Treatment complexities among patients with tuberculosis in a high HIV prevalence cohort in the United States.

AIDS Res Hum Retroviruses. 2018 Aug 14;:

Authors: Bizune D, Kempker R, Kagei M, Yamin A, Mohamed O, Holland DP, Oladele A, Wang YF, Rebolledo PA, Blumberg H, Ray SM, Schechter MC

Abstract
The association between human immunodeficiency virus (HIV) infection and tuberculosis (TB) mortality has been studied extensively, but the impact of HIV on other clinically relevant aspects of TB care such as TB drug-related adverse events (AE), hospital readmissions, and TB treatment duration is less well characterized. We describe the association of HIV infection with TB clinical complexities and outcomes in a high HIV prevalence cohort in the United States. This is a retrospective cohort study among patients treated for culture-confirmed TB between 2008-2015 at an inner-city hospital in Atlanta, GA. Univariate analysis was used to estimate association of HIV with TB treatment interruption due to AE, hospital readmissions, and treatment duration. Final unfavorable TB treatment outcome was defined as death, loss to follow-up, or recurrent TB. Logistic regression modeling was used to estimate association of HIV with final unfavorable outcomes. Among 274 patients with TB, 96 (35%) had HIV co-infection. HIV-positive patients had more TB treatment interruptions due to AE (34% vs 15%), were more likely to have a hospital readmission (50% vs 21%), and received longer TB treatment (9.9 vs 8.8 months) compared to HIV-negative patients (p<.01 for all). HIV-infection was not associated with final unfavorable outcomes in univariate [odds ratio (OR)=1.86; 95%CI 0.99-3.49] or multivariate analysis (aOR=1.13; 95%CI 0.52-2.39) (p≥.05 for both). While HIV infection was not associated with final unfavorable TB outcomes, TB/HIV co-infected patients had more complex treatment course underscoring the importance of maintaining resources and expertise to treat co-infected patients in our and similar settings.

PMID: 30105915 [PubMed - as supplied by publisher]

A new non-dilution rapid desensitization protocol successfully applied to all-grade platinum hypersensitivity.

Cancer Chemother Pharmacol. 2018 Aug 13;:

Authors: Chung SJ, Kang SY, Kang RY, Kim YC, Lee KH, Kim TY, Han SW, Kang HR

Abstract
PURPOSE: Desensitization is a safe alternative for patients with hypersensitivity reactions (HSRs) to platinum-based chemotherapeutic agents and widely used in real practice by employing stepwise administration of multiple serial dilutions of the culprit drugs. However, its labor-intensive nature has required a simpler protocol that is easier to prepare and perform.
METHODS: We performed an observational study of patients with platinum HSR who underwent a new non-dilution one-bag desensitization protocol. Premedication consisted of Montelukast as well as H1 and H2 blockers. The outcomes and safety profiles of a new protocol were assessed.
RESULTS: A total of 36 patients were recruited (oxaliplatin 23, carboplatin 9, and cisplatin 4) and the most common grade of HSR presented was grade 2 (61.1%), followed by grade 3 (25%), and grade 1 (13.9%). Of 175 desensitization procedures, all cases were successfully completed in re-administration of culprit chemotherapeutic platinum agents; 146 (83.4%) had no breakthrough reactions (BTRs) while 29 (16.6%) did. Most BTRs were mild reactions (grade 1, 51.7%) or moderate reactions (grade 2, 44.8%) of Brown's Scale. Although there was one case of asymptomatic mild hypotension (grade 3, 3.5%), categorized as severe reaction, dyspnea, desaturation, and anaphylaxis did not occur. The proportion of severe HSRs was significantly lower than that of initial HSRs (3.5% vs. 25%, P = 0.0167).
CONCLUSIONS: The new non-dilution desensitization protocol was safe and effective for re-administration of culprit platinum agents in patients with a history of HSRs. Therefore, this new protocol can be used as an alternative to existing protocols using multiple serial dilutions.

PMID: 30105458 [PubMed - as supplied by publisher]

Genetic polymorphisms associated with adverse reactions of molecular-targeted therapies in renal cell carcinoma.

Med Oncol. 2018 Jan 04;35(2):16

Authors: Yamamoto K, Yano I

Abstract
The prognosis of patients with metastatic renal cell carcinoma has drastically improved due to the development of molecular-targeted drugs and their use in clinical practice. However, these drugs cause some diverse adverse reactions in patients and sometimes affect clinical outcomes of cancer therapy. Therefore, predictive markers are necessary to avoid severe adverse reactions, to establish novel and effective prevention methods, and to improve treatment outcomes. Some genetic factors involved in these adverse reactions have been reported; however, perspectives on each adverse response have not been integrated yet. In this review, genetic polymorphisms relating to molecular-targeted therapy-induced adverse reactions in patients with renal cell carcinoma are summarized in the points of pharmacokinetic and pharmacodynamic mechanisms. We also discuss about the relationship between systemic drug exposure and adverse drug reactions.

