title: Phase II study of doxorubicin and cisplatin in patients with metastatic hepatocellular carcinoma.
abstract: OBJECTIVE
  The outcome of systemic chemotherapy in metastatic hepatocellular carcinoma (HCC) patients had been disappointing. Based on the demonstrated antitumor activities and different mechanisms of action and toxicity profiles, we designed a phase II trial of combination therapy with doxorubicin and cisplatin in metastatic HCC patients anticipating a synergistic interaction of the combination.
  
  
  METHODS
  From January 1998 to January 2003, 42 consecutive patients with metastatic HCC were accrued. The regimen consisted of doxorubicin 60 mg/m2 delivered as an intravenous infusion over 30 min on day 1, followed by cisplatin 60 mg/m2 infused over 1 h on day 1. The cycle was repeated every 28 days. The objective tumor response was evaluated after two or three courses of chemotherapy. The serum alpha-fetoprotein level was measured at the start of every cycle.
  
  
  RESULTS
  In total, 122 cycles of the regimen were administered, with a median of three cycles per patient (range one to eight cycles). The median age of the patients was 45 years (range 19-61 years), and 37 were evaluable for treatment response. The objective response rate was 18.9% (95% CI 8.0-35%) with one complete response and six partial responses. Six patients (16.2%) had stable disease and 24 patients (64.9%) had progression. Median overall survival of 37 patients was 7.3 months (95% CI 5.9-8.6 months). The median time to progression of all evaluable patients was 6.6 months (95% CI 5.4-7.8 months). Of 37 evaluable patients, 12 32.4%, 95% CI 18.0-49.8%) showed more than 50% decrease in AFP level from their baseline AFP and the median time to decrease in AFP by more than 50% was 1.8 months with a range of 0.7-4.7 months. The chemotherapy was well tolerated and the most common grade 3/4 side effects were neutropenia (14.3%), thrombocytopenia (11.9%), and diarrhea (9.5%).
  
  
  CONCLUSIONS
  Combination chemotherapy with doxorubicin and cisplatin in metastatic HCC patients showed modest antitumor activity with relatively tolerable adverse effects. The objective response rate of the regimen was comparable to those found in other phase II trials, but the search for the optimal chemotherapy should be continued.
authors.affiliation: Division of Hematology/Oncology, Department of Medicine, Samsung Medical Center, Sungkyunkwan University School of Medicine, 135-710, Seoul, Korea.
authors.forename: Jeeyun
authors.initials: J
authors.lastname: Lee
authors.forename: Joon Oh
authors.initials: JO
authors.lastname: Park
authors.forename: Won Seog
authors.initials: WS
authors.lastname: Kim
authors.forename: Se Hoon
authors.initials: SH
authors.lastname: Park
authors.forename: Keon Woo
authors.initials: KW
authors.lastname: Park
authors.forename: Moon Seok
authors.initials: MS
authors.lastname: Choi
authors.forename: Joon Hyoek
authors.initials: JH
authors.lastname: Lee
authors.forename: Kwang Cheol
authors.initials: KC
authors.lastname: Koh
authors.forename: Seung Woon
authors.initials: SW
authors.lastname: Paik
authors.forename: Byung Chul
authors.initials: BC
authors.lastname: Yoo
authors.forename: Jaewon
authors.initials: J
authors.lastname: Joh
authors.forename: Kihyun
authors.initials: K
authors.lastname: Kim
authors.forename: Chul Won
authors.initials: CW
authors.lastname: Jung
authors.forename: Young Suk
authors.initials: YS
authors.lastname: Park
authors.forename: Young-Hyuck
authors.initials: YH
authors.lastname: Im
authors.forename: Won Ki
authors.initials: WK
authors.lastname: Kang
authors.forename: Mark H
authors.initials: MH
authors.lastname: Lee
authors.forename: Keunchil
authors.initials: K
authors.lastname: Park
mesh_terms: D000328:Adult; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use* / Q000633:toxicity; D006528:Carcinoma, Hepatocellular / Q000188:drug therapy* / Q000401:mortality / Q000473:pathology; D002945:Cisplatin / Q000008:administration & dosage; D004317:Doxorubicin / Q000008:administration & dosage; D005260:Female; D006801:Humans; D008113:Liver Neoplasms / Q000188:drug therapy* / Q000401:mortality / Q000473:pathology; D008297:Male; D008875:Middle Aged; D009362:Neoplasm Metastasis; D016019:Survival Analysis; D013997:Time Factors; D016896:Treatment Outcome
chemical_list: D004317:Doxorubicin; D002945:Cisplatin