A phase III study of doxorubicin (A) versus cisplatin (P)/ interferonα-2b (I)/ doxorubicin (A)/ fluorouracil (F) combination chemotherapy (PIAF) for inoperable hepatocellular carcinoma (HCC)
4026 Background: Patients with inoperable HCC have a grave prognosis with a median survival of about 4 months. Single agent A has been commonly used but response rate (RR) has been <20%. A phase II study using combination PIAF has shown to be promising with RR of 26%. The objectives of this study were to compare A vs PIAF in patients with inoperable HCC. Methods: This is a phase III randomized study. Eligible patients include: histological proven inoperable HCC, adequate organ functions. Baseline radiological investigations were performed by CT (preferably) or US. They were randomized to either 3-weekly A(60mg/m2) or PIAF ( P 20mg/m2 d1–4,I 5 MU/m2 d1–4, A 40 mg/m2 d1, F 4000 mg/m2 d1–4) treatment. The primary endpoint was overall survival and the secondary endpoints were response rates and toxicities. Responses were graded according to WHO criteria. Toxicities were recorded according to NCI CTC. Results: The planned accrual was 200 patients (100 per arm). We report here the outcome of the first 180 patients. 170 patients were assessable for response; 4 patients did not have measurable disease, while 6 did not receive any chemotherapy. 82 of 89 in the A arm and 88 of 91 in the PIAF arm were assessable for response. Patients in A and PIAF arms received a median of 4 and 3 cycles of chemotherapy respectively. In A arm, there were 1 CR, 8 PR, 35 SD, 28 PD, 10 unknown; RR 10.9% (95%CI 4.2–17.7%). In PIAF arm, there were 18 PR, 30 SD, 19 PD, 21 unknown; RR 20.4% (95%CI 12.0–28.8%). There was no significant difference in the RR (p=0.091). Based on intention-to-treat analysis, the median survival of the A and PIAF arms were 7.1 (95%CI 5.4–9.8) and 8.4 (95%CI 6.2–12.8) months respectively (p=0.8701). Conclusions: There is no significant difference in response rates and overall survival between A and PIAF. The prognosis of patients with inoperable HCC remains poor. Toxicity data will be available at presentation. Further study using novel agents/combination is warranted. Acknowledgements: Interferon α-2b was supplied by Schering-Plough Division of SOL Ltd. No significant financial relationships to disclose.