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01.04.2015 | Original Article

Phase II study of mFOLFOX3 (5-fluorouracil, leucovorin, oxaliplatin) as second-line treatment after gemcitabine failure in patients with unresectable/metastatic biliary tract cancer

verfasst von: In Gyu Hwang, Joung-Soon Jang, Sung Yong Oh, Myung Hwan Rho, Suee Lee, Young Suk Park, Joon Oh Park, Eun Mi Nam, Hyo Rak Lee, Hyun Jung Jun, Kyong-Choun Chi

Erschienen in: Cancer Chemotherapy and Pharmacology | Ausgabe 4/2015

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Abstract

Purpose

We conducted a phase II trial of 5-fluorouracil and oxaliplatin combination chemotherapy as a second-line treatment in unresectable/metastatic biliary tract cancer patients who had failed gemcitabine-based chemotherapy.

Methods

Patients treated with gemcitabine-based palliative treatment were enrolled in this study. Patients were received modified FOLFOX3 (mFOLFOX3) consists of oxaliplatin 85 mg/m² (day 1) and leucovorin 30 mg (days 1, 2) followed by 5-fluorouracil 1,500 mg/m² (days 1, 2) every 2 weeks.

Results

Between March 2010 and June 2012, a total of 30 patients were enrolled in this study. Twenty-eight patients were measurable for treatment response. One achieved complete response, and one a partial response was observed. Overall response rate was 7.1 % (95 % confidence interval 0.9–23.5 %). The median progression-free survival was 1.6 months, and the median overall survival was 4.4 months. Grade 3–4 hematologic toxicities included neutropenia (6.7 %) and thrombocytopenia (3.4 %). The most common non-hematologic toxicity was neuropathy (22.2 %). However, the most common grade 3–4 non-hematologic toxicity was hyperbilirubinemia (5.0 %). There was one treatment-related death due to neutropenic infection.

Conclusion

mFOLFOX3 as a second-line regimen has modest effect and tolerable toxicity in unresectable/metastatic biliary tract cancer patients who have been treated previously via gemcitabine-based chemotherapy.

Bae J-M, Won Y-J, Jung K-W, J-G P (2002) Annual report of the Korea central cancer registry program 2000: based on registered data from 131 hospitals. Cancer Res Treat 34(2):77–83

Anderson CD, Pinson CW, Berlin J, Chari RS (2004) Diagnosis and treatment of cholangiocarcinoma. Oncologist 9(1):43–57CrossRefPubMed

Valle J, Wasan H, Palmer DH, Cunningham D, Anthoney A, Maraveyas A, Madhusudan S, Iveson T, Hughes S, Pereira SP, Roughton M, Bridgewater J, Investigators ABCT (2010) Cisplatin plus gemcitabine versus gemcitabine for biliary tract cancer. N Engl J Med 362(14):1273–1281. doi:10.1056/NEJMoa0908721 CrossRefPubMed

Woynarowski JM, Faivre S, Herzig MC, Arnett B, Chapman WG, Trevino AV, Raymond E, Chaney SG, Vaisman A, Varchenko M, Juniewicz PE (2000) Oxaliplatin-induced damage of cellular DNA. Mol Pharmacol 58(5):920–927PubMed

Raymond E, Lawrence R, Izbicka E, Faivre S, Von Hoff DD (1998) Activity of oxaliplatin against human tumor colony-forming units. Clin Cancer Res Off J Am Assoc Cancer Res 4(4):1021–1029

Andre T, Reyes-Vidal JM, Fartoux L, Ross P, Leslie M, Rosmorduc O, Clemens MR, Louvet C, Perez N, Mehmud F, Scheithauer W (2008) Gemcitabine and oxaliplatin in advanced biliary tract carcinoma: a phase II study. Br J Cancer 99(6):862–867. doi:10.1038/sj.bjc.6604628 CrossRefPubMedCentralPubMed

Jang JS, Lim HY, Hwang IG, Song HS, Yoo N, Yoon S, Kim YH, Park E, Byun JH, Lee MA, Oh SJ, Lee KH, Kim BS, Oh SC, Kim SY, Lee SJ (2010) Gemcitabine and oxaliplatin in patients with unresectable biliary cancer including gall bladder cancer: a Korean Cancer Study Group phase II trial. Cancer Chemother Pharmacol 65(4):641–647. doi:10.1007/s00280-009-1069-7 CrossRefPubMed

Lim JY, Jeung HC, Mun HS, Lee DK, Paik YH, Lee SJ, Yoon DS, Cho JY (2008) Phase II trial of oxaliplatin combined with leucovorin and fluorouracil for recurrent/metastatic biliary tract carcinoma. Anticancer Drugs 19(6):631–635. doi:10.1097/CAD.0b013e3283017f94 CrossRefPubMed

Nehls O, Klump B, Arkenau HT, Hass HG, Greschniok A, Gregor M, Porschen R (2002) Oxaliplatin, fluorouracil and leucovorin for advanced biliary system adenocarcinomas: a prospective phase II trial. Br J Cancer 87(7):702–704. doi:10.1038/sj.bjc.6600543 CrossRefPubMedCentralPubMed

10.

