑到含有紫杉烷的三联体作为局部晚期（LA）SCCHN 的诱导化疗的良好结果，DIP（多西紫杉醇、异环磷酰胺、顺铂）在该环境中作为一项 I 期剂量和序列探索研究的一部分进行了研究。
D（60 或 75mg/m2）以 60 分钟输注，第 1 天；I（1000mg/m2/天），用美司钠持续输注至 I 后 12 小时，第 1-5 天，24 小时输注；P（50 或 75mg/m2）第 1 或 5 天，24 小时输注。周期每 21 天重复一次。根据国家癌症研究所通用毒性标准 2（NCI-CTC2）每周评估毒性，根据世界卫生组织（WHO）标准每 2 个周期评估反应。然后计划进行放射治疗（RT，累积剂量 70Gy）或放化疗（CRT），均采用常规分割。
22 例患者（18 例男性，4 例女性；年龄 41-66 岁，表现状态 0-1，2 例 T4N0，3 例 T3N2，11 例 T4N2，3 例 T 未知 N3，1 例 T1N3 和 2 例 T4N3）接受了中位数为 4 个 DIP 周期（范围 1-5）的治疗。18 例患者发生 4 级中性粒细胞减少症，5 例和 1 例患者分别发生 3 级和 4 级血小板减少症，5 例患者发生 3 级贫血。胃肠道和黏膜毒性通常为轻度/中度。两名患者因血管并发症（可能与 DIP 无关）而无法进行局部治疗。此外，一名患者在 DIP 的第 1 天 13 死亡（中性粒细胞减少性败血症和心肌梗死）。其余患者接受 RT（n=2）或 CRT（n=17；其中 16 例接受吉西他滨）。2x DIP 的反应率为 95%（1 例完全缓解，19 例部分缓解，1 例疾病稳定）；4x DIP 后完全缓解率增加至 42%。没有明显的剂量或序列效应。幸存患者的最小随访时间为 51 个月，中位无复发生存期为 13.8 个月，中位总生存期为 18.8 个月。只有 4 例患者在远处部位复发。
DIP 在未经治疗的局部晚期 SCCHN 中具有高度活性，但该人群中 DIP 的毒性相当大。
