entecavir and Neoplasms

Nucleoside analogs are extremely useful for the development of therapeutic agents to control viral diseases and cancer. Among the numerous modifications on the nucleoside skeleton, replacement of the oxygen of the furanose ring by a CH2 group resulted in increased flexibility and higher resistance to phosphorylases and led to carbocyclic nucleoside analogs (or carbanucleosides). The broad spectrum of biological activities of carbocyclic nucleosides led to tremendous research interest in their syntheses. The article documents recent strategies for the synthesis of active carbocyclic nucleosides by presenting individual case studies, such as the neplanocins, entecavir and selected fluorinated carbocyclic nucleosides. Furthermore, it provides new insights into new directions for more potent and active carbocyclic nucleoside analogs.

Topics: Adenosine; Animals; Antineoplastic Agents; Antiviral Agents; Drug Discovery; Guanine; Halogenation; Humans; Neoplasms; Nucleosides; Virus Diseases; Viruses

Patients with hepatitis B virus (HBV) infection have a risk of reactivation after chemotherapy. All patients undergoing chemotherapy should be screened for HBV infection. No large-scale studies have been conducted to examine HBV screening practice in Japan.. We analyzed health insurance claims equivalent data linked with a nationwide hospital-based cancer registry. Patients diagnosed with cancer in 2014, who were aged 20 years and older and those who underwent systemic anticancer treatment in 2014-15 were included. We assessed the HBV screening rates by the HBsAg or anti-HBc tests, HBV-DNA tests, and entecavir prescriptions. Multiple logistic regression models were used to identify factors related to the receipt of screening.. Of 177,597 patients (mean [SD] age, 65.6 [12.2] years), 82.6% and 12.9% patients had a solid tumor and hematologic malignancy, respectively. Among them, 88.1%, 6.3%, and 5.5% received cytotoxic chemotherapy, targeted therapy, and anti-CD20 antibodies, respectively. Overall, 70.6% of patients were screened. The positive predictor of HBV screening was receiving anti-CD20 antibodies [odds ratio (OR); 2.23, 95% confidence interval (CI) 2.06-2.41, p < 0.001] and negative predictors were age ≥ 85 (OR 0.76, 95% CI 0.71-0.81), age 75-84 (OR 0.77, 95% CI 0.75-0.79) and targeted therapy (OR 0.69, 95% CI 0.67-0.72). Among the screened patients, 13.2% were tested for HBV-DNA, and 1.49% were prescribed entecavir.. The HBV screening rate in Japan is higher than in other countries. Further improvement of the HBV screening rate is needed to prevent reactivation and avoidable deaths of patients with HBV infection.

Topics: Aged; Aged, 80 and over; Antibodies, Monoclonal; Antigens, CD20; Antineoplastic Agents; Female; Guanine; Hepatitis B; Hepatitis B Antibodies; Hepatitis B Surface Antigens; Hepatitis B virus; Humans; Japan; Male; Mass Screening; Middle Aged; Neoplasms; Odds Ratio; Virus Activation

The renal protective effect of telbivudine (LdT) was verified by a previous meta-analysis. It was left unclear, however if this effect offsets the associated risk of virological breakthrough in hepatitis B e-antigen-negative (HBeAg-) patients receiving chemotherapy (C/T).Records of 260 HBeAg-, non-cirrhotic cancer patients undergoing systemic C/T with prophylactic LdT or entecavir (ETV) were retrospectively investigated. The investigation was conducted 6 months after completion of C/T, patient death from cancer, or antiviral modification. Treatment duration, outcome, change of renal function, and reason for antiviral modification were analyzed. The primary endpoint was the occurrence of virological breakthrough during prophylaxis C/T and the change in renal function.Of the 126 HBeAg- patients treated with LdT, 3 (2.38%) experienced HBV virological breakthroughs, whereas none of the patients treated with ETV (P = .07) did. The estimated glomerular filtration rate for the patients treated with LdT was essentially unaltered, decreasing only slightly from 87.5 ± 23.1 to 87.3 ± 21.3 ml/minute/1.73 m (P = .55), while the rate for the ETV-treated patients was significantly lowered from 95.7 ± 32.2 to 85.5 ± 85.7 ml/minute/1.73 m (P = .0009).The absolute risk reduction ARR is 27.8% - 21.2% = 6.6%, comparing ETV with LdT for reduction of renal function impairment and the absolute risk increase for virological breakthrough during C/T, the absolute risk increase (ARI) is 2.38% - 0% = 2.38%. The overall likelihood of being helped over being harmed was 2.77. With careful selection of patients with the criteria of HBeAg-status and non-hematologic cancer, it is feasible that telbivudine raise lower probability of virological breakthroughs during prophylaxis treatment.

