Oxaliplatin, 5-fluorouracil/leucovorin and epirubicin as first-line treatment in advanced gastric carcinoma: a phase II study

B Neri, P Pantaleo, E Giommoni, R Grifoni, C Paoletti, V Rotella, D Pantalone, A Taddei, A Mercatelli, P Tonelli, B Neri, P Pantaleo, E Giommoni, R Grifoni, C Paoletti, V Rotella, D Pantalone, A Taddei, A Mercatelli, P Tonelli

Abstract

The association between oxaliplatin and 5-fluorouracil (5-FU) has been extensively reported to improve prognosis of gastric cancer patients. The present study is aimed at evaluating response rate and the toxicity profile of the association with oxaliplatin, 5-FU/lecovorin and epirubicin in gastric cancer patients with locally advanced or metastatic disease. Thirty-six patients have been enrolled and 35 evaluated. The treatment schedule was oxaliplatin (100 mg m(-2)), 5-FU (400 mg m(-2)), leucovorin (40 mg m(-2)) and epirubicin (60 mg m(-2)) intravenously. administered every 3 weeks for 6 months, for a total of 185 therapy cycles . Response rate and toxicity were assessed according to the international WHO criteria. Every patient received a mean of 5.3 therapy cycles in a day-hospital setting. Sixteen of 35 patients (46%) showed an objective response, two complete response and 14 partial response. Median time to progression was 33 weeks with an overall median survival of 49 weeks. During the study, anaemia grade 3 and neutropenia grade 3 were observed in 9 and 11% of patients respectively. A grade 3 periferic sensorial neuropathy was observed in 6% of patients. No life threatening or cardiac toxicity was recorded. The regimen used showed anticancer activity against gastric carcinoma, a tolerable toxicity profile and excellent patient compliance.

Figures

Figure 1
Figure 1
Kaplan–Meier estimates of time to progression among patients with gastric cancer treated with oxaliplatin, 5-fluorouracil/leucovorin and epirubicin regimen.
Figure 2
Figure 2
Kaplan–Meier estimates of OS among patients with gastric cancer treated with oxaliplatin, 5-fluorouracil/leucovorin and epirubicin regimen.

