Phase II Study of Oral Tegafur-Uracil and Folinic Acid as First-line Therapy for Metastatic Colorectal Cancer: Taiwan Experience

Lin, Jia-Chuan

doi:10.1093/jjco/hyd124

Cited by 10 publications

(6 citation statements)

References 18 publications

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“…Phase II trials in advanced colorectal cancer have shown that an oral regimen of UFT/LV is well tolerated and is at least as efficient as treatment with 5-FU administered by continuous i.v. infusion with or without LV [162][163][164][165][166][167][168][169][170][171][172][173][174]. The objective RR in these studies ranged from 20%-40%, and median overall survival was around 13 months.…”

Section: Phase II Trials In Colorectal Cancermentioning

confidence: 99%

Clinical Studies of Three Oral Prodrugs of 5-Fluorouracil (Capecitabine, UFT, S-1): A Review

2002

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Although 5-fluorouracil (5-FU) was first introduced in 1957, it remains an essential part of the treatment of a wide range of solid tumors. 5-FU has antitumor activity against epithelial malignancies arising in the gastrointestinal tract and breast as well as the head and neck, with single-agent response rates of only 10%-30%. Although 5-FU is still the most widely prescribed agent for the treatment of colorectal cancer, less than one-third of patients achieve objective responses. Recent research has focused on the biomodulation of 5-FU to improve the cytotoxicity and therapeutic effectiveness of this drug in the treatment of advanced disease. As all the anticancer agents, 5-FU leads to several toxicities. The toxicity profile of 5-FU is schedule dependent. Myelotoxicity is the major toxic effect in patients receiving bolus doses. Hand-foot syndrome (palmar-plantar erythrodysesthesia), stomatitis, and neuro-and cardiotoxicities are associated with continuous infusions. Other adverse effects associated with both bolus-dose and continuous-infusion regimens include nausea and vomiting, diarrhea, alopecia, and dermatitis. All these reasons explain the need for more effective and less toxic fluoropyrimidines.In the first part of this review, we briefly present the metabolic pathways of 5-FU responsible for the efficacy and toxicity of this drug. This knowledge is also necessary to understand the target(s) of biomodulation.The second part is devoted to a review of the literature on three recent prodrugs of 5-FU, i.e., capecitabine, UFT (ftorafur [FTO] plus uracil), and S-1 (FTO plus 5-chloro-2,4-dihydroxypyridine plus potassium oxonate). The pharmacological principles that have influenced the development of these new drugs and our current knowledge of the clinical pharmacology of these new agents, focusing on antitumor activity and toxicity, are presented.The literature was analyzed until March 2002. This review is intended to be as exhaustive as possible since it was conceived as a work tool for readers wanting to go further. The Oncologist 2002;7:288-323 The Oncologist 2002;7:288-323 www.TheOncologist.com Correspondence: M. Malet-Martino, Ph.D., Groupe de RMN Biomédicale, Laboratoire des IMRCP (UMR CNRS 5623), Université Paul Sabatier, 118, route de Narbonne, 31062 Toulouse Cédex, France. Telephone: 33-561-556271; Fax: 33-561-557625; e-mail: martino@chimie.ups-tlse.fr Received January 24, 2002; accepted for publication April 5, 2002. ©AlphaMed Press 1083-7159/2002 The Oncologist ® LEARNING OBJECTIVESAfter completing this course, the reader will be able to:1. Define the main oral prodrugs of fluorouracil.2. Know the indications of the new oral prodrugs of fluorouracil.3. Review the main toxicities and drug interactions of oral prodrugs of fluorouracil.4. Evaluate the benefit(s) of using an oral prodrug of fluorouracil compared with classical treatments.Access and take the CME test online and receive one hour of AMA PRA category 1 credit at CME.TheOncologist.com CME CME by guest on http://theoncologist.a...

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Section: Phase II Trials In Colorectal Cancermentioning

confidence: 99%

Clinical Studies of Three Oral Prodrugs of 5-Fluorouracil (Capecitabine, UFT, S-1): A Review

2002

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“…The safety analysis of the phase III trial, JCOG0205, [ 29 ] revealed that the UFT/LV group had fewer neutropenic events. In a phase II study [ 37 ] evaluating the toxicity profile of oral UFT in Chinese patients with metastatic colorectal cancer, Lin et al had revealed that the most frequently observed adverse effects were nausea and diarrhea. Furthermore, the myelosuppression event was mild, resulting in no episode of febrile neutropenia and less documented infection.…”

Section: Discussionmentioning

confidence: 99%

Uracil-tegafur vs fluorouracil as postoperative adjuvant chemotherapy in Stage II and III colon cancer

