Ochiai Takumi, Nishimura Kazuhiko, Watanabe Tomoo, Kitajima Masayuki, Nakatani Akinori, Nagayasu Kiichi, Naito Shigetoshi, Sato Tsuyoshi, Kishine Kenji, Abe Yu, Hara Chihiro, Yamada Susumu, Mashiko Satomi, Nagaoka Isao
Department of Surgery, Tobu Chiiki Hospital, Tokyo Metropolitan Health and Medical Treatment Corporation, Tokyo 125-8512, Japan.
Department of Pharmacy, Tobu Chiiki Hospital, Tokyo Metropolitan Health and Medical Treatment Corporation, Tokyo 125-8512, Japan.
Oncol Lett. 2017 Nov;14(5):6045-6052. doi: 10.3892/ol.2017.6960. Epub 2017 Sep 15.
Leucovorin (FOL) and fluorouracil (5-FU) plus oxaliplatin (l-OHP; FOLFOX) or FOL and 5-FU plus irinotecan (SN-38; FOLFIRI) are widely used as first-line chemotherapy regimens in the treatment of advanced colorectal cancer (CRC). However, second-line chemotherapy must be abandoned in certain cases due to disease progression, adverse effects or high medical cost. Therefore, the most effective regimen should be selected as first-line chemotherapy. We reported that individualization of first-line treatment (FOLFOX/FOLFIRI/Dual/Poor responder) was possible using the collagen gel droplet-embedded culture drug sensitivity test (CD-DST) and that individualized first-line chemotherapy with CD-DST may improve the prognosis of patients with unresectable CRC. The aim of the present prospective cohort study was to evaluate the individualization of first-line chemotherapy using CD-DST, with a focus on prognosis. Between March 2008 and December 2015, tumor specimens were obtained from 120 patients with CRC who had not received preoperative chemotherapy. CD-DST was performed and the growth inhibition rate (IR) was determined by exposure for 24 h with 5-FU and l-OHP (6.0 and 3.0 µg/ml, respectively) and 5-FU and SN-38 (6.0 and 0.2 µg/ml, respectively). The cumulative distribution of IR values under each condition was evaluated on the basis that the clinical response to FOLFOX and FOLFIRI is equivalent (~50%). The prognosis of dual responder was improved compared with that of poor responders, however this difference was identified to be significant. There was no different prognosis between patients treated with an appropriate first-line regimen and patients treated with an inappropriate first-line regimen in dual responders. However, in poor responders, there were significant differences of prognosis between patients treated with an appropriate first-line regimen and patients treated with an inappropriate first-line regimen (P=0.036). In conclusion, the results from the present study suggest that administration of the recommended first-line regimen using CD-DST for patients with unresectable CRC is important for the improvement of prognosis, particularly in poor responders.
亚叶酸（FOL）、氟尿嘧啶（5-FU）联合奥沙利铂（l-OHP；FOLFOX）或FOL、5-FU联合伊立替康（SN-38；FOLFIRI）被广泛用作晚期结直肠癌（CRC）的一线化疗方案。然而，由于疾病进展、不良反应或高昂的医疗费用，在某些情况下必须放弃二线化疗。因此，应选择最有效的方案作为一线化疗。我们报告了使用胶原凝胶滴包埋培养药物敏感性试验（CD-DST）实现一线治疗个体化（FOLFOX/FOLFIRI/双敏感/低反应者）是可行的，并且采用CD-DST的个体化一线化疗可能改善不可切除CRC患者的预后。本前瞻性队列研究的目的是评估使用CD-DST进行一线化疗的个体化情况，重点关注预后。在2008年3月至2015年12月期间，从120例未接受术前化疗的CRC患者中获取肿瘤标本。进行CD-DST，并通过分别用5-FU和l-OHP（分别为6.0和3.0μg/ml）以及5-FU和SN-38（分别为6.0和0.2μg/ml）处理24小时来测定生长抑制率（IR）。基于对FOLFOX和FOLFIRI的临床反应相当（约50%）来评估每种条件下IR值的累积分布。双敏感者的预后较低反应者有所改善，但这种差异被确定具有显著性。在双敏感者中，接受合适一线方案治疗的患者与接受不合适一线方案治疗的患者之间预后无差异。然而，在低反应者中，接受合适一线方案治疗的患者与接受不合适一线方案治疗的患者之间预后存在显著差异（P=0.036）。总之，本研究结果表明，对于不可切除的CRC患者，使用CD-DST给予推荐的一线方案对改善预后很重要，尤其是在低反应者中。