Topics: Acute Kidney Injury; Adult; Aged; Antineoplastic Agents; Antiviral Agents; Female; Glomerular Filtration Rate; Guanine; Hepatitis B e Antigens; Humans; Kidney Function Tests; Male; Middle Aged; Neoplasms; Retrospective Studies; Telbivudine

This study investigated whether hepatitis B surface antigen (HBsAg) could predict hepatitis B virus (HBV) relapse after cessation of entecavir or tenofovir disoproxil fumarate (TDF) prophylaxis for chronic hepatitis B cancer patients who are undergoing chemotherapy.. The study enrolled 122 hepatitis B e-antigen-negative cancer patients who underwent chemotherapy with entecavir or TDF for antiviral prophylaxis and posttreatment follow-up for at least 6 months.. Of the 122 patients, 52 and 18 experienced virological and clinical relapse, which had 3-year cumulative incidences of 46.6% and 18.6%, respectively. Multivariate analysis showed that end-of-treatment HBsAg levels and baseline HBV-DNA ≥ 2000 IU/mL were independent predictors of virological relapse. The best HBsAg cutoff value was 500 IU/mL. An end-of-treatment HBsAg of 500 IU/mL was useful for predicting virological relapse in patients with baseline HBV-DNA < 2000 IU/mL (3-year rate: 21.3% vs 46.4%, P = 0.038, in patients with HBsAg < 500 and ≥ 500 IU/mL, respectively), but not in patients with baseline HBV-DNA ≥ 2000 IU/mL. Of the 52 patients who experienced virological relapse, 13 experienced transient virological relapse. Patients with baseline HBV-DNA level < 2000 IU/mL experienced a higher rate of transient virological relapse (42.1% vs 15.2%, P = 0.031). Three patients experienced hepatic decompensation upon alanine aminotransferase flares, and no patient died after timely retreatment. Ten patients experienced posttreatment HBsAg loss, and the 3-year HBsAg loss rate was 30.7% in patients with end-of-treatment HBsAg < 100 IU/mL.. The baseline HBV-DNA and end-of-treatment HBsAg levels could predict virological relapse after withdrawal of entecavir and TDF prophylaxis for chemotherapy.

Topics: Adult; Aged; Biomarkers; Female; Follow-Up Studies; Guanine; Hepatitis B Surface Antigens; Hepatitis B, Chronic; Humans; Male; Middle Aged; Multivariate Analysis; Neoplasms; Predictive Value of Tests; Recurrence; Secondary Prevention; Tenofovir; Time Factors

The risk of renal events in HBsAg-positive cancer patients receiving tenofovir disoproxil fumarate (TDF) or entecavir (ETV) antiviral prophylaxis during chemotherapy has not been evaluated. This study aimed to evaluate the renal safety of TDF and ETV during chemotherapy. Consecutive, 219 HBsAg-positive cancer patients treated with TDF (n = 106) or ETV (n = 113) for antiviral prophylaxis during chemotherapy with baseline serum creatinine (SCr) <1.2 mg/dL were retrospectively enrolled. Serial SCr levels and estimated glomerular filtration rate (eGFR) were monitored. The incidence of acute kidney injury (AKI) during antiviral prophylaxis was 33% and 38.9% in TDF and ETV groups, respectively (P = 0.441), while the incidence of sustained kidney injury was 11.3% and 11.5%, respectively (P = 1.000). By multivariate analysis, diuretics use (hazard ratio (HR) = 2.011, P = 0.042) and serum albumin levels (HR = 0.441, P = 0.001) were independent predictors of AKI; serum albumin levels (HR = 0.252, P = 0.002) was the only factor associated with sustained kidney injury; age (HR = 2.752, P < 0.001), baseline SCr levels (HR = 3.386, P < 0.001), and serum albumin levels (HR = 0.437, P = 0.001) were factors associated with a new eGFR <60 mL/min. 34.9% of patients in TDF group and 35.4% in ETV group had deteriorated chronic kidney disease (CKD) stage at the end of follow-up, respectively. There were no significant differences in the risk of renal events or CKD stage migration between TDF and ETV groups. Renal events may develop in about one-third of HBsAg-positive cancer patients undergoing chemotherapy. The risk of renal function impairment was comparable between patients treated with TDF and ETV antiviral prophylaxis.

