The drug sorafenib was developed by Bayer and Onyx Pharmaceuticals, and is approved for the treatment of primary kidney cancer, advanced primary liver cancer and radioactive iodine resistant advanced thyroid carcinoma. A recent study found that lower starting doses of sorafenib does not negatively affect outcomes in patients with advanced differentiated thyroid cancer and multiple comorbidities. According to Ramona Dadu, MD, from The University of Texas MD Anderson Cancer Center, said in a press release. “Our data suggest that treatment with sorafenib, when administered by experienced specialists outside of a clinical trial setting, resulted in similar efficacy and tolerability as previously reported in clinical trials. But, most importantly, we showed that the efficacy and tolerability of sorafenib in treatment-naive differentiated thyroid cancer patients does not appear to be negatively influenced by lower starting daily doses.”
Researchers reviewed 75 patient medical records that had been treated at MD Anderson Cancer Center from mid 2005. All patients were adults with advanced, metastatic differentiated thyroid cancer who had been administered a regimen of sorafenib as first-line therapy. Information on relevant demographic and clinical data was collected as well. Patients were then grouped by sorafenib total starting dose.
Fifty one patients were placed in group 1 that had a starting dose of 800 mg/day (400 mg twice daily), and 24 patients were placed in group 2 who received starting doses of less than 800 mg/day. Outcomes were evaluated in terms of treatment failure, time to disease progression, treatment discontinuation, dose reduction and interruption rates.
Researchers report that group 1 had a failure time of 10 months (95% CI, 5.6-14.3), and group 2 had a failure time of 8 months (95% CI, 3.4-12.5). Group 1 patients had a median OS of 56 months (95% CI, 30.6-81.3) and group 2 patients had an OS time of 30 months (95% CI, 16.1-43.8).
The rate of treatment discontinuation due to progression of disease was 79% in group 1 and 91% in group 2, and the rate treatment discontinuation due to toxicity was 21% in group 1 and 9% in group 2 (P=.304). Dose reductions occurred in 59% of patients in group 1 and 43% of patients in group 2 (P=.29), and rates of interruption were 65% in group 1 and 67% in group 2 (P=.908).
Researchers determined that due to the unexpected similar rates of dosage decrease, interruption and discontinuation between the two doses, the low starting dose of the drug should be reversed for cases of differentiated thyroid cancer in which full dosing is thought to be unsafe.
Herb Chen, MD, chief of surgery at the University of Wisconsin, notes, these findings demonstrate a potential for treatment of differentiated thyroid cancer individuals unable to tolerate full-dose sorafenib. “While there is a trend toward a small difference in response rate between those starting on a lower dose vs. a standard dose, it is likely that these patients benefited from lower dose therapy. This is noteworthy, as many patients cannot tolerate the standard dosing, and thus this study provides the first evidence that using the lower dosing regimen may be an effective strategy to treat thyroid cancer patients.”