CoChat
Sign Up
Cited by 382Colorectal Cancer Treatments and StudiesCancer therapeutics and mechanismsCancer Treatment and Pharmacology

Clinical studies of three oral prodrugs of 5-fluorouracil (capecitabine, UFT, S-1): A review

Open access
Malet-Martino, M., Martino, R.·2002·The Oncologist
DOI 10.1634/theoncologist.7-4-288
Open this paper in CoChat — free accountOpen PDF

Abstract

Learning Objectives: After completing this course, the reader will be able to: Define the main oral prodrugs of fluorouracil. Know the indications of the new oral prodrugs of fluorouracil. Review the main toxicities and drug interactions of oral prodrugs of fluorouracil. 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 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 claims and statistics of this paper haven’t been checked yet.

Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.

A few free checks a day · papers already verified open instantly · results are public

Integrity signals

Registry

Crossref · 10.1634/theoncologist.7-4-288

Cites

229 of 229 references verified0 citation errors · 0 not checkable

Statistics

Claims the paper makes

The claims and statistics of this paper haven’t been checked yet.

Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.

A few free checks a day · papers already verified open instantly · results are public

Claims other papers make about this one

Each is checked against this paper’s own text: does it say what the citing paper says it does?

  • Capecitabine needs to be transformed into 5-fluorouracil for direct cytotoxicity, mediated by thymine phosphorylase.

    “Capecitabine (CAP) needs to be transformed into 5-fluorouracil (5-FU) for direct cytotoxicity, which is mediated by thymine phosphorylase (TP) [2].”

    From Drug Resistance in Colorectal Cancer: From Mechanism to Clinic (2022) · cites this paper as [2]

Self-check

Percentages, sums and reported differences re-computed from the paper’s own numbers.

The self-check needs the paper’s full text.

