Abstract
Recently, we reported a highly active regimen in advanced gastric cancer including a weekly administration of cisplatin, epidoxorubicin, leucovorin, 5-fluorouracil with the support of filgrastim. In order to simplify the administration and to decrease the toxicity of these drugs, mainly epidoxorubicin-induced alopecia, we designed a regimen including an infusional 5-fluorouracil schedule according to the de Gramont regimen, cisplatin and mitomycin C replacing epidoxorubicin. Forty-five patients with advanced or metastatic gastric cancer were treated with cisplatin 50 mg m−2 i.v. on day 1, every 2 weeks, 6S-stereoisomer-leucovorin 100 mg m−2 i.v. followed by 5-fluorouracil 400 mg m−2 i.v. bolus and 600 mg m−2 i.v. in a 22-h infusion, on days 1 and 2, every 2 weeks, and mitomycin C 7 mg m−2 i.v. bolus on day 2, every 6 weeks. Grades 3–4 toxicities (National Cancer Institute-Common Toxicity Criteria) consisted mainly of neutropenia and thrombocytopenia. Five patients had a complete response and 16 had a partial response for an overall response rate of 46.7% (95% confidence interval, 32.1–61.2%). The median survival was 11 months. The combination of cisplatin, 5-fluorouracil and leucovorin according to de Gramont, and mitomycin C seems to be an active and safe regimen in the treatment of advanced gastric cancer. Because of its low cost it may be suggested for patients not enrolled into clinical trials.
This is a preview of subscription content, access via your institution
Access options
Subscribe to this journal
Receive 24 print issues and online access
$259.00 per year
only $10.79 per issue
Buy this article
- Purchase on Springer Link
- Instant access to full article PDF
Prices may be subject to local taxes which are calculated during checkout
References
Arbuck SG, Douglass HO, Trave F, Milliron S, Baroni M, Nava H, Emrich LJ, Rustum YM (1987) A phase II trial of 5-fluorouracil and high-dose intravenous leucovorin in gastric carcinoma. J Clin Oncol 5: 1150–1156
Becker K, Rinas B, Widmann B, Heider A, Niederle N (1997) 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 16: 283a
Cascinu S, Labianca R, Alessandroni P, Marcellini M, Silva RR, Pancera G, Testa E, Martignoni G, Barni S, Frontini L, Zaniboni A, Luporini G, Cellerino R, Catalano G (1997) Intensive weekly chemotherapy for advanced gastric cancer using fluorouracil, cisplatin, epi-doxorubicin, 6S-leucovorin, glutathione, and filgrastim: a report from the Italian Group for the Study of Digestive Tract Cancer. J Clin Oncol 15: 3313–3319
Cascinu S, Labianca R, Graziano F, Pancera G, Barni S, Frontini L, Luporini G, Cellerino R, Catalano G (1998) Intensive weekly chemotherapy for locally advanced gastric cancer using 5-fluorouracil, cisplatin, epidoxorubicin, 6S-leucovorin, glutathione and filgrastim: a report from the Italian Group for the Study of Digestive Tract Cancer (GISCAD). Br J Cancer 78: 390–393
de Gramont A, Bosset JF, Milan C, Rougier P, Bouchè O, Etienne PL, Morvan F, Louvet C, Guillot T, Francois E, Bedenne L (1997) Randomized trial comparing monthly low-dose leucovorin and fluorouracil bolus with bimonthly high-dose leucovorin and fluorouracil bolus plus continuous infusion for advanced colorectal cancer: a French Intergroup Study. J Clin Oncol 15: 808–815
Findlay M, Cunningham D, Norman A, Mansi J, Nicolson M, Hickish T, Nicolson V, Nash A, Sacks N, Ford H, Carter R, Hill A (1994) A phase II study in advanced gastro-oesophageal cancer using epirubicin and cisplatin in combination with continuous infusion 5-fluorouracil (ECF). Ann Oncol 5: 609–616
