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Sunitinib increased toxicities, did not improve response rate in advanced hepatocellular carcinoma
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Sunitinib 50 mg per day did not improve objective response rates in patients with advanced hepatocellular carcinoma, according to data from an open-label, multicenter, phase-2 study. In addition, the treatment was associated with severe toxicities.
Due to its failure to reach the expected response rate of 15% as assessed using the RECIST criteria, the trial did not proceed to the second stage.
The study included 37 patients aged older than 18 with advanced hepatocellular carcinoma. They were enrolled and treated between February 2006 and July 2006. Patients were assigned to repeated cycles of oral sunitinib (Sutent; CPPI CV, Pfizer) 50 mg/day for four weeks. The primary endpoint was objective response rate according to RECIST criteria. Secondary endpoints included disease control rate, PFS, time to tumor progression, OS and safety.
The median number of cycles was two; four patients withdrew during the first four weeks. Sixteen patients required dose reductions, 12 required treatment delays due to toxicity and 16 required permanent discontinuation due to adverse events. Among the 36 patients who discontinued treatment, 15 were due to progression, 11 to adverse events, five to death, two to withdrawing consent and three for other reasons. Four deaths may have been treatment related.
Treatment-related grade-1 and -2 nonhematologic adverse events included asthenia (43.2%), anorexia (37.8%), diarrhea (35.1%), epistaxis (29.7%), nausea (29.7%) and hand-foot syndrome (29.7%). Common grade-3 and -4 adverse events included thrombocytopenia (37.8%), neutropenia (24.3%), leucopenia (13.5%), anemia (10.8%), asthenia (13.5%) and hand-foot syndrome (10.8%).
One patient had a confirmed partial response and 13 patients showed stable disease for more than three months. The median PFS was 3.7 months (95% CI, 1.8-6.5), median time to tumor progression was 5.3 months (95% CI, 2.7-7.9) and median OS was 8.0 months (95% CI, 4.4-13.1).
“The combination of the severity of adverse events, difficulty in interpreting toxicity, the number of dose reductions and treatment delays due to adverse events and the occurrence of a significant number of possible treatment-related deaths in this study suggests that the dose of 50 mg/day sunitinib, given on a four-weeks on-treatment followed by two weeks off-treatment schedule, should not be used in this patient population for future studies,” the researchers wrote.
Faivre S. Lancet. 2009;doi:10.1016/S1470-2045(09)70171-8.