PMID: 29302760 [PubMed - indexed for MEDLINE]

Hematological adverse effects in breast cancer patients treated with cyclin-dependent kinase 4 and 6 inhibitors: a systematic review and meta-analysis.

Breast Cancer. 2018 Jan;25(1):17-27

Authors: Kassem L, Shohdy KS, Lasheen S, Abdel-Rahman O, Bachelot T

Abstract
BACKGROUND: The introduction of specific cyclin-dependent kinase 4 and 6 (CDK4/6) inhibitors significantly improved progression-free survival in hormone receptor-positive metastatic breast cancer. CDK 4/6 inhibitors induce cell cycle arrest via liberating the tumor suppressor retinoblastoma protein from CDK4/6 inhibitory effect. Preliminary studies suggested an increase in the hematological toxicities which might affect the quality of life in such palliative setting.
METHODS: We searched PubMed, ASCO, ESMO and San Antonio meeting databases for randomized phase II/III trials in metastatic breast cancer receiving CDK4/6 inhibitors with safety data provided on the incidence of hematological adverse effects.
RESULTS: Our search identified 1012 citations that were screened for relevance. Thirty-six studies were found to be potentially eligible. After excluding the ineligible studies, six studies were deemed to be eligible for meta-analysis. The risk ratio (RR) was 11.31 [95% confidence interval (CI) 8.06-15.87; p < 0.0001] for all-grade leucopenia, 14.86 (95% CI 11.37-19.41; p < 0.0001) for all-grade neutropenia, 9.04 (95% CI 3.78-21.63; p < 0.0001) for all-grade thrombocytopenia and 3.57 (95% CI 2.65-4.81; p < 0.0001) for all-grade anemia. The RR for grade 3/4 leucopenia was 33.86 (95% CI 14.59-78.57; p < 0.0001), for grade 3/4 neutropenia was 44.00 (95% CI 24.72-78.33; p < 0.0001), for grade 3/4 thrombocytopenia was 5.70 (95% CI 2.03-16.01; p = 0.001) and for grade 3/4 anemia was 2.80 (95% CI 1.45-5.41; p = 0.002). There was no significant increase in the RR of febrile neutropenia with RR of 3.29 (95% CI 0.93-11.57; p = 0.06).
CONCLUSION: Our analysis provides evidence that the use of CDK 4/6 inhibitors is associated with an increased risk of all-grade and high-grade hematological adverse events, which seems to be a class-effect, but not of febrile neutropenia compared with hormonal therapy alone.

PMID: 29147869 [PubMed - indexed for MEDLINE]

So Many Antihyperglycemics: How to Choose? A Practical Approach.

Can J Diabetes. 2017 Oct;41(5):469-473

Authors: Cheng AYY

Abstract
Guidelines from around the world have stressed the importance of glycemic control in the management of patients with type 2 diabetes (T2DM) to reduce the risk of developing complications. To achieve this goal, both lifestyle and pharmacologic therapies are available. There are 9 classes of antihyperglycemic therapies available in Canada and each class provides a different mechanism of action to address the pathophysiology of T2DM. Metformin remains the first choice for pharmacologic therapy. Thereafter, individualization is essential. If there is significant hyperglycemia at diagnosis, initial combination therapy should be considered. The choice of therapy after metformin depends on a number of factors with the first consideration being the presence or absence of cardiovascular disease. If present, an agent with proven cardiovascular benefit should be added. Otherwise, individualization should be based on desired glycemic lowering, risk of hypoglycemia, effect on weight, cardiovascular effects, other side effects and accessibility.

PMID: 28600118 [PubMed - indexed for MEDLINE]

17 new pubmed citations were retrieved for your search. Click on the search hyperlink below to display the complete search results:

("drug-induced" OR "drug-related") AND ("adverse events" OR "side effects" OR "side-effects")

These pubmed results were generated on 2018/08/14

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17 new pubmed citations were retrieved for your search. Click on the search hyperlink below to display the complete search results:

("drug-induced" OR "drug-related") AND ("adverse events" OR "side effects" OR "side-effects")

These pubmed results were generated on 2018/08/14

PubMed comprises more than millions of citations for biomedical literature from MEDLINE, life science journals, and online books. Citations may include links to full-text content from PubMed Central and publisher web sites.

Phase I, open-label study of pasireotide in patients with BRAF-wild type and NRAS-wild type, unresectable and/or metastatic melanoma.

