Shin D M, Glisson B S, Khuri F R, Ginsberg L, Papadimitrakopoulou V, Lee J J, Lawhorn K, Gillenwater A M, Ang K K, Clayman G L, Callender D L, Hong W K, Lippman S M
Department of Thoracic/Head and Neck Medical Oncology, The University of Texas M.D. Anderson Cancer Center, Houston 77030, USA.
J Clin Oncol. 1998 Apr;16(4):1325-30. doi: 10.1200/JCO.1998.16.4.1325.
To assess the activity and toxicity profile of combined taxol (paclitaxel), ifosfamide, and platinum (cisplatin) (TIP) in patients with recurrent or metastatic squamous cell carcinoma (SCC) of the head and neck.
Recurrent or metastatic head and neck SCC patients received paclitaxel 175 mg/m2 in a 3-hour infusion on day 1; ifosfamide 1,000 mg/m2 in a 2-hour infusion on days 1 through 3; mesna 600 mg/m2 on days 1 through 3; and cisplatin 60 mg/m2 on day 1, repeated every 3 to 4 weeks. All were premedicated with dexamethasone, diphenhydramine, and cimetidine. Prophylactic hematopoietic growth factors were not permitted.
Fifty-two patients were assessable for response and toxicity; 53 for survival (local-regional recurrence alone in 57% and distant metastasis with or without local-regional recurrence in 43%). Overall response rate was 58% (30 of 52) of patients; complete response rate was 17% (nine of 52) of patients, with six complete responses that continued for a median 15.7+ months. Median follow-up of all patients was 17.7 months. Median survival was 8.8 months (95% confidence interval [CI] 8.1 to 17.5 months). Toxicity was relatively well tolerated and caused no deaths. The most frequent moderate-to-severe toxicity (90% of patients) was transient grades 3 to 4 neutropenia; neutropenic fever occurred in 27%. Grade 3 peripheral neuropathy occurred in three patients, none had grade 4. Grade 3 mucositis occurred in only one patient, none had grade 4.
TIP had major activity in this setting, with a 58% objective response rate, 17% complete response rate, durable complete responses (six of nine persisting), and relatively well-tolerated toxicity, with no toxic deaths. The activity of TIP, a novel taxol-cisplatin-based regimen, in recurrent or metastatic head and neck SCC should be confirmed in a phase III trial.
评估紫杉醇、异环磷酰胺和顺铂联合方案（TIP）对复发性或转移性头颈部鳞状细胞癌（SCC）患者的活性及毒性特征。
复发性或转移性头颈部SCC患者在第1天接受3小时静脉输注紫杉醇175mg/m²；在第1至3天接受2小时静脉输注异环磷酰胺1000mg/m²；在第1至3天接受美司钠600mg/m²；在第1天接受顺铂60mg/m²，每3至4周重复一次。所有患者均使用地塞米松、苯海拉明和西咪替丁进行预处理。不允许使用预防性造血生长因子。
52例患者可评估疗效和毒性；53例可评估生存情况（57%为单纯局部区域复发，43%为有或无局部区域复发的远处转移）。总体缓解率为58%（52例中的30例）；完全缓解率为17%（52例中的9例），其中6例完全缓解持续时间中位数为15.7 +个月。所有患者的中位随访时间为17.7个月。中位生存期为8.8个月（95%置信区间[CI] 8.1至17.5个月）。毒性相对耐受性良好，未导致死亡。最常见的中重度毒性（90%的患者）为短暂的3至4级中性粒细胞减少；27%的患者发生中性粒细胞减少性发热。3例患者出现3级周围神经病变，无4级病例。仅1例患者出现3级黏膜炎，无4级病例。
TIP在这种情况下具有主要活性，客观缓解率为58%，完全缓解率为（17%），持久完全缓解（9例中的6例持续存在），且毒性相对耐受性良好，无毒性死亡。TIP作为一种基于紫杉醇和顺铂的新方案，在复发性或转移性头颈部SCC中的活性应在III期试验中得到证实。
