Schöffski P, Catimel G, Planting A S, Droz J P, Verweij J, Schrijvers D, Gras L, Schrijvers A, Wanders J, Hanauske A R
Department of Hematology-Oncology, Hannover University Medical School, Germany.
Ann Oncol. 1999 Jan;10(1):119-22. doi: 10.1023/a:1008360323986.
Docetaxel and cisplatin are among the most active antitumor agents in head and neck cancer, and phase I studies found the combination of the two drugs to be feasible. The EORTC ECSG performed a multicenter phase II study in patients with locally advanced, recurrent or metastatic squamous cell carcinoma of the head and neck to evaluate the antitumor efficacy and toxicity of this combination.
Eligibility criteria included written informed consent, a WHO performance status < 2, life expectancy of > 12 weeks, and adequate bone marrow, liver and renal function. Neoadjuvant pretreatment with cisplatin-based chemotherapy or prior radiotherapy were allowed. Patients were ineligible if pretreated with taxoids, had CNS involvement, concurrent malignancy, peripheral neuropathy, or no measurable disease. Treatment consisted of docetaxel 100 mg/m2 (one-hour i.v. infusion), followed by cisplatin 75 mg/m2 (three-hour i.v. infusion), repeated every three weeks. Supportive care included hydration, 5HT3-antagonists, and corticosteroids.
Forty-four patients (median age 55 years, range 35-76) entered the trial; 41 patients were eligible, 164 cycles of treatment were evaluable for toxicity, and 31 patients for response. Fourteen patients had undergone prior surgery, 15 had received radiotherapy, and five had had chemotherapy. A median number of four treatment cycles (range 1-6) was given. Hematologic and non-hematologic toxicities were common, but hypersensitivity reactions and fluid retention were very infrequent due to corticosteroid prophylaxis. Four patients were taken off the study due to toxicity, and one toxic death occurred due to pneumonia. Among 41 eligible patients, objective responses as confirmed by independent review included six complete remissions and 16 partial remissions, resulting in an overall response rate of 53.7% (95% confidence interval: 37.4%-69.3%). Responses occurred in locally advanced, recurrent and metastatic disease, both in pre- and non-pretreated patients. Of 22 evaluable, non-pretreated patients with locally advanced or metastatic disease, five achieved complete responses, and 14 partial responses. Observed among nine evaluable pretreated patients with locally advanced or metastatic head and neck cancer were one complete response and two partial responses.
The combination of docetaxel and cisplatin is feasible and active in locally advanced, recurrent, and metastatic squamous cell carcinoma of the head and neck.
多西他赛和顺铂是头颈癌中最有效的抗肿瘤药物之一，I期研究发现这两种药物联合使用是可行的。欧洲癌症研究与治疗组织（EORTC）头颈癌协作组（ECSG）对局部晚期、复发或转移性头颈鳞状细胞癌患者进行了一项多中心II期研究，以评估这种联合用药的抗肿瘤疗效和毒性。
入选标准包括书面知情同意、世界卫生组织（WHO）体能状态<2、预期寿命>12周以及骨髓、肝脏和肾功能良好。允许采用以顺铂为基础的化疗进行新辅助预处理或先前接受过放疗。如果患者先前接受过紫杉类药物治疗、有中枢神经系统受累、并发恶性肿瘤、周围神经病变或无可测量病灶，则不符合入选条件。治疗方案为多西他赛100mg/m²（静脉滴注1小时），随后顺铂75mg/m²（静脉滴注3小时），每三周重复一次。支持性治疗包括补液、5-羟色胺3（5HT3）拮抗剂和皮质类固醇。
44例患者（中位年龄55岁，范围35 - 76岁）进入试验；41例患者符合条件，164个治疗周期可评估毒性，31例患者可评估疗效。14例患者曾接受过手术，15例接受过放疗，5例接受过化疗。中位给予4个治疗周期（范围1 - 6个）。血液学和非血液学毒性很常见，但由于使用皮质类固醇预防，过敏反应和液体潴留非常罕见。4例患者因毒性退出研究，1例因肺炎发生毒性死亡。在41例符合条件的患者中，经独立审查确认的客观缓解包括6例完全缓解和16例部分缓解，总缓解率为53.7%（95%置信区间：37.4% - 69.3%）。缓解发生在局部晚期、复发和转移性疾病患者中，包括预处理和未预处理患者。在22例可评估的未预处理局部晚期或转移性疾病患者中，5例实现完全缓解，14例部分缓解。在9例可评估的预处理局部晚期或转移性头颈癌患者中观察到1例完全缓解和2例部分缓解。
多西他赛和顺铂联合用药在局部晚期、复发和转移性头颈鳞状细胞癌中是可行且有效的。
