凯斯西储大学的克利夫兰诊所勒纳医学院
美国国立癌症研究所（NCI）头颈肿瘤指导委员会前主席
本届国际头颈肿瘤学会议中，来自凯斯西储大学的克利夫兰诊所勒纳医学院的 David J. Adelstein教授针对头颈肿瘤中同期化疗药物，剂量及方案的选择，结合国内外最新发表的文献进行了深度且生动的解读。
一. 头颈肿瘤同期放化疗中化疗药物的选择，卡铂能否代替顺铂：
目前顺铂单药是公认的头颈肿瘤同期放化疗的标准方案，然而其肾毒性，耳毒性，骨髓毒性及高致吐性等毒副反应不容小觑。与顺铂相比，卡铂在降低不良反应方面明显优于顺铂，那么卡铂相比顺铂能否带来同等的生存获益呢？综合现有的证据，Dr. Adelstein总结道：目前顺铂作为同期化疗的证据更充分；卡铂相较于顺铂不良反应明显降低，疗效基本相当，但目前仍存在争议，未来需要更多证据的支持。
二. 同期化疗中什么样的给药方案最佳？每周or每三周？
多项既往发表的研究，如1998年发表在Journal of Clinical Oncology上INT 0099试验，2003年发表在Journal of Clinical Oncology上的INT 0126试验，2004年发表在New England Journal of Medicine上的 EORTC 22931试验等均支持同期放化疗中使用大剂量，每三周，顺铂单药同期化疗。然而该方案在执行过程中的依从性不尽如人意：上述各项研究中接受了3程同期顺铂化疗的病人仅60-70%。
相比三周方案，每周方案被认为可以在降低毒性翻涌的同时，达到相同的生存获益及更好的依从性的。综合发表的多项研究，Dr. Adelstein认为该结论目前仍缺乏足够的证据。现有证据仍支持每三周方案较每周方案更有效，同时毒性反应也更大。然而，三周方案带来的生存获益到底是总剂量导致的（因为更多的化疗往往带来更大的毒性反应），还是由于执行方案不同带来的目前仍不明确。
三. 同期化疗多大剂量是最合适的？
那么，同期中多大剂量的顺铂能够在带来足够生存获益同时最大程度降低不良反应呢？Kian Ang在 2004年发表在JCO上的一篇评述中首次提出200 mg/m2 的累积剂量足以带来生存获益，且获益情况与每周或三周给药方案无关。综合发表的多项研究，Dr. Adelstein认为相比与给药方案相比，200 mg/m2累积顺铂剂量作为针对所有头颈部肿瘤的阈值或许略武断。从某种程度上讲，总剂量或许比给要方案更加重要。值得注意的是，头颈部肿瘤是由各种不同的肿瘤组成的，最佳的顺铂剂量在预后不同的头颈肿瘤间也存在差异。
英文原文
Chemotheray choices:Which platin, how and how often?
David J. Adelstein
Cleveland Clinic Lerner College of Medicine of Case Western Reserve University
We invited Professor. David J. Adelstein, from the Cleveland Clinic Lerner College of Medicine of Case Western Reserve University, to share his perspective on the topic “Chemotherapy choices: which platin, how much and how often?” Professor Adelstein shared his perspectives on the following aspects:
1. Regimen choice for head and neck cancer patients during concurrent chemotherapy: can we substitute carboplatin for cisplatin?
For head and neck squamous cell carcinoma (HNSCC), cisplatin is the standard agent used in definitive concurrent chemoradiotherapy (CCRT). Despite its efficacy, the toxicity profile limits its use during highly-intensive CCRT. Different from the toxicity profiles of cisplatin, carboplatin is less toxic. Therefore, if they are equally effective, carboplatin would be preferred. Yet, can we substitute carboplatin for cisplatin? Based on the evidence published, Professor Adelstein believes that both drugs have activity, however, cisplatin is better tested, and appears to be modestly more effective.
2. During concurrent chemoradiotherapy, what is the optimal cisplatin administration schedule?
Much of the high quality evidence supporting concurrent chemoradiotherapy in HNSCC has been generated for the high-dose, every 3 week cisplatin regimen. However, the problem is that this regimen is difficult to administer, and compliance with 3 doses every three weeks has not been optimal (ranging from 60-70% according to published trials). Therefore, weekly low-dose cisplatin is increasingly being used in concurrent chemoradiotherapy regimens for locoregionally advanced HNSCC, based on the assumptions that weekly treatment is less toxic, equally efficacious, and allows for better compliance. However, Professor Adelstein believes that the current evidence is still insufficient to support the universal use of low dose weekly cisplatin instead of the high-dose, every 3 week cisplatin regimen.
3. During concurrent chemoradiotherapy, what is the optimal cisplatin dose?
Since the compliance with 3 doses every three weeks has not been optimal, the question was raised: what is the optimal cisplatin dose? The importance of a third planned cisplatin cycle was first questioned by Ang et al., who reviewed the compliance with CCRT in RCTs, and found that a substantial fraction of patients failed to receive the third cycle, and a cumulative dose of 200 mg/m2 was sufficient to yield beneficial antitumor effects, irrespective of the administration schedule. Based on the evidence published, Professor Adelstein believes that 200 mg/m2 cumulative cisplatin dose is an arbitrary threshold, which may not be applicable for all head and neck malignancies. Although total cisplatin dose is likely more important than the drug administration schedule, treatment intensity requirements may differ between favorable diseases like NPC and HPV+ OPC, and the less favorable oral cavity or hypopharyngeal cancers.
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