Cites

Flagged first, then by citations

Research works printed but not linked: 110

  1. Pinedo HM, Peters GJ. Fluorouracil: biochemistry and phar- macology. J Clin Oncol 1988;6:1653-1664.
  2. Lemaire L, Arellano M, Malet-Martino M et al. A novel metabolite of 5-fluorouracil in humans: 2-fluoro-3-hydrox- ypropionic acid. Proc Am Assoc Cancer Res 1996;37:1225a.
  3. Seifert P, Baker LH, Reed ML et al. Comparison of continu- ously infused 5-fluorouracil with bolus injection in treatment of patients with colorectal adenocarcinoma. Cancer 1975;36:123-128.
  4. Peters GJ, Ackland SP. New antimetabolites in preclinical and clinical development. Exp Opin Invest Drugs 1996;5:637-679.
  5. Reigner B, Blesch K, Weidekamm E. Clinical pharmacoki- netics of capecitabine. Clin Pharmacokinet 2001;40:85-104.
  6. Taguchi T, Ishitani K, Saitoh K et al. A Japanese phase I study of continuous twice daily treatment with capecitabine in patients with advanced and/or metastatic solid tumors. Ann Oncol 1996;7:299a.
  7. Cao S, Lu K, Ishitsuka H et al. Antitumor efficacy of capecitabine against fluorouracil-sensitive and -resistant tumors. Proc Am Soc Clin Oncol 1997;16:795a.
  8. Abushullaih S, Saad E, Hoff PM. Characterizing hand-foot syndrome (HFS) caused by capecitabine. Proc Am Soc Clin Oncol 2000;19:2403a.
  9. Lauman MK, Mortimer J. Effect of pyridoxine on the incidence of palmar plantar erythroderma (PPE) in patients receiving capecitabine. Proc Am Soc Clin Oncol 2001;20:1565a.
  10. Chin SF, Tchen N, Oza AM et al. Use of "bag balm" as topi- cal treatment of palmar-plantar erythrodysesthesia syndrome (PPES) in patients receiving selected chemotherapeutic agents. Proc Am Soc Clin Oncol 2001;20:1632a.
  11. O'Reilly SM, Moiseyenko V, Talbot DC et al. A randomized phase II study of Xeloda ™ (capecitabine) vs paclitaxel in breast cancer patients failing previous anthracycline therapy. Proc Am Soc Clin Oncol 1998;17:627a.
  12. Cervantes G, Torrecillas L, Erazo AA et al. Capecitabine (XELODA) as treatment after failure to taxanes for metasta- tic breast cancer. Proc Am Soc Clin Oncol 2000;19:469a.
  13. Wong ZW, Wong KK, Chew L et al. Capecitabine as an oral chemotherapeutic agent in the treatment of refractory metastatic breast carcinoma (MBC). Proc Am Soc Clin Oncol 2000;19:466a.
  14. Watanabe T, Katsumata N, Sasaki Y et al. A multicenter phase II trial of Xeloda ™ (capecitabine) in patients with doc- etaxel-refractory advanced/metastatic breast cancer. Proc Am Soc Clin Oncol 2001;20:1991a.
  15. Blum JL, Dieras V, Lo Russo PM et al. Multicenter, phase II study of capecitabine in taxane-pretreated metastatic breast carcinoma patients. Cancer 2001;92:1759-1768.
  16. Sundaram S, Lancaster D, Silva J et al. Oral capecitabine is an active and well tolerated primary palliative treatment in patients with metastatic breast cancer who progress after high dose chemotherapy and autologous stem cell support. Proc Am Soc Clin Oncol 2000;19:223a.
  17. Jakob A, Schupp M, Knop S et al. A phase II study of capecitabine in patients, who relapsed after high dose chemotherapy followed by peripheral blood stem cell trans- plantation for metastatic breast cancer. Proc Am Soc Clin Oncol 2001;20:1966a.
  18. Kusama M, Sano M, Ikeda T et al. A phase II study of Xeloda ™ (capecitabine) in patients with advanced/metastatic breast carcinoma. Proc Am Soc Clin Oncol 2001;20:1924a.
  19. Procopio G, Bajetta E, Catena L et al. A phase II study of capecitabine in elderly patients with advanced breast cancer. Proc Am Soc Clin Oncol 2001;20:3134a.
  20. Lozano RD, Patt YZ, Hassan MM et al. Oral capecitabine (Xeloda) for the treatment of hepatobiliary cancers (hepato- cellular carcinoma, cholangiocarcinoma and gallbladder cancer). Proc Am Soc Clin Oncol 2000;19:1025a.
  21. Koizumi W, Taguchi T. A phase II study of capecitabine (Xeloda ™ ) in patients with advanced/metastatic gastric carcinoma. Proc Am Soc Clin Oncol 2001;20:2320a.
