Drug & Device Development

Bevacizumab combo "encouraging" for advanced hepatoma

Last Updated: 2011-02-17 16:05:11 -0400 (Reuters Health)

NEW YORK (Reuters Health) - In patients with unresectable and untransplantable hepatocellular carcinoma (HCC), combination chemotherapy with bevacizumab, oxaliplatin and capecitabine demonstrates "encouraging efficacy and good tolerability," according to a new study.

Dr. Weijing Sun and colleagues at the University of Pennsylvania, Philadelphia, reported the results of the small non-randomized phase 2 study online on January 24 in Cancer.

They enrolled patients from July 2004 to June 2007, which was before the tyrosine kinase inhibitor sorafenib emerged as "an attractive first-line therapy" following studies reported in 2008 and 2009.

They add, however, that the sorafenib trials leave "many unanswered questions and considerations." For example, they say, sorafenib might be substantially less effective when the underlying disease is hepatitis B rather than hepatitis C.

In addition, in both earlier studies of sorafenib, the vast majority of patients were fully functional, with ECOG performance status 0. In comparison, 60% of patients in the current study had ECOG scores of 1 or 2. The Eastern Cooperative Oncology Group (ECOG) score rates performance status on a scale of 0-5, where 0 is fully active, 1 is physically restricted and 5 is dead.

The 40 patients in the new study all had advanced unresectable and untransplantable HCC and had not been treated with radiotherapy or systemic chemotherapy.

All received bevacizumab (Avastin, Genentech), capecitabine and oxaliplatin in a 21-day treatment cycle.

Bevacizumab 5 mg/kg and oxaliplatin 130 mg/m2 were infused intravenously on day 1 of each cycle. Capecitabine 825 mg/m2 was given orally twice daily on days 1 to 14 of each cycle.

Participants completed a mean of 8.7 cycles and a median of 5 cycles of treatment.

The disease control rate was roughly 77%: eight patients (20%) had partial responses and 23 (57.3%) had stable disease.

In 36 evaluable patients, the median progression-free survival was 6.8 months and the median overall survival was 9.8 months.

There were no complete responses, although one patient improved to the point where previously unresectable lesions could be removed; this patient is alive more than three years later.

Tolerability of the study regimen was reported as good, with less than 10% of patients having hematologic toxicities of grade 3 or 4.

Nonsurgical treatments such as hepatic artery embolization, radiofrequency ablation and cryoablation are often used to improve survival in these patients, but as the authors note, not all patients are suitable.

This protocol, they conclude, "is an attractive option for further study as first- or second-line therapy for advanced and metastatic hepatocellular carcinoma."

The study was supported by Genentech; Dr. Sun is on the company's speaker list.

SOURCE: http://bit.ly/dHuFGw

Cancer 2011.