【原】乳腺癌肝转移的奥沙利铂全身化疗或肝动脉化疗＋卡培他滨口服化疗

　　已知卡培他滨、奥沙利铂对转移性乳腺癌和肝脏肿瘤有效，而肝动脉栓塞灌注化疗对肝脏肿瘤有效。不过，奥沙利铂全身化疗或肝动脉栓塞灌注化疗＋卡培他滨口服化疗对乳腺癌肝转移患者的效果尚不明确。

　　2018年12月10日，欧洲乳腺癌专科学会《乳腺》在线发表丹麦哥本哈根大学海莱乌和根措夫特医院、瑞典隆德大学斯科讷医院的两项II期研究报告，探讨了奥沙利铂全身化疗或肝动脉栓塞灌注化疗＋卡培他滨口服化疗对于乳腺癌肝转移患者的有效性和安全性。

　　该两项II期研究MA0918和MA0919于2009年10月～2016年9月入组乳腺癌肝转移患者52例，其中肝转移14例、伴肝外转移38例，既往接受转移性乳腺癌化疗0～6次，中位2次。连续口服卡培他滨1300mg/m²联合奥沙利铂85mg/m²全身化疗与肝动脉化疗±可降解淀粉微球栓塞隔周交替。对其中4例患者进行奥沙利铂药代动力学分析。所有患者接受奥沙利铂全身化疗和肝动脉化疗±可降解淀粉微球栓塞时进行采样。

　　结果，总缓解率为42.3%（95%置信区间：28.7～56.8%），完全缓解率为7.7%，部分缓解率为34.6%。

　　中位无进展生存10.8个月（95%置信区间：6.9～14.7个月），中位总生存27.6个月（95%置信区间：20.4～34.8个月）。

　　毒性一般，最常见的3级不良事件为手足综合征、神经病变、疲劳、腹痛，发生率分别为15.4%、9.6%、9.6%、9.6%。腹痛仅见于肝动脉栓塞灌注化疗，可以控制。除了腹痛，全身化疗与肝动脉栓塞灌注化疗相比，毒性相似并且可以控制。

　　全身化疗与肝动脉栓塞灌注化疗相比，奥沙利铂的全身血药浓度相似。

　　因此，该研究结果表明，奥沙利铂肝动脉栓塞灌注化疗联合卡培他滨对于乳腺癌肝转移患者安全有效，缓解率较高，中位无进展生存和总生存时间较长。

Breast. 2018 Dec 10;43:113-119. [Epub ahead of print]

Hepatic arterial therapy with oxaliplatin and systemic capecitabine for patients with liver metastases from breast cancer.

S.C. Lindgaard, C.M. Brinch, B.K. Jensen, H.H. Norgaard, K.L. Hermann, S. Theile, F.O. Larsen, B.V. Jensen, H. Michelsen, K.M. Nelausen, V.H. Holm, L. Ekblad, Peter G. Soerensen, D.L. Nielsen.

Herlev & Gentofte Hospital, University of Copenhagen, Herlev, Denmark; Lund University, Skane University Hospital, Lund, Sweden.

HIGHLIGHTS

• HAT with oxaliplatin in patients with MBC is safe and efficient.

• In these phase 2 trials, the overall RR was 42.3%, median PFS 10.8 months, and median OS 27.6 months.

• HAT represents a potential loco-regional treatment for liver metastases.

• Abdominal pain was only seen after intrahepatic treatment but was manageable.

• Besides abdominal pain, toxicity was comparable and manageable between i.v. and HAT administrations.

OBJECTIVES: Hepatic arterial treatment (HAT) for liver metastases in patients with metastatic breast cancer (MBC) has only been investigated in few studies.

MATERIALS AND METHODS: Two phase II trials were initiated simultaneously to evaluate capecitabine in combination with oxaliplatin in patients with MBC and liver metastases. These two trials are reported together. Continuous capecitabine (1300 mg/m2) was combined with oxaliplatin (85 mg/m2) alternating between systemic treatment and HAT followed by degradable starch microspheres with EmboCept S every second week. Four patients participated in a pharmacokinetic analysis of oxaliplatin. Each patient had samples taken when receiving oxaliplatin systemically and as HAT with and without EmboCept S.

RESULTS: Totally, 52 patients received HAT: 14 with liver metastases only and 38 patients with additional limited metastatic disease. The patients had previously received a median of 2 (range 0-6) chemotherapeutic regimens for MBC. The response rate was 42.3% (95% confidence interval (CI) 28.7-56.8%) with 7.7% complete and 34.6% partial responses. Median progression free survival was 10.8 months (95% CI 6.9-14.7 months) and median overall survival 27.6 months (95% CI 20.4-34.8 months). The toxicity was moderate with hand-foot syndrome (15.4%), neuropathy (9.6%), fatigue (9.6%), and abdominal pain (9.6%) being the most common grade 3 adverse events. There was no clear difference between systemic blood concentrations of oxaliplatin when given systemic or as HAT.

CONCLUSION: HAT oxaliplatin in combination with capecitabine is safe and efficient in patients with MBC. The results are promising with high response rates and a long median progression free and overall survival.

KEYWORDS: Breast neoplasms, Capecitabine, Chemoembolization, Phase II, Oxaliplatin

DOI: 10.1016/j.breast.2018.12.002