  22. Endo M, Shinbori N, Fukase Y et al. Induction of thymidine phosphorylase expression and enhancement of efficacy of capecitabine or 5′-deoxy-5-fluorouridine by cyclophosphamide in mammary tumor models. Int J Cancer 1999;83:127-134. 103
  23. Khoury P, Villalona-Calero M, Blum J et al. Phase I study of capecitabine in combination with paclitaxel in patients with previously treated metastatic breast cancer. Proc Am Soc Clin Oncol 1998;17:793a. 106
  24. Elza-Brown K, Dees EC, Wolff AC et al. A phase I study of capecitabine and weekly paclitaxel in advanced solid tumors [abstract]. Proc Am Soc Clin Oncol 2000;19:921J. 108
  25. Diaz-Rubio E, Evans J, Tabernero J et al. Phase I study of capecitabine in combination with oxaliplatin in patients with advanced or metastatic solid tumors. Proc Am Soc Clin Oncol 2000;19:772a. 111
  26. DeSantis S, Zeuli M, Di Constanzo F et al. Oxaliplatin and capecitabine in advanced colorectal cancer: a dose-finding trial. Proc Am Soc Clin Oncol 2001;20:559a. 113
  27. Thomas R, Quinn M, Wilson R et al. A phase I trial of capecitabine (CAPE) and oxaliplatin (OHP). Proc Am Soc Clin Oncol 2001;20:530a. 114
  28. Scleucher N, Tewes M, Achterrath W et al. Extended phase I study of capecitabine in combination with a weekly sched- ule of irinotecan as first-line chemotherapy in metastatic colorectal cancer. Proc Am Soc Clin Oncol 2001;20:561a. 117
  29. Nole F, Catania C, Mandala M et al. Phase I study of vinorelbine (V) and capecitabine (C) in advanced breast cancer (ABC). Proc Am Soc Clin Oncol 2000;19:428a. 118
  30. Welt A, Borquez D, Oberhoff C et al. Phase I study of capecitabine and vinorelbine in pretreated patients with metastatic breast cancer. Proc Am Soc Clin Oncol 2001;20:1979a. 119
  31. Herrmann R, Borner M, Morant R et al. Combining gem- citabine (GEM) and capecitabine (CAP) in advanced pan- creatic cancer. Results of a phase I trial. Proc Am Soc Clin Oncol 2000;19:1038a. 120
  32. Holden SN, Eckhardt SG, Fisher S et al. A phase I pharma- cokinetic (PK) and biological study of the farnesyl trans- ferase inhibitor (FTI) R115777 and capecitabine in patients (PTS) with advanced solid malignancies. Proc Am Soc Clin Oncol 2001;20:316a. Clinical Studies of Three Oral Prodrugs of 5-Fluorouracil (Capecitabine, UFT, S-1) 122
  33. Kimmel KH, Kindler HL, Janisch L et al. Phase I dose-find- ing study of CI-994 in combination with capecitabine in patients with advanced solid tumors. Proc Am Soc Clin Oncol 2001;20:345a. 123
  34. Ngan S, Zalcberg J, Kell A et al. A phase I study of capecitabine combined with radiotherapy for locally advanced potentially operable rectal cancer. Proc Am Soc Clin Oncol 2001;20:591a. 125
  35. Yoon WH, Choi JH, Kim JR et al. Enhanced tumoricidal effect of preoperative chemoradiation using capecitabine for locally advanced rectal cancer. Proc Am Soc Clin Oncol 2001;20:2165a. 127
  36. Venturini M, Del Mastro L, Merlano M et al. Dose finding study of capecitabine in combination with docetaxel and epirubicin in prior untreated advanced breast cancer patients. Proc Am Soc Clin Oncol 2000;19:419a. 128
  37. Evans TRJ, Paul J, McInnes A et al. A phase I and PK study of capecitabine in combination with epirubicin (E) and cis- platin (C) in patients with advanced oesophagogastric (OG) adenocarcinoma. Proc Am Soc Clin Oncol 2001;20:651a. 129
  38. Meza LA, Amin B, Horsey M et al. A phase II study of capecitabine in combination with paclitaxel as first or sec- ond line therapy in patients with metastatic breast cancer (MBC). Proc Am Soc Clin Oncol 2001;20:2029a. 132
  39. Tonkin K, Scarfe AG, Koski S et al. Preliminary results of a phase I/II study of weekly docetaxel (Taxotere) combined with intermittent capecitabine (Xeloda) for patients with anthracycline pre-treated metastatic breast cancer. Proc Am Soc Clin Oncol 2001;20:2016a. 133
