Bisphosphonates for breast cancer

 

Abstract

Background

Bone is the most common site of metastatic disease associated with breast cancer (BC). Bisphosphonates inhibit osteoclast-mediated bone resorption.

Objectives

To assess the effect of Bisphosphonates on skeletal events (SEs), bone pain, quality of life (QOL) and survival in women with early (E) and advanced breast cancer (ABC).

Search methods

The specialised register maintained by the Cochrane Breast Cancer Group was searched January 2007. Additional handsearching was conducted of journals and proceedings of key meetings.

Selection criteria

Randomised studies comparing Bisphosphonates and placebo, or different Bisphosphonates in women with metastatic BC.

Data collection and analysis

Two reviewers independently assessed trials and extracted data. Toxicity information was collected from the trials.

Main results

Twenty one randomised studies were included. In nine studies (2189 women with ABC and existing bone metastases), compared with placebo or no bisphosphonates, bisphosphonates reduced SE risk by 17% (RR 0.83; 95% confidence interval (CI) 0.78 to 0.89; P < 0.00001). This benefit was most certain with intravenous (IV) pamidronate 90 mg (RR 0.77; 95% CI 0.69-0.87), IV zolendronate 4mg (RR 0.59; 95% CI 0.42 - 0.82) and oral (PO) clodronate 1600 mg (pooled RR 0.84; 95% CI 0.72-0.98). Direct comparison of IV zolendronate and IV pamidronate confirms at least equivalent efficacy in a single large study.

Bisphosphonates reduced SE rate in 12 studies (median reduction 28%, range 14-48%) with statistically significant reductions reported in 10 studies. Women with ABC and clinically evident bone metastases treated with Bs showed significant delays in the median time to SE. Compared with placebo or no B, treatment with Bs significantly improved bone pain in seven studies. Improvements in global QOL with Bisphosphonates compared to placebo were reported in the three ibandronate studies.

Treatment with Bisphosphonates does not appear to affect survival in women with ABC. Bisphosphonates in women with ABC without clinically evident bone metastases do not reduce SE incidence.

In three studies of PO clodronate(1653 women with EBC), skeletal metastases were not significantly reduced (RR 0.82; 95% CI 0.66-1.01; P = 0.07), and there was heterogeneity among these studies.

Reported toxicity was generally mild but osteonecrosis of the jaw has since been identified as a potential problem with long term IV Bisphosphonates highlighting a need for maintaining good oral care prior to and during treatment.

Authors' conclusions

In women with ABC and clinically evident bone metastases, Bisphosphonates (PO,IV)) reduce the risk of developing SEs and SE rate, as well as delaying the time to SE. Some Bisphosphonates may also reduce bone pain and may improve QOL. The optimal timing and duration of treatment is uncertain.

 

Plain language summary

Bisphosphonates for breast cancer.

When breast cancer has spread to the bones (bone metastases ), bisphosphonate drugs (added to anti-cancer treatment for breast cancer) can reduce pain, fractures and other bone problems. Women and men with advanced breast cancer commonly develop bone metastases. Cancer in bones can cause pain, fractures, hypercalcaemia (too much calcium in the blood) and spinal cord compression. This is because cancer deposits can erode into bone using bone-absorbing cells. Bisphosphonates are drugs that reduce the activity of these bone-absorbing cells. This review of trials in women with advanced breast cancer with bone metastases found that the use of bisphosphonates (in addition to their other cancer treatments) can reduce these serious bone problems. Adverse effects are not common, and include mild gut reactions, transient fever and hypocalcaemia, depending on which drug is used.

