Chemotherapy for advanced, recurrent or metastatic endometrial carcinoma

 

Abstract

Background

Endometrial adenocarcinoma is a common gynaecological cancer, but a comparatively small proportion of patients present with or develop recurrent or advanced disease. Progestogens are widely used, with little evidence of their efficacy. Co-morbidity including obesity and cardiac disease and concerns over toxicity have prevented more extensive studies of cytotoxic chemotherapy, although there are a number of active agents.

Objectives

To assess any benefits or adverse effects of cytotoxic chemotherapy in women with advanced, recurrent or metastatic endometrial adenocarcinoma.

Search methods

The major medical literature databases were searched for all known randomised controlled trials (RCTs), as were trials registers and reference lists of relevant publications.

Selection criteria

RCTs comparing chemotherapy versus another intervention (including different chemotherapy) in advanced disease were considered. Trials of adjuvant treatment or for sarcomatous tumours were excluded.

Data collection and analysis

Data were extracted from the papers by reviewers and authors of included studies contacted for further information.

Main results

Eleven eligible trials were identified which entered 2288 patients between 1974 and 2000. A meta-analysis of the 6 trials comparing more with less chemotherapy with combination was possible and included 1135 patients. Progression-free survival (PFS) was significantly improved (Hazard Ratio (HR) = 0.80, 95% Confidence Interval (CI) 0.71 to 0.90, p = 0.004), but there was only a trend toward improved survival (HR = 0.90, 95% CI 0.80 to 1.03). Toxicity was in general higher with the combination chemotherapy regimens. Only one trial showed a significant survival benefit from the addition of paclitaxel to combination chemotherapy, but this was at the expense of increased toxicity. There was insufficient evidence to assess whether there was any benefit from cytotoxic chemotherapy in terms of symptom control or QOL compared with best supportive care. There were no comparative trials of chemotherapy with endocrine therapy.

Authors' conclusions

The optimum cytotoxic drug regimen for advanced endometrial adenocarcinoma has still to be defined although our review suggests that it may contain paclitaxel or platinum. These mainly North American and European trial populations represent a highly selected subgroup of the 10,000 women dying annually from this disease. Future trials should include measures of QOL and symptom control in addition to PFS and overall survival (OS). They should also consider comparison of endocrine therapy and cytotoxic chemotherapy in patients with no prior drug therapy. Stratification of patients should take into account other prognostic factors including co-morbidity and prior radiation treatment.

 

Plain language summary

The best drug treatment for women with advanced cancer of the womb is still not clear

These women have a poor prognosis. Giving extra drugs seems to reduce disease progression by a small amount. However, it does not seem to allow women to live longer. Also, more chemotherapy seems to cause a greater amount of serious short-term side effects. Paclitaxel or platinum drugs may be better than other drugs. The effect of drug therapy on long-term side effects, control of symptoms and quality of life (QOL) was poorly studied. Also, no studies compared drug therapy with hormone therapy.

 

摘要

背景

末期、復發、或轉移性子宮內膜癌之化學治療

子宮內膜癌 (endometrial adenocarcinoma) 是一種常見之婦科癌症，但是相對較小部分之病患會以末期肺並表現，或是發展出復發。黃體素類已為廣泛使用，但其功效僅有極少證據。儘管存在諸多之活性劑，但包括肥胖及心臟病之共病以及對於毒性之顧慮使得我們無法針對細胞毒性化療進行更廣泛之研究。

目標

評估細胞毒性化療對於具有末期、復發、或轉移性子宮內膜癌之女性的任何效益或不良副作用。

搜尋策略

搜尋主要醫學文獻資料庫，以及試驗登錄庫及相關刊物之參考文獻表列，以辨識所有已知之隨機對照試驗 (RCTs) 。

選擇標準

將比較化療與另一干預措施 (包括不同之化療) 之RCTs納入考慮。排除輔助治療或針對肉瘤性腫瘤之試驗。

資料收集與分析

由回顧作者自研究報告摘錄數據，並與所收錄研究之作者聯繫以取得進一步之資訊。

主要結論

在1974年至2000年間，共辨識出11項適用之試驗，其中共收案2288名病患。可對其中6項試驗進行整合分析，該等試驗係針對較多與較少化療與組合療法，並包括1135名病患。無進程存活率 (progressionfree survival；PFS) 顯著改善 (風險比 (HR) = 0.80, 95% 信賴區間 (CI) 0.71 to 0.90, p = 0.004) ，但僅有存活率改善之趨勢 (HR = 0.90, 95% CI 0.80 to 1.03) 。組合藥物化療療程一般而言具有較高之毒性。僅有1項試驗顯示對於組合性化療添加paclitaxel具有顯著之存活效益，但此種結果之代價為較高之毒性。細胞毒性化療相對於最佳之支持性療法，就症狀控制或QOL而言。並無足夠證據可評估是否具有任何效益。並無任何針對化療與內分泌療法之比較性試驗，。

作者結論

對於末期子宮內膜腺癌之最佳細胞毒性藥物療程仍待定義，但我們的回顧建議，其可含有paclitaxel或鉑。此等主要為北美及歐洲之試驗對象群體代表了每年因此疾病而死亡之10,000名女性亞群。未來之試驗應包含PFS及整體存活率 (OS) 及對於QOL及症狀控制之量測。其應亦考量針對並無先前藥物治療的病患所進行之內分泌療法與細胞毒性化療的比較。病患之分層應將其他預後因子納入考量，包括共病以及先前之放射治療。

翻譯人

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

總結

對於末期子宮癌症女性之最佳藥物治療仍屬未明。這些女性具有較差之預後。給予額外之藥物似乎可少量減少疾病之進程。然而，其似乎並無法使這些女性存活得更久。同時，更多的化療似乎會造成較多之嚴重短期副作用。Paclitaxel或鉑類藥物可能優於其他藥物。藥物療法對於長期副作用、症狀控制及生活品質 (quality of life；QOL) 之作用並無良好的研究。同時，並無任何研究針對藥物療法與荷爾蒙療法進行比較。