Glimelius B, Ekstrom K, Hoffman K, Graf W, Sjoden PO, Haglund U, Svensson C, Enander LK, Linne T, Sellstrom H, Heuman R (1997) Randomised comparison between chemotherapy plus supportive cancer with best supportive care in advanced gastric cancer. Ann Oncol 8: 163–168
Graziano F, Catalano V, Baldelli AM, Giordani P, Testa E, Lai V, Catalano G, Battelli N, Cascinu S (2000) A phase II study of weekly docetaxel as salvage chemotherapy for advanced gastric cancer. Ann Oncol 11: 1263–1266
Kaplan EL, Meier P (1958) Nonparametric estimation from incomplete observations. J Am Stat Assoc 53: 457–481
Kim NK, Park YS, Heo DS, Suh C, Kim SY, Park KC, Kang YK, Shin DB, Kim HT, Kim HJ, Kang WK, Suh CI, Bang YJ (1993) A phase III randomized study of 5-fluorouracil and cisplatin versus 5-fluorouracil, doxorubicin, and mitomycin C, versus 5-fluorouracil alone in the treatment of advanced gastric cancer. Cancer 71: 3813–3818
Kollmannsberger C, Quietzsch D, Haag C, Lingenfelser T, Schroeder M, Hartmann JT, Baronius W, Hempel V, Clemens M, Kanz L, Bokemeyer C (2000) A phase II study of paclitaxel, weekly, 24-hour continuous infusion 5-fluorouracil, folinic acid and cisplatin in patients with advanced gastric cancer. Br J Cancer 83: 458–463
Kretzschmar A, Reichardt P, Thuss-Patience PC, Hohenberger P, Benter T, Dorken B, Kohne CH (2000) Weekly 24-hour infusion of high-dose 5-fluorouracil plus folinic acid in combination with mitomycin C for the treatment of advanced gastric cancer. Oncology 59: 14–17
Lacave AJ, Baron FJ, Anton LM, Estrada E, De Sande LM, Palacio I, Esteban P, Gracia JM, Buesa JM, Fernandez OA et al (1991) Combination chemotherapy with cisplatin and 5-fluorouracil 5-day infusion in the therapy of advanced gastric cancer: a phase II trial. Ann Oncol 2: 751–754
Leichman L, Berry BT (1991) Cisplatin therapy for adenocarcinoma of the stomach. Semin Oncol 18: Suppl 3 25–33
Mavroudis D, Kourousis C, Androulakis N, Kalbakis K, Agelaki S, Kakolyris S, Souglakos J, Sarra E, Vardakis N, Hatzidaki D, Sarmonis G, Georgoulias V (2000) Frontline treatment of advanced gastric cancer with docetaxel and granulocyte colony-stimulating factor (G-CSF): a phase II trial. Am J Clin Oncol 23: 341–344
Mitry E, Artru P, Taieb J, Boige V, Vaillant JN, Clavero-Fabri MC, Lesur G, Dupuy P, Ducreux M, Rougier P (2000) Combination of leucovorin, 5-fluorouracil bolus and infusion, and cisplatin (LV5FU2-P regimen) in the treatment of advanced upper gastrointestinal carcinomas (AUGIC). Ann Oncol 11: Suppl 4 65
Murad AM, Santiago FF, Petroianu A, Rocha PR, Rodrigues MA, Rausch M (1993) Modified therapy with 5-fluorouracil, doxorubicin, and methotrexate in advanced gastric cancer. Cancer 72: 37–41
National Cancer Institute (1990) Guidelines for reporting of adverse drug reactions: Cancer therapy evaluation program. Washington, DC, National Cancer Institute,. 1–17
Pyrhonen S, Kuitunen T, Nyandoto P, Kouri M (1995) 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 71: 587–591
Ross P, Norman A, Cunningham D, Webb A, Ivesson T, Padhani A, Prendiville J, Watson M, Massey A, Popescu R, Oates J (1997) A prospective randomized trial of protracted venous infusion 5-fluorouracil with or without mitomycin C in advanced colorectal cancer. Ann Oncol 8: 995–1001
Ross P, Cunningham D, Scarffe H, Nicolson M, Seymour M, Harper P, Price T, Hill A, Anderson H, Iveson T, Hickish T, Lofts F, Norman A (1999) Results of a randomised trial comparing ECF with MCF in advanced oesophago-gastric cancer. Eur J Cancer 35: Suppl 4 S137