Topics: Acute Kidney Injury; Adult; Aged; Aged, 80 and over; Antiviral Agents; Chemoprevention; Drug-Related Side Effects and Adverse Reactions; Female; Guanine; Hepatitis B; Hepatitis B Surface Antigens; Humans; Incidence; Male; Middle Aged; Neoplasms; Retrospective Studies; Risk Assessment; Tenofovir

Although antiviral prophylaxis is essential in hepatitis B patients in the context of cancer chemotherapy, there is little evidence-based consensus regarding the appropriate prevention strategy depending on the underlying type of cancer and viral status. This retrospective study included a comprehensive cohort of 302 hepatitis B surface antigen-positive patients with various cancers undergoing chemotherapy and antiviral prophylaxis. The rates of hepatitis B virus (HBV) reactivation during antiviral therapy (>1 log10 IU/mL increase or positive conversion of serum HBV DNA) and relapse when off antivirals ([re]appearance of HBV DNA >2,000 IU/ml with related alanine aminotransferase elevation) were evaluated, together with the associated risk factors, in a competing risks analysis where cancer death was considered as the competing event. During antiviral prophylaxis, HBV was reactivated in six patients (1.9%), who had leukemia (n = 4) or lymphoma (n = 2) and were treated with lamivudine (n = 4) or entecavir (n = 2). The incidence rate of HBV relapse in 127 off-prophylaxis patients was 21.3% during a median post-antiviral period of 11.7 months. Lymphoma, pre-prophylactic HBV DNA ≥2,000 IU/ml, and age ≥50 years were independent predictors of off-treatment HBV relapse (adjusted hazard ratios 5.25, 3.07, and 0.34, respectively; Ps < 0.05). Antiviral and anticancer drugs, duration of consolidation on antiviral prophylaxis, and HBeAg positivity were not independent predictors. In conclusion, hepatitis B flare-ups are not rare in patients receiving cancer chemotherapy during and after anti-HBV prophylaxis, even when potent antivirals are used. Patients with hematopoietic or lymphoid neoplasms or high viral burdens should receive prolonged and powerful HBV prophylaxis. J. Med. Virol. 88:1576-1586, 2016. © 2016 Wiley Periodicals, Inc.

Topics: Adult; Alanine Transaminase; Antineoplastic Agents; Antiviral Agents; DNA, Viral; Female; Guanine; Hepatitis B Antibodies; Hepatitis B Surface Antigens; Hepatitis B virus; Hepatitis B, Chronic; Humans; Lamivudine; Lymphoma; Male; Middle Aged; Neoplasms; Retrospective Studies; Risk Assessment; Viral Load; Virus Activation

Limited data is available on the clinical outcomes of telbivudine (LdT) and entecavir (ETV) in pre-emptive antiviral chemoprophylaxis. This study aimed to evaluate the clinical efficacy and renal safety of LdT and ETV in patients with chronic hepatitis B (CHB) who received cytotoxic chemotherapy.. Altogether 290 treatment-naïve CHB patients undergoing intense chemotherapy were enrolled to receive daily 600 mg of LdT or 0.5 mg of ETV as pre-emptive antiviral chemoprophylaxis.. The ETV group had significantly higher proportion of patients with undetectable hepatitis B viral (HBV) DNA load compared with LdT at week 24 (73.0% vs 50.3%, P = 0.000). The cumulative rates of virological breakthrough in the LdT and ETV groups were 9.15% and 3.65% at the second year of therapy, respectively (P = 0.059), which was associated with detectable HBV DNA at week 24 (P = 0.000). The MELD score of the LdT group was significantly lower than that of the ETV group after the first year (4.53 vs 7.53, P = 0.002) and the second year (1.96 vs 7.09, P = 0.000) of antiviral therapy. Moreover, the estimated glomerular filtration rate (eGFR) was significantly improved in the LdT group than in the ETV group after two years of antiviral therapy.. LdT has a lower clinical efficacy in viral suppression than ETV, but LdT is associated with greater extent of improvement in liver and renal functions of patients in pre-emptive prophylaxis for cytotoxic chemotherapy.

