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作者：Roxanne Nelson  
出處：WebMD醫學新聞

　　January 26, 2010 — 根據2010年第一期考科藍系統性綜論資料庫的一項綜合分析結果，放射線治療加上化學治療，對罹患子宮頸癌女性可以附加些許但顯著的好處；這些結果也顯示輔助化學治療是有好處的，雖然還需要更多的數據。
　　
　　來自13項臨床研究的數據顯示，相較於那些僅接受放射線治療病患，接受化學放射治療的病患其5年存活率高了6%（危險比值[HR]為0.81；P<0.001）。
　　
　　研究者們表示，另外兩項研究顯示，化學治療在化學放射治療後進行，存活上的好處更大；這兩項研究的HR為0.46（95%信賴區間[CI]為0.32-0.66；P<0.001），換算為5年死亡風險下降54%，絕對存活好處增加19%（範圍自60%至79%）。
　　
　　第三項發現是，以鉑金類藥物（HR為0.83；P=0.017）相較於非鉑金類藥物（HR為0.77；P=0.009），化學治療有顯著的存活好處。
　　
　　主要試驗作者，來自英國倫敦MRC臨床研究單位綜合分析團隊的Claire Vale博士表示，我們進行的研究型式是使用個別病患資料的系統性綜論與綜合分析，這常被稱為是系統性綜論的黃金標準或是圭臬；因此，我想我們所提供的是，這項系統性綜論是有關使用化學放射治療的強烈證據，且可能是目前為止最佳的證據。
　　
　　即使如此，她向Medscape腫瘤學表示，治療任何子宮頸癌患者需要根據許多因子，包括腫瘤分期、整體健康狀況以及個人偏好。部分女性並不適合接受化學放射治療，因此，對她們來說，其他治療，例如僅接受放射線治療，將必須納入考量。
　　
　　Vale博士表示，可能需要在隨機分派控制研究中進一步評估使用輔助化學治療的效果；就我所知，研究領域對於這項議題相當感興趣。
　　
　　【綜合分析需要釐清數據】
　　作者們表示，在5項臨床研究發表後，國家癌症機構（NCI）於1999年發佈一項臨床警訊，建議罹患子宮頸癌女性應該同時進行化學放射治療，而非僅接受放射線治療。這些建議使得許多診斷出子宮頸癌的女性之後改變她們的治療療程。
　　
　　作者們寫到，雖然之後兩項綜論報告許多預後評量有所改善，包括整體存活率、免於惡化存活率、以及接受化學放射治療再發率，這些結果的闡釋是複雜的，且留下許多問題有待解答。研究結果之間仍存有異源性，不同研究之間預後評估的定義也不同，以及收納在該項分析中研究的控制組治療有所差異。
　　
　　因此，考科藍的研究者們進行了一項更新所有隨機分派控制研究個體病患數據的研究，以進一步評估化學放射治療對所有預後的效果。
　　
　　總共有15項研究（3452位受試者）符合收納到這項分析的條件。這些研究都是針對高風險、初期或局部惡化子宮頸癌女性。
　　
　　存活病患的後續追蹤時間中位數為5.2年，收納的這些研究都有整體存活、免於發生疾病存活、免於發生局部疾病存活與免於腫瘤轉移存活數據。
　　
　　【所有預後評量都看到好處】
　　除了改善整體存活率，化學放射治療也會降低局部與遠端再發率以及疾病惡化，且改善免於疾病惡化存活率。免於疾病惡化的HR為0.78（95% CI為0.70-0.87；P<0.001），換算為5年時的絕對好處為8%（從50%到58%），而5年時免於局部疾病存活率的相似且有顯著絕對好處（9%；P<0.001），局部再發/惡化所需時間（6%；P=0.00009）以及免於腫瘤轉移存活率（7%；P<0.001）。
　　
　　作者們表示，5年時腫瘤轉移所需時間的進步較小，且比較沒有那麼令人信服（4%；P=0.04）。
　　
　　作者們表示，腫瘤分期不同，存活好處大小是有差異的，但是其他病患亞群則沒有類似的發現。
　　
　　化學放射治療的急性血液與腸胃毒性發生率比較高，但是僅有少數的研究評估晚期毒性。目前研究數據顯示僅有1%~3%女性發生嚴重的晚期毒性反應，因此，這些數據尚不足夠評估嚴重的晚期毒性是否會受到治療種類影響。
　　
　　作者們的結論是，這些結果支持了NCI警訊的建議，但也顯示該治療方法對所有女性的應用性，以及非鉑金類化學放射治療的好處。


Meta-Analysis Provides Strong Support for Chemoradiotherapy in Cervical Cancer

By Roxanne Nelson
Medscape Medical News

January 26, 2010 — Adding chemotherapy to radiotherapy adds a modest but significant benefit in women with cervical cancer, according to a meta-analysis reported in the first 2010 issue of the Cochrane Database of Systematic Reviews. The results also suggest that adjuvant chemotherapy is beneficial, although more data are needed.

