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Phase 1-2 trial of PTK787/ZK222584 combined with intravenous doxorubicin for treatment of patients with advanced hepatocellular carcinoma
Implication for antiangiogenic approach to hepatocellular carcinoma
Article first published online: 13 JUL 2010
Copyright © 2010 American Cancer Society
Volume 116, Issue 21, pages 5022–5029, 1 November 2010
How to Cite
Yau, T., Chan, P., Pang, R., Ng, K., Fan, S. T. and Poon, R. T. (2010), Phase 1-2 trial of PTK787/ZK222584 combined with intravenous doxorubicin for treatment of patients with advanced hepatocellular carcinoma. Cancer, 116: 5022–5029. doi: 10.1002/cncr.25372
- Issue published online: 13 JUL 2010
- Article first published online: 13 JUL 2010
- Manuscript Accepted: 20 JAN 2010
- Manuscript Revised: 22 DEC 2009
- Manuscript Received: 27 OCT 2009
- advanced hepatocellular carcinoma;
This phase 1-2 trial assessed the efficacy and tolerability of an oral angiogenesis inhibitor—PTK787/ZK222584 (PTK)—in combination with intravenous doxorubicin for the treatment of advanced hepatocellular carcinoma (HCC) patients.
In phase 1, advanced HCC patients received PTK at escalating doses together with doxorubicin 60 mg/m2 given as an intravenous bolus every 3 weeks to establish the maximum tolerated dose (MTD). Subsequently, in phase 2, all patients received the same regimen with oral PTK at the MTD dose every 3 weeks for a maximum of 6 cycles.
Nine patients were recruited in phase 1, with the MTD established as 750 mg daily. Overall, 27 patients received the regimen with PTK at 750 mg daily. The median age was 52 years (range, 23-73 years), and 63 percent of patients were chronic hepatitis B carriers. Notably, the majority of patients had Child-Pugh B cirrhosis. The overall response rate was 26.0%, with all the responding patients having partial response. Another 20% of patients achieved stable disease for at least 12 weeks. The median progression-free survival was 5.4 months (range, 0.27-23.6 months), and overall survival was 7.3 months (range, 0.8-23.6 months). The commonest grade 3 or 4 nonhematological toxicities were mucositis (11%) and alopecia (7%), respectively. Grade 3 or 4 neutropenia was observed in 7 (26%) patients; 2 had neutropenic sepsis.
The combination of PTK with intravenous doxorubicin shows encouraging activity in treating advanced HCC patients. Cancer 2010. © 2010 American Cancer Society.