頭頸腫瘤中同期化療藥物、劑量及方案的選擇

編譯：腫瘤資訊來源：腫瘤資訊專家介紹：

David J. Adelstein教授

凱斯西儲大學的克利夫蘭診所勒納醫學院

美國國立癌症研究所（NCI）頭頸腫瘤指導委員會前主席

本屆國際頭頸腫瘤學會議中，來自凱斯西儲大學的克利夫蘭診所勒納醫學院的 David J. Adelstein教授針對頭頸腫瘤中同期化療藥物，劑量及方案的選擇，結合國內外最新發表的文獻進行了深度且生動的解讀。

一. 頭頸腫瘤同期放化療中化療藥物的選擇，卡鉑能否代替順鉑：

目前順鉑單葯是公認的頭頸腫瘤同期放化療的標準方案，然而其腎毒性，耳毒性，骨髓毒性及高致吐性等毒副反應不容小覷。與順鉑相比，卡鉑在降低不良反應方面明顯優於順鉑，那麼卡鉑相比順鉑能否帶來同等的生存獲益呢？綜合現有的證據，Dr. Adelstein總結道：目前順鉑作為同期化療的證據更充分；卡鉑相較於順鉑不良反應明顯降低，療效基本相當，但目前仍存在爭議，未來需要更多證據的支持。

二. 同期化療中什麼樣的給藥方案最佳？每周or每三周？

多項既往發表的研究，如1998年發表在Journal of Clinical Oncology上INT 0099試驗，2003年發表在Journal of Clinical Oncology上的INT 0126試驗，2004年發表在New England Journal of Medicine上的 EORTC 22931試驗等均支持同期放化療中使用大劑量，每三周，順鉑單葯同期化療。然而該方案在執行過程中的依從性不盡如人意：上述各項研究中接受了3程同期順鉑化療的病人僅60-70%。

相比三周方案，每周方案被認為可以在降低毒性翻湧的同時，達到相同的生存獲益及更好的依從性的。綜合發表的多項研究，Dr. Adelstein認為該結論目前仍缺乏足夠的證據。現有證據仍支持每三周方案較每周方案更有效，同時毒性反應也更大。然而，三周方案帶來的生存獲益到底是總劑量導致的（因為更多的化療往往帶來更大的毒性反應），還是由於執行方案不同帶來的目前仍不明確。

三. 同期化療多大劑量是最合適的？

那麼，同期中多大劑量的順鉑能夠在帶來足夠生存獲益同時最大程度降低不良反應呢？Kian Ang在 2004年發表在JCO上的一篇評述中首次提出200 mg/m2 的累積劑量足以帶來生存獲益，且獲益情況與每周或三周給藥方案無關。綜合發表的多項研究，Dr. Adelstein認為相比與給藥方案相比，200 mg/m2累積順鉑劑量作為針對所有頭頸部腫瘤的閾值或許略武斷。從某種程度上講，總劑量或許比給要方案更加重要。值得注意的是，頭頸部腫瘤是由各種不同的腫瘤組成的，最佳的順鉑劑量在預后不同的頭頸腫瘤間也存在差異。

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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