| 2014年3月24日，日本MHLW批准大鹏药业Taiho Pharma的Lonsurf（TAS-102）（曲氟胸苷+tipiracil），用于治疗不可切除型或复发型晚期结直肠癌。 Lonsurf是一种新型抗代谢复方药物，由抗肿瘤核苷类似物FTD（三氟胸苷，trifluridine）和胸苷磷酸化酶抑制剂TPI（tipiracil）组成,用于对其他疗法（化疗及生物疗法）不再响应的难治性转移性结直肠癌（mCRC）患者的治疗。其中，FTD可在DNA复制过程中取代胸腺嘧啶直接掺入DNA双链，干扰癌细胞DNA的合成；TPI则能够抑制与FTD分解相关的胸腺磷酸化酶，减少FTD的降解。临床试验显示,与安慰剂组相比,Lonsurf治疗组的转移性结直肠癌死亡率显著性降低32%。Lonsurf由大冢制药开发,已于2014年3月获得日本监管部门批准,欧洲商业化权利归属施维雅公司。 New Drugs Online Report for trifluridine + tipiracil Information Generic Name: trifluridine + tipiracil Trade Name: Lonsurf Synonym: TAS-102 Entry Type: New molecular entity Development and Regulatory status UK: Recommended for approval (Positive opinion) EU: Recommended for approval (Positive opinion) US: Approved (Licensed) UK launch Plans: Available only to registered users Actual UK launch date: Comments Feb 16: EU positive opinion for treatment of adults with metastatic CRC who have been previously treated with, or are not considered candidates for, available therapies including fluoropyrimidine-, oxaliplatin- and irinotecan-based chemotherapies, anti-VEGF agents, and anti-EGFR agents [15]. 26/02/2016 12:40:12 Nov 15: UK launch is planned for Jun 2016 [14]. 23/11/2015 12:16:55 Sep 15: Lonsurf is manufactured by Taiho Oncology in Princeton, New Jersey [13]. 28/09/2015 10:57:22 Sep 15: Otsuka has signed a $130 million partnership with Servier for it to market the drug in the EU [13]. 28/09/2015 10:56:21 Sep 15: Approved in US to treat refractory metastatic colorectal cancer in patients whose tumours have spread despite first-line therapies [12]. 23/09/2015 09:08:01 Mar 15: Filed in the EU. The submission is based on data from the PIII RECOURSE trial [10]. 04/03/2015 11:39:58 Feb 15: The PDUFA goal date is December 19, 2015. [9] 24/02/2015 10:23:15 Dec 14: Taiho announced that it has completed its rolling New Drug Application (NDA) submission to the US FDA for TAS-102 (trifluridine or tipiracil hydrochloride) which is supported by the results from the Phase III RECOURSE trial [8]. 23/12/2014 12:08:16 Oct 14: Following positive results from the PIII RECOURSE trial (n=800), the US FDA granted Fast Track designation for TAS-102 (trifluridine and tipiracil hydrochloride) for the treatment of refractory metastatic colorectal cancer in pts whose disease had progressed after or who were intolerant to standard therapies. [7] 21/10/2014 12:44:50 Jun 14: A regulatory submission in Europe is planned in 2015 [6]. 02/07/2014 11:59:10 PIII trial to start June 2012 [2] 01/06/2012 13:09:20 Trial or other data Nov 15: NICE FAD due Sep 2016 according to Servier [14]. 23/11/2015 12:19:49 May 15: Results of RECOURSE trial published in NEJM [11]. 17/05/2015 18:35:09 Jun 14: In the PIII RECOURSE trial, TAS-102 improved median overall survival in patients with refractory metastatic colorectal cancer by 1.8 months compared to placebo [6]. 02/07/2014 11:58:56 Mar 13: Estimated RECOURSE completion date December 2014 [4]. 11/03/2013 14:56:42 Aug 12: Japanese PII trial published early online in Lancet Oncology. Eligible pts were 20 years or older; had confirmed colorectal adenocarcinoma; have an ECOG performance status of between 0 and 2; had a treatment history of two or more regimens of standard chemotherapy; and were refractory or intolerant to fluoropyrimidine, irinotecan, and oxaliplatin. Pts were randomised to TAS-102 (n=112; 35 mg/m2 given orally twice a day in a 28-day cycle [2-week cycle of 5 days of treatment followed by a 2-day rest period, and then a 14-day rest period]) or placebo (n=57); all pts received best supportive care. After a median follow up period of 11.3 months, median overall survival, the primary endpoint, was 9.0 months in the TAS-102 arm & 6.6 months in the placebo group (hazard ratio for death 0.56, 80% CI 0.44-0.71, 95% CI 0.39-0.81; p=0.0011). 