Purpose: This study was performed to investigate the activity and safety of high dose 5-fluorouracil (5-FU) given as a weekly 24-hour infusion in combination with folinic acid plus mitomycin C in patients with advanced gastric cancer. Patients and Methods: Chemonaive patients with locally advanced inoperable, recurrent or metastatic gastric cancer were treated with 15 mg/m2 i.v. mitomycin C as bolus on day 1 of a 7-week cycle followed by a 2-hour infusion of folinic acid (500 mg/m2) and a 24-hour infusion of 5-FU (2,600 mg/m2) given on days 1, 8, 15, 22, 29, and 36 as outpatient treatment. Results: Thirty evaluable patients (median age 58 years and median ECOG performance status 1) received 1–4 cycles (median 3). 53% of the patients had liver metastases. Treatment-related toxicity was low with 10% of patients experiencing diarrhea ≥grade 3, 3% mucositis grade 3 and 3% nausea grade 3 (CTC). Hematological toxicity was mild with 13% thrombopenia grade 3 and no leukopenia grade 4. Eleven patients achieved a partial remission (major response rate 37%; 95% confidence interval 22–53%). Median time to progression was 5 months and median overall survival time was 7 months. Conclusion: This regimen is a well-tolerated outpatient treatment for patients with advanced gastric cancer with efficacy being comparable to other chemotherapy protocols.

Keywords:
Folinic acid, Gastric cancer, 5-Fluorouracil, Mitomycin C
1.
Pyrhonen S, Kuitunen T, Nyandoto P, Kouri M: Randomised comparison of fluorouracil, epidoxorubicin and methotrexate (FEMTX) plus supportive care with supportive care alone in patients with non-resectable gastric cancer. Br J Cancer 1995;71:587–591.
2.
Murad AM, Santiago FF, Petroianu A, Rocha PR, Rodrigues MA, Rausch M: Modified therapy with 5-fluorouracil, doxorubicin, and methotrexate in advanced gastric cancer. Cancer 1993;72:37–41.
3.
Glimelius B, Ekstrom K, Hoffman K, Graf W, Sjoden PO, Haglund U, Svensson C, Enander LK, Linne T, Sellstrom H, Heuman R: Randomized comparison between chemotherapy plus best supportive care with best supportive care in advanced gastric cancer. Ann Oncol 1997;8:163–168.
4.
Wils JA, Klein HO, Wagener DJ, Bleiberg H, Reis H, Korsten F, Conroy T, Fickers M, Leyvraz S, Buyse M, et al: Sequential high-dose methotrexate and fluorouracil combined with doxorubicin – A step ahead in the treatment of advanced gastric cancer: A trial of the European organization for Research and Treatment of Cancer Gastrointestinal Tract Cooperative Group. J Clin Oncol 1991;9:827–831.
5.
Webb A, Cunningham D, Scarffe JH, Harper P, Norman A, Joffe JK, Hughes M, Mansi J, Findlay M, Hill A, Oates J, Nicolson M, Hickish T, O’Brien M, Iveson T, Watson M, Underhill C, Wardley A, Meehan M: Randomized trial comparing epirubicin, cisplatin, and fluorouracil versus fluorouracil, doxorubicin, and methotrexate in advanced esophagogastric cancer. J Clin Oncol 1997;15:261–267.
6.
Waters JS, Norman A, Cunningham D, Scarffe JH, Webb A, Harper P, Joffe JK, Mackean M, Mansi J, Leahy M, Hill A, Oates J, Rao S, Nicolson M, Hickish T: Long-term survival after epirubicin, cisplatin and fluorouracil for gastric cancer: Results of a randomized trial. Br J Cancer 1999;80:269–272.
7.
Cervantes A, Aranda E, Sastre J, Abad A, Anton A, Torregrosa F, Carrato A, Navarro M, Llanos M, Garcia-Conde J, Diaz-Rubio E: Weekly high dose continuous infusion 5-fluorouracil in metastatic gastric cancer. A phase II trial of the Spanish group for gastrointestinal tumor therapy. Proc Am Soc Clin Oncol 1997;16:284a.
8.
