A phase II study of irinotecan in patients with advanced hepatocellular carcinoma.
BACKGROUND
Advanced hepatocellular carcinoma has a poor prognosis. In a Phase II clinical trial, two academic centers assessed irinotecan, a topoisomerase-1 inhibitor with broad spectrum clinical activity, in patients who had advanced hepatocellular cancer.


METHODS
Patients who had had up to one prior chemotherapy regimen were eligible. Bidimensionally measurable disease, a good performance status, and adequate major organ function were required. At a starting dose of 125 mg/m2, irinotecan was administered weekly for 4 weeks followed by a 2 week break, which constituted 1 treatment cycle. Patients were restaged radiologically after two cycles of therapy. Dose attenuations were made as indicated for toxicity.


RESULTS
Fourteen patients were enrolled over a 10-week period in 1997. There were ten males and four females. The median age was 58 years (range, 38-74 yrs). The Eastern Cooperative Oncology Group median performance status was 1 (range, 0-1). Two patients had prior chemotherapy (14%), and 1 patient (7%) had had radiation. A total of 30 cycles of therapy were delivered (median, 1; range, 1-6). Considerable toxicity was observed, mostly neutropenia, diarrhea, nausea, vomiting, and fatigue. All patients required at least one dose attenuation for toxicity. One partial response (7%; confidence interval, 0-20%) was noted to last 7 months. One patient had transient stable disease, and all others (86%) had progression of disease as their best response.


CONCLUSIONS
Irinotecan had modest activity in advanced hepatocellular cancer. Toxicity was substantial, presumably reflecting impaired underlying liver function or poor ability to metabolize and eliminate the drug. The current study indicated that continued new therapy assessment is warranted for this disease.
O'Reilly
E M
EM
Department of Medicine, Solid Tumor Division, GI Oncology Service, Memorial Sloan-Kettering Cancer Center, New York, New York 10021, USA. oreillye@mskcc.org
Stuart
K E
KE
Sanz-Altamira
P M
PM
Schwartz
G K
GK
Steger
C M
CM
Raeburn
L
L
Kemeny
N E
NE
Kelsen
D P
DP
Saltz
L B
LB
D000328:Adult; D000368:Aged; D000972:Antineoplastic Agents, Phytogenic / Q000008:administration & dosage / Q000009:adverse effects / Q000494:pharmacology*; D002166:Camptothecin / Q000008:administration & dosage / Q000009:adverse effects / Q000031:analogs & derivatives* / Q000494:pharmacology*; D006528:Carcinoma, Hepatocellular / Q000188:drug therapy* / Q000473:pathology; D003967:Diarrhea / Q000139:chemically induced; D005221:Fatigue / Q000139:chemically induced; D005260:Female; D006801:Humans; D000077146:Irinotecan; D008113:Liver Neoplasms / Q000188:drug therapy* / Q000473:pathology; D008297:Male; D008875:Middle Aged; D009325:Nausea / Q000139:chemically induced; D009503:Neutropenia / Q000139:chemically induced; D011379:Prognosis; D016896:Treatment Outcome; D014839:Vomiting / Q000139:chemically induced
D000972:Antineoplastic Agents, Phytogenic; D000077146:Irinotecan; D002166:Camptothecin