  40. Kim TW, Ahn JH, Lee JH et al. A phase II trial of capecitabine (X) and cisplatin (P) in previously untreated advanced gastric cancer (AGC). Proc Am Soc Clin Oncol 2001;20:662a. 134
  41. Borner MM, Mueller S, Roth A et al. Phase II study of capecitabine (CAP) + oxaliplatin (OXA) in first line and sec- ond line treatment of advanced or metastatic colorectal cancer (ACC). Proc Am Soc Clin Oncol 2001;20:546a. 135
  42. Akhtar SU, Mathew P, Lin J et al. Phase II trial of capecitabine and carboplatin in patients with newly diagnosed advanced non-small cell carcinoma of the lung (NSCLC). Proc Am Soc Clin Oncol 2001;20:2862a. 136
  43. Cassata A, Chiara Stani S, Alu M et al. Ongoing phase II trial with two schedules of irinotecan (CPT-11) in combina- tion with capecitabine as first line chemotherapy in patients with advanced colorectal cancer (ACRC). Proc Am Soc Clin Oncol 2001;20:573a. 137
  44. Domenech G, Perez A, Vogel C. Vinorelbine/capecitabine (VINOCAP) combination remission induction therapy for metastatic breast cancer (MBC). Proc Am Soc Clin Oncol 2001;20:1939a. 138
  45. Campos LT, Alvarez RH, Sanford B et al. Gemcitabine (GEM) and capecitabine (CPC) in advanced pancreatic can- cer (APC) and solid tumors. A single institution experience. Proc Am Soc Clin Oncol 2001;20:2315a. 139
  46. Venturini M, Del Mastro L, Durando A et al. TEX (Taxotere, Epirubicin and Xeloda) regimen as first line chemotherapy in advanced breast cancer. A multicenter phase II study. Proc Am Soc Clin Oncol 2001;20:1938a. 141
  47. Michaud LB, Gauthier MA, Wodjylo JR et al. Improved therapeutic index with lower dose capecitabine in metastatic breast cancer (MBC) patients (Pts). Proc Am Soc Clin Oncol 2000;19:402a. 147
  48. O'Shaughnessy J, Blum J. A retrospective evaluation of the impact of dose reduction in patients treated with Xeloda (capecitabine). Proc Am Soc Clin Oncol 2000;19:400a. 148
  49. Park DJ, Stoehlmacher J, Zhang W et al. Human thymidylate synthase gene polymorphism determines response to capecitabine chemotherapy in advanced colorectal cancer. Proc Am Soc Clin Oncol 2001;20:514a. 150
  50. Spicer D, Muggia F, Tulpule A et al. Phase I circadian dos- ing of daily oral uracil (U) plus 1-(tetrahydro-2-furanyl)-5- fluorouracil (FT) with leucovorin (LV). Proc Am Soc Clin Oncol 1991;10:342a. 158
  51. Saltz LB, Leichman CG, Young CW et al. A fixed-ratio com- bination of uracil and tegafur (UFT) with low dose leucovorin. An active oral regimen for advanced colorectal cancer. Cancer 1995;75:782-785. 166
  52. Feliu J, Gonzalez-Baron M, Espinosa E et al. Uracil and tegafur modulated with leucovorin; an effective regimen with low toxicity for the treatment of colorectal carcinoma in the elderly. Cancer 1997;79:1884-1889. 169
  53. Aranda E, Anton-Torres A, Sastre J et al. UFT plus leucov- orin (LV) in advanced colorectal cancer (CCR). A phase II trial. Proc Am Soc Clin Oncol 1999;18:940a. 171
  54. Thomas MB, Langleben A, Rinaldi D et al. A phase II study of UFT + leucovorin given as a twice-daily (BID) regimen in the treatment of patients (Pts) with metastatic colorectal cancer (MCC). Proc Am Soc Clin Oncol 2001;20:564a. 174
  55. Pazdur R, Douillard J-Y, Skillings JR et al. Multicenter phase III study of 5-fluorouracil (5-FU) or UFT ™ in combination with leucovorin (LV) in patients with metastatic colorectal cancer. Proc Am Soc Clin Oncol 1999;18:1009a. 176
  56. Carmichael J, Popiela T, Radstone D et al. Randomized com- parative study of Orzel ® (oral Uracil/Tegafur (UFT ™ ) plus leu- covorin (LV)) versus parenteral 5-fluorouracil (5-FU) plus LV in patients with metastatic colorectal cancer. Proc Am Soc Clin Oncol 1999;18:1015a. 177
  57. Mitomi T, Tsuchiya S, Hiki Y et al. A randomized controlled study on adjuvant chemotherapy with UFT in curatively resected colorectal cancer. Proc Am Soc Clin Oncol 1993;12:690a. 179
