Abstract
Background
Histologically diffuse-type gastric cancer is well known to have a poor prognosis and is often complicated with abdominal and pleural effusions. We evaluated the efficacy of a low dose of cisplatin combined with methotrexate and 5-fluorouracil (MFP therapy) in diffuse-type advanced gastric cancer.
Methods
The study group comprised 47 patients. Patients with pleural effusion or ascites were actively enrolled. Methotrexate (30 mg/m2 per day) plus 5-fluorouracil (600 mg/m2 per day) was administered on days 1 and 8. Cisplatin (6 mg/m2 per day) was given daily for 14 days after which there was 14 day's rest. Calcium leucovorin (15 mg) was administered after methotrexate.
Results
The overall response rate was 38.3%. Ascites disappeared or decreased in 15 of 23 patients (disappeared in 9). Pleural effusion disappeared or decreased in 6 of 8 patients (disappeared in 4). Of the 21 patients with poor oral intake at study entry, 15 (71.4%) were able to orally ingest food. Hematologic toxicity of grade 3 or higher comprised leukopenia in 10 patients (21.3%) and neutropenia in 9 (19.1%). Nonhematologic toxicity included anorexia and nausea/vomiting, in 1 patient each (2.1%). The median survival time was 211 days.
Conclusion
MFP therapy is useful for the management of diffuse-type inoperable and recurrent gastric cancer, even in patients with conditions such as pleural effusion, ascites, or lymphangitis carcinomatosa who have a poor prognosis or cannot eat solid food.
Article PDF
Similar content being viewed by others
Avoid common mistakes on your manuscript.
References
JR Bertino WL Sawicki CA Lindquist VS Gupta (1977) ArticleTitleSchedule-dependent antitumor effects of methotrexate and 5-fluorouracil Cancer Res 37 327–8 Occurrence Handle830420 Occurrence Handle1:CAS:528:DyaE2sXotlKqsg%3D%3D
T Konishi M Hiraishi K Mafune T Miyama T Hirata K Mori et al. (1994) ArticleTitleTherapeutic efficacy and toxicity of sequential methotrexate and 5-fluorouracil in gastric cancer Anticancer Res 14 1277–9 Occurrence Handle8067696 Occurrence Handle1:STN:280:DyaK2czks1OmtA%3D%3D
KJ Scanlon EM Newman Y Lu DG Priest (1986) ArticleTitleBiochemical basis for cisplatin and 5-fluorouracil synergism in human sovarian carcinoma cells Proc Natl Acad Sci USA 83 8923–5 Occurrence Handle3466165 Occurrence Handle1:CAS:528:DyaL2sXktlKjtQ%3D%3D Occurrence Handle10.1073/pnas.83.23.8923
T Shirasaka Y Shimamoto H Ohshimo H Saito M Fukushima (1993) ArticleTitleMetabolic basis of the synergistic antitumor activities of 5-fluorouracil and cisplatin in rodent tumor models in vivo Cancer Chemother Pharmacol 32 167–72 Occurrence Handle8500219 Occurrence Handle1:CAS:528:DyaK3sXmtFKrt78%3D Occurrence Handle10.1007/BF00685830
R Dickinson P Presgrave J Levi S Milliken R Woods (1989) ArticleTitleSequential moderate-dose methotrexate and 5-fluorouracil in advanced gastric adenocarcinoma Cancer Chemother Pharmacol 24 67–8 Occurrence Handle2720894 Occurrence Handle1:STN:280:DyaL1M3kvFKntA%3D%3D Occurrence Handle10.1007/BF00254110
G Blijham H Bleiberg N Duez M Buyse (1990) ArticleTitleAn EORTC phase II study of sequential methotrexate-fluorouracil in locally advanced or metastatic gastric cancer. The EORTC Gastrointestinal Cancer Cooperative Group Eur J Cancer 26 63–5 Occurrence Handle2138482 Occurrence Handle1:STN:280:DyaK3c7pvVOhug%3D%3D Occurrence Handle10.1016/0277-5379(90)90259-V
