DAAs aid treatment of hepatitis C patients with cancer

Direct-acting antiviral (DAA) agents can be safely administered along with selected chemotherapeutic agents in hepatitis C virus (HCV)-infected cancer patients who are monitored closely, according to a new study.

Guidelines are available for special HCV-infected populations, such as patients infected with HIV infection, but no recommendations exist for cancer patients. Recently published recommendations on the management of HCV-infected patients with hematologic malignancies or undergoing hematopoietic cell transplantation do not address the issue of using concomitant DAAs and chemotherapy.

Clinicians have been hesitant to use chemotherapy at the same time with DAA agents because of the fear of adverse reactions. “We showed for the first time that this combination can be safe and highly effective in selected patients infected with HCV,” senior author Harrys A. Torres, MD, associate professor of medicine at The University of Texas MD Anderson Cancer Center in Houston, told Medical Economics .

The researchers published their results in the December 2016 Alimentary Pharmacology and Therapeutics.

Torres and colleagues administered concomitant treatment with DAAs and chemotherapy to 21 patients either for virological reasons in two-thirds of patients or oncologic reasons in one-third. DAAs included sofosbuvir, ledipasvir, simeprevir and daclatasvir with or without ribavirin.

Next: The results

Slightly more than half of the patients had constitutional adverse events; one-third had either hematological or gastrointestinal adverse events. Physicians changed the DAA regimens in two patients in anticipation of drug–drug interactions with daclatasvir and dexamethasone.

The overall sustained virologic response rate was 95%.

The increase in liver enzymes by HCV may prevent physicians from administering chemotherapeutic agents who fear acute flares of HCV infection. “DAA agents cause a rapid decrease in the viral load with an associated decrease of liver enzyme tests, thereby permitting the use of chemotherapy,” said Torres.

DAA therapy has been shown to halt liver disease progression even in advanced cirrhosis. “There has been recent documentation that DAAs in this setting can prevent further damage of HCV to the liver and restore some liver function. This way the need of transplantation may be avoided. DAA therapy should therefore be started at any stage of liver disease,” he said.

A systematic approach is the best way to avoid drug-drug interactions. “First, physicians need to do a meticulous search in online databases. These databases are easy to use and categorize the interactions. Second, during treatment clinicians need to be very careful in the evaluation of the patients and ask specifically about adverse events. We think that under this close monitoring, interactions are minimized and the patients have the optimal benefit,” said Torres.

Adverse events improved after the necessary adjustments of chemotherapy and ribavirin. Serious adverse events usually appeared within the first two weeks to four weeks of concomitant treatment, and therefore close monitoring during this interval is crucial to identify adverse events, he said.

Close monitoring is particularly important because “in everyday clinical practice there are several instances where the issue of concomitant treatment is raised. We hope that we will influence physicians to change clinical practice in order for patients to benefit from concomitant treatment,” said Torres.