Data from 13 trials showed that patients treated with chemoradiotherapy had a 6% improvement in 5-year survival, compared with those treated with radiotherapy alone (hazard ratio (HR), 0.81; P?< .001).

The researchers noted that in 2 other trials, a larger survival benefit was seen when chemotherapy was administered after chemoradiotherapy. The HR for these 2 trials was 0.46 (95% confidence interval [CI], 0.32?- 0.66; P?< .001), which represents a 54% reduction in the risk for mortality and an absolute survival benefit of 19% at 5 years (range, 60% to 79%).

A third finding was that a significant survival benefit was observed for both platinum-based (HR, 0.83; P?= .017) and nonplatinum-based (HR, 0.77; P?= .009) chemoradiotherapy.

"The type of study that we did — a systematic review and meta-analysis using individual patient data — is often said to be the gold standard or yardstick of systematic reviews," said lead author Claire Vale, PhD, from the Meta-Analysis Group, MRC Clinical Trials Unit in London, United Kingdom. "Therefore, I think that what we have provided in doing this review is strong evidence about the use of chemoradiotherapy, and probably the best evidence available to date."

Even so, she told Medscape Oncology, the treatment of any individual woman with cervical cancer is based on many factors, including tumor stage, general health, and personal preference. "There are some women for whom chemoradiotherapy will not suitable, so for them, other treatments, such as radiotherapy alone, will necessarily be considered," she said.

The use of adjuvant chemotherapy might need to be further assessed in randomized controlled trials, Dr. Vale added. "As far as I am aware, there is considerable interest about this question in the research community."

Meta-Analysis Needed to Clarify Data

Following the publication of 5 clinical trials, the National Cancer Institute (NCI) issued a clinical alert in 1999 recommending that "concomitant chemoradiotherapy should be considered instead of radiotherapy alone in women with cervical cancer," the authors note. These recommendations led to a subsequent change in therapeutic regimens for many women diagnosed with cervical cancer.

Although 2 subsequent reviews reported improvements in several outcome measures, including overall survival, progression-free survival, and recurrence rates with chemoradiotherapy, the interpretation of results was complicated and left unanswered questions, write the authors. There was heterogeneity in trial results, inconsistency in the definition of outcomes between trials, and different control-group treatments in the studies included in these analyses.

Therefore, the Cochrane researchers conducted a meta-analysis that included updated individual patient data from all randomized controlled trials to better evaluate the effectiveness of chemoradiotherapy for all outcomes.

A total of 15 studies (3452 participants) met the eligibility criteria for inclusion in the analysis. The studies all looked at women with high-risk early-stage or locally advanced cervical cancer.

The median follow-up time for living patients across all 15 trials was 5.2 years, and data on overall survival, disease-free survival, locoregional disease-free survival, and metastases-free survival were available for all trials included in the analysis.

Benefit Seen Across All Outcomes

In addition to improving overall survival, chemoradiotherapy also reduced local and distant recurrence and progression, and improved disease-free survival. The HR of 0.78 (95% CI, 0.70?- 0.87; P?< .001) for disease-free survival translated to an absolute benefit of 8% at 5 years (from 50% to 58%), and similar and significant absolute benefits for chemoradiotherapy were seen for 5-year locoregional disease-free survival (9%; P?< .001), time to locoregional recurrence/progression (6%; P?= .00009), and metastases-free survival (7%; P?< .001).

The authors note that for time to metastases at 5 years, the improvement was smaller and "less convincing" (4%; P?= .04).

A suggestion of a difference in the size of the survival benefit was observed with tumor stage, but not with other patient subgroups, note the authors.

The incidence of acute hematologic and gastrointestinal toxicity was higher with chemoradiotherapy, but only a few of the trials measured late toxicity. Thus, the data were insufficient to evaluate whether serious late toxicity is affected by the type of treatment, although available data suggest that only about 1% to 3% of women experience serious late toxicities.

"These results endorse the recommendations of the NCI alert, but also demonstrate their applicability to all women and a benefit of nonplatinum-based chemoradiotherapy," the authors conclude.

Cochrane Database Syst Rev. 2010;1:CD008285.