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英文药名：Lonsurf tablet（trifluridine/tipiracil(TAS-102)）
中文药名：tipiracil盐酸盐/曲氟尿苷复方片
生产厂家：大鹏药品
药品介绍
LONSURF(trifluridine and tipiracil tablet)-是一种新型抗代谢复方药，将为难治性转移性结直肠癌（mCRC）患者提供一种重要的新治疗选择
2015年9月22日，美国FDA批准抗癌复方新药Lonsurf(trifluridine/tipiracil)的合成。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。Lonsurf(trifluridine/tipiracil/TAS-102)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。其中，FTD可在DNA复制过程中取代胸腺嘧啶直接掺入DNA双链，导致DNA功能障碍，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，维持FTD的血药浓度。
作用机制
LONSURF是基于胸苷核苷类似物，曲氟尿苷，和胸苷磷酸化酶抑制剂，tipiracil组成，在克分子浓度比值1:0.5(重量比值，1:0.471)。包括tipiracil通过胸苷磷酸化酶抑制其代谢增加曲氟尿苷暴露。
摄入癌细胞后，曲氟尿苷背掺入至DNA，干扰DNA合成和抑制细胞增殖。曲氟尿苷/tipiracil在异种移植物小鼠显示对KRAS野生型和突变体人结肠直肠癌的抗肿瘤活性。
适应证和用途
LONSURF是曲氟尿苷，核苷代谢抑制剂，和tipiracil，胸苷磷酸化酶抑制剂，的联用适用为患者有转移结肠直肠癌以前治疗过用基于氟嘧啶[fluoropyrimidine]-，奥沙利铂[oxaliplatin]-和伊立替康[irinotecan]-化疗，一种抗-VEGF生物学治疗，和如RAS野生型，一种抗-EGFR治疗的治疗。
剂量和给药方法
⑴ 推荐剂量：35 mg/m2/dose口服每天2次在每28天疗程第1至5天和第8至12 of天。
⑵ 早晨和傍晚餐完成后1小时内服用LONSURF。
剂型和规格
片：
⑴15 mg 曲氟尿苷/6.14 mg tipiracil
⑵20 mg 曲氟尿苷/8.19 mg tipiracil
包装规格
LONSURF 15-6.14MG TAB 20/EA TRIFLURIDINE/TIPIRACIL 64842-1025-01
LONSURF 20-8.19MG TAB 20/EA TRIFLURIDINE/TIPIRACIL 64842-1020-01
LONSURF 15-6.14MG TAB 60/EA TRIFLURIDINE/TIPIRACIL 64842-1025-03
LONSURF 20-8.19MG TAB 60/EA TRIFLURIDINE/TIPIRACIL 64842-1020-03
LONSURF®(trifluridine and tipiracil)
Pharmacological Class:
Antineoplastic thymidine-based nucleoside analog + thymidine phosphorylase inhibitor.
Active Ingredient(s):
Trifluridine, tipiracil; 15mg/6.14mg, 20mg/8.19mg; tablets.
Company
Taiho Oncology, Inc.
Indication(s):
Treatment of metastatic colorectal cancer in patients previously treated with fluoropyrimidine-, oxaliplatin- and irinotecan-based chemotherapy, an anti-VEGF biological therapy, and if RAS wild-type, an anti-EGFR therapy.
Pharmacology:
Lonsurf consists of trifluridine, a thymidine-based nucleoside analog, and tipiracil, a thymidine phosphorylase inhibitor. Inclusion of tipiracil increases trifluridine exposure by inhibiting its metabolism by thymidine phosphorylase. Following uptake into cancer cells, trifluridine is incorporated into DNA and inhibits cell proliferation.
Clinical Trials:
The clinical efficacy and safety of Lonsurf were evaluated in an international, randomized, double-blind, placebo-controlled study conducted in 800 patients with previously treated metastatic colorectal cancer (CRC). Study patients were randomized 2:1 to receive Lonsurf plus best supportive care (BSC) or matching oral placebo plus BSC.
The major efficacy outcome measure was overall survival (OS) and an additional outcome measure that was progression-free survival (PFS). All patients received prior treatment with fluoropyrimidine-, oxaliplatin-, and irinotecan-based chemotherapy.
A statistically significant improvement in OS and PFS were demonstrated in patients in the Lonsurf plus BSC arm vs. the placebo plus BSC arm. Median OS was 7.1 months (95% CI: 6.5, 7.8) in the Lonsurf arm vs. 5.3 months (95% CI: 4.6, 6.0) in the placebo arm; (hazard ratio [HR] = 0.68, [95% CI: 0.58, 0.81]; P <0.001). Patients in the Lonsurf arm also demonstrated greater PFS than the placebo arm (HR = 0.47, [95% CI: 0.40, 0.55]; P <0.001).
For more clinical trial data, see full labeling.
