Transarterial infusion chemotherapy with cisplatin plus S-1 for hepatocellular carcinoma treatment: a phase I trial

BMC Cancer

Tetsuji Terazawa¹  Shunsuke Kondo²  Hiroko Hosoi¹  Chigusa Morizane¹  Satoshi Shimizu³  Shuichi Mitsunaga³  Masafumi Ikeda³  Hideki Ueno¹  Takuji Okusaka¹ 

[1] Department of Hepatobiliary and Pancreatic Oncology, National Cancer Center Hospital, Tokyo, Japan

[2] Department of Experimental Therapeutics, Exploratory Oncology Research & Clinical Trial Center, National Cancer Center, 5-1-1 Tsukiji Chuo-ku, 104-0045 Tokyo, Japan

[3] Department of Hepatobiliary and Pancreatic Oncology, National Cancer Center Hospital East, Chiba, Japan

关键词: S-1;    Cisplatin;    Transarterial infusion chemotherapy;    Hepatocellular carcinoma;   

Others  :  858857
DOI  :  10.1186/1471-2407-14-301

 received in 2013-10-21, accepted in 2014-04-23,  发布年份 2014

【 摘 要 】

Background

In Japan, transarterial infusion chemotherapy using cisplatin (CDDP-TAI) is frequently used for advanced hepatocellular carcinoma (HCC). Moreover, oral chemotherapy with S-1, an oral fluoropyrimidine derivative, has also elicited promising responses in HCC patients. We determined the recommended dosage for CDDP-TAI plus S-1 combination therapy for advanced HCC.

Methods

Twelve Child–Pugh class A or B patients with advanced HCC who met the eligibility criteria were enrolled in this phase I trial. Patients received CDDP-TAI (infusion, day 1) plus S-1 (oral administration, days 1–21) every 5 weeks until disease progression.

Results

Cisplatin (65 mg/m²) was administered with S-1 at 50 mg · m^-2 day^-1 (level 1, 3 patients), 60 mg · m^-2 day^-1 (level 2, 3 patients), or 80 mg · m^-2 day^-1 (level 3, 6 patients). The total number of treatment courses was 25 (median, 2 courses/patient; range, 1–6 courses). Dose-limiting toxicity was not observed in any patient at any level; therefore, the recommended dosage for cisplatin and S-1 in combination was level 3. Grade 3 adverse events were elevated alanine aminotransferase levels (2 patients), elevated aspartate aminotransferase levels (2 patients), anemia (1 patient), and decreased platelet counts (1 patient). Median progression-free survival and overall survival were 73 days and 328 days, respectively. The disease control rate was 58% (7/12); 17% (2/12) of patients achieved partial response and 42% (5/12) achieved stable disease. CDDP-TAI plus S-1 is safe for the treatment of HCC.

Conclusion

The recommended dosage for further evaluation of this combination therapy in phase II studies is 65 mg/m² CDDP and 80 mg/m² S-1.

Trial registration

UMIN; number: UMIN000003113

【 授权许可】

   
2014 Terazawa et al.; licensee BioMed Central Ltd.

【 图 表 】

【 参考文献 】

• [1]Bruix J, Sherman M: Practice Guidelines Committee, American Association for the Study of Liver Diseases. Management of hepatocellular carcinoma. Hepatology 2005, 42:1208-1236.
• [2]Cheng AL, Kang YK, Chen Z, Tsao CJ, Qin S, Kim JS, Luo R, Feng J, Ye S, Yang TS, Xu J, Sun Y, Liang H, Liu J, Wang J, Tak WY, Pan H, Burock K, Zou J, Voliotis D, Guan Z: Efficacy and safety of sorafenib in patients in the Asia-Pacific region with advanced hepatocellular carcinoma: a phase III randomised, double-blind, placebo-controlled trial. Lancet Oncol 2009, 10:25-34.
• [3]Llovet JM, Ricci S, Mazzaferro V, Hilgard P, Gane E, Blanc JF, de Oliveira AC, Santoro A, Raoul JL, Forner A, Schwartz M, Porta C, Zeuzem S, Bolondi L, Greten TF, Galle PR, Seitz JF, Borbath I, Häussinger D, Giannaris T, Shan M, Moscovici M, Voliotis D, Bruix J, SHARP Investigators Study Group: Sorafenib in advanced hepatocellular carcinoma. N Engl J Med 2008, 359:378-390.
• [4]Furuse J, Okusaka T, Kaneko S, Kudo M, Nakachi K, Ueno H, Yamashita T, Ueshima K: Phase I/II study of the pharmacokinetics, safety and efficacy of S-1 in patients with advanced hepatocellular carcinoma. Cancer Sci 2010, 101:2606-2611.
• [5]Yoshikawa M, Ono N, Yodono H, Ichida T, Nakamura H: Phase II study of hepatic arterial infusion of a fine-powder formulation of cisplatin for advanced hepatocellular carcinoma. Hepatol Res 2008, 38:474-483.
• [6]Esaki T, Nakano S, Tatsumoto T, Kuroki-Migita M, Mitsugi K, Nakamura M, Niho Y: Inhibition by 5-fluorouracil of cis-diamminedichloroplatinum(II)-induced DNA interstrand cross link removal in a HST-1 human squamous carcinoma cell line. Cancer Res 1992, 52:6501-6506.
• [7]Rougier P, Ducreux M, Mahjoubi M, Pignon JP, Bellefqih S, Oliveira J, Bognel C, Lasser P, Ychou M, Elias D, Cvitkovic E, Armand JP, Droz JP: Efficacy of combined 5-fluorouracil and cisplatinum in advanced gastric carcinomas. A phase II trial prognostic factor analysis. Eur J Cancer 1994, 30:1263-1269.
• [8]Koizumi W, Narahara H, Hara T, Takagane A, Akiya T, Takagi M, Miyashita K, Nishizaki T, Kobayashi O, Takiyama W, Toh Y, Nagaie T, Takagi S, Yamamura Y, Yanaoka K, Orita H, Takeuchi M: 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.
• [9]Shirasaka T: Development history and concept of an oral anticancer agent S-1 (TS-1): its clinical usefulness and future vistas. Jpn J Clin Oncol 2009, 39:2-15.
• [10]Ikeda K, Yoshisue K, Matsushima E, Nagayama S, Kobayashi K, Tyson CA, Chiba K, Kawaguchi Y: Bioactivation of tegafur to 5-fluorouracil is catalyzed by cytochrome P-450 2A6 in human liver microsomes in vitro. Clin Cancer Res 2000, 6:4409-4415.