Literature DB >> 19770625

S9511: a Southwest Oncology Group phase II study of trimetrexate, 5-fluorouracil, and leucovorin in unresectable or metastatic adenocarcinoma of the stomach.

Charles D Blanke1, Kari Chansky, Kathy L Christman, Scott A Hundahl, Brian F Issell, Peter J Van Veldhuizen, G Thomas Budd, James L Abbruzzese, John S Macdonald.   

Abstract

OBJECTIVE: The primary objective of this trial was to evaluate the response rate for trimetrexate in conjunction with 5-FU and leucovorin (LV) (= TFL) in the treatment of advanced gastric cancer in a phase II, cooperative group setting.
METHODS: Patients with locally advanced, unresectable, or metastatic adenocarcinoma of the stomach received trimetrexate 110 mg/m IV over 60 minutes day 1, followed by 5-FU 500 mg/m IV bolus and LV 200 mg/m IV over 60 minutes day 2, followed by oral LV 15 mg every 6 hours x 7 doses, all weekly for 6 weeks followed by 2 weeks of rest, continued until progression.
RESULTS: Characteristics for 37 eligible patients: median age 63 (range: 23-83); male/female: 69% of 31%; performance status 0/1/2 15/20/1. The confirmed response rate was 19%, and median overall survival was 6 months. Two patients died as a result of therapy, 1 because of infection without significant neutropenia, and 1 due to perforation of a responding gastric lesion. Seventy-two percent experienced grades 3 and 4 toxicity, most commonly diarrhea, fatigue, and lymphopenia.
CONCLUSIONS: This regimen achieves response rates comparable to other 5-FU-based regimens, when used in treatment of incurable gastric cancer. Toxicity appears manageable.

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Year:  2010        PMID: 19770625      PMCID: PMC2967385          DOI: 10.1097/COC.0b013e318199fb84

Source DB:  PubMed          Journal:  Am J Clin Oncol        ISSN: 0277-3732            Impact factor:   2.339


  29 in total

1.  Sequential trimetrexate, 5-fluorouracil and folinic acid are effective and well tolerated in metastatic colorectal carcinoma. The phase II study group of the AIO.

Authors:  H Szelényi; P Hohenberger; H Lochs; N Haboubi; W E Berdel; E Thiel; E D Kreuser
Journal:  Oncology       Date:  2000-05       Impact factor: 2.935

2.  Trimetrexate: clinical development of a nonclassical antifolate.

Authors:  P J O'Dwyer; R J DeLap; S A King; A J Grillo-Lopez; D F Hoth; B Leyland-Jones
Journal:  NCI Monogr       Date:  1987

3.  The influence of methotrexate pretreatment on 5-fluorouracil metabolism in L1210 cells.

Authors:  E Cadman; R Heimer; C Benz
Journal:  J Biol Chem       Date:  1981-02-25       Impact factor: 5.157

4.  Schedule-dependent antitumor effects of methotrexate and 5-fluorouracil.

Authors:  J R Bertino; W L Sawicki; C A Lindquist; V S Gupta
Journal:  Cancer Res       Date:  1977-01       Impact factor: 12.701

5.  A double-blind placebo-controlled randomized phase III trial of 5-fluorouracil and leucovorin, plus or minus trimetrexate, in previously untreated patients with advanced colorectal cancer.

Authors:  C D Blanke; J Shultz; J Cox; M Modiano; R Isaacs; B Kasimis; R Schilsky; J Fleagle; M Moore; N Kemeny; D Carlin; L Hammershaimb; D Haller
Journal:  Ann Oncol       Date:  2002-01       Impact factor: 32.976

6.  Integrated analysis of overall survival in two randomised studies comparing 5-fluorouracil/leucovorin with or without trimetrexate in advanced colorectal cancer.

Authors:  C J A Punt; C D Blanke; J Zhang; L Hammershaimb
Journal:  Ann Oncol       Date:  2002-01       Impact factor: 32.976

7.  CPT-11 plus cisplatin in patients with advanced, untreated gastric or gastroesophageal junction carcinoma: results of a phase II study.

Authors:  Jaffer A Ajani; Jackie Baker; Peter W T Pisters; Linus Ho; Paul F Mansfield; Barry W Feig; Chusilp Charnsangavej
Journal:  Cancer       Date:  2002-02-01       Impact factor: 6.860

8.  Pharmacology and toxicity of a potent "nonclassical" 2,4-diamino quinazoline folate antagonist, trimetrexate, in normal dogs.

Authors:  E C Weir; A R Cashmore; R N Dreyer; M L Graham; N Hsiao; B A Moroson; W L Sawicki; J R Bertino
Journal:  Cancer Res       Date:  1982-05       Impact factor: 12.701

9.  Uptake and efficacy of trimetrexate (TMQ, 2,4-diamino-5-methyl-6-[(3,4,5-trimethoxyanilino)methyl] quinazoline), a non-classical antifolate in methotrexate-resistant leukemia cells in vitro.

Authors:  B A Kamen; B Eibl; A Cashmore; J Bertino
Journal:  Biochem Pharmacol       Date:  1984-05-15       Impact factor: 5.858

10.  Randomized phase II study of irinotecan, leucovorin and 5-fluorouracil (ILF) versus cisplatin plus ILF (PILF) combination chemotherapy for advanced gastric cancer.

Authors:  S H Park; E Nam; J Park; E K Cho; D B Shin; J H Lee; W K Lee; M Chung; S I Lee
Journal:  Ann Oncol       Date:  2007-12-13       Impact factor: 32.976

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