Abstract
Background
The aim of this study was to establish the efficacy and safety of doxifluridine and docetaxel for patients with advanced or recurrent gastric cancer.
Methods
The regimen consisted of oral administration of doxifluridine 533 mg/m2 per day on days 1–14 and an intravenous infusion of docetaxel 50 mg/m2 on day 8. The primary endpoint was the overall response rate. The secondary endpoints were overall survival, progression-free survival, and toxicities.
Results
Between June 2004 and December 2006, a total of 40 eligible patients were enrolled in this study. Seven of them showed a partial response, with an overall response rate of 17.5%. The response rate was 18.8% in 32 patients with refractory tumors. The median progression-free survival time and the median overall survival time were 2.6 months and 12.7 months, respectively, in all 40 patients; and 2.6 months and 14.0 months, respectively, in the 32 patients with refractory tumors. Grade 3/4 hematological toxicity included neutropenia in 52.5%, leukocytopenia in 17.5%, and febrile neutropenia in 7.5%. Grade 3 or more nonhematological toxicities were infrequent.
Conclusion
The combination chemotherapy of doxifluridine and docetaxel was well tolerated and relatively effective when used as a second-line chemotherapy for advanced or recurrent gastric cancer.
Article PDF
Similar content being viewed by others
Explore related subjects
Discover the latest articles and news from researchers in related subjects, suggested using machine learning.Avoid common mistakes on your manuscript.
References
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.
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.
Glimelius B, Hoffman K, Haglund U Nyren O, Sjoden PO. Initial or delayed chemotherapy with best supportive care in advanced gastric cancer. Ann Oncol 1994;5:189–190.
Koizumi W, Kurihara M, Nakano S, Hasegawa K. Phase II study of S-1, a novel oral derivative of 5-fluorouracil, in advanced gastric cancer. Oncology 2000;58:191–197.
Sakata Y, Ohtsu A, Horikoshi N, Sugimachi K, Mitachi Y, Taguchi T. Late phase II study of novel oral fluoropyrimidine anticancer drug S-1 (1 M tegafur-0.4 M gimestat-1 M otastat potassium) in advanced gastric cancer patients. Eur J Cancer 1998;34:1715–1720.
Yamada Y, Shirao K, Ohtsu A, Boku N, Hyodo I, Saitoh H, et al. Phase II trial of paclitaxel by 3-h infusion for advanced gastric cancer with short premedication for prophylaxis against paclitaxel-associated hypersensitivity. Ann Oncol 2001;12:1133–1137.
Yamaguchi K, Tada M, Horikoshi N, Otani T, Takiuchi H, Saitoh S, et al. Phase II study of paclitaxel 3-h infusion in patients with advanced gastric cancer. Gastric Cancer 2002;5:55–57.
Taguchi T, Sakata Y, Kanamaru R, Kurihara M, Suminaga M, Ota J, et al. Late phase II clinical study of RP56976 (docetaxel) in patients with advanced/recurrent gastric cancer. a Japanese Cooperative Study Group trial (group A). Jpn J Cancer Chemother 1998;25:1915–1924.
Mai M, Sakata Y, Kanamaru R, Kurihara M, Suminaga M, Ota J, et al. A late phase II clinical study of RP56976 (docetaxel) in patients with advanced or recurrent gastric cancer. A cooperative study group trial (group B). Jpn J Cancer Chemother 1999;26:487–496.
Futatsuki K, Wakui A, Nakao I, Sakata Y, Kambe M, Shimada Y, et al. Late phase II study of irinotecan hydrochloride (CPT-11) in advanced gastric cancer. Jpn J Cancer Chemother 1994;21:1033–1038.
Wang LG, Liu XM, Kreis W, Budman DR. The effect of antimicrotubule agents on signal transduction pathways of apoptosis: a review. Cancer Chemother Pharmacol 1999;44:355–361.
Van Cutsem E, Moiseyenko VM, Tjulandin S, Majlis A, Constenla M, Boni C, et al. Phase III study of docetaxel and cisplatin plus fluorouracil compared with cisplatin and fluorouracil as first-line therapy for advanced gastric cancer: a report of the V325 study. J Clin Oncol 2006;24:4991–4997.
Ishitsuka H, Miwa M, Takemoto K, Fukuoka K, Itoga A, Maruyama H. Role of uridine phosphorylase for antitumor activity of 5′-deoxy-5-fluorouridine. Gann 1980;71:112–123.
Niitani H, Kimura K, Saito T, Nakao I, Abe O, Urushizaki I, et al. Phase II study of 5′-deoxy-5-fluorouridine (5′-DFUR) on patients with malignant cancer. Multi-institutional cooperative study. Jpn J Cancer Chemother 1985;12:2044–2051
Miwa M, Ura M, Nishida M, Sawada N, Ishikawa T, Mori K, et al. Design of a novel oral fluoropyrimidine carbamate, capecitabine, which generates 5-fluorouracil selectively in tumours by enzymes concentrated in human liver and cancer tissue. Eur J Cancer 1998;34:1274–1281.