Topics: Aged; Antineoplastic Agents; Antiviral Agents; DNA, Viral; Female; Glomerular Filtration Rate; Guanine; Hepatitis B virus; Hepatitis B, Chronic; Humans; Kidney; Male; Middle Aged; Neoplasms; Retrospective Studies; Secondary Prevention; Telbivudine; Thymidine; Virus Activation

Comparative effectiveness of different nucleos(t)ide analogues for preventing hepatitis B virus reactivation induced by cytotoxic chemotherapy has not been elucidated. The prophylactic drug of choice remains controversial.. Our objective was to compare the effectiveness of tenofovir, telbivudine and entecavir with lamivudine in preventing the reactivation of hepatitis B virus caused by chemotherapy.. This retrospective cohort study consecutively screened all patients who were positive for hepatitis B virus surface antigen and received chemotherapy for malignant diseases in a teaching hospital in Taiwan. Eligible patients were grouped according to whether they received nucleos(t)ide analogues before (prophylactic group) or during chemotherapy (historical control). Those who received antiviral prophylaxis were further classified by the medications that included lamivudine, telbivudine, entecavir and tenofovir. The incidence of hepatitis, liver decompensation and interruption of chemotherapy were audited.. A total of 212 consecutive patients were enrolled into analysis. Those who prophylactically used nucleos(t)ide analogues (n = 177) had significantly lower rates of liver decompensation (0.6% vs 20%, P < 0.01), interruption of chemotherapy (0% vs 40%, P < 0.01) and incidence of hepatitis (4.5% vs 100%, P < 0.01), as compared with their historical control (n = 35). In the prophylactic group, there was no difference among tenofovir, telbivudine, entecavir and lamivudine users in the incidence of hepatitis, liver decompensation and interruption of chemotherapy.. Lamivudine, telbivudine, entecavir and tenofovir are all effective as the prophylactic antiviral therapy to prevent reactivation of hepatitis B induced by chemotherapy.

Topics: Adolescent; Adult; Aged; Aged, 80 and over; Antineoplastic Agents; Antiviral Agents; Cytotoxins; Female; Guanine; Hepatitis B virus; Hepatitis B, Chronic; Humans; Lamivudine; Male; Middle Aged; Neoplasms; Retrospective Studies; Telbivudine; Tenofovir; Thymidine; Virus Activation; Young Adult

Nucleos(t)ide analogues reduce the incidence of hepatitis B virus (HBV) reactivation in cancer patients undergoing systemic cytotoxic chemotherapy but the experience of solid tumors remains limited. Aims. The aim of this study was to compare the efficacy of entecavir and lamivudine in the prophylaxis of HBV reactivation in solid tumor patients undergoing systemic cytotoxic chemotherapy.. HBsAg seropositive patients undergoing systemic cytotoxic chemotherapy for solid tumors with prophylactic entecavir and lamivudine between January 2006 and June 2013 were retrospectively investigated. The incidence of HBV reactivation and outcome of the patients were analyzed. The risk factors of HBV reactivation were examined.. A total of 213 patients (entecavir group, 70 patients; lamivudine group, 143 patients) were evaluated. Less incidence of HBV reactivation was noticed in entecavir group than in lamivudine group (0% vs. 7.0%, P = 0.02). No HBV reactivation was noticed in the patients with a baseline HBV DNA level < 2000 IU/mL. A baseline HBV DNA level ≥ 2000 IU/mL, HBeAg, and lamivudine were significantly associated with HBV reactivation. Subgroup analysis of the patients with a baseline HBV DNA level ≥ 2000 IU/mL found that lamivudine was significantly associated with HBV reactivation. Most of the reactivation events were properly managed by using tenofovir disoproxil fumarate. The incidence of hepatitis during chemotherapy and disruption of chemotherapy was similar between patients using entecavir and lamivudine with a baseline HBV DNA level ≥ or < 2000 IU/mL.. A baseline HBV DNA level ≥ 2000 IU/mL, HBeAg, and lamivudine were the risk factors of HBV reactivation during systemic cytotoxic chemotherapy in solid tumor patients. Entecavir was superior to lamivudine in terms of less incidence of reactivation in the patients with a baseline HBV DNA level ≥ 2000 IU/mL. Both agents were equally efficacious in the patients with HBV DNA levels < 2000 IU/mL.

Topics: Antiviral Agents; Demography; DNA, Viral; Female; Guanine; Hepatitis B virus; Humans; Lamivudine; Male; Middle Aged; Neoplasms; Treatment Outcome; Virus Activation; Withholding Treatment