Combination therapy with sorafenib and bevacizumab in patients with advanced solid tumors results in enhanced antitumor activity, particularly in those with epithelial ovarian cancer.

Combination therapy with sorafenib and bevacizumab in patients with advanced solid tumors results in enhanced antitumor activity, particularly in those with epithelial ovarian cancer.

Senior investigator Dr. Elise C. Kohn told Reuters Health that her group "combined two newer molecularly targeted agents, sorafenib (Nexavar) and bevacizumab (Avastin), with intriguing results."

In the August 1st issue of the Journal of Clinical Oncology, Dr. Kohn of the National Cancer Institute, Bethesda, and colleagues point out that sorafenib inhibits Raf kinase and vascular endothelial growth factor (VEGF) receptor. The monoclonal antibody bevacizumab also targets VEGF. The investigators hypothesized that the pair would complement inhibition of VEGF signaling.

In a phase I trial, the researchers studied 39 patients with solid tumors including ovarian cancer, renal cancer, melanoma and sarcoma.

The patients started therapy with 200 mg of sorafenib twice daily and bevacizumab 5 mg/kg every other week, doses well below those used with single-agent therapy.

However, 29 of the patients (74 per cent) required reduction to sorafenib to 200 mg once daily. Hand-foot-syndrome and hypertension were among the problems encountered. All but one patient who remained in the study for six months required a dose reduction.

Partial responses lasting from four to more than 22 months were seen in six of the 13 patients with ovarian cancer. One of the three patients with renal cancer maintained a response for 14 months. Altogether, partial remission or disease stabilization for a median of six months was achieved by 22 (59 per cent) of 37 patients available for follow-up.

"Increased toxicity was seen compared to what would be expected for either agent alone," continued Dr. Kohn, "but we also observed clinical benefit, particularly in ovarian cancer patients, who experienced prolonged tumor shrinkage and stabilization."

"These results," she concluded, "although promising, must be tested in larger groups of patients to assess if there is any true benefit of the combination."

J Clin Oncol 2008;26:3709-3714