  58. Espinosa E, Gonzalez-Baron M, Feliu J et al. UFT-leucov- orin as adjuvant treatment for Dukes' B2-C colon cancer. Proc Am Soc Clin Oncol 1998;17:1059a. 182
  59. Ohwada S, Kawate S, Kawashima Y et al. Postoperative adjuvant immunochemotherapy using protein-bound poly- saccharide K (PSK) and tegafur/uracil (UFT) improves dis- ease-free survival: results of a randomized controlled trial (GOSG-C study). Proc Am Soc Clin Oncol 2001;20:582a. 186
  60. Castellano D, Gravalos C, Garcia-Alfonso P et al. Phase I/II study of escalating doses of irinotecan (CPT-11) in combi- nation with UFT/folinic acid (FA) in patients (Pts) with advanced colorectal cancer (CRC). Proc Am Soc Clin Oncol 2001;20:577a. 189
  61. Cruz JJ, Mendez M, Pujol E et al. Weekly irinotecan (CPT- 11) in combination with oral uracil and ftorafur (UFT) plus folinic acid (FA) as first line treatment in advanced colorec- tal cancer (CRC). Preliminary results. Proc Am Soc Clin Oncol 2001;20:2186a. 191
  62. Sazaki K, Takasaka H, Kawasaki H et al. Weekly low dose irinotecan (CPT-11) combined with oral 5-FU (and isovolin) in patients with metastatic colorectal cancer (CRC) on an out-patient treatment basis. Proc Am Soc Clin Oncol 2001;20:2241a. 192
  63. Mel JR, Vieitez JM, Garcia Alfonso P et al. Raltitrexed (Tomudex) combined with UFT: a phase I/II dose-escalation study in metastatic CRC. Proc Am Soc Clin Oncol 2000;19:1108a. 193
  64. Douillard JY, Seitz JF. A phase I study of oral uracil/tegafur (UFT) plus leucovorin (LV) combined with oxaliplatin in patients with metastatic colorectal cancer (CRC). Proc Am Soc Clin Oncol 2001;20:572a. 196
  65. Yoshikawa R, Kusunoki M, Yanagi H et al. New chemother- apeutic strategy for colorectal cancer by "pharmacokinetic modulating chemotherapy (PMC)". Proc Am Soc Clin Oncol 2001;20:3085a. 199
  66. Yamagi H, Kusunoki M, Yoshikawa R et al. Clinical results of pharmacokinetic modulating chemotherapy (PMC) in combi- nation with hepatic arterial 5-FU infusion and oral UFT after resection of hepatic colorectal metastases. Proc Am Soc Clin Oncol 2001;20:556a. 201 Minsky BD. UFT ® plus oral leucovorin calcium (Orzel ™ ) and radiation in combined modality therapy: a comprehensive review. Int J Cancer 2001;96:1-10. 202
  67. Feliu J, Calvillo J, Escribano A et al. Neoadjuvant therapy of rectal carcinoma with UFT-folinic acid (LV) plus radiotherapy (RT). Proc Am Soc Clin Oncol 1999;18:917a. 205
  68. Pfeiffer P. Concurrent UFT/L-leucovorin and curative intended radiotherapy (60 Gy) in patients with locally advanced rectal cancer (LARC): a phase I/II trial. Proc Am Soc Clin Oncol 2000;19:992a. 206
  69. Fernandez-Martos C, Aparicio J, Bosch C et al. Pre-opera- tive therapy (PT) with oral uracil and tegafur (UFT) and con- comitant irradiation (RT) in operable rectal cancer (RC). Preliminary results of a multicenter phase II study. Proc Am Soc Clin Oncol 2001;20:590a. 208
  70. Feliu J, Gonzalez-Baron M, Garcia-Giron C et al. Treatment of patients with advanced gastric carcinoma with the combi- nation of etoposide plus oral tegafur modulated by uracil and leucovorin. A phase II study of the ONCOPAZ Cooperative Group. Cancer 1996;78:211-216. 214
  71. Sato A, Kurihara M, Koizumi W et al. A phase II study of UFT plus cisplatin (UFTP) therapy in patients with advanced gastric cancer. Proc Am Soc Clin Oncol 2000;19:1087a. 218
  72. Jeen YT, Yoon SY, Shin SW et al. Phase II trial of epirubicin, cisplatin, oral uracil and tegafur, and leucovorin in patients with advanced gastric carcinoma. Cancer 2001;91:2288-2293. 219
  73. Ichinose Y, Takanashi N, Yano T et al. A phase II trial of oral tegafur and uracil plus cisplatin in patients with inoper- able nonsmall cell lung cancer. Cancer 1995;75:2677-2680. 227
  74. Ichinose Y, Yosimori K, Yoneda S et al. UFT plus cisplatin combination chemotherapy in the treatment of patients with advanced nonsmall cell lung carcinoma: a multiinstitutional phase II trial. For the Japan UFT Lung Cancer Study Group. Cancer 2000;88:318-323. 232