M Murakami K Ota T Miyazaki Y Niitsu A Wakui M Yokoyama et al. (1987) ArticleTitleSequential methotrexate — 5-fluorouracil (MTX-5FU) treatment for patients with advanced gastric and colorectal cancer (in Japanese with English abstract) Jpn J Cancer Chemother 14 2482–90 Occurrence Handle1:STN:280:DyaL2s3pslGksA%3D%3D
T Sasaki K Ota J Ibayashi Y Sakata T Matsuoka M Ishikawqa et al. (1989) ArticleTitleRandomized muticenter trial: sequential methotrexate and 5-fluorouracil (MTX-5FU) versus 5-fluorouracil alone in advanced gastric and colorectal cancer (in Japanese with English abstract) Jpn J Cancer Chemother 16 2545–55 Occurrence Handle1:STN:280:DyaL1Mznt12kug%3D%3D
AJ Lacave FJ Baron LM Anton E Estrada LM De Sande I Palacio et al. (1991) ArticleTitleCombination chemotherapy with cisplatin and 5-fluorouracil 5-day infusion in the therapy of advanced gastric cancer: A phase II trial Ann Oncol 2 751–4 Occurrence Handle1801881 Occurrence Handle1:STN:280:DyaK387pvVyhuw%3D%3D
NK Kim YS Park DS Heo C Suh SY Kim KC Park et al. (1993) ArticleTitleA 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 3813–18 Occurrence Handle8508349 Occurrence Handle1:STN:280:DyaK3s3osVCqsg%3D%3D Occurrence Handle10.1002/1097-0142(19930615)71:12<3813::AID-CNCR2820711205>3.0.CO;2-5
P Rougier M Ducreux M Mahjoubi JP Pignon S Bellefqih J Oliveira et al. (1994) ArticleTitleEfficacy of combined 5-fluorouracil and cisplatinum in advanced gastric carcinomas. A phase II trial with prognostic factor analysis Eur J Cancer 30 1263–9 Occurrence Handle10.1016/0959-8049(94)90170-8
A Ohtsu Y Shimada S Yoshida H Saito S Seki K Morise et al. (1994) ArticleTitlePhase II study of protracted infusional 5-fluorouracil combined with cisplatinum for advanced gastric cancer: report from the Japan Clinical Oncology Group (JCOG) Eur J Cancer 30 2091–3 Occurrence Handle10.1016/0959-8049(94)00350-E
Y Maehara H Anai H Kusumoto K Sugimachi (1987) ArticleTitlePoorly differentiated human gastric carcinoma is more sensitive to antitumor drugs than is well-differentiated carcinoma Eur J Surg Oncol 13 203–6 Occurrence Handle3036603 Occurrence Handle1:STN:280:DyaL2s3kslegsg%3D%3D
InstitutionalAuthorNameJapanese Research Society for Gastric Cancer (1995) Japanese classification of gastric carcinoma EditionNumberFirst English edition Kanehara Tokyo
World Health Organization. WHO handbook for reporting results of cancer treatment. Geneva: WHO offset/Publication No. 48; 1979
EL Kaplan P Meier (1958) ArticleTitleNonparametric estimation from incomplete observations J Am Stat Assoc 53 457–81 Occurrence Handle10.2307/2281868
J Jolivet KH Cowan GA Curt NJ Clendeninn BA Chabner (1983) ArticleTitleThe pharmacology and clinical use of methotrexate N Engl J Med 309 1094–104 Occurrence Handle6353235 Occurrence Handle1:CAS:528:DyaL3sXmtVGnsrs%3D Occurrence Handle10.1056/NEJM198311033091805
HW Bruckner JJ Lokich DM Stablein (1982) ArticleTitleStudies of Baker's antifol, methotrexate, and razoxane in advanced gastric cancer. A Gastrointestinal Tumor Study Group Report Cancer Treat Rep 66 1713–17 Occurrence Handle7116348 Occurrence Handle1:STN:280:DyaL3s%2FgtFOgsQ%3D%3D
