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多西他赛与卡铂作为早期T期和晚期N期鼻咽癌新辅助治疗的II期研究。

A Phase II study of docetaxel and carboplatin as neoadjuvant therapy for nasopharyngeal carcinoma with early T status and advanced N status.

作者信息

Johnson Faye M, Garden Adam, Palmer J Lynn, Kies Merrill, Clayman Gary, Brumfield Brenda, Khuri Fadlo R, Morrison William, Papadimitrakopoulou Vassiliki, Diaz Eduardo M, Glisson Bonnie S

机构信息

Department of Thoracic/Head and Neck Medical Oncology, The University of Texas M. D. Anderson Cancer Center, Houston, Texas 77030, USA.

出版信息

Cancer. 2004 Mar 1;100(5):991-8. doi: 10.1002/cncr.20079.

Abstract

BACKGROUND

Promising results from a Phase II trial of induction chemotherapy and sequential radiotherapy for advanced nasopharyngeal carcinoma (NPC) at The University of Texas M. D. Anderson Cancer Center (Houston, TX) and two retrospective reviews of the authors' historical experience with NPC demonstrated that distant failure was directly correlated with advanced lymph node status. Furthermore, local control was excellent for patients with T1-3 disease that was managed with radiation alone or with a sequential approach involving chemotherapy. Neoadjuvant chemotherapy (primarily with cisplatin + 5-fluorouracil) was associated with a significantly decreased risk of distant metastasis and with improved survival. Based on these findings, the authors evaluated a novel induction regimen involving docetaxel and carboplatin for patients with previously untreated T1-2N2-3M0 NPC.

METHODS

Docetaxel (80 mg/m2 on Day 1) and carboplatin (to an area under the time-concentration curve of 6 on Day 1) were administered every 21 days for 3 cycles, after which radiotherapy was administered. NPC was restaged with magnetic resonance imaging and nasopharyngoscopy 3 weeks after the completion of chemotherapy and 6 weeks after the completion of radiotherapy.

RESULTS

Over 5 years, 18 patients were enrolled in the study. Grade 4 neutropenia and Grade 2 fatigue were observed in 51% and 28% of chemotherapy courses, respectively. After chemotherapy, 2 patients had complete responses, 14 had partial responses, 1 had a minor response, and 1 had progressive disease. The latter two patients and one patient who had a partial response underwent off-study chemoradiotherapy. After radiotherapy or chemoradiotherapy, 12 patients had complete responses and 6 had partial responses. Seven patients had recurrent disease; two had local recurrences, and five had distant metastases.

CONCLUSIONS

Although unlikely to be superior to cisplatin + 5-fluorouracil, the trial regimen could be administered quickly in the outpatient setting, was logistically more convenient for the patient, and was devoid of serious nonhematologic toxic effects. We believe that the risk-based approach examined in the current study merits further investigation.

摘要

背景

德克萨斯大学MD安德森癌症中心(得克萨斯州休斯顿)针对晚期鼻咽癌(NPC)开展的一项诱导化疗及序贯放疗II期试验取得了令人鼓舞的结果,同时作者对NPC历史经验的两项回顾性研究表明,远处转移与晚期淋巴结状态直接相关。此外,对于仅接受放疗或采用包含化疗的序贯方法治疗的T1 - 3期疾病患者,局部控制效果良好。新辅助化疗(主要使用顺铂 + 5 - 氟尿嘧啶)与远处转移风险显著降低及生存率提高相关。基于这些发现,作者评估了一种针对先前未治疗的T1 - 2N2 - 3M0期NPC患者的新型诱导方案,该方案包含多西他赛和卡铂。

方法

多西他赛(第1天80mg/m²)和卡铂(第1天达到时间 - 浓度曲线下面积为6)每21天给药1次,共3个周期,之后进行放疗。化疗完成后3周以及放疗完成后6周,通过磁共振成像和鼻咽镜检查对NPC进行重新分期。

结果

在5年时间里,18名患者入组该研究。分别有51%和28%的化疗疗程观察到4级中性粒细胞减少和2级疲劳。化疗后,2例患者完全缓解,14例部分缓解,1例轻度缓解,1例疾病进展。后两名患者以及1例部分缓解的患者接受了非研究性放化疗。放疗或放化疗后,12例患者完全缓解,6例部分缓解。7例患者出现疾病复发;2例为局部复发,5例为远处转移。

结论

尽管该试验方案不太可能优于顺铂 + 5 - 氟尿嘧啶,但它可以在门诊环境中快速给药,对患者在后勤保障方面更便利,且没有严重的非血液学毒性作用。我们认为当前研究中所检验的基于风险的方法值得进一步研究。

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