Verderame F, Russo A, Di Leo R, Badalamenti G, Santangelo D, Cicero G, Valerio MR, Gulotta G, Tomasello G, Gebbia N, Fulfaro F (2006) Gemcitabine and oxaliplatin combination chemotherapy in advanced biliary tract cancers. Annals Oncol 17(Suppl 7):vii68–vii72. doi:10.1093/annonc/mdl955

11.

He S, Shen J, Sun X, Liu L, Dong J (2014) A phase II FOLFOX-4 regimen as second-line treatment in advanced biliary tract cancer refractory to gemcitabine/cisplatin. J Chemother 26(4):243–247. doi:10.1179/1973947813Y.0000000133 CrossRefPubMed

12.

Lim KH, Han SW, Oh DY, Im SA, Kim TY, Bang YJ (2012) Outcome of infusional 5-fluorouracil, doxorubicin, and mitomycin-C (iFAM) chemotherapy and analysis of prognostic factors in patients with refractory advanced biliary tract cancer. Oncology 83(2):57–66. doi:10.1159/000338795 CrossRefPubMed

13.

Oh SY, Jeong CY, Hong SC, Kim TH, Ha CY, Kim HJ, Lee GW, Hwang IG, Jang JS, Kwon HC, Kang JH (2011) Phase II study of second line gemcitabine single chemotherapy for biliary tract cancer patients with 5-fluorouracil refractoriness. Invest New Drugs 29(5):1066–1072. doi:10.1007/s10637-010-9417-3 CrossRefPubMed

14.

Roth A, Schleyer E, Schoppmeyer K, Kluge R, Wittekind C, Mossner J, Wiedmann M (2011) Imatinib mesylate for palliative second-line treatment of advanced biliary tract cancer: a bicentric phase II study. Onkologie 34(8–9):469–470. doi:10.1159/000331065 CrossRefPubMed

15.

Sasaki T, Isayama H, Nakai Y, Mizuno S, Yamamoto K, Yagioka H, Yashima Y, Kawakubo K, Kogure H, Togawa O, Matsubara S, Ito Y, Sasahira N, Hirano K, Tsujino T, Toda N, Tada M, Omata M, Koike K (2012) Multicenter phase II study of S-1 monotherapy as second-line chemotherapy for advanced biliary tract cancer refractory to gemcitabine. Invest New Drugs 30(2):708–713. doi:10.1007/s10637-010-9553-9 CrossRefPubMed

16.

Yi JH, Thongprasert S, Lee J, Doval DC, Park SH, Park JO, Park YS, Kang WK, Lim HY (2012) A phase II study of sunitinib as a second-line treatment in advanced biliary tract carcinoma: a multicentre, multinational study. Eur J Cancer 48(2):196–201. doi:10.1016/j.ejca.2011.11.017 CrossRefPubMed

17.

Lamarca A, Hubner RA, David Ryder W, Valle JW (2014) Second-line chemotherapy in advanced biliary cancer: a systematic review. Ann Oncol 25(12):2328–2338. doi:10.1093/annonc/mdu162 CrossRefPubMed

18.

Katayose Y, Ohtsuka H, Kitamura Y, Masuda K, Nakagawa K, Yamamoto K, Yoshida H, Onogawa T, Motoi F, Naitoh T, Rikiyama T, Egawa S, Unno M (2012) An analysis of a second-line S-1 monotherapy for gemcitabine-refractory biliary tract cancer. Hepatogastroenterology 59(115):691–695. doi:10.5754/hge11530 PubMed

19.

Shoda J, Ishige K, Sugiyama H, Kawamoto T (2012) Biliary tract carcinoma: clinical perspectives on molecular targeting strategies for therapeutic options. J Hepatobiliary Pancreat Sci 19(4):342–353. doi:10.1007/s00534-012-0520-z CrossRefPubMed

Titel: Phase II study of mFOLFOX3 (5-fluorouracil, leucovorin, oxaliplatin) as second-line treatment after gemcitabine failure in patients with unresectable/metastatic biliary tract cancer
verfasst von: In Gyu Hwang
Joung-Soon Jang
Sung Yong Oh
Myung Hwan Rho
Suee Lee
Young Suk Park
Joon Oh Park
Eun Mi Nam
Hyo Rak Lee
Hyun Jung Jun
Kyong-Choun Chi
Publikationsdatum: 01.04.2015
Verlag: Springer Berlin Heidelberg
Erschienen in: Cancer Chemotherapy and Pharmacology / Ausgabe 4/2015
Print ISSN: 0344-5704
Elektronische ISSN: 1432-0843
DOI: https://doi.org/10.1007/s00280-015-2691-1

Springer Medizin

Phase II study of mFOLFOX3 (5-fluorouracil, leucovorin, oxaliplatin) as second-line treatment after gemcitabine failure in patients with unresectable/metastatic biliary tract cancer