57 (50%) of 113 pts given TAS-102 in the safety population had neutropenia of grade 3 or 4, 32 (28%) leucopenia, & 19 (17%) anaemia. No pt given placebo had grade 3 or worse neutropenia or leucopenia; three (5%) of 57 had grade 3 or worse anaemia. Serious adverse events occurred in 19% pts in the TAS-102 group & in 9% in the placebo group. No treatment-related deaths occurred [3]. 30/08/2012 10:12:50 May 12: The global PIII trial (RECOURSE) will start in June 2012. The double-blind, placebo-controlled RCT will compare TAS-102 with best supportive care in 800 patients with advanced recurrent colorectal cancer that is both unresectable and relapsed/refractory to standard chemotherapies (including fluoropyrimidines, irinotecan, oxaliplatin, bevacizumab and, in the case of patients with tumours with wild-type KRAS gene, an anti-EGFR monoclonal antibody). The primary endpoint is overall survival [2]. 01/06/2012 13:09:33 July 11: Phase II trial in 172 patients refractory to standard chemotherapy for metastatic colorectal cancer who have received at least two or more regimens containing a fluoropyrimidine, irinotecan, and oxaliplatin. Patients were randomly assigned to the TAS-102 (n=114) or a placebo (n=58). The primary endpoint was overall survival. TAS-102 and placebo were administered at dose of 70mg/m2/day twice daily for five days followed by two days rest and repeated twice. This was followed by a 14-day rest period to make a 28-day schedule for one course. In both cohorts, the 28-day cycle was repeated until the established criteria for termination were met. [1] 25/07/2011 08:47:39 TAS-102 is a novel oral nucleoside antitumor agent with a novel mechanism of action, composed of a mixture of Trifluorothymidine (FTD), which demonstrates antitumor effects through incorporation into DNA, and 5-chloro-6-(2-iminopyrrolidin-1-yl)-methyl-2,4(1H,3H)-pyrimidinedione hydrochloride (TPI), which inhibits the degradation of FTD. [1] 25/07/2011 08:44:53 References Available only to registered users Category BNF Category: Other antineoplastic drugs (08.01.05) Pharmacology: a mix of FTD, which has antitumour effects through incorporation into DNA, and TPI which inhibits FTD degradation Epidemiology: The age-standardised incidence rate per 100,000 population in the UK in 2008 was 47.2 (29.4 colon, 17.8 rectum). The figures were higher for men than women for both colon and rectal cancers [5]. Indication: Colorectal cancer Additional Details: metastatic in adults previously treated with, or are not considered suitable for fluoropyrimidine-based chemotherapy, anti-VEGF therapy, and/or anti-EGFR therapy Method(s) of Administration Oral Company Information Name: Servier US Name: Otsuka Further Information Anticipated commissioning route (England) NHSE High cost drug list? Awaiting Update In NICE timetable: Yes When: / Note: awaiting update Implications Available only to registered users |
抗癌复方新药Lonsurf（TAS-102）获日本批准治疗晚期结直肠癌简介：
2014年3月24日，日本MHLW批准大鹏药业Taiho Pharma的Lonsurf（TAS-102）（曲氟胸苷+tipiracil），用于治疗不可切除型或复发型晚期结直肠癌。Lonsurf是一种新型抗代谢复方药物，由抗肿瘤核苷类似物FTD（三 ... 责任编辑：admin
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