MILAN (EGMN)–A systematic review of 11 trials involving 2,269 women supports the common American practice of prolonging first-line chemotherapy in metastatic breast cancer until disease progression.

Longer chemotherapy duration was associated with a 36% reduction in the risk of progression (hazard ratio, 0.64; P less than .001,) and a 9% reduction in the risk of death (HR, 0.91; P = .04), lead author Dr. Alessandra Gennari reported at the annual congress of the European Society for Medical Oncology.

In subgroup analyses, the effect of longer chemotherapy was independent of time of randomization (either before or after induction chemotherapy), trial design (same vs. different maintenance), duration of chemotherapy in the control arm (fewer than six cycles vs. six or more cycles), and concomitant endocrine therapy (yes or no).

“In a pragmatic way, these results support the clinical approach of prolonging first-line chemotherapy in the absence of significant toxicity and disease progression,” said Dr. Gennari of the Galliera Hospital in Genoa, Italy.

Despite many years of research, the optimal length of first-line chemotherapy is still a matter of debate among clinical oncologists. Although many American clinicians administer first-line chemotherapy in metastatic breast disease until progression, chemotherapy in Europe is often given for a predetermined number of cycles, with duration dictated by treatment response, tolerability, and physician preference, Dr. Gennari explained during a press briefing at the meeting.

The National Comprehensive Cancer Network guidelines for metastatic breast cancer also state that “due to the lack of overall survival differences, the use of prolonged versus shorter chemotherapy needs to be weighted against the detrimental effects of continuous chemotherapy on overall quality of life.”

“The first question that all patients with metastatic disease ask is not ‘How [long] will I live?’ but ‘How many cycles of chemotherapy will I receive?’ ” she told reporters. “It should be clear that today the best answer is ‘As long as you can, because this means you will remain free of disease and possibly live longer.’ ”

The meta-analysis included 11 trials conducted between 1987 and 2010, of which 10 were published in peer-reviewed journals.

Invited discussant Dr. Miguel Martin said the meta-analysis features trials with very different designs and strategies, and he questioned whether the standard arms would be considered standard today since, for example, six used different anthracycline combinations and three used only three to four cycles of chemotherapy. He also suggested there could be a potential literature bias since many negative trials are rejected or never submitted for publication, and that trial registration at Web sites such as clinicaltrials.gov started only in 1997.

“Even considering all the mentioned caveats, this Italian study provides support for the administration of chemotherapy until disease progression,” said Dr. Martin of the Hospital General Universitario Gregorio Marañón in Madrid.

Assuming that the median overall survival of metastatic breast cancer after first-line chemotherapy is 24 months, he said that longer chemotherapy is associated with an absolute improvement in median progression-free survival of around 3 months and an absolute increase in overall survival of around 2 months.

“Do more prolonged side effects justify a gain of 3 months of progression-free survival and 2 months for overall survival? I guess that most patients would accept that in exchange for more toxicity,” Dr. Martin said.

Dr. Gennari said that several open questions remain, including what the optimal maintenance chemotherapy is and whether oncologists should maintain patients on the same drugs or give planned sequences using different single agents. Also unclear is the role for prolonged low-dose maintenance therapy and what the optimal association of chemotherapy is with targeted agents such as anti-HER2 and antiangiogenesis therapies.

The Italian Association for Cancer Research supported the trial. Dr. Gennari and her colleagues disclosed no conflicts of interest. Dr. Martin disclosed no conflicts.

Copyright (c) 2010 Elsevier Global Medical News. All rights reserved. This material may not be published, broadcast, rewritten, or redistributed.

米兰(EGMN)—— 一项纳入11项试验总共2,269例女性的系统评价证实的确应该延长转移性乳腺癌患者的一线化疗时间，直至疾病进展，这与美国现行的常规治疗方案相符。

 

这项meta分析纳入了11项于1987~2010年开展的试验，其中10项都发表于同行评审的期刊。其结果为，延长化疗时间与疾病进展风险降低36% (危险比：0.64；P <0.001)以及死亡风险降低9% (危险比：0.91；P < 0.04)相关。亚组分析显示，延长化疗时间所产生的效应与随机分组的时间(诱导化疗之前或之后)、试验设计(维持期相同或不同)、对照组的化疗持续时间(< 6个疗程或≥6个疗程)以及是否同时接受内分泌治疗等因素均无关。

 

从实际的角度来看，上述研究结果支持只要患者没有出现明显的毒性反应或疾病进展，就应该延长一线化疗的时间。目前临床肿瘤学家对于一线化疗的最佳持续时间仍然存在分歧。欧洲通常只予以事先确定的疗程数量，化疗持续时间是取决于治疗的应答情况、患者的耐受性以及医生的偏好。美国国家癌症综合治疗联盟制定的转移性乳腺癌诊疗指南也指出：“由于总生存期上的差异不大，因此在决定是采用长期还是短期化疗时，需要权衡继续化疗对于总体生活质量的负面影响。”

 

特邀评论员、西班牙马德里Gregorio Marañón大学总医院的Miguel Martin博士认为，这项meta分析存在一定的局限性，如所纳入的试验在设计和策略上存在很大的差异，另外，还存在潜在的文献偏倚。此外，在延长化疗时间获得3个月的无进展生存期和2个月的总生存期与化疗不良反应也随之延长的代价方面令人质疑。

 

该研究由意大利癌症研究协会资助。研究者声明无相关利益冲突。

 

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