DJ Fernandes JR Bertino (1980) ArticleTitle5-Fluorouracil-methotrexate synergy: enhancement of 5-fluorodeoxyridylate binding to thymidylate synthase by dihydropteroylpolyglutamates Proc Natl Acad Sci USA 77 5663–7 Occurrence Handle6160578 Occurrence Handle1:CAS:528:DyaL3MXhsFSjsbg%3D Occurrence Handle10.1073/pnas.77.10.5663
E Cadman R Heimer L Davis (1979) ArticleTitleEnhanced 5-fluorouracil nucleotide formation after methotrexate administration: explanation for drug synergism Science 205 1135–7 Occurrence Handle472732 Occurrence Handle1:CAS:528:DyaE1MXlvVKmsr8%3D
E Cadman R Heimer C Benz (1981) ArticleTitleThe influence of methotrexate pretreatment on 5-fluorouracil metabolism in L1210 cells J Biol Chem 256 1695–704 Occurrence Handle6161926 Occurrence Handle1:CAS:528:DyaL3MXhtlajurs%3D
SI Hironaka N Boku A Ohtsu F Nagashima Y Sano M Muto et al. (2000) ArticleTitleSequential methotrexate and 5-fluorouracil therapy for gastric cancer patients with bone metastasis Gastric Cancer 3 19–23 Occurrence Handle11984704 Occurrence Handle10.1007/PL00011684
T Konishi T Miyama S Sakamoto T Hirata K Mafune M Hiraishi et al. (1992) ArticleTitleActivities of thymidylate synthetase and thymidine kinase in gastric cancer Surg Oncol 1 215–21 Occurrence Handle1341254 Occurrence Handle1:STN:280:DyaK2c%2FntlCmsg%3D%3D Occurrence Handle10.1016/0960-7404(92)90067-U
PG Johnston HJ Lenz CG Leichman KD Danenberg CJ Allegra PV Danenberg et al. (1995) ArticleTitleThymidylate synthase gene and protein expression correlate and associated with response to 5-fluorouracil in human colorectal and gastric tumors Cancer Res 55 1407–12 Occurrence Handle7882343 Occurrence Handle1:CAS:528:DyaK2MXkslWis7c%3D
PG Johnston ER Fisher HE Rockette B Fisher N Wolmark JC Drake et al. (1994) ArticleTitleThe role of thymidylate synthase expression in prognosis and outcome of adjuvant chemotherapy in patients with rectal cancer J Clin Oncol 12 2640–7 Occurrence Handle7989939 Occurrence Handle1:STN:280:DyaK2M%2FotFyjtw%3D%3D
M Beer G Cocconi G Ceci M Varini F Cavalli (1983) ArticleTitleA phase II study of cisplatin in advanced gastric cancer Eur J Cancer Clin Oncol 19 717–20 Occurrence Handle6683644 Occurrence Handle1:STN:280:DyaL3s3mt1Sitw%3D%3D Occurrence Handle10.1016/0277-5379(83)90003-2
AJ Lacave I Izarzugaza LM Anton Aparicio M Valle Pereda JM Gracia Marco JM Buesa (1983) ArticleTitlePhase II clinical trial of cis-dichlorodiammineplatinum in gastric cancer Am J Clin Oncol 6 35–8 Occurrence Handle6682284 Occurrence Handle1:STN:280:DyaL3s7nsFCqsQ%3D%3D Occurrence Handle10.1097/00000421-198306010-00005
L Leichman B McDonald A Dindogru M Samson VK Vaitkevicius (1984) ArticleTitleCisplatin. An active drug in the treatment of disseminated gastric cancer Cancer 53 18–22 Occurrence Handle6317158 Occurrence Handle1:STN:280:DyaL2c%2FotFOnsQ%3D%3D Occurrence Handle10.1002/1097-0142(19840101)53:1<18::AID-CNCR2820530105>3.0.CO;2-J
SE Vogl FJ Camacho PF Engstrom JM Bennett (1984) ArticleTitlePhase II trial of cisplatin in advanced gastric cancer Cancer Treat Rep 68 1497–8 Occurrence Handle6542449 Occurrence Handle1:STN:280:DyaL2M%2FnsVaruw%3D%3D
K Aabo H Pedersen M Rorth (1985) ArticleTitleCisplatin in the treatment of advanced gastric carcinoma: a phase II study Cancer Treat Rep 69 449–50 Occurrence Handle4039628 Occurrence Handle1:STN:280:DyaL2M3gtFCluw%3D%3D
