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Background None of the current guidelines recommend antiviral therapy for inactive hepatitis B virus (HBV) carriers (IHCs). Methods In this real-world, multicenter, nonrandomized study, 32 participants meeting the inclusion criteria were enrolled 1:1 for treatment with peginterferon α-2b or monitoring without treatment based on participant preference. The expected treatment duration was 48 weeks. The primary end point was hepatitis B surface antigen (HBsAg) loss. The HBV vaccine could be injected after HBsAg loss. Results All patients had HBsAg levels of Conclusions This study provides justification for further studies of short-course peginterferon α-2b for the functional cure of IHCs with low HBsAg levels. Additionally, HBV vaccine injection is beneficial after interferon-induced HBsAg loss.

WOS: 000401318800009, Objectives: Interferon (IFN) treatment has many neuropsychiatric side effects such as depression and anxiety disorder. Although untreated depression is a major contributor to dosage reduction or premature discontinuation of the IFN treatment, it is found that depressive symptoms among patients undergoing hepatitis C virus (HCV) treatment are commonly overlooked during routine clinical interviews. Besides depression, anxiety disorders are shown to affect adherence to pegylated IFN (Peg-IFN) treatment in patients with hepatitis C. Despite the occurrence of neuropsychiatric side effects of IFN treatment being widely reported in patients with hepatitis C, there are few studies studying patients infected with hepatitis B virus (HBV). The aim of this prospective study was to evaluate the incidence and risk factors of depressive and anxiety disorders that occur during Peg-IFN treatment of patients with HBV. Methods: The sample consisted of volunteer patients who were diagnosed with HBV infection and who were decided to receive IFN treatment. During the study period, all consecutive patients with HBV infection and who would have IFN treatment were informed about the study and invited to participate. Thirty-seven chronic hepatitis B (CHB) patients were recruited for the study, but four of them were excluded due to psychiatric diagnosis at the initiation of the treatment. Therefore, the sample consisted of 33 patients with CHB, meeting the inclusion criteria. The participants had psychiatric assessment before the treatment and at 1st, 3rd, 6th, and 12th months. At each visit, the subjects were assessed with Clinical Global Impressions Scale, Hamilton Rating Scale for Depression (HRSD), and Hamilton Anxiety Rating Scale (HAM-A). Results: Among the 33 patients with HBV, 22 (66.7%) were men. Mean age was 35.97 +/- 10.73 years. While follow-up, 6 patients dropped out from the study. Also, 13 patients were excluded from the study as they developed depression and/or anxiety disorder. Mean baseline HRSD and HAM-A scores were smaller than the following visits' scores. The difference was not statistically significant only for the 12th month assessments. Totally 14 (42.4%) patients developed depression/anxiety disorder during 1 year follow-up. Six (42.86%) of them received the diagnosis at the 1st month, 3 (21.43%) at the 3rd, 4 (28.57%), at 6th months, and 1 (7.14%) at the 12th month. When we compared the patients who developed depression/anxiety disorder with the patients who did not develop any psychiatric disorder, we found that the mean baseline HRSD score (t = 2.303, p =.028) and female percentage (p =.017) were statistically significantly higher in the depression/anxiety disorder group. Conclusions: There is an incidence of 42.4% for depression and/or anxiety disorders during Peg-IFN treatment. Females and patients with subsyndromal depressive symptoms should be referred to a psychiatrist and closely monitored especially for the first three months of the IFN treatment.

Imatinib revolutionized gastrointestinal stromal tumor (GIST) treatment but median-progression-free-survival of unresectable/metastatic disease is < 2 y. B-RAFV600-mutated-melanoma responds to vemurafenib dramatically but median-progression-free-survival is < 9 mo. Combining imatinib with immunotherapy (peginterferon α-2b) in GIST showed significant induction of antitumor immunity and highly promising clinical outcomes. This strategy warrants further testing in other malignancies.

Aksöz, Elif (Balikesir Author), Objective: Treatment of chronic hepatitis C virus (HCV) infection with pegylated interferon (PegIFN) and ribavirin causes haematological side effects such as anemia, neutropenia and trombocytopenia. This study aimed to evaluate and compare the haematological side effects of PegIFN α-2a and PegIFN α-2b with ribavirin in the treatment of chronic HCV infection. Methods: 103 patients treated with PegIFN α-2b plus ribavirin and 70 patients treated with PegIFN α-2a plus ribavirin were included in this retrospective study. Patients’ haematological parameters in first and third month’s visits were compared with pretreatment test results. Results: In all patients, 21.2% had anemia (haemoglobin, Amaç: Kronik hepatit C virusu (HCV) infeksiyonunun pegile interferon (PegIFN) ve ribavirinle tedavisi, anemi, lökopeni ve trombositopeni gibi hematolojik yan etkilere yol açabilmektedir. Bu çalışmada, kronik HCV tedavisinde ribavirinle birlikte kullanılan PegIFN α-2a ile PEGIFN α-2b’nin hematolojik yan etkilerinin karşılaştırılması amaçlandı. Yöntemler: Bu retrospektif çalışmaya PegIFN α-2b ve ribavirin tedavisi alan 103 hastayla PegIFN α-2a ve ribavirin tedavisi alan 70 hasta dahil edildi. Tedavinin birinci ve üçüncü aylarında yapılan kontrollerdeki hematolojik parametreler tedavi öncesi değerleriyle karşılaştırıldı. Bulgular: Üçüncü ayın sonunda tüm hastaların %21.2’sinde anemi (hemoglobin

