Single agent versus combination chemotherapy for metastatic breast cancer
Editorial Group: Cochrane Breast Cancer Group
Published Online: 15 APR 2009
Assessed as up-to-date: 11 NOV 2008
Copyright © 2009 The Cochrane Collaboration. Published by John Wiley & Sons, Ltd.
How to Cite
Carrick S, Parker S, Thornton CE, Ghersi D, Simes J, Wilcken N. Single agent versus combination chemotherapy for metastatic breast cancer. Cochrane Database of Systematic Reviews 2009, Issue 2. Art. No.: CD003372. DOI: 10.1002/14651858.CD003372.pub3.
- Publication Status: New search for studies and content updated (no change to conclusions)
- Published Online: 15 APR 2009
Combination chemotherapy regimens are frequently favoured over single agents for the treatment of metastatic breast cancer, in an attempt to achieve superior tumour response rates. It is not known however whether giving more intensive chemotherapy regimens results in better health outcomes, when both survival and toxicity are considered, and whether better response rates and rates of progression free survival actually translate to better overall survival.
To compare single agent with combination chemotherapy for the treatment of metastatic breast cancer.
We searched the Cochrane Breast Cancer Group Specialised Register November 2008. Handsearching of recent conference proceedings was also undertaken.
Randomised trials of single agent chemotherapy compared to combination therapy in metastatic breast cancer.
Data collection and analysis
Two authors independently assessed trials for eligibility and quality, and extracted data. Hazard ratios were derived for reported time-to-event outcomes.Response rates were analysed as dichotomous variables. Toxicity and quality of life data were extracted where present.
Forty three eligible trials (48 comparisons) were identified. These included 9742 women, 55% of whom were receiving first-line treatment for metastatic disease. For overall survival there was a statistically significant difference in favour of the combination regimens with no heterogeneity (HR 0.88, 95% CI 0.83-0.93, p<0.00001). Results were very similar when trials of first-line treatment were analysed, and for analyses where the single agent was also included in the combination regimen. Combination regimens showed a statistically significant advantage for survival over single agent taxane (HR 0.82; 95% CI 0.75-0.89, p<0.00001), but not anthracycline (HR 0.94.86-1.02, p=0.15).
Combination regimens were also associated with significantly better time to progression (HR 0.78, 95% CI 0.74 - 0.82, p<0.00001) and response (RR 1.29, 95% CI 1.14 -1.45, p<0.0001) although heterogeneity was statistically significant in both instances and probably due to clinical diversity of the participants and interventions.
Women receiving combination regimens experienced a statistically significant detrimental effect on white cell count, increased alopecia and nausea and vomiting.
Combination chemotherapy regimens show a statistically significant advantage for survival, tumor response and time to progression in women with metastatic breast cancer but they also produce more toxicity. An unresolved question is whether combination regimens are more effective than single agents given sequentially.
Plain language summary
Single agent versus combination chemotherapy for metastatic breast cancer
Metastatic breast cancer is cancer that has advanced and spread beyond the breast and regional lymph nodes. Although many women will live with advanced disease for many years, treatment is aimed at the alleviation of symptoms rather than cure. The first choice of treatment for advanced disease is dependent on hormone status (whether the tumour is stimulated to grow by oestrogen and progesterone) or whether the tumour overexpresses human epidermal growth factor receptor-2 (HER-2) and can be treated with trastuzumab (herceptin). Most women with advanced disease will however receive chemotherapy (anti-cancer agents) either as their first treatment, because their disease has become resistant to some treatments, or in combination with other types of treatments. Chemotherapy drugs can be given alone (single agent) or two or more drugs can be given together (combination chemotherapy). The aim of this review was to compare whether using a more intensive regimen (more than one drug) was better than the single agent treatment for women with advanced disease. We identified 43 eligible trials (48 comparisons- as some trials tested more than one comparison). These trials included 9742 women, 55% of whom were receiving their first treatment with chemotherapy for metastatic disease. The review found a benefit for the combination chemotherapy for survival (all trials). This was also the case when trials of first-line treatment only were analysed, and whether the single agent was also included in the combination or not. Combination treatments were also associated with significantly better time to progression (time after treatment until the disease progressed) and response (whether the tumour gets smaller as a result of the treatment). Women receiving combination treatment however experienced more adverse effects of treatment including a decrease in their white cell count, increased hair loss and nausea and vomiting. For women making a decision about treatment, it should be noted that this review was not able to address the issue of whether combination regimens are more effective than sequential treatment with different single agents. Some individual trials raised the possibility that giving a multiagent regimen sequentially with immediate cross-over from one agent to the next on progression may result in survival times similar to that seen when all the agents are given together
An important consideration for women with advanced disease is the balance between the benefit of treatment and the harms or adverse effects that these treatments may have. Unfortunately only 11 trials in this review reported information relating to quality of life. In general, survival gains with combination therapy came at the cost of a significant increase in toxicity and impact on other psychological and social factors which are known to contribute to a sense of quality of life for this group of women. There were insufficient data in this review to comment on the overall impact of the two treatment options on net clinical benefit from the women's perspective. Women with advanced disease will therefore need to seek the information to allow them to make decisions about the potential benefits of additional treatments (small survival gains) in progressing metastatic disease and the impact this can have on their quality of life.