AJ Lacave J Wils E Diaz-Rubio M Clavel A Planting H Bleiberg et al. (1985) ArticleTitlecis-Platinum as second-line chemotherapy in advanced gastric adenocarcinoma. A phase II study of the EORTC Gastrointestinal Tract Cancer Cooperative Group Eur J Cancer Clin Oncol 21 1321–4 Occurrence Handle4076293 Occurrence Handle1:STN:280:DyaL28%2FotF2qtg%3D%3D Occurrence Handle10.1016/0277-5379(85)90311-6
JD Hainsworth DH Johnson FA Greco (1992) ArticleTitleCisplatin-based combination chemotherapy in the treatment of poorly differentiated carcinoma and poorly differentiated adenocarcinoma of unknown primary site: results of a 12-year experience J Clin Oncol 10 912–22 Occurrence Handle1375284 Occurrence Handle1:STN:280:DyaK383mvV2ntw%3D%3D
B Drewinko BW Brown JA Gottlieb (1973) ArticleTitleThe effect of cis-diamminedichloroplatinum (II) on cultured human lymphoma cells and its therapeutic implications Cancer Res 33 3091–5 Occurrence Handle4760525 Occurrence Handle1:CAS:528:DyaE2cXhsVWhsr0%3D
JF Belliveau MR Posner L Ferrari GW Crabtree FJ Cummings MC Wiemann et al. (1986) ArticleTitleCisplatin administered as a continuous 5-day infusion: plasma platinum levels and urine platinum excretion Cancer Treat Rep 70 1215–17 Occurrence Handle3756943 Occurrence Handle1:STN:280:DyaL2s%2Fgt1amsg%3D%3D
T Konishi T Hirata T Miyama M Hiraishi K Mafune J Yohida et al. (1992) ArticleTitleMechanism of synergism and clinical results of sequential methotrexate and 5-fluorouracil in the treatment of gastric cancer (in Japanese with English abstract) Jpn J Cancer Chemother 19 946–53 Occurrence Handle1:STN:280:DyaK38zivVGhtA%3D%3D
T Yamao Y Shimada K Shirao A Ohtsu N Ikeda I Hyodo et al. (2004) ArticleTitleA phase II study of sequential methotrexate and 5-fluorouracil for advanced gastric cancer with malignant ascites: a report from the Gastrointestinal Oncology Study Group of the Japan Clinical Oncology Group, JCOG 9603 Trial Jpn J Clin Oncol 34 316–22 Occurrence Handle15333683 Occurrence Handle10.1093/jjco/hyh063
M Tahara A Ohtsu N Boku F Nagashima M Muto Y Sano et al. (2001) ArticleTitleSequential methotrexate and 5-fluorouracil therapy for gastric cancer patients with peritoneal dissemination: a retrospective study Gastric Cancer 4 212–8 Occurrence Handle11846065 Occurrence Handle1:CAS:528:DC%2BD38XislCksbc%3D Occurrence Handle10.1007/s10120-001-8012-x
T Konishi T Noie J Yoshida K Mafune M Makuuchi (1999) ArticleTitleTreatment of peritoneal dissemination of gastric cancer with sequential methotrexate and 5-fluorouracil Gastric Cancer 2 52–6 Occurrence Handle11957071 Occurrence Handle10.1007/s101200050021
A Thyss G Milano J Kubar M Namer M Schneider (1986) ArticleTitleClinical and pharmacokinetic evidence of a life-threatening interaction between methotrexate and ketoprofen Lancet I 256–8 Occurrence Handle10.1016/S0140-6736(86)90786-5
Author information
Authors and Affiliations
Rights and permissions
About this article
Cite this article
Nakayama, N., Koizumi, W., Tanabe, S. et al. A phase II study of combined chemotherapy with methotrexate, 5-fluorouracil, and low-dose cisplatin (MFP) for histologically diffuse-type advanced and recurrent gastric cancer (KDOG9501). Gastric Cancer 9, 185–191 (2006). https://doi.org/10.1007/s10120-006-0371-x
Received:
Accepted:
Issue Date:
DOI: https://doi.org/10.1007/s10120-006-0371-x