  75. Yoshino I, Yohena T, Kitajima M et al. UFT plus cisplatin with concurrent radiotherapy for locally advanced non-small cell lung cancer (NSCLC). A phase II study. Proc Am Soc Clin Oncol 2000;19:1981a. 233
  76. Vega-Villegas ME, Lopez-Brea M, Rivera F et al. A phase II study of UFT, vinorelbine and cisplatin (UFTVP) in advanced Clinical Studies of Three Oral Prodrugs of 5-Fluorouracil (Capecitabine, UFT, S-1) (stage III-B and IV) non small cell lung cancer (NSCLC). Proc Am Soc Clin Oncol 2001;20:2741a. 236
  77. Yoshimori K, Okumura M, Kamio K et al. A phase I/II study of cisplatin (CDDP), docetaxel (TXT) and UFT in patients with advanced non-small cell lung cancer (NSCLC). Proc Am Soc Clin Oncol 2001;20:1367a. 237
  78. Ito H, Takeda Y, Uno T et al. A phase I/II trial of UFT and low-dose cisplatin plus concurrent thoracic radiotherapy (TRT) for resected P-NII non-small cell lung cancer. Proc Am Soc Clin Oncol 1999;18:1966a. 243
  79. Dickson N, Nicholson BP, Cohen A et al. A phase I trial of UFT, leucovorin (L) and paclitaxel (P) as first or second line therapy in patients (pts) with metastatic breast cancer (MBC). Proc Am Soc Clin Oncol 1999;18:422a. 245
  80. Klaasen U, Lang S, Borquez D et al. Oral UFT/leucovorin (LV) in combination with paclitaxel (P) in the second line treatment of patients (pts) with metastatic breast cancer (MBC): results of a phase I/II trial. Proc Am Soc Clin Oncol 1999;18:404a. 246
  81. Lebedinsky CA, Breier SM, Ayaviri C et al. Dose-finding study of UFT modulated by folic acid in combination with weekly paclitaxel (Taxol) in patients with metastatic breast cancer (MBC). Proc Am Soc Clin Oncol 2000;19:854a. 247
  82. Herrero A, Artal-Cortes A, Martinez-Trufero J et al. Phase I- II trial of increasing dose, continuous UFT plus leucovorin with fixed dose three-weekly doxorubicin (D) and paclitaxel (P) in locally advanced breast cancer (LABC). Proc Am Soc Clin Oncol 2000;19:600a. 248
  83. Gregory RK, Johnston SR, Ellis PA et al. An open label non randomised phase I/II trial of oral UFT/leucovorin therapy in combination with bolus epirubicin and cyclophosphamide (ECU) in patients with locally advanced (LABC) or metasta- tic (MBC) breast cancer. Proc Am Soc Clin Oncol 2000;19:432a. 249
  84. Fumoleau P, Bonneterre J, Kerbrat P et al. A phase I dose- finding trial of UFT/leucovorin (LV) in combination with vinorelbine (VNB) in patients with metastatic breast cancer (MBC). Proc Am Soc Clin Oncol 2001;20:1974a. 251
  85. Lueck HJ, Scholz U, Rossner D et al. Phase I study of weekly paclitaxel in combination with oral uracil/ftorafur (UFT) plus leucovorin (LV) in the treatment of patients (Pts) with anthracycline-resistant metastatic breast cancer. Proc Am Soc Clin Oncol 2001;20:2024a. 252
  86. Bunnell CA, Partridge A, Burstein H et al. A phase I study of oral cyclophosphamide and UFT + leucovorin (Orzel) in women with advanced breast cancer. Proc Am Soc Clin Oncol 2001;20:2015a. 253
  87. Richardet E, Mickiewicz E, Lerzo G et al. UFT + leucovorin (LV) in advanced breast cancer (ABC): preliminary results in heavily pretreated patients (HPP). Proc Am Soc Clin Oncol 1999;18:869a. 256
  88. Yardley DA, Jones SF, Greco FA et al. A phase II trial of Orzel (UFT + leucovorin) in women with previously treated metasta- tic breast cancer. Proc Am Soc Clin Oncol 2001;20:2031a. 258
  89. Rivera E, Hizinski M, Hutchins L et al. A study of UFT + leucovorin (L) given as a three times daily (TID) regimen in the treatment of patients (Pts) with metastatic breast cancer (MBC). Proc Am Soc Clin Oncol 2001;20:1989a. 259
  90. Hortobagyi GN, Ibrahim N, Young R et al. A study of UFT + leucovorin (L) given as a twice daily (BID) regimen in the treatment of patients (PTS) with metastatic breast cancer (MBC). Proc Am Soc Clin Oncol 2001;20:186a. 260