Cancer survivors often relapse due to evolving drug-resistant clones and repopulating tumor stem cells. Our preclinical study demonstrated that terminal cancer patient's lymphocytes can be converted from tolerant bystanders in vivo into effective cytotoxic T-lymphocytes in vitro killing patient's own tumor cells containing drug-resistant clones and tumor stem cells. We designed a clinical trial combining peginterferon α-2b with imatinib for treatment of stage III/IV gastrointestinal stromal tumor (GIST) with the rational that peginterferon α-2b serves as danger signals to promote antitumor immunity while imatinib's effective tumor killing undermines tumor-induced tolerance and supply tumor-specific antigens in vivo without leukopenia, thus allowing for proper dendritic cell and cytotoxic T-lymphocyte differentiation toward Th1 response. Interim analysis of eight patients demonstrated significant induction of IFN-γ-producing-CD8(+), -CD4(+), -NK cell, and IFN-γ-producing-tumor-infiltrating-lymphocytes, signifying significant Th1 response and NK cell activation. After a median follow-up of 3.6 years, complete response (CR) + partial response (PR) = 100%, overall survival = 100%, one patient died of unrelated illness while in remission, six of seven evaluable patients are either in continuing PR/CR (5 patients) or have progression-free survival (PFS, 1 patient) exceeding the upper limit of the 95% confidence level of the genotype-specific-PFS of the phase III imatinib-monotherapy (CALGB150105/SWOGS0033), demonstrating highly promising clinical outcomes. The current trial is closed in preparation for a larger future trial. We conclude that combination of targeted therapy and immunotherapy is safe and induced significant Th1 response and NK cell activation and demonstrated highly promising clinical efficacy in GIST, thus warranting development in other tumor types.

International audience; OBJECTIVE: Injection drug users are often excluded from hepatitis C virus (HCV) treatment. This study compares sustained virological response, adherence, and quality of life in patients with or without a history of illicit drug use in routine clinical practice. METHODS: This is a post-hoc analysis of a prospective, observational study conducted in 1860 patients who received peginterferon alpha-2b/ribavirin combination therapy. Nondrug users (NDUs) were defined as patients without a history of drug addiction; former drug users (FDUs) as patients who had stopped using illicit drugs or opioid maintenance therapy and active drug users (ADUs) as patients using illicit drugs or on opioid maintenance therapy. Virological response, adherence, and the health-related quality of life were assessed by the measure of HCV RNA in the serum, self-report and 36-item short-form health survey Questionnaire, respectively. RESULTS: The analyzed population included 1038 (56%) NDUs, 578 (31%) FDUs, and 244 (13%) ADUs. About 85% of ADUs were on opioid maintenance therapy and 25% used illicit drugs. Although ADUs had a more chaotic lifestyle and more psychiatric disorders, sustained virological response of ADUs (58%) did not differ from that of NDUs (49%) and FDUs (51%) (P=0.133). Adherence rates were 39% in NDUs and FDUs, and 37% in ADUs (P=0.883). Health-related quality of life was improved in the three groups after the end of treatment. CONCLUSION: Our study suggests that HCV therapy in ADUs on opioid maintenance therapy is as effective as in other HCV patients. The effectiveness of HCV therapy in illicit drug users needs to be evaluated in further studies.

Purpose High-dose pegylated interferon α-2b (peginterferon α-2b) significantly decreased disease recurrence in patients with resected stage III melanoma in a clinical study. We investigated the pharmacokinetics (PK) and safety of high-dose peginterferon α-2b in patients with high-risk melanoma. Methods For PK analysis, 32 patients received peginterferon α-2b 6 μg/(kg week) subcutaneously for 8 weeks (induction) then 3 μg/(kg week) for 4 weeks (maintenance). PK profiles were determined at weeks 1, 8, and 12. Exposure–response relationships between peginterferon α-2b and absolute neutrophil count (ANC) and alanine aminotransferase (ALT) level were also studied. Results Peginterferon α-2b was well-absorbed following SC administration, with a median Tmax of 24 h. Mean half-life estimates ranged from 43 to 51 h. The accumulation factor was 1.69 after induction therapy. PK parameters showed moderate interpatient variability. PK profiles were described by a one-compartmental model with first-order absorption and first-order elimination. Toxicity was profiled and was acceptable; observed side effects were similar to those previously described. Dose reduction produced proportional decreases in exposure and predictable effects on ANC in an Imax model; however, a PK/pharmacodynamic (PK/PD) relationship between peginterferon α-2b and ALT could not be established with high precision. Conclusions Peginterferon α-2b was well-absorbed and sustained exposure to peginterferon α-2b was achieved with the doses tested. These data confirm and extend previous PK observations of peginterferon α-2b in melanoma and solid tumors. Our PK/PD model of exposure and ANC effect provides useful information for prediction of peginterferon α-2b-related hematologic toxicity. Electronic supplementary material The online version of this article (doi:10.1007/s00280-010-1326-9) contains supplementary material, which is available to authorized users.