Hsu CH, Yeh KH, Chen LT, Liu JM, Jan CM, Lin JT, Chen YC, Cheng AL: Weekly 24-hour infusion of high-dose 5-fluorouracil and leucovorin in the treatment of advanced gastric cancers. An effective and low-toxic regimen for patients with poor general condition. Oncology 1997;54:275–280.
9.
Vanhoefer U, Wilke H, Weh HJ, Clemens M, Harstrick A, Stahl M, Hossfeld DK, Seeber S: Weekly high-dose 5-fluorouracil and folinic acid as salvage treatment in advanced gastric cancer. Ann Oncol 1994;5:850–851.
10.
Schnall S, Macdonald JS: Mitomycin therapy in gastric cancer. Oncology 1993;50(suppl 1):70–77.
11.
Ross A, Norman A, Cunningham D, Webb A, Iveson T, Padhani A, Prendville J, Watson M, Massey A, Popescu R, Oates J: A prospective randomized trial of protracted venous infusion 5-fluorouracil with or without mitomycin C in advanced colorectal cancer. Ann Oncol 1997;8:995–1001.
12.
Becker K, Rinas B, Weidmann B, Heider A, Niederle N: High-dose 5-fluorouracil/folinic acid (HD-5-FU/FA) plus mitomycin C (MMC) in patients with refractory colorectal cancer. Proc Am Soc Clin Oncol 1997;16:283a.
13.
Wilke H, Korn M, Köhne CH, Fink U, Preusser P, Vanhoefer U, Wiegmann T, Stahl M, Harstrick A, Klaassen U, Schmoll HJ, Seeber S: Phase II results of weekly infusional high dose FU (HD-FU) plus folinic acid (FA) and biweekly cisplatin (C) for advanced gastric cancer. Ann Oncol 1996;7:46.
14.
Wilke H, Preusser P, Fink U, Achterrath W, Meyer HJ, Stahl M, Lenaz L, Meyer J, Siewert JR, Geerlings H, et al: New developments in the treatment of gastric carconima. Semin Oncol 1990;17:61–70.
15.
Wils J: Treatment of gastric cancer. Curr Opin Oncol 1998;10:357–361.
16.
Ajani JA: Chemotherapy for gastric carcinoma: New and old options. Oncology (Huntingt) 1998;12:44–47.
17.
Poplin EA, LoRusso P, Lokich JJ, Gullo JJ, Leming PD, Schulz JJ, Veach SR, McCulloch W, Baker L, Schein P: Randomized clinical trial of mitomycin-C with or without pretreatment with WR-2721 in patients with advanced colorectal cancer. Cancer Chemother Pharmacol 1994;33:415–419.
18.
Ross PJ, Cunningham D, Scarffe JH, Nicolson M, Seymour M, Harper P, Price T, Hill A, Anderson H, Iveson T, Hickich T, Lofts F, Norman A: Results of a randomized trial comparing ECF with MCF in advanced oesophago-gastric cancer. Proc Am Soc Clin Oncol 1999;18:272a.
© 2000 S. Karger AG, Basel
2000
Copyright / Drug Dosage / Disclaimer
Copyright: All rights reserved. No part of this publication may be translated into other languages, reproduced or utilized in any form or by any means, electronic or mechanical, including photocopying, recording, microcopying, or by any information storage and retrieval system, without permission in writing from the publisher.
Drug Dosage: The authors and the publisher have exerted every effort to ensure that drug selection and dosage set forth in this text are in accord with current recommendations and practice at the time of publication. However, in view of ongoing research, changes in government regulations, and the constant flow of information relating to drug therapy and drug reactions, the reader is urged to check the package insert for each drug for any changes in indications and dosage and for added warnings and precautions. This is particularly important when the recommended agent is a new and/or infrequently employed drug.
Disclaimer: The statements, opinions and data contained in this publication are solely those of the individual authors and contributors and not of the publishers and the editor(s). The appearance of advertisements or/and product references in the publication is not a warranty, endorsement, or approval of the products or services advertised or of their effectiveness, quality or safety. The publisher and the editor(s) disclaim responsibility for any injury to persons or property resulting from any ideas, methods, instructions or products referred to in the content or advertisements.
You do not currently have access to this content.