Chen¹,

Lee

et al. 2021

Medicine

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We conducted a population-based cohort study enrolling patients with Stage II and III colon cancer receiving postoperative adjuvant chemotherapy with uracil and tegafur (UFT) or fluorouracil (5-FU) from the Taiwan National Health Insurance Research Database from 2000 to 2015. The outcomes of the current study were disease-free survival (DFS) and overall survival (OS). Hazard ratios (HRs) were calculated by multivariate Cox proportional hazard regression models. We compared our effectiveness results from the literature by meta-analysis, which provided the best evidence. Severe adverse events were compared in meta-analysis of reported clinical trials. In the nationwide cohort study, UFT (14,486 patients) showed DFS similar to postoperative adjuvant chemotherapy (adjusted HR 1.037; 95% confidence interval [CI] 0.954–1.126; P = .397) and OS (adjusted HR 0.964; 95% CI 0.891–1.041; P = .349) compared with the 5-FU (866 patients). Our meta-analysis confirmed the similarity of effectiveness and found the incidence of leucopaenia was statistically significantly reduced in UFT (risk ratio 0.12; 95% CI 0.02–0.67; I 2 = 0%). Through our analysis, we have confirmed that UFT is a well-tolerated adjuvant therapy choice, and has similar treatment efficacy as 5-FU in terms of DFS and OS in patients with Stage II and III colon cancer.

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“…UFUR has been preferred over 5-FU as an agent for combining with other chemotherapeutic agents such as irinotecan (the FOLF-IRI regimen) by some physicians in Japan and Taiwan [8,24,25]. LV was reported to be capable of enhancing the anti-tumor efficacy of 5-FU in the treatment of metastatic colorectal cancer.…”

Section: Discussionmentioning

confidence: 99%

Both XELIRI And TEGAFIRI Togetherwith Bevacizumab are Effective for Recurrent or Metastatic Colorectal Cancer: A Real-Life Experience

Tc¹,

Pn²

2020

COO

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Objective:To evaluate a surgeon's experience of combination chemotherapy comprising different regimens of fluorouracil with or without irinotecan together with bevacizumab with respect to response rate for patients with recurrent or metastatic colorectal cancer. Methods:Metastatic or recurrent colorectal cancer patients treated with bevacizumab were retrospectively analyzed from January 2009 to March 2018. They were grouped according to the type of regimen: group I: fluorouracil together with bevacizumab every 2 weeks; group II: irinotecan with fluorouracil (FOLFIRI), with bevacizumab every 2 weeks; group III: irinotecan with tegafur-uracil and leucovorin (TEGAFIRI), with bevacizumab every 2 weeks; and group IV: irinotecan with capecitabine (XELIRI), with bevacizumab every 2 weeks. They were followed until September 2017 or death. Results:The cohort comprised 140 patients: 15 (group I), 18 (group II), 36 (group III), and 71 (group IV). The median progression-free survival was 10.52 (group I), 8.00 (group II), 11.02 (group III), and 14.10 (group IV) months. Meanwhile, the median overall survival was 17.48 (group I), 20.52 (group II), 27.70 (group III), and 22.16 (group IV) months, without significant difference in the treatment cycle among the groups. The rate of diarrhea, and hand foot syndrome, and poor appetite was similar between groups III and IV, while that of oral ulcer was slightly higher in group IV than that in group III. One patient (0.71%) in group IV developed colon perforation after seven courses of chemotherapy but recovered well after emergent surgery. Conclusions:Both XELIRI and TEGAFIRI with bevacizumab are feasible and yield acceptable outcomes for recurrent or metastatic colorectal cancer. This combination is advantageous because it does not require admission and additional apparatus for administration, has shorter infusion time, is well-tolerated by most patients, and has acceptable hematological and non-hematological side effects.

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Phase II Study of Oral Tegafur-Uracil and Folinic Acid as First-line Therapy for Metastatic Colorectal Cancer: Taiwan Experience

Abstract: The data from our study indicate that oral tegafur-uracil plus folinic acid is an active and tolerable first-line treatment for Chinese patients with metastatic colorectal cancer, with the additional advantage of being easily administered at home.

Cited by 10 publications

References 18 publications

Clinical Studies of Three Oral Prodrugs of 5-Fluorouracil (Capecitabine, UFT, S-1): A Review

Clinical Studies of Three Oral Prodrugs of 5-Fluorouracil (Capecitabine, UFT, S-1): A Review

Uracil-tegafur vs fluorouracil as postoperative adjuvant chemotherapy in Stage II and III colon cancer

Both XELIRI And TEGAFIRI Togetherwith Bevacizumab are Effective for Recurrent or Metastatic Colorectal Cancer: A Real-Life Experience

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