Delving into the Latest Updates on Tegafur/Leucovorin calcium/Gimeracil/Oteracil Potassium with Synapse

Overview

Basic Info

Drug Type

Small molecule drug

Synonyms

Folinic acid/S-1, Gimeracil/oteracil potassium/tegafur/calcium folinate, Gimeracil/oteracil potassium/tegafur/folinic acid

+ [6]

Target

TYMS

Mechanism

TYMS inhibitors(Thymidylate synthase inhibitors), DNA synthesis inhibitors

Therapeutic Areas

NeoplasmsDigestive System Disorders

Active Indication-

Inactive Indication

Advanced gastric carcinoma

Originator Organization

Taiho Pharmaceutical Co., Ltd.

Active Organization-

Inactive Organization

Taiho Pharmaceutical Co., Ltd.

Drug Highest PhasePendingPhase 3

First Approval Date-

Regulation-

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Structure

Molecular FormulaC5H4ClNO2

InChIKeyZPLQIPFOCGIIHV-UHFFFAOYSA-N

CAS Registry103766-25-2

View All Structures (4)

Author: Wakatsuki, Takeru ; Ishizuka, Naoki ; Mikami, Shinya ; Wada, Takeyuki ; Yoshikawa, Takaki ; Nakayama, Izuma ; Ohashi, Manabu ; Shoji, Hirokazu ; Nunobe, Souya ; Boku, Narikazu ; Doi, Ayako ; Kumagai, Koshi ; Takashima, Atsuo ; Sano, Takeshi ; Chin, Keisho ; Yamaguchi, Kensei ; Izawa, Naoki ; Iwasa, Satoru ; Ida, Satoshi ; Takahari, Daisuke ; Katai, Hitoshi

BACKGROUNDWe investigated the feasibility of perioperative chemotherapy with S-1 and leucovorin (TAS-118) plus oxaliplatin in patients with locally advanced gastric cancer.METHODSPatients with clinical T3-4N1-3M0 gastric cancer received four courses of TAS-118 (40-60 mg/body, orally, twice daily for seven days) plus oxaliplatin (85 mg/m², intravenously, day one) every two weeks preoperatively followed by gastrectomy with D2 lymphadenectomy, followed by postoperative chemotherapy with either 12 courses of TAS-118 monotherapy (Step 1) or eight courses of TAS-118 plus oxaliplatin (Step 2). The primary endpoints were completion rates of preoperative chemotherapy with TAS-118 plus oxaliplatin and postoperative chemotherapy with TAS-118 monotherapy (Step 1) or TAS-118 plus oxaliplatin (Step 2).RESULTSAmong 45 patients enrolled, the preoperative chemotherapy completion rate was 88.9% (90% CI 78.0-95.5). Major grade ≥ 3 adverse events (AEs) were diarrhoea (17.8%) and neutropenia (8.9%). The R0 resection rate was 95.6% (90% CI 86.7-99.2). Complete pathological response was achieved in 6 patients (13.3%). Dose-limiting toxicity was not observed in 31 patients receiving postoperative chemotherapy (Step 1, n = 11; Step 2, n = 20), and completion rates were 90.9% (95% CI 63.6-99.5) for Step 1 and 80.0% (95% CI 59.9-92.9) for Step 2. No more than 10% of grade ≥ 3 AEs were observed in patients receiving Step 1. Hypokalaemia and neutropenia occurred in 3 and 2 patients, respectively, receiving Step 2. The 3-year recurrence-free and overall survival rates were 66.7% (95% CI 50.9-78.4) and 84.4% (95% CI 70.1-92.3), respectively.CONCLUSIONSPerioperative chemotherapy with TAS-118 plus oxaliplatin with D2 gastrectomy is feasible.

01 Aug 2020·The Lancet OncologyQ1 · MEDICINE

TAS-118 plus oxaliplatin in advanced gastric cancer: is it worth it?