ESMO Open. 2018;3(5):e000388

Authors: Dummer R, Michielin O, Nägeli MC, M Goldinger S, Campigotto F, Kriemler-Krahn U, Schmid H, Pedroncelli A, Micaletto S, Schadendorf D

Abstract
Introduction: Somatostatin analogues exert antitumour activity via direct and indirect mechanisms. The present study was designed to assess the safety and efficacy of pasireotide in patients with BRAF-wild type (WT) and NRAS-WT metastatic melanoma.
Patients and methods: Patients with unresectable and/or metastatic melanoma or Merkel cell carcinoma were eligible. Pasireotide was administered at different doses for ≤8 weeks in dose-escalation phase, followed by long-acting pasireotide 80 mg or lower dose in case of toxicity in follow-up phase up to six additional months. Primary endpoint was safety in the first 8 weeks of dose-escalation phase.
Results: The study was terminated early due to slow recruitment. Of the 10 patients with metastatic melanoma enrolled, only four reached the high dose level: two patients reached 3600 µg in dose-escalation and follow-up phases and two patients reached 3600 µg in dose-escalation and long-acting pasireotide 80 mg in follow-up phases and were stable for >5 months. Most common adverse events (AEs) during dose-escalation phase in ≥2 patients (20%) were: diarrhoea (50%), nausea (50%), fatigue (20%), hyperglycaemia (20%), hypophosphatemia (20%), chills (20%) and tumour pain (20%). Grade 3 or 4 study drug-related AEs were diarrhoea and nausea, reported in one patient. Partial response was documented in one patient and stable disease in another.
Conclusions: Pasireotide was well tolerated, and safety results were similar to those previously reported in other indications. Further studies are needed to evaluate its antitumour activity alone and in combination with other drugs in melanoma.

PMID: 30094073 [PubMed]

Identifying Adverse Events Using International Classification of Diseases, Tenth Revision Y Codes in Korea: A Cross-sectional Study.

J Prev Med Public Health. 2018 Jan;51(1):15-22

Authors: Ock M, Kim HJ, Jeon B, Kim YJ, Ryu HM, Lee MS

Abstract
Objectives: The use of administrative data is an affordable alternative to conducting a difficult large-scale medical-record review to estimate the scale of adverse events. We identified adverse events from 2002 to 2013 on the national level in Korea, using International Classification of Diseases, tenth revision (ICD-10) Y codes.
Methods: We used data from the National Health Insurance Service-National Sample Cohort (NHIS-NSC). We relied on medical treatment databases to extract information on ICD-10 Y codes from each participant in the NHIS-NSC. We classified adverse events in the ICD-10 Y codes into 6 types: those related to drugs, transfusions, and fluids; those related to vaccines and immunoglobulin; those related to surgery and procedures; those related to infections; those related to devices; and others.
Results: Over 12 years, a total of 20 817 adverse events were identified using ICD-10 Y codes, and the estimated total adverse event rate was 0.20%. Between 2002 and 2013, the total number of such events increased by 131.3%, from 1366 in 2002 to 3159 in 2013. The total rate increased by 103.9%, from 0.17% in 2002 to 0.35% in 2013. Events related to drugs, transfusions, and fluids were the most common (19 446, 93.4%), followed by those related to surgery and procedures (1209, 5.8%) and those related to vaccines and immunoglobulin (72, 0.3%).
Conclusions: Based on a comparison with the results of other studies, the total adverse event rate in this study was significantly underestimated. Improving coding practices for ICD-10 Y codes is necessary to precisely monitor the scale of adverse events in Korea.

PMID: 29397642 [PubMed - indexed for MEDLINE]

Potential drug-drug interactions of OMBITASVIR, PARITAPREVIR/ritonavir ± DASABUVIR ± ribavirin in clinical practice.

J Gastroenterol Hepatol. 2018 May;33(5):1100-1107

Authors: González-Colominas E, Londoño MC, Morillas RM, Torras X, Mojal S, Lens S, López D, Gallego A, Mariño Z, Ardèvol M, Pagès N, Solà R, Carrión JA

Abstract
BACKGROUND & AIMS: Drug-drug interactions (DDIs) with ombitasvir/paritaprevir/ritonavir with or without dasabuvir and with or without ribavirin (OBV/PTV/r ± DSV ± RBV) are common in clinical trials. Our aim was to analyze the prevalence and management of potential DDIs and adverse events (AEs) related to DDIs in patients with chronic hepatitis C (CHC) receiving OBV/PTV/r ± DSV ± RBV in clinical practice.
METHODS: 177 CHC patients started OBV/PTV/r ± DSV ± RBV in 4 Spanish hospitals and were screened for potential DDIs using the University of Liverpool database. Patients were classified according to the most serious potential DDIs at baseline and AEs during therapy.
RESULTS: At least one potential DDI was found in 110 (62.1%) patients: 100 (56.5%) had at least one manageable potential DDI and 10 (5.6%) at least one contraindicated. Patients with potential DDIs were receiving a higher number of concomitant drugs (4 vs. 2, P < 0.001). Routine medication was modified at baseline due to potential DDIs in 49 (27.7%) patients. During antiviral treatment, 67 (37.9%) patients presented at least one AE. In 9 (4.5%) patients, a DDI was suspected between OBV/PTV/r ± DSV ± RBV and the concomitant drug, requiring antiviral discontinuation in 4 patients.
CONCLUSIONS: Potential DDIs are frequent with OBV/PTV/r ± DSV ± RBV, although a change in baseline medication is made in only one-quarter of patients. More than half of