Transarterial infusion chemotherapy with cisplatin plus S-1 for hepatocellular carcinoma treatment: a phase I trial.
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/m(2)) 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.


CONCLUSIONS
The recommended dosage for further evaluation of this combination therapy in phase II studies is 65 mg/m(2) CDDP and 80 mg/m(2) S-1.


BACKGROUND
UMIN; number: UMIN000003113.
Tetsuji
T
Terazawa
Department of Experimental Therapeutics, Exploratory Oncology Research & Clinical Trial Center, National Cancer Center, 5-1-1 Tsukiji Chuo-ku, 104-0045 Tokyo, Japan. shkondo@ncc.go.jp.
Shunsuke
S
Kondo
Hiroko
H
Hosoi
Chigusa
C
Morizane
Satoshi
S
Shimizu
Shuichi
S
Mitsunaga
Masafumi
M
Ikeda
Hideki
H
Ueno
Takuji
T
Okusaka
D000328:Adult; D000368:Aged; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000008:administration & dosage*; D006528:Carcinoma, Hepatocellular / Q000188:drug therapy* / Q000473:pathology; D002945:Cisplatin / Q000008:administration & dosage*; D018572:Disease-Free Survival; D004338:Drug Combinations; D005260:Female; D006801:Humans; D007564:Japan; D008113:Liver Neoplasms / Q000188:drug therapy* / Q000473:pathology; D008297:Male; D008875:Middle Aged; D010094:Oxonic Acid / Q000008:administration & dosage*; D005641:Tegafur / Q000008:administration & dosage*; D016896:Treatment Outcome
D004338:Drug Combinations; C079198:S 1 (combination); D005641:Tegafur; D010094:Oxonic Acid; D002945:Cisplatin