Q1 · MEDICINE

Article

Author: Adenis, Antoine ; Samalin, Emmanuelle

A review.Practices are changing overtime,and geog. differences in the treatment of localised and metastatic gastric cancer are becoming increasingly less pronounced,even though some medications are not available or are not reimbursed equally in all countries.Regarding the use of fluoropyrimidines,capecitabine or S-1 can be used as an alternative to infusional fluorouracil in doublet regimens.In addition ciplatin or oxaliplatin are viewed as platinum agents with similar effectiveness when incorporated in doublet or triplet regimens although this aspect remains a matter of debate.S-1 plus cisplatin has been widely used in eastern Asia,whereas infusional fluorouracil (plus leucovorin) or capecitabine,combined with oxaliplatin or cisplatin,are standard practices in Europe and North America.As a conclusion to the SOLAR study,Kang and colleagues suggest that the combination of TAS-118 plus oxaliplatin could be a new first-line standard chemotherapy for advanced gastric cancer,in Asian patients.First,it would have been reasonable to the added value of leucovorin to S-1,by comparing TAS-118 (S-1 plus leucovorin) plus oxaliplatin with S-1 plus oxaliplatin (rather than S-1 plus cisplatin).Second,as the TAS-118 plus oxalipaltin combination appears effective in patients with Lauren's diffuse-type histol. and poor prognosis,we suggest clin. research should focus on this group.Third,TAS-118 plus oxaliplatin deserves to also be tested in non-Asian patients,although it is known that S-1 is not equally tolerated in non-Asian patients and Asian patients.Finally,ongoing phase 3 trials will elucidate the role of many promising compounds such as trifluridine-tipiracil,anti-CLDN18.2 monoclonal antibodies (zolbetuximab), or checkpoint inhibitors, in other clin. relevant subsets of patients with advanced HER2-neg. gastric cancer ,including frail or fit patients, with diffuse type histol., and CLDN18.2-pos. or microsatellite-unstable tumors.

01 Aug 2020·The Lancet OncologyQ1 · MEDICINE

S-1 plus leucovorin and oxaliplatin versus S-1 plus cisplatin as first-line therapy in patients with advanced gastric cancer (SOLAR): a randomised, open-label, phase 3 trial

Q1 · MEDICINE

Article

Author: Ryu, Min-Hee ; Miyata, Yoshinori ; Baba, Hideo ; Kang, Yoon-Koo ; Hara, Hiroki ; Tsuda, Masahiro ; Nakayama, Norisuke ; Chung, Ik-Joo ; Chung, Hyun Cheol ; Chin, Keisho ; Kadowaki, Shigenori ; Lee, Keun-Wook ; Bang, Yung-Jue ; Hyodo, Ichinosuke ; Hosaka, Hisashi ; Hironaka, Shuichi ; Park, Se Hoon ; Boku, Narikazu ; Oh, Sang Cheul

BACKGROUNDS-1 plus leucovorin and oxaliplatin showed promising efficacy for treatment of advanced gastric cancer in a randomised phase 2 study. We aimed to evaluate the efficacy and safety of oral TAS-118 (S-1 plus leucovorin) and oxaliplatin versus S-1 plus cisplatin in patients with advanced gastric cancer.METHODSWe did a randomised, open-label, phase 3 trial in 62 centres across Japan and South Korea. Patients aged 20 years or older, with a histologically confirmed advanced gastric cancer with negative or unknown HER2 status, with Eastern Cooperative Oncology Group performance status of 0 or 1, measurable or evaluable metastatic lesions, and no previous treatment were randomly assigned (1:1) via an interactive web response system using the minimisation method, stratified by performance status, presence of a measurable lesion, and country, to receive TAS-118 (S-1 40-60 mg and leucovorin 25 mg orally twice daily for 7 days) plus oxaliplatin (85 mg/m² intravenously on day 1) every 2 weeks, or S-1 (40-60 mg orally twice daily) for 21 days plus cisplatin (60 mg/m² intravenously on day 1 or 8) every 5 weeks. The primary endpoint was overall survival in patients who had advanced gastric cancer with measurable or evaluable metastatic lesions and who received the study drug. Safety was assessed in all patients who received the study drug. This study was registered at ClinicalTrials.gov, NCT02322593.FINDINGSBetween Jan 28, 2015, and Dec 5, 2016, 711 patients were randomised to TAS-118 plus oxaliplatin (n=356) or S-1 plus cisplatin (n=355). 11 untreated patients and 19 ineligible patients were excluded from the primary analysis (TAS-118 plus oxaliplatin group n=347, S-1 plus cisplatin group n=334) following recommendation from the independent data monitoring committee. After median follow-up of 26·0 months (IQR 22·0-32·8), median overall survival was 16·0 months (95% CI 13·8-18·3) in the TAS-118 plus oxaliplatin group and 15·1 months (95% CI 13·6-16·4) in the S-1 plus cisplatin group (hazard ratio 0·83, 95% CI 0·69-0·99; p=0·039). The most common grade 3 or higher adverse events in the 352 patients in the TAS-118 plus oxaliplatin group and the 348 patients in the S-1 plus cisplatin group were anaemia (56 [16%] vs 64 [18%]), neutropenia (54 [15%] vs 88 [25%]), decreased appetite (53 [15%] vs 46 [13%]), diarrhoea (33 [9%] vs 15 [4%]), and peripheral sensory neuropathy (30 [9%] vs one [<1%]). Serious adverse events were observed in 155 (44%) of 352 patients in the TAS-118 plus oxaliplatin group and 159 (46%) of 348 patients in the S-1 plus cisplatin group. Two treatment-related deaths occurred in the TAS-118 plus oxaliplatin group (pulmonary tuberculosis and viral pneumonia).INTERPRETATIONTAS-118 plus oxaliplatin showed a clinically meaningful improvement in efficacy compared with S-1 plus cisplatin, and could be considered a new first-line treatment option for advanced gastric cancer in Asian patients.FUNDINGTaiho Pharmaceutical and Yakult Honsha.