  91. Rivera F, Lopez-Brea M, Lopez-Vega JM et al. High activ- ity of UFT, vinorelbine and cisplatin (UFTVP) as induction chemotherapy for locally advanced squamous cell head and neck carcinoma (SCHNC). Proc Am Soc Clin Oncol 1997;16:1376a. 267
  92. Colevas AD, Amrein PC, Gomolin H et al. A phase II study of combined oral uracil and ftorafur with leucovorin for patients with squamous cell carcinoma of the head and neck. Cancer 2001;92:326-331. 268
  93. de Castro J, Lopez Alvarez M, Rodriguez Jaraiz A et al. Phase II trial of gemcitabine and UFT modulated by leucov- orin in patients with advanced pancreatic cancer. Proc Am Soc Clin Oncol 2000;19:1040a. 269
  94. de Castro J, Bolanos M, Cruz MA et al. Phase II trial of pro- longed infusion gemcitabine plus UFT for the treatment of advanced pancreatic cancer. Preliminary results. Proc Am Soc Clin Oncol 2001;20:2310a. 270
  95. Nishimura K, Nonomura N, Tokizane T et al. Oral combina- tion chemotherapy for hormone-refractory prostate cancer on an outpatient basis. Proc Am Soc Clin Oncol 2001;20:2385a. 271
  96. Ukimura O, Kamoi K, Hongo F et al. Oral administration of dexamethasone in combination with UFT and cyclophos- phamide for the treatment of hormone-refractory prostate cancer. Proc Am Soc Clin Oncol 2001;20:2412a. 272
  97. Horiuchi M, Inuyama Y, Miyake H. Efficacy of surgical adjuvant with tegafur and uracil (UFT) in resectable head and neck cancer: a prospective randomized study. Proc Am Soc Clin Oncol 1994;13:918a. 273
  98. Rueda A, Ribelles N, Mons E et al. Neoadjuvant (Neo) chemotherapy (Ct) followed by radiochemotherapy (Rct) in advanced head and neck carcinoma (Chn) [abstract]. Proc Am Soc Clin Oncol 2000;19:1694E. 276
  99. Childs H, Spencer S, Raben D et al. Phase I study of com- bined UFT plus leucovorin (L) and radiation therapy (RT) for pancreatic cancer. Proc Am Soc Clin Oncol 1999;18:956a. 280
  100. Pienta KJ, Smith DC, Fardig J et al. Phase II trial of oral uracil/ftorafur (UFT) plus leucovorin in patients with hor- mone-refractory prostate cancer. Proc Am Soc Clin Oncol 2000;19:1414a. 281
  101. Kubota Y, Hosaka M, Fukushima S et al. Prophylactic oral UFT therapy for superficial bladder cancer. Cancer 1993;71:1842-1845. 282
  102. Hoff PM, Wenske CA, Medgyesy DC et al. Phase I and pharmacokinetic (PK) study of a novel oral fluoropyrimidine S-1. Proc Am Soc Clin Oncol 1999;18:665a. 300
  103. Meropol NJ, Leishman CG, Yeslow G et al. Phase I and pharmacokinetic study of single daily oral administration of S-1. Proc Am Soc Clin Oncol 2001;20:361a. 302
  104. Horikoshi N, Mitachi Y, Sakata Y et al. S-1, new oral fluo- ropyrimidine is very active in patients with advanced gastric cancer (early phase II study). Proc Am Soc Clin Oncol 1996;15:466a. 303
  105. Taguchi T, Horikoshi N, Kinoshita H et al. Early phase II study of S-1 in patients with advanced breast cancer. Proc Am Soc Clin Oncol 1996;15:151a. 305
  106. Fujii M, Kanzaki J, Satake B et al. Early phase II study of S- 1 in patients with advanced head and neck cancer. Proc Am Soc Clin Oncol 1996;15:894a. 307
  107. Kurihara M, Koizumi W, Hasegawa K et al. Late phase II study of S-1, a novel oral fluoropyrimidine derivative in patients with advanced gastric cancer. Proc Am Soc Clin Oncol 1998;17:1007a. 308
  108. Baba H, Ohtsu A, Sakata Y et al. Late phase II study of S-1 in patients with advanced colorectal cancer in Japan. Proc Am Soc Clin Oncol 1998;17:1065a. 311
  109. Sano M, Saeki T, Takashima S et al. Late phase II study of S-1 in patients with advanced and/or recurrent breast cancer. Proc Am Soc Clin Oncol 2000;19:404a. 313
  110. Yamada Y, Shirao K, Matsumura Y et al. Comparison of 5- fluorouracil and F-β-alanine pharmacokinetics in patients receiving protracted venous infusion of 5-fluorouracil and oral S-1. Proc Am Soc Clin Oncol 2001;20:362a. 322