Roth AD, Maibach R, Martinelli G, Fazio N, Aapro MS, Pagani O, Morant R, Borner MM, Herrmann R, Honegger H, Cavalli F, Alberto P, Castiglione M, Goldhirsch A (2000) Docetaxel (Taxotere)-cisplatin (TC): an effective drug combination in gastric carcinoma. Swiss Group for Clinical Cancer Research (SAKK), and the European Institute of Oncology (EIO). Ann Oncol 11: 301–306
Rougier P, Mahjoubi M, Lasser P, Ducreux M, Oliveira J, Ychou M, Pignon JP, Elias D, Bellefqih S, Bognel C, Lusinchi A, Cvitkovic E, Droz JP (1994) Neoadjuvant chemotherapy in locally advanced gastric carcinoma-A phase II trial with combined continuous intravenous 5-fluorouracil and bolus cisplatinum. Eur J Cancer 30A: 1269–1275
Schipper DL, Wagener DJT (1996) Chemotherapy of gastric cancer. Anticancer Drugs 7: 137–149
Schnall S, Macdonald JS (1993) Mitomycin therapy in gastric cancer. Oncology 50: Suppl 1 70–77
Simon R (1989) Optimal II stage designs for phase II clinical trials. Controlled Clin Trials 10: 1–10
Sulkes A, Smyth J, Sessa C, Dirix LY, Vermorken JB, Kaye S, Wanders J, Franklin H, LeBail N, Verweij J (1994) Docetaxel (Taxotere) in advanced gastric cancer: Results of a phase II clinical trial. Br J Cancer 70: 380–383
Vanhoefer U, Rougier P, Wilke H, Ducreux MP, Lacave AJ, Van Cutsem E, Planker M, Dos Santos JG, Piedbois P, Paillot B, Bodenstein H, Schmoll HJ, Bleiberg H, Nordlinger B, Couvreur ML, Baron B, Wils JA (2000) Final results of a randomized phase III trial of sequential high-dose methotrexate, fluorouracil, and doxorubicin versus etoposide, leucovorin, and fluorouracil versus infusional fluorouracil and cisplatin in advanced gastric cancer: a trial of the European Organization for Research and Treatment of Cancer Gastrointestinal Tract Cancer Cooperative Group. J Clin Oncol 18: 2648–2657
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 (1997) Randomized trial comparing epirubicin, cisplatin, and fluorouracil versus fluorouracil, doxorubicin, and methotrexate in advanced esophagogastric cancer. J Clin Oncol 15: 261–267
Wilke H, Korn M, Vanhoefer U, Fink U, Stahl M, Preusser P, Kohne CH, Klaassen U, Harstrick A, Schmoll HJ, Seeber S (1996) Weekly infusional 5-fluorouracil plus/minus other drugs for the treatment of advanced gastric cancer. J Infus Chemother 6: 123–126
Young RC (1990) Mechanism to improve chemotherapy effectiveness. Cancer 65: 815–822
Author information
Authors and Affiliations
Corresponding author
Rights and permissions
About this article
Cite this article
Cascinu, S., Baldelli, A., Catalano, V. et al. Infusional 5-fluorouracil, cisplatin and mitomycin C in advanced gastric cancer: A low cost effective regimen. Br J Cancer 86, 213–217 (2002). https://doi.org/10.1038/sj.bjc.6600046
Received:
Revised:
Accepted:
Published:
Issue Date:
DOI: https://doi.org/10.1038/sj.bjc.6600046
Keywords
This article is cited by
-
Bimonthly regimen of high-dose leucovorin, infusional 5-fluorouracil, docetaxel, and cisplatin (modified DCF) in advanced gastric adenocarcinoma
Gastric Cancer (2013)
-
Pegylated liposomal doxorubicin, 5-fluorouracil and cisplatin versus mitomycin-C, 5-fluorouracil and cisplatin for advanced gastric cancer: a randomized phase II trial
Cancer Chemotherapy and Pharmacology (2011)
-
Bi-weekly chemotherapy with cisplatin, epirubicin, folinic acid and 5-fluororacil continuous infusion plus g-csf in advanced gastric cancer: a multicentric phase II study
Cancer Chemotherapy and Pharmacology (2006)