有43個適合分析的試驗(48個研究)被確定。 包括9742名婦女，55％的人正在接受第一線治療轉移性乳癌。組合化療藥物治療轉移性乳癌優於單一化療藥物，整體存活率統計有顯著差異(HR 0.88, 95% CI 0.83 – 0.93, p < 0.00001)。當就第一線化療藥物作分析且包括組合化療藥物治療含此第一線化療藥物，則結果十分相似。在統計上，組合化療藥物療效比單一化療藥物taxane有顯著的生存優勢(HR 0.82; 95% CI 0.75 – 0.89, p < 0.00001)，但比單一化療藥物anthracyline則沒有顯著的生存優勢(H .94.86 – 1.02, p = 0.15) 雖然臨床參與者與介入者有臨床多樣性使得異質性有顯著不同，組合化療藥物治療轉移性乳癌仍有明顯改善疾病進展時間(HR 0.78, 95% CI 0.74 – 0.82, p < 0.00001)與腫瘤反應率(RR 1.29, 95% CI 1.14 −1.45, p < 0.0001)。接受組合化療藥物治療婦女明顯有較低白血球，且明顯較易脫髮，噁心和嘔吐。
此翻譯計畫由臺灣國家衛生研究院(National Health Research Institutes, Taiwan)統籌。
轉移性乳癌是癌細胞已擴散操超過乳腺和局部淋巴結。儘管許多婦女將度過晚期疾病生活多年，治療的目的是在減輕症狀，而不是治癒。晚期疾病治療的藥物選擇要看激素狀態(是否有雌激素和孕激素刺激腫瘤生長)，以及是否有人類表皮增長因子感受器官2 (human epidermal growth factor receptor2 (HER2))來決定是否可以trastuzumab (herceptin)來治療。多?晚期疾病婦女將接受眾多化療藥物之一作為他們的第一線治療，因為腫瘤對某一種化療藥物或組合兩種或兩種以上之化療藥物有抵抗性。本綜合回顧文獻研究的目地在比較治療轉移性乳癌是否組合化療藥物優於單一化療藥物。我們確定43個合格試驗(48個比較，因為某些試驗有一個以上的比較)。這些試驗包括9742女性，55％的人是第一次接受化療治療轉移性疾病。本綜合回顧文獻研究發現所有試驗皆顯示組合化療藥物比單一化療藥物有較高存活率。當就第一線化療藥物作分析且包括組合化療藥物治療是否含此第一線化療藥物的試驗也顯示一樣的結果。組合化療藥物治療轉移性乳癌仍有明顯改善疾病進展時間(治療後，直至疾病進展的時間)與腫瘤反應率(腫瘤是否由於治療?得小)。接受組合化療藥物治療婦女明顯有較低白血球，且明顯較易脫髮，噁心和嘔吐。對婦女作出有關治療的決定，值得注意的是，本綜合回顧文獻研究未能解決的問題是是否組合化療藥物治療優於單一藥物有順序地投予。一些個別的試驗提出了一種可能性方案，多種有次序的從一個化療藥物立即直接給予下一種化療藥物可能比同時一起給予有較高存活率。治療婦女晚期疾病有一個重要的考慮是在治療的好處與化療藥物副作用之間取得平衡。可惜只有11個試驗報告有關生活品質的訊息。一般來說，接受組合化療藥物治療的婦女必須承受更大藥物毒性及付出心理和社會因素生活品質之代價。本綜合回顧文獻研究沒有足夠的數據判定以婦女的觀點來看這二個治療選擇的整體臨床效益。因此晚期疾病婦女需要?找信息有關轉移性乳癌的化療藥物所具潛在的好處與對他們生活品質影響多大，以便他們做決定治療的選擇。