Continuing Therapy beyond Adjuvant Chemotherapy to Optimise Cure in Advanced Ovarian Cancer: a Dream Coming True?

Full Article

RKC Ngan

Hong Kong J Radiol 2010;13(Suppl):S33-41

The GOG111 and OV-10 were pivotal studies published in 1996 and 2000 respectively which established paclitaxel / cisplatin as standard postoperative adjuvant chemotherapy for advanced epithelial ovarian cancers. A second major breakthrough in the ensuing past decade has yet to be witnessed. Carboplatin has been proven to confer similar efficacy when combined with paclitaxel with much less neurotoxicity in the GOG158 and AGO studies that were reported in 2003, and have since been adopted as standard clinical practice. Replacing paclitaxel with docetaxel, delivery of cisplatin intraperitoneally, or adding a third agent to form triplets have not produced impressive improvements. Moreover, they were not widely accepted due to technical difficulties and unacceptable toxicities. For stage III/IV cancers, despite a high clinical response rate of 70 to 80% and a pathological complete response rate of ~30% after 6 to 8 cycles of paclitaxel / carboplatin following primary cytoreductive surgery, the median overall survival remains relatively low at ~26 months for those with bulky residuum, and ~60 months for those with optimal cytoreduction, translating into a 5-year overall survival of ~30 to 40%. The median progression-free survival remains at around 16 months only for patients with stage IV and stage III disease after suboptimal cytoreduction, and at 24 months only even for those with stage III after optimal cytoreduction. The resulting low 5-year progression-free survival of approximately 20% indicated continuous disease relapses or progression following postoperative chemotherapy and hence the concept of effective consolidation or maintenance therapy appeared attractive. Over the years, studies involving sequential / consolidation standard-dose oral or intravenous ‘second-line’ chemotherapy, intraperitoneal chemotherapy, highdose chemotherapy with stem cell transplantation, external beam radiotherapy or intraperitoneal radiotherapy with radioactive phosphorus or radioactive monoclonal antibody have largely failed to improve outcomes. More recently, results of randomised studies testing biological therapies such as interferon, CA125-specific monoclonal antibody, multi-targeting agents and anti-angiogenesis targeted therapy have also been reported, but yielded variable results. Early results from 2 recent randomised studies suggest progression-free survival benefit by adding bevacizumab concurrently with, and then as prolonged maintenance therapy following postoperative adjuvant paclitaxel / carboplatin chemotherapy.



治療晚期卵巢癌後的輔助化療以外再施以持續療法為病人帶來最佳效果: 夢想是否可以成真?


分別發表在1996及2000年的兩項關鍵性研究(GOG111及OV-10)確立了用紫杉醇(paclitaxel)/順鉑 (cisplatin)作為晚期上皮性卵巢癌的標準術後輔助化療,在其後十年卻再沒有突破。在2003年發表的GOG158及AGO研究指出,卡鉑(carboplatin)加紫杉醇和以往的順鉑加紫杉醇效果相若,而且神 經毒性大幅度減少,自此被引入作為標準臨床使用。把多西他賽(docetaxel)替代紫杉醇,並在腹 腔內注入順鉑,或加入第三種製劑,療效並不顯著增加;而且由於技術上的困難和毒性反應有所增 加,這些方法不被廣泛接受。第三/四期卵巢癌患者在進行第一次卵巢癌減積手術並接受6至8周期紫 杉醇加卡鉑的化療後,儘管有70至80%的高反應率及30%的病理完全反應率,總存活率中位數仍處於 低水平。有大型殘餘腫瘤的病人,中位生存期約為26個月;而腫瘤減積達至最佳效果的病人,中位 生存期則約為60個月;相當於30至40%的五年生存率。腫瘤減積未達至最佳效果的第三/四期病人, 其無惡化生存期的中位數只有大約16個月。就算是腫瘤減積達理想效果的第三期病人,其無惡化生 存期中位數亦只有24個月。只有20%的五年總生存率,顯示癌病在接受化療後會不斷復發或繼續惡 化,因此進行有效的鞏固治療或維持治療的概念顯得很吸引。多年來,有很多研究關於序貫或鞏固 性的治療,如用標準劑量的口服或靜脈注射的二線化療、腹腔化療、高劑量化療併幹細胞移植、體 外放射治療、或以放射性磷及放射性單克隆抗體作腹腔內放射治療,可是它們大多數都未能提升療 效。最近有一些測試生物治療的隨機對照研究,如使用干擾素、CA125單克隆抗體、多靶向製劑及 抗血管生長標靶治療等,但報導的療效並不一致。兩個近期發表的隨機對照研究中,其早期結果顯 示術後紫杉醇加卡鉑輔助化療中加入同步貝伐珠單抗(bevacizumab),及以其作為維持療法有助延 長無惡化生存期。