Legal Classification:
Rx
Adults:
Take within 1 hour after completion of AM & PM meals. Initially 35mg/m2 twice daily on Days 1–5 and 8–12 of each 28-day cycle until disease progression or unacceptable toxicity; max 80mg per dose (based on trifluridine component). Dose modifications: see full labeling.
Children:
Not established.
Warnings/Precautions:
Obtain CBC prior to and on Day 15 of each cycle, and as clinically indicated. Do not initiate cycle until ANC ≥1,500/mm3 or febrile neutropenia is resolved, platelets ≥75,000/mm3 or Grade 3/4 non-hematological adverse reactions resolved to Grade 0/1. Withhold dose if ANC <500/mm3 or febrile neutropenia, platelets <50,000/mm3, or Grade 3/4 non-hematological adverse reactions occur; upon recovery, resume at a reduced dose (see full labeling). Moderate or severe hepatic impairment: not studied. Moderate renal impairment: may require dose modification; severe (CrCl <30mL/min) or ESRD: not studied. Elderly. Pregnancy. Females of reproductive potential must use effective contraception during treatment; males must use condoms during and for ≥3 months after final dose. Nursing mothers: not recommended (during and for 1 day after final dose).
Adverse Reaction(s)
Anemia, neutropenia, asthenia/fatigue, nausea, thrombocytopenia, decreased appetite, diarrhea, vomiting, abdominal pain, pyrexia.
How Supplied:
Tabs—20, 40, 60
LAST UPDATED:
12/17/2015
LONSURF® (trifluridine and tipiracil) approved for refractory metastatic colorectal cancer
LONSURF was approved by the U.S. Food and Drug Administration on September 22, 2015, for the treatment of patients with metastatic colorectal cancer who have been previously treated with fluoropyrimidine-, oxaliplatin- and irinotecan-based chemotherapy, an anti-VEGF biological therapy, and if RAS wild-type, an anti-EGFR therapy.
Important Safety Information
WARNINGS AND PRECAUTIONS
Severe Myelosuppression: In Study 1, LONSURF caused severe and life-threatening myelosuppression (Grade 3-4) consisting of anemia (18%), neutropenia (38%), thrombocytopenia (5%), and febrile neutropenia (3.8%). One patient (0.2%) died due to neutropenic infection. In Study 1, 9.4 percent of LONSURF-treated patients received granulocyte-colony stimulating factors.
Obtain complete blood counts prior to and on Day 15 of each cycle of LONSURF and more frequently as clinically indicated. Withhold LONSURF for febrile neutropenia, Grade 4 neutropenia, or platelets less than 50,000/mm3. Upon recovery, resume LONSURF at a reduced dose.
Embryo-Fetal Toxicity: LONSURF can cause fetal harm when administered to a pregnant woman. Advise pregnant women of the potential risk to the fetus. Advise females of reproductive potential to use effective contraception during treatment with LONSURF.
USE IN SPECIFIC POPULATIONS
Lactation: It is not known whether LONSURF or its metabolites are present in human milk. There are no data to assess the effects of LONSURF or its metabolites on the breastfed infant or the effects on milk production. Because of the potential for serious adverse reactions in breastfeeding infants, advise women not to breastfeed during treatment with LONSURF and for one day following the final dose.
Male Contraception: Advise males with female partners of reproductive potential to use condoms during treatment with LONSURF and for at least 3 months after the final dose.
Geriatric Use: Grade 3 or 4 neutropenia and thrombocytopenia and Grade 3 anemia occurred more commonly in patients 65 years old or older who received LONSURF.
Renal Impairment: Patients with moderate renal impairment may require dose modifications for increased toxicity. No patients with severe renal impairment were enrolled in Study 1.
Hepatic Impairment: Patients with moderate or severe hepatic impairment were not enrolled in Study 1.
ADVERSE REACTIONS
Most Common Adverse Drug Reactions in Patients Treated with LONSURF (> or = 5 percent): The most common adverse drug reactions in LONSURF-treated patients vs placebo-treated patients with refractory mCRC, respectively, were: asthenia/fatigue (52% vs 35%), nausea (48% vs 24%), decreased appetite (39% vs 29%), diarrhea (32% vs 12%), vomiting (28% vs 14%), abdominal pain (21% vs 18%), pyrexia (19% vs 14%), stomatitis (8% vs 6%), dysgeusia (7% vs 2%), and alopecia (7% vs 1%).
Additional Important Adverse Drug Reactions: The following occurred more frequently in LONSURF-treated patients compared to placebo: infections (27% vs 15%), and pulmonary emboli (2% vs 0%).
Interstitial lung disease (0.2%), including fatalities, has been reported in clinical studies and clinical practice settings in Asia.
Laboratory Test Abnormalities in Patients Treated with LONSURF: Laboratory test abnormalities in LONSURF-treated patients vs placebo-treated patients with refractory mCRC, respectively, were: anemia (77% vs 33%), neutropenia (67% vs 1%), and thrombocytopenia (42% vs 8%).
https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=f5beed22-d71d-4c0d-8dca-2c7317d65d85 |
