Abstract
Purpose
We performed a single-institution retrospective study to evaluate the efficacy and toxicities of oxaliplatin, 5-fluorouracil (5-FU), leucovorin (LV) combination chemotherapy as salvage treatment in patients with metastatic or advanced gastric cancer.
Methods
Sixty-two patients with advanced gastric cancer previously treated were eligible for the study. Patients received oxaliplatin 100 mg/m2 and LV 100 mg/m2 (2-h intravenous infusion) followed by 5-FU 2,400 mg/m2 (46-h continuous infusion) every 2 weeks, and responses were assessed after every three cycles.
Results
Fifty-nine out of 62 patients were assessable for response. Among them, 46 patients had previously been treated with cisplatin based chemotherapy. Patients had a median age of 57 years (range 32–76 years), 72.6% had an Eastern Cooperative Oncology Group performance status of 0 or 1. Total 296 courses of chemotherapy were administered as second-line (67.7%) or third-line (27.4%), and the median courses per patient was three cycles. Out of 59 evaluable patients, 14 partial responses were observed (overall response rate, 22.6%). Stable disease was observed in 22 patients (35.5%), and progressive disease in 23 patients (37.1%). The median response duration, time to progression, and overall survival were 2.3, 3.0, and 8.0 months, respectively. The major toxicities were neutropenia, mucositis, and peripheral neuropathy. Grade 3 or 4 hematologic toxicities included neutropenia in nine patients (14.5%) and thrombocytopenia in one patient (1.6%). Other grade 3 or 4 toxicities included mucositis in one patient (1.6%) and vomiting in two patients (3.2%). Grade 1 or 2 peripheral neuropathy were observed in 18 patients (29.0%), however there were no cases of grade 3 or 4 peripheral neuropathy and no treatment-related deaths.
Conclusion
The combination of oxaliplatin, 5-FU and LV was effective and safe salvage chemotherapy in advanced gastric cancer patients.
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References
Shin HR, Won YJ, Jung KW et al (2005) Nationwide cancer incidence in Korea, 1999–2001; first result using the national cancer incidence database. Cancer Res Treat 37:325–331
Epelbaum R, Haim N, Stein M, Cohen Y, Robinson E (1987) Treatment of advanced gastric cancer with DDP (cisplatin), adriamycin, and 5-fluorouracil (DAF). Oncology 44:201–206
Lopez M, Di Lauro L, Papaldo P, Conti EM (1986) Treatment of advanced measurable gastric carcinoma with 5-fluorouracil, adriamycin, and BCNU. Oncology 43:288–291
Becouarn Y, Agostini C, Trufflandier N, Boulanger V (2001) Oxaliplatin: available data in non-colorectal gastrointestinal malignancies. Crit Rev Oncol Hematol 40:265–272
Raymond E, Faivre S, Woynarowski JM, Chaney SG (1998) Oxaliplatin: mechanism of action and antineoplastic activity. Semin Oncol 25:4–12
Kollmannsberger C, Rick O, Derigs HG et al (2002) Activity of oxaliplatin in patients with relapsed or cisplatin-refractory germ cell cancer: a study of the German Testicular Cancer Study Group. J Clin Oncol 20:2031–2037
Extra JM, Espie M, Calvo F, Ferme C, Mignot L, Marty M (1990) Phase I study of oxaliplatin in patients with advanced cancer. Cancer Chemother Pharmacol 25:299–303
Degardin M, Cappelaere P, Krakowski I, Fargeot P, Cupissol D, Brienza S (1996) Phase II trial of oxaliplatin (L-OHP) in advanced, recurrent and/or metastatic squamous cell carcinoma of the head and neck. Eur J Cancer B Oral Oncol 32B:278–279
Louvet C, Andre T, Lledo G et al (2002) Gemcitabine combined with oxaliplatin in advanced pancreatic adenocarcinoma: final results of a GERCOR multicenter phase II study. J Clin Oncol 20:1512–1518
Monnet I, Brienza S, Hugret F et al (1998) Phase II study of oxaliplatin in poor-prognosis non-small cell lung cancer (NSCLC). ATTIT. Association pour le Traitement des Tumeurs Intra Thoraciques. Eur J Cancer 34:1124–1127
Andre T, Bensmaine MA, Louvet C et al (1999) Multicenter phase II study of bimonthly high-dose leucovorin, fluorouracil infusion, and oxaliplatin for metastatic colorectal cancer resistant to the same leucovorin and fluorouracil regimen. J Clin Oncol 17:3560–3568
Raymond E, Buquet-Fagot C, Djelloul S et al (1997) Antitumor activity of oxaliplatin in combination with 5-fluorouracil and the thymidylate synthase inhibitor AG337 in human colon, breast and ovarian cancers. Anticancer Drugs 8:876–885