Cited by

Sorted by citations

Related

Authors
Malet-Martino, M., & Martino, R.
Affiliations
  • Groupe de RMN Biomédicale, Laboratoire des IMRCP, Université Paul Sabatier, Toulouse, France
  • Université Toulouse III - Paul Sabatier (FR)
ORCID
Martino, R.
Venue
The Oncologist
Publisher
Oxford University Press (OUP)
Published
2002-08-01
Volume
7
Issue
4
Pages
288-323
ISSN
  • 1083-7159 (ISSN-L)
  • 1549-490X
DOI
10.1634/theoncologist.7-4-288
OpenAlex
W2103359811
Cited by
382
References
229
Citations by year
2026: 7 · 2025: 13 · 2024: 11 · 2023: 18 · 2022: 19 · 2021: 15 · 2020: 14 · 2019: 15 · 2018: 20 · 2017: 20 · 2016: 24 · 2015: 20 · 2014: 23 · 2013: 21 · 2012: 18
FWCI
4.88
Type
journal article
Language
en
Open access
Licence
academic.oup.com/journals/pages/open_access/funder_policies/chorus/standard_publication_model (vor)
Locations
  • The Oncologist (publishedVersion)
  • PubMed (publishedVersion)
Topics
  • Health Sciences › Medicine › Oncology › Colorectal Cancer Treatments and Studies
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Cancer therapeutics and mechanisms
  • Health Sciences › Medicine › Oncology › Cancer Treatment and Pharmacology
Keywords
5-fluorouracil, oral prodrug, capecitabine, UFT, S-1, fluoropyrimidine, 5-fluorouracil metabolism, drug toxicity, drug interactions, myelosuppression, hand-foot syndrome, stomatitis, cardiotoxicity, neurotoxicity, colorectal cancer, breast cancer, solid tumors
MeSH terms
Capecitabine, Administration, Oral, Antineoplastic Agents, Deoxycytidine, Fluorouracil, Tegafur, Humans, Neoplasms, Prodrugs, Pyridines, Uracil, Treatment Outcome

About these checks

Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.

Statistics and arithmetic are recomputed, not judged.

Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.

What counts as a claim ›How we measure confidence ›How we check this ›

Are you an author, or do you see a problem with this page? Request a review