Schwartz David L, Montgomery R Bruce, Yueh Bevan, Donahue Michael, Anzai Yoshimi, Canby Raylene, Buelna Raelene, Anderson Leslie, Boyd Charles, Hutson Janice, Keegan Kathryn
Radiation Oncology Service, Seattle VA Puget Sound Health Care System, Seattle, Washington, USA.
Cancer. 2005 Jun 15;103(12):2534-43. doi: 10.1002/cncr.21085.
The current Phase I/II study assessed induction docetaxel/carboplatin given weekly for 4 weeks, followed by weekly docetaxel/carboplatin and concomitant boost radiotherapy (CB-XRT) for locally advanced head and neck squamous cell carcinoma.
Twenty patients with Stage III or IV (M0) disease of the oropharynx, supraglottic larynx, or hypopharynx were enrolled. Patients initially received docetaxel 20 mg/m2 and carboplatin area under the curve (AUC) 2 weekly x 4. Patients with stable (SD) or responding disease subsequently received dose-escalated docetaxel (10-20 mg/m2 in sequential patient cohorts) and carboplatin AUC 1 weekly x 5 with CB-XRT (1.8 gray [Gy] every day x 15 days, followed by 1.8/1.5 Gy twice per day x 13 days).
All patients were evaluable, and 15 patients (5 patients with Stage III disease, 10 patients with Stage IV disease) completed all planned therapy. The target docetaxel dose level of 20 mg/m(2) weekly with radiotherapy was achieved with no dose-limiting toxicities. The most frequent maximum toxicities during chemoradiotherapy were Grade 3 mucositis, dysphagia, and/or pain. Primary site responses after induction included 4 patients with partial responses, 11 patients with SD, and 5 patients with disease progression. Fifteen patients (75%) continued to receive chemoradiotherapy, with 14 patients attaining a complete response (CR). Overall, a clinicopathologic neck CR after chemoradiotherapy was achieved in 9 of 10 patients. One patient had persistent primary disease and underwent salvage surgery, whereas another died of unrelated causes before neck assessment. Thirteen patients remain free of any disease event, with a median follow-up of 15 months (range, 3-29 months).
This regimen was feasible, safe, and particularly well tolerated. Early Phase II outcomes revealed promising activity in patients completing all treatment. Initial induction response results suggested that further investigation of this regimen with more aggressive induction therapy is warranted.
当前的I/II期研究评估了每周一次给予多西他赛/卡铂诱导治疗4周，随后每周给予多西他赛/卡铂并同步推量放疗（CB-XRT）用于局部晚期头颈部鳞状细胞癌的疗效。
纳入20例口咽、声门上喉或下咽III期或IV期（M0）疾病患者。患者最初接受多西他赛20mg/m²和卡铂曲线下面积（AUC）2，每周一次，共4次。疾病稳定（SD）或有反应的患者随后接受剂量递增的多西他赛（在连续患者队列中为10 - 20mg/m²）和卡铂AUC 1，每周一次，共5次，并联合CB-XRT（每天1.8格雷[Gy]，共15天，随后每天两次，每次1.8/1.5Gy，共13天）。
所有患者均可评估，15例患者（5例III期疾病患者，10例IV期疾病患者）完成了所有计划治疗。实现了每周20mg/m²多西他赛联合放疗的目标剂量水平，且无剂量限制性毒性。放化疗期间最常见的最大毒性反应为3级黏膜炎、吞咽困难和/或疼痛。诱导治疗后的原发部位反应包括4例部分缓解患者、11例SD患者和5例疾病进展患者。15例患者（75%）继续接受放化疗，14例患者达到完全缓解（CR）。总体而言，10例患者中有9例在放化疗后实现了颈部临床病理CR。1例患者原发疾病持续存在并接受了挽救性手术，而另1例患者在颈部评估前死于无关原因。13例患者无任何疾病事件发生，中位随访时间为15个月（范围3 - 29个月）。
该方案可行、安全，耐受性尤其良好。II期早期结果显示，完成所有治疗的患者有令人鼓舞的活性。初始诱导反应结果表明，有必要对该方案采用更积极的诱导治疗进行进一步研究。
