Though hepatocellular carcinoma(HCC) is one of the ten most common cancers in the world, the prognosis is dismal because most tumors are not suitable for surgical resection at the time of diagnosis. Doxorubicin is the only chemotherapeutic agent generally accepted to be of some use in its treatment. Doxorubicin is first described by Olweny et al in 1975 to cause regression in all ll HCC subjects evaluated, later trials showed response rate varying from 0% to 44%. However, the median survival was not increased. In 1988, intravenous ifosfamide has also been reported in unresectable HCC to induce partial remission and more longer survival duration than previous study. Therefore, we conducted a phase II trial ifosfamide, and combining ifosfamide and doxorubicin in previously untreated patients with histologically confirmed HCC and evaluate the efficacy and combining effect of ifosfamide. Each cycle consisted of ifosfamide 1.5gm/§³ i.v. days 1~5 with mesna in single therapy and ifosfamide 1.3gm/§³ i.v. days 1~5 with mesna and doxorubicin 40mg/§³ i.v. day 1 in combination chemotherapy, repeated every 4 weeks. Thirty-three patients were enrolled (ifosfamide: 16, ifosfamide and doxorubicin: 17). Five patients were not evaluated beacause of lost to follow-up and refusal to further therapy. Of twenty-eight evaluable patients, four patients achieved partial remissions, one in ifosfamide and three in combination chemotherapy and overall remission rate was 14%(8% in ifosfamide and 19% in combination chemotherapy). The median remission duration of ifosfamide and combining ifosfamide and doxorubicin were 5 and 4.5 months, respectively. The median follow-up duration were 2.5 months(0.5~8.5 months) in ifosfamide and 4 months(0.5~10 months) in combination chemotherapy. The median survivals in ifosfamide and combination chemotherapy were 2.5 months and 4.5 months, respectively(p=0.16 for survival curves by log rank test). Hematologic side effects(WHO Gr¡A2) of evaluable 92 cycles of chemotherapy (ifoefamide: 33, ifosfamide and doxorubicin: 59) were anemia in 5 occassions (ifosfamide: 1, ifosfamide and doxorubicin: 4), leukopenia in 10 occasions(ifosfamide: 2, ifosfamide and doxorubicin: 8), and 1 occassion thrombocytopenia in combination chemotherapy. Non-hematologic side effects(WHO Gr¡A2) included alopecia(7%), nausea and vomiting(21%), without hemorrhagic cystitis and other toxicities. In conclusion, ifosfamide, and ifosfamide and doxorubicin combination chemotherepy seems to be similar effect for far advanced hepatocellular carcinoma and can not be prolongation of patients survival. Since those responses seen were generally incomplete and transient, further clinical trials of this agent used in combination or sequentially with other agents are indicated.
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