 

摘要

背景

雙磷酸鹽類藥物用於乳癌治療

骨骼是乳癌患者最常轉移的部位。雙磷酸類製劑能抑制蝕骨細胞所引起之骨在吸收作用。

目標

評估雙磷酸鹽用於早期轉移性乳癌女性患者，對其骨骼問題，骨頭疼痛及生活品質之影響。

搜尋策略

經由註冊、專業的考科藍乳癌小組收尋2007年1月資料，另外以人工進行期刊及會議紀錄蒐尋。

選擇標準

以隨機研究比較雙磷酸鹽類藥物與安慰劑，或不同的雙磷酸鹽類藥物對轉移性乳癌女性患者的影響。

資料收集與分析

經由二位評論者獨立評估研究試驗及分析資料。毒性資料由試驗報告中收集。

主要結論

收集了21個隨機研究。9個試驗(包括2189位早期轉移性乳癌和骨轉移女性患者)，與安慰劑或未使用雙磷酸鹽類藥物比較，使用雙磷酸鹽類藥物這一組降低骨骼問題17% (RR 0.83; 95% confidence interval (CI) 0.78 至0.89; P < 0.00001)。以靜脈注射pamidronate 90 mg (RR 0.77; 95% C .69 – 0.87)，靜脈注射zolendronate 4mg (RR 0.59; 95% CI 0.42 .82) 和口服clodronate 1600 mg (RR 0.84; 95% C .72 – 0.98)所得到的成效較佳。在一大型研究顯示，直接比較靜脈注射zolendronate和pamidronate具有相同的療效。雙磷酸鹽類在12個研究顯示出雙磷酸鹽類治療能降低發生骨骼問題的比率(平均降低28% ，範圍由14% 到48%)。其中10個研究呈現顯著統計意義。早期轉移性乳癌和臨床上明顯骨轉移的女性患者以雙磷酸鹽類藥物治療顯示明顯延緩發生骨骼問題的平均時間。在7個研究顯示，與雙磷酸鹽類製劑、安慰劑或未使用雙磷酸鹽類藥物比較，使用雙磷酸鹽類這一組能明顯降低骨骼疼痛問題。在3個以ibandronate做研究的試驗顯示，與安慰劑比較，雙磷酸鹽類能提高總體的生活品質。以雙磷酸鹽類藥物治療，對早期轉移性乳癌女性患者的存活率並不會影響。早期轉移性乳癌和臨床上明顯骨轉移的女性患者以雙磷酸鹽類藥物治療，不會降低骨骼問題的發生率。在以口服clodronate的3個研究(1653位早期乳癌女性患者)顯示對骨轉移並沒有明顯降低(RR 0.82; 95% CI 0.66 – 1.01; P .07)，而這3個研究有其差異性。使用雙磷酸鹽類藥物其毒性報告通常是輕微的，但使用長效靜脈注射雙磷酸鹽類會造成下顎骨壞死的潛在問題曾經被報導過，顯示在使用雙磷酸鹽類藥物，在治療期間持續做好對口腔照顧的重要性。

作者結論

轉移性乳癌和臨床上明顯骨轉移的女性患者以(口服，靜脈注射)雙磷酸鹽類藥物治療，降低發展成為骨骼問題和降低骨骼問題和的比率，同時也延緩發展成為骨骼問題的時間。有些雙磷酸鹽類藥物同時也可能降低骨骼疼痛和改善生活品質。最理想的治療時間和治療期間尚未確定。

翻譯人

本摘要由中山醫學大學附設醫院李建瑩翻譯。

此翻譯計畫由臺灣國家衛生研究院(National Health Research Institutes, Taiwan)統籌。

總結

標題：雙磷酸鹽類藥物用於乳癌治療。當乳癌患者有骨轉移時，雙磷酸鹽類藥物(乳癌患者抗腫瘤藥物之輔助治療)能降低疼痛，骨折和其他骨頭問題。轉移性乳癌的女性與男性患者通常會發展成為骨轉移。骨骼癌症通常會導致疼痛，高血鈣(血液中鈣離子太多)和脊椎壓迫。這是因為癌症的沉澱物會經由骨吸收細胞侵蝕至骨頭。此篇回顧轉移性乳癌合併骨轉移女性患者的研究發現使用雙磷酸鹽類藥物(乳癌患者抗腫瘤藥物之輔助治療)能降低這些嚴重骨頭問題。當使用雙磷酸鹽類藥物，發生副作用的情形並不高，包括輕度的腸道反應，短暫發燒和低血鈣。