Use of Growth Factors in Treatment of Hepatitis C Viral Infection in Cancer Patients

Treatment for hepatitis C viral (HCV) infection is associated with significant hematological side effects including anemia, neutropenia and thrombocytopenia. These side effects often lead to discontinuation or reduction in the dose of AV. Prolonged dose reduction or discontinuation in AV therapy might reduce the probability of attaining a sustained virological response. For that reason, hematopoietic growth factors (GFs) are used to offset these side effects and allow continuation of AV therapy. Because studies have linked use of GFs in cancer patients to increased risk of tumor progression, tumor recurrence, and thromboembolic events, we evaluated the effectiveness and safety of GFs in cancer patients with chronic HCV infection receiving AV therapy.

Medical records of all cancer patients treated for HCV infection at our institution between 08/2009 and 08/2012 were evaluated retrospectively. Data regarding the use of GFs to manage hematological side effects of AV were analyzed. Characteristics of patients who completed AV therapy were compared to those who did not. Categorical variables were compared using Chi square test or Fischer's exact test, and continuous variables were compared using independent two sample t-test.

Twenty four of 28 (86%) patients treated for HCV infection during the study period experienced AV-induced hematological toxicity. Twenty four (86%) patients had solid tumors [breast cancer (n=8), hepatocellular carcinoma (n=4), cervical cancer (n=2), and cancer of the floor of the mouth, endometrium, lung, nasopharynx, pancreas, prostate, tonsil, anus, glioblastoma, and uveal melanoma (1 patient each)] and 4 (14%) patients had hematological malignancies [non Hodgkin lymphoma (n=3) and myelodysplastic syndrome (n=1)]. GFs were administered in 15 patients (57%). GFs received were pegfilgrastim (n=9), filgrastim (n=3), darbepoetin alpha (n=9), epoetin alpha (n=2), eltrombopag (n=3), and romiplostim (n=1), with 9 (60%) of these patients receiving more than one GF. Complete treatment data were available for 20 of these 24 patients (83%); 2 patients having received AV therapy twice for a total of 22 AV regimens administered. Patients who completed AV therapy were more likely to have received GFs than those who did not (5/6; 83% vs. 10/16; 63%; p=0.6). Dual therapy with pegylated interferon alpha 2 and ribavirin was used in 15 (68%) regimens and triple therapy with pegylated interferon alpha 2, ribavirin and telaprevir or boceprevir was administered in 7 (32%) regimens. GF administration during the two types of regimens was comparable [(n=10) 67% vs. (n=5) 71%, p=1.0]. When compared to those on triple therapy, more patients on dual therapy were able to complete AV therapy when GFs were used [(n=0) 0% vs. (n=5) 50%, p=0.1]. Overall maintenance of full-dose AV was more common among those who received GFs compared to those who did not (100% vs 33%, p=0.01), particularly pegylated interferon alpha 2(100% vs 17%, p=0.04) and ribavirin (75% vs 36%, p=0.3). Patients who did not complete AV therapy required more blood transfusions despite use of darbepoetin alpha (40% vs. 0%; p=0.46). In terms of safety, 1 out of 3 patients who received eltrombopag developed portal vein thrombosis after 10 weeks of triple AV therapy with pegylated interferon alpha 2a, ribavirin and telaprevir. It remains unclear if the thrombus developed as a consequence of eltrombopag or underlying hepatocellular carcinoma. No significant side effects were seen with the use of other GFs. Five patients failed AV therapy due to hematological side effects in spite of GF use. All 5 patients had genotype 1infection, and developed a median nadir (range) hemoglobin, absolute neutrophil count and platelet count of 5.8 (5.2 – 6.7) g/dL, 590 (280 – 1,620) cells/μL and 55,000 (6,000 – 286,000) cells/μL, respectively within 9 (2 – 11) weeks of AV therapy.

The use of GFs helps to maintain and complete full-dose AV therapy for chronic HCV infection in cancer patients. These agents appear to be well-tolerated and safe.

Torres:Vertex, Merck: Consultancy. Kroll:Leo: Honoraria, Travel Expenses, Travel Expenses Other; Optimer: Consultancy; Aplagon: Membership on an entity's Board of Directors or advisory committees.