References

    1. Al Batran SE, Atmaca A, Hegewisch-Becher S (2004) Phase II trial of biweekly infusional fluorouracile, folinic acid, and oxaliplatin in patients with advanced gastric cancer. J Clin Oncol 22: 658–663
    1. De Vita F, Orditura M, Matano E, Bianco R, Carlomagno C, Infusino S, Damiano V, Simeone E, Diadema MR, Lieto E, Castellano P, Pepe S, De Placido S, Galizia G, Di Martino N, Ciardiello F, Catalano G, Bianca AR (2005) A phase II study biweekly oxaliplatin plus infusional 5-fluorouracil and folinic acid (FOLFOX-4) as first-line treatment, of advanced gastric cancer patients. Br J Cancer 26: 1644–1649
    1. Extra JM, Marthy M, Brienza S, Misset JL (1998) Pharmacokinetics and safety profile of oxaliplatin. Semin Oncol 25(2): 13–22
    1. Kaplan EL, Meyer P (1958) Non-parametric estimation for incomplete observations. J Am Stat Assoc 53: 357–481
    1. Launchbury AP, Habboubi N (1993) Epirubicin and doxorubicin: a comparison of their characteristics, therapeutic activity and toxicity. Cancer Treat Rev 19: 197–201
    1. Lee J, Kang WK, Kwon JM, Oh SY, Lee HR, Kim HJ, Park BB, Lim HY, Han MJ, Park JO, Park YS (2007) Phase II trial of irinotecan plus oxaliplatin and 5-fluorouracil/lecovorin in patients with untreated metastatic gastric adenocarcinoma. Ann Oncol 18: 88–92
    1. Lentner C (1982) Exact confidence limits. In: Geigy Scientific Tables 89–102, Charlotte Lentnere, Anthony Wink (eds), Ciba Geigy: Switzerland
    1. Lordick F, Lorenzen S, Stollfuss J, Vehling-Kaiser U, Kullmann F, Hentrich M, Zumschlinge R, Dietzfelbinger H, Thoedtmann J, Henning M, Seroneit T, Duyster J, Peshel C, Bredenkamp R (2005) Phase II study of weekly oxaliplatin plus infusional fluorouracil and folinic acid as first-line treatment in metastatic gastric cancer. Br J Cancer 93: 190–194
    1. Macdonald JS, Wooley PV, Smythe T, Ueno W, Hoth D, Schein PS (1979) 5-Fluorouracil, adriamycin and mitomycin C (FAM) combination chemotherapy in the treatment of advanced gastric cancer. Cancer 44: 42–47
    1. Machover D, Diaz-Rubio E, de Gramont A, Schift A, Gastiaburu JJ, Brienza S, Itzhaki M, Metzger G, N'Daw D, Vignoud J, Abad A, Francois E, Gamelin E, Marty M, Sastre J, Seitz JF, Ychou M (1996) Two consecutive phase II studies of oxaliplatin for treatment of patients with advanced colorectal carcinoma who were resistant to previous treatment with fluoropyrimidines. Ann Oncol 7: 95–98
    1. Misset JL, Bleiberg H, Sutherland W, Bekradda M, Cvitkovic E (2000) Oxaliplatin clinical activity. A review. Crit Rev Oncol Hematol 35: 75–93
    1. Park YH, Kim BS, Ryoo BY, Yang SH (2006) A phase II study of capecitabine plus 3 weekly oxaliplatin as first-line therapy for patients with advanced gastric cancer. Br J Cancer 94(7): 959–963
    1. Parkin DM, Bray F, Ferlay J, Pisani P (2001) Estimating the World Cancer Burden: GLOBOCAN 2000. Int J Cancer 94: 153–156
    1. Preusser P, Wilke H, Achterrath W, Fink U, Lenaz L, Heinicke A, Meyer J, Meyer HJ, Buente H (1989) Etoposide, doxorubicin and cisplatin in advanced measurable gastric cancer. J Clin Oncol 7: 1310–1317
    1. Raymond E, Chaney SG, Taamma A, Cvitkovic E (1998) Oxaliplatin: a review of preclinical and clinical studies. Ann Oncol 9: 1–19
    1. Simon R (1989) Optimal two-stage designs for phase II clinical trials. Control Clin Trials 10: 1–10
    1. Thuss-Patience PC, Kretzchmar A, Repp M, Kingreen D, Hennesser D, Micheel S, Pink D, Scholz C, Dorken B, Reichardt P (2005) Docetaxel and continuous-infusion fluorouracil versus epirubicin, cisplatin and fluorouracil for advanced gastric adenocarcinama: a randomized phase II study. J Clin Oncol 23(3): 494–501
    1. Wagner AD, Grothe W, Behl S, Kleber G, Grothey A, Haerting J, Fleig WE (2005) Chemotherapy for advanced gastric cancer. Cochrane Database of Systematic Reviews Issue 2 Art. No. CD004064. DOI: 10.1002/4651858.CD004064.pub2
    1. Wilke H, Preusser P, Fink U, Achterrath W, Meyer HJ, Stahl M, Lenaz L, Siewert JR, Geerlings H (1991) New developments in the treatment of gastric carcinoma. Semin Oncol 17: 61–70
    1. Woo IS, Moon DH, Shim BY, Lee MA, Byun JH, Kim KW, Kang JH, Choi MG, Chung IS, Hong YS, Park SY, Lee KS (2005) A phase II study of epirubicin, cisplatin and uracil-tegafur for advanced gastric carcinoma. Jpn J Clin Oncol 35(1): 13–17
    1. World Health Organization (1979) Handbook for Reporting Results of Cancer Treatment W.H.O offset publication No.48. Geneva

Source: PubMed

Sponsors and Collaborators

Medical Conditions

Drug Interventions

3
Subscribe