(ChemotherapyAdvisor) – Sorafenib should not be used concurrently with stereotactic body radiotherapy (SBRT) for patients with advanced liver cancer except in clinical trials, advised authors of a safety and toxicity Phase I trial, data from which was presented at the American Society for Radiation Oncology’s (ASTRO’s) 54th Annual Meeting in Boston, MA.

“Sequential SBRT followed by sorafenib, rather than a concurrent approach, is recommended” based on the study’s findings, reported lead author Laura A Dawson, MD, of the Princess Margaret Hospital in Toronto, Ontario, Canada, and coauthors. “Strategies to reduce toxicity from SBRT and sorafenib are needed.”

Low liver Veff (effective liver volume irradiated <30%, dose range: 39-54 Gy in 6 fractions over 2 weeks) hepatocellular carcinoma (HCC) SBRT delivered concurrently with oral sorafenib 400 mg daily “appears tolerable” but high liver Veff (30-60%), “400 mg was not tolerable due to luminal GI toxicity, and sorafenib 200 mg by mouth daily was the maximally-tolerated dose,” the authors said.

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Sorafenib is a tyrosine kinase inhibitor with antiangiogenesis properties. The study was undertaken to identify the maximal tolerated sorafenib dose before, during, and after SBRT for HCC. Dose-limiting toxicity was noted in two of three evaluable patients in the high-Veff arm of the study; one patient developed a Grade 3 large bowel bleed 3.5 months after SBRT and another patient developed a Grade 3 bowel obstruction 3 months after SBRT, the authors reported.

“Two other patients were taken off study prior to SBRT due to liver enzyme increase and tumor rupture after 7 and 3 days of sorfenib respectively,” they added. “Thus, sorafenib was de-escalated to 200 mg (oral) daily. 1 of 6 evaluable patients at this dose level developed dose-limiting toxicity (tumor rupture, after 5 weeks of sorafenib and SBRT, with death at 8 weeks).”

Median survival among a total of 12 evaluable patients, including those with dose-limiting toxicities, was 7.4 months (2 – 12.3 months), they reported. Overall survival data has not yet accrued; follow-up is ongoing, the authors said.

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