100 Deals associated with Tegafur/Leucovorin calcium/Gimeracil/Oteracil Potassium

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R&D Status

10 top R&D records.

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Indication	Highest Phase	Country/Location	Organization	Date
Advanced gastric carcinoma	Phase 3	KR	Taiho Pharmaceutical Co., Ltd.	01 Dec 2014
Advanced gastric carcinoma	Phase 3	JP	Taiho Pharmaceutical Co., Ltd.	01 Dec 2014

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Clinical Result

Indication

Phase

Evaluation

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Study	Phase	Population	Analyzed Enrollment	Group	Results	Evaluation	Publication Date


NCT02322593 (SOLAR \| SOLAR study, CTgov)	Phase 3	Advanced gastric carcinoma	711	TAS-118+Oxaliplatin (TAS-118/Oxaliplatin)	(blunmeiqwg) = coufbyadjz nejhtgobyk (ftypwgxrsq, evmsrilubk - kdysmoufjy) View more	-	20 Dec 2021
NCT02322593 (SOLAR \| SOLAR study, CTgov)	Phase 3	Advanced gastric carcinoma	711	S-1+cisplatin (S-1/Cisplatin)	(blunmeiqwg) = ekhavbtbnr nejhtgobyk (ftypwgxrsq, bvpncnyjnf - vqtwlvokmn) View more	-	20 Dec 2021
EPOC1604 (ESMO2019)	Phase 2	Advanced gastric carcinoma	20	TAS-114 and S-1 combination	(qpkejxgfqk) = zhxhuukjcj fxkcipdtkx (hfkjvjfzml, 0.1 - 24.9) View more	-	29 Sep 2019
NCT02322593 (SOLAR study, ESMO_GI2019)	Phase 3	Advanced gastric carcinoma First line HER2-negative	711	TAS-118 plus oxaliplatin	hylhyzieaj(jqzretrbwn) = gbiohbtoff cgatoidvrl (swhiotxjyv ) View more	Positive	03 Jul 2019
NCT02322593 (SOLAR study, ESMO_GI2019)	Phase 3	Advanced gastric carcinoma First line HER2-negative	711	S-1 plus cisplatin	hylhyzieaj(jqzretrbwn) = wfibmdsifc cgatoidvrl (swhiotxjyv ) View more	Positive	03 Jul 2019
JPRN-JapicCTI-132172 (GRAPE, ASCO2017)	Phase 3	Pancreatic Cancer	-	TAS-118 (S-1 plus leucovorin)TAS-118 (S-1 plus leucovorin)TAS-118 (S-1 plus leucovorin)	(hcadlbnklm) = uxxcdzwxvu vipzfqwreo (vgeudoenqn ) View more	Negative	30 May 2017
JPRN-JapicCTI-132172 (GRAPE, ASCO2017)	Phase 3	Pancreatic Cancer	-	S-1	(hcadlbnklm) = svmltrirni vipzfqwreo (vgeudoenqn ) View more	Negative	30 May 2017
ASCO2013	Phase 2	Metastatic Colorectal Carcinoma	36	Gemcitabine and S-1 combination	(efcznqwhbt) = anndnefxzs kldqtbpcpj (jemlfmfthl, 4.5 - 28.9) View more	Positive	20 May 2013
ASCO2012	Phase 2	Recurrent Non-Small Cell Lung Cancer First line	23	Tailored S-1 regimen	(uduygfvpcq) = xlicxmsnqq bghczzapkz (mayadeuppr, 50.8 - 88.4) View more	-	20 May 2012
Study 0601 (ASCO2009)	Phase 2	Non-Small Cell Lung Cancer First line	40	Irinotecan and S-1 combination	(samfebfwbh) = nxuiztadfi ruwgdryavi (fpyzauhksd, 16.6–46.5) View more	-	20 May 2009