Sawada N, Ishikawa T, Fukase Y, Nishida M, Yoshikubo T, Ishitsuka H. Induction of thymidine phosphorylase activity and enhancement of capecitabine efficacy by taxol/taxotere in human cancer xenografts. Clin Cancer Res 1996;4:1013–1019.
Nishimura R, Tominaga T, Mitsuyama S, Aoyama H, Asaga T, Ohno S, et al. Combination chemotherapy with docetaxel and doxifluridine showed a beneficial outcome in advanced or recurrent breast cancer patients with longer disease-free interval. Anticancer Res 2004;24:2085–2091.
Sato A, Shimada K, Matsukawa M, Taguchi S. A phase I study of combination chemotherapy of docetaxel and doxifluridine for unresectable or recurrent gastric cancer. Presented at the 76th annual meeting of the Japanese Gastric Cancer Association, 2004. p. 1646.
Takiuchi H, Goto M, Imamura H, Furukawa H, Imano M, Imamoto H, et al. Multi-center phase II study for combination therapy with paclitaxel/doxifluridine to treat advanced/recurrent gastric cancer showing resistance to S-1 (OGSG 0302). Jpn J Clin Oncol 2008;38:176–181.
Boku N, Yamamoto S, Shirao K, Doi T, Sawaki A, Koizumi W, et al. Randomized phase III study of 5-fluorouracil (5-FU) alone versus combination of irinotecan and cisplatin (CP) versus S-1 alone in advanced gastric cancer (JCOG 9912). Presented at the 43rd Annual Meeting of American Society of Clinical Oncology, Chicago, IL, June 1–5, 2007 (abstract LBA4513).
Koizumi W, Narahara H, Hara T, Takagane A, Akiya T, Takagi M, et al. S-1 plus cisplatin versus S-1 alone for first-line treatment of advanced gastric cancer (SPIRITS trial): a phase III trial. Lancet Oncol 2008;9:215–221.
Imamura H, Ishii H, Tsuburaya A, Hatake K, Imamoto H, Esaki T, et al. Randomized phase III study of irinotecan plus S-1 (IRIS) versus S-1 alone as first-line treatment for advanced gastric cancer (GC0301/TOP-002). Presented at the 2008 Gastrointestinal Cancers Symposium, Orlando, FL, January 25–27, 2008 (abstract 5).
Kunisaki C, Imada T, Yamada R, Hatori S, Ono H, Otsuka Y, et al. Phase II study of docetaxel plus cisplatin as a second-line combined therapy in patients with advanced gastric carcinoma. Anticancer Res 2005;25:2973–2978.
Park SH, Kang WK, Lee HR, Park J, Lee KE, Lee SH, et al. Docetaxel plus cisplatin as second-line therapy in metastatic or recurrent advanced gastric cancer progressing on 5-fluorouracilbased regimen. Am J Clin Oncol 2004;27:477–480.
Sym SJ, Chang HM, Kang HJ, Lee SS, Ryu MH, Lee JL, et al. A phase II study of irinotecan and docetaxel combination chemotherapy for patients with previously treated metastatic or recurrent advanced gastric cancer. Cancer Chemother Pharmacol 2008;63:1–8.
Nguyen S, Rebischung C, Van Onqueval J, Flesch M, Bennamoun M, André T, et al. Epirubicin-docetaxel in advanced gastric cancer: two phase II studies as second and first line treatment. Bull Cancer 2006;93:E1–6.
Rosati G, Bilancia D, Germano D, Dinota A, Romano R, Reggiardo G, et al. Reduced dose intensity of docetaxel plus capecitabine as second-line palliative chemotherapy in patients with metastatic gastric cancer: a phase II study. Ann Oncol 2007;18:128–132.
Barone C, Basso M, Schinzari G, Pozzo C, Trigila N, D’Argento E, et al. Docetaxel and oxaliplatin combination in second-line treatment of patients with advanced gastric cancer. Gastric Cancer 2007;10:104–111.
Author information
Authors and Affiliations
Rights and permissions
About this article
Cite this article
Yoshikawa, T., Tsuburaya, A., Shimada, K. et al. A phase II study of doxifluridine and docetaxel combination chemotherapy for advanced or recurrent gastric cancer. Gastric Cancer 12, 212–218 (2009). https://doi.org/10.1007/s10120-009-0528-5
Received:
Accepted:
Published:
Issue Date:
DOI: https://doi.org/10.1007/s10120-009-0528-5