Al-Batran SE, Atmaca A, Hegewisch-Becker S et al (2004) Phase II trial of biweekly infusional fluorouracil, folinic acid, and oxaliplatin in patients with advanced gastric cancer. J Clin Oncol 22:658–663
Cavanna L, Artioli F, Codignola C et al (2006) Oxaliplatin in combination with 5-fluorouracil (5-FU) and leucovorin (LV) in patients with metastatic gastric cancer (MGC). Am J Clin Oncol 29:371–375
De Vita F, Orditura M, Matano E et al (2005) A phase II study of biweekly oxaliplatin plus infusional 5-fluorouracil and folinic acid (FOLFOX-4) as first-line treatment of advanced gastric cancer patients. Br J Cancer 92:1644–1649
Lordick F, Lorenzen S, Stollfuss J et al (2005) Phase II study of weekly oxaliplatin plus infusional fluorouracil and folinic acid (FUFOX regimen) as first-line treatment in metastatic gastric cancer. Br J Cancer 93:190–194
Louvet C, Andre T, Tigaud JM et al (2002) Phase II study of oxaliplatin, fluorouracil, and folinic acid in locally advanced or metastatic gastric cancer patients. J Clin Oncol 20:4543–4548
Therasse P, Arbuck SG, Eisenhauer EA et al (2000) New guidelines to evaluate the response to treatment in solid tumors. European Organization for Research and Treatment of Cancer, National Cancer Institute of the United States, National Cancer Institute of Canada. J Natl Cancer Inst 92:205–216
Levi F, Misset JL, Brienza S et al (1992) A chronopharmacologic phase II clinical trial with 5-fluorouracil, folinic acid, and oxaliplatin using an ambulatory multichannel programmable pump. High antitumor effectiveness against metastatic colorectal cancer. Cancer 69:893–900
Parkin DM, Bray F, Ferlay J, Pisani P (2005) Global cancer statistics, 2002. CA Cancer J Clin 55:74–108
Glimelius B, Ekstrom K, Hoffman K et al (1997) Randomized comparison between chemotherapy plus best supportive care with best supportive care in advanced gastric cancer. Ann Oncol 8:163–168
Kim DY, Kim JH, Lee SH et al (2003) Phase II study of oxaliplatin, 5-fluorouracil and leucovorin in previously platinum-treated patients with advanced gastric cancer. Ann Oncol 14:383–387
Chao Y, Yeh KH, Chang CJ et al (2004) Phase II study of weekly oxaliplatin and 24-h infusion of high-dose 5-fluorouracil and folinic acid in the treatment of advanced gastric cancer. Br J Cancer 91:453–458
Oh SY, Kwon HC, Seo BG, Kim SH, Kim JS, Kim HJ (2007) A phase II study of oxaliplatin with low dose leucovorin and bolus and continuous infusion 5-fluorouracil (modified FOLFOX-4) as first line therapy for patients with advanced gastric cancer. Acta Oncol 46:336–341
Kim SG, Oh SY, Kwon HC et al (2007) A phase II study of irinotecan with bi-weekly, low-dose leucovorin and bolus and continuous infusion 5-fluorouracil (modified FOLFIRI) as salvage therapy for patients with advanced or metastatic gastric cancer. Jpn J Clin Oncol 37:744–749
Ueda S, Hironaka S, Boku N, Fukutomi A, Yoshino T, Onozawa Y (2006) Combination chemotherapy with irinotecan and cisplatin in pretreated patients with unresectable or recurrent gastric cancer. Gastric Cancer 9:203–207
Park SH, Choi EY, Bang SM et al (2005) Salvage chemotherapy with irinotecan and cisplatin in patients with metastatic gastric cancer failing both 5-fluorouracil and taxanes. Anticancer Drugs 16:621–625
Kim ST, Kang WK, Kang JH et al (2005) Salvage chemotherapy with irinotecan, 5-fluorouracil and leucovorin for taxane- and cisplatin-refractory, metastatic gastric cancer. Br J Cancer 92:1850–1854
Lee JL, Ryu MH, Chang HM et al (2008) A phase II study of docetaxel as salvage chemotherapy in advanced gastric cancer after failure of fluoropyrimidine and platinum combination chemotherapy. Cancer Chemother Pharmacol 61:631–637
Acknowledgments
This study was supported in part by a grant of the Korea Health 21 R&D Project, Ministry of Health & Welfare, Republic of Korea (A040151 and A010250).
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Seo, H.Y., Kim, D.S., Choi, Y.S. et al. Treatment outcomes of oxaliplatin, 5-FU, and leucovorin as salvage therapy for patients with advanced or metastatic gastric cancer: a retrospective analysis. Cancer Chemother Pharmacol 63, 433–439 (2009). https://doi.org/10.1007/s00280-008-0753-3
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DOI: https://doi.org/10.1007/s00280-008-0753-3