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根据一项发表于1月3日新英格兰医学期刊的研究结果显示，对过去未受治疗的胃食道癌患者而言，capecitanbine（Xeloda）与oxaliplatin（Eloxatin）显然与fluorouracil（5-FU）与cisplatin（Platinol）在提升整体存活率上一样有效。
试验作者Naureen Starling生物工学学士向Medscape肿瘤学表示，她是一位英国萨里大学癌症研究机构的临床研究学者，ECF（epirubicin、cisplatin与持续输注fluorouracil）疗程在欧洲被广泛地应用于治疗进展性与早期胃食道癌症；在我们的研究中，我们想要研究fluorouracil在这个疗程中是否可以被capecitabine取代，以及cisplatin是否可以被oxaliplatin取代；我们研究的特色是因此使用了二乘二阶乘试验设计，以四种治疗组进行研究。
胃癌与食道癌仍然是世界各地癌症相关死亡常见的原因，且病患被发现时大都是已经是恶化、无法手术、或是已经转移的疾病，其预后是很差的，5年的存活率介于10~15%之间；相较于最佳的支持性疗法，使用缓和化学疗法治疗进展性疾病已经被证实可以改善存活率，但是研究者表示，目前没有进展性癌症第一线治疗的黄金标准疗程。
Starling学士解释，缺乏统一的标准疗程，部分是因为所有的疗程针对大部分病患都无法延长平均存活时间超过9个月；Cisplatin/fluorouracil疗程是很常用的，但疗效不佳。
最近将docetaxel加入了cisplatin/fluorouracil疗程已经改善了平均存活率，但仍然仅达到9.2个月，仅使用cisplatin/fluorouracil的则是8.6个月，且毒性是增加的。
研究者随机分派了1022位病患，接受epirubicin与cisplatin加上fluorouracil（ECF）或是capecitabine（ECX）三重疗法、或是epirubicin与oxaliplatin加上fluorouracil（EOF）或是capecitabine（EOX）三重疗法，她们的主要试验终点是包含capecitabine的治疗疗效不会比fluorouracil差，而包含oxaliplatin的治疗疗效不会比cisplatin差。
Starling学士解释，这项研究的设计使得来自fluorouracil的结果可以综合在一起（ECF + EOF）、且与capecitabine组综合的结果（ECX + EOX）进行比较，这项研究设计也让cisplatin组的结果可以综合在一起（ECF + ECX）且与oxaliplatin组综合的结果（EOF + EOX）相互比较。
她表示，在事前设计好的分析中，每个实验组都可以与ECF参照组疗程进行比较。
平均后续追踪时间为17.1个月，且ECF、ECX、EOF与EOX组的平均存活率分别为9.9个月、9.9个月、9.3个月与11.2个月；在追踪1年时，存活率分别为37.7%、40.8%、40.4%与46.8%；当他们针对未恶化存活率时，研究者在意向治疗群体的二乘二设计中，并未看到任何显著的差异，当她们比较每个组与ECF组时，同样未发现任何差异；除此之外，病患族群之间的整体反应率也没有差异。
Starling学士表示，在其研究中，他们展现了capecitabine取代ECF疗程时，其效果与fluorouracil相当，前者疗程在欧洲经常被用于治疗胃食道癌症，当capecitabine与fluorouracil比较时，在整体存活率有未达统计上显著差异的改善，这些结果将因此支持以capecitabine取代ECF疗程中的fluorouracil。
当在ECF疗程中，oxaliplatin被发现跟cisplatin一样有效，且从安全性的角度来看这样的疗程有许多优点；Oxaliplatin发生栓塞事件机率较低，且发生肾毒性、秃头、与第三/四级中性球低下的机率较低；然而，使用oxaliplatin相较于cisplatin有较高的第三/四级腹泻与第三/四级神经病变机率。
EOX疗程，将ECF疗程中的fluorouracil与cisplatin以capecitabine与oxaliplatin取代，延长平均存活的时间最长（11.2个月）；Starling学士表示，以病患的方便性、毒性与疗效考量，EOX是进展性胃食道癌症的参考疗程。
这项研究部分由Hoffmann-La罗氏与赛诺菲安万特药厂、以及皇家马斯登医院肠胃道单位临床研究基金赞助；许多作者，包括Starling接受Hoffmann-La罗氏与赛诺菲安万特药厂的顾问以及/或是演讲费用。
Alternative Regimen Effective in Untreated Advanced Esophagogastric Cancer
By Roxanne Nelson
Medscape Medical News
According to a new study published in the January 3 issue of the New England Journal of Medicine, capecitabine (Xeloda) and oxaliplatin (Eloxatin) appear to be as effective as fluorouracil (5-FU) and cisplatin (Platinol), in terms of overall survival, in patients with previously untreated esophagogastric cancer.
"The ECF [epirubicin, cisplatin, and infusional fluorouracil] regimen is widely used in the treatment of advanced and early-stage esophagogastric cancer in Europe," study author Naureen Starling, BSc, MBBS, a clinical research fellow at the Institute of Cancer Research, Surrey, United Kingdom, told Medscape Oncology. "In our study we wanted to address the question as to whether fluorouracil in this regimen could be replaced by capecitabine and whether cisplatin could be replaced by oxaliplatin. A key feature of our study was, therefore, the use of 4 treatment arms in a 2 by 2 factorial trial design."
Gastric and esophageal cancers remain common causes of cancer-related mortality worldwide, and the majority of patients present with advanced, inoperable, or metastatic disease. The prognosis is poor, with 5-year survival rates in the range of 10% to 15%. Palliative chemotherapy for advanced disease has been shown to improves survival, compared with the best supportive care, but there is no single global standard regimen for the first-line treatment of advanced disease, the researchers note.
"The lack of a universal standard regimen is partly based on the fact that all regimens fail to result in a median survival of beyond 9 months in most cases," Dr. Starling explained. "The cisplatin/fluorouracil regimen is commonly used in parts of the world but efficacy is poor."
The recent addition of docetaxel to the cisplatin/fluorouracil regimen has improved median survival, but it still only reaches 9.2 months, compared with 8.6 months for cisplatin/fluorouracil alone, and toxicity is increased.
The researchers randomly assigned 1002 patients to receive triplet therapy with epirubicin and cisplatin plus either fluorouracil (ECF) or capecitabine (ECX), or triplet therapy with epirubicin and oxaliplatin plus either fluorouracil (EOF) or capecitabine (EOX). Their primary end point was noninferiority in overall survival for the therapies containing capecitabine compared with fluorouracil, and for the therapies containing oxaliplatin compared with cisplatin.
Dr. Starling explained that the study design allowed results from the fluorouracil groups to be pooled (ECF + EOF) and compared with the pooled results of the capecitabine groups (ECX + EOX). The design also permitted results from the cisplatin groups to be pooled (ECF + ECX) and compared with results from the oxaliplatin groups (EOF + EOX).
"In a prespecified analysis, each of the experimental arms could be compared to the reference regimen of ECF," she said.
Median follow-up was 17.1 months, and median survival for the ECF, ECX, EOF, and EOX groups were 9.9 months, 9.9 months, 9.3 months, and 11.2 months, respectively. At 1 year, survival rates were 37.7%, 40.8%, 40.4%, and 46.8%, respectively. When they looked at rates of progression-free survival, the researchers did not see any significant differences in the 2-by-2 comparisons in the intention-to-treat population, nor did they see significant differences when they compared each study group with the ECF group. In addition, the overall response rate did not differ significantly among the patient cohorts.
"In our study we demonstrated that capecitabine was as effective as fluorouracil when substituted in the ECF regimen that is commonly used for the treatment of esophagogastric cancer in Europe," said Dr. Starling. "There was also a statistically nonsignificant trend for improved survival with capecitabine as compared with fluorouracil. These results would therefore support the replacement of fluorouracil with capecitabine in the ECF regimen."
Oxaliplatin was found to be as effective as cisplatin when substituted in the ECF regimen, and had several advantages from a safety perspective. Oxaliplatin was associated with significantly fewer thromboembolic events, and less renal toxicity, alopecia, and grade 3/4 neutropenia. There was, however, a modest increase in grade 3/4 diarrhea and grade 3/4 peripheral neuropathy.
The EOX regimen, in which both fluorouracil and cisplatin in the ECF regimen were substituted with capecitabine and oxaliplatin, respectively, was associated with the longest median survival (11.2 months). "Based on patient convenience, toxicity, and efficacy, EOX is a new reference regimen for advanced esophagogastric cancer," said Dr. Starling.
The study was supported in part by Hoffmann–La Roche and Sanofi-Aventis, and the Gastrointestinal Unit Clinical Research Fund of the Royal Marsden Hospital.
Several of the authors, including Dr. Starling, received consulting and/or lecture fees from Hoffmann–La Roche and/or Sanofi-Aventis
New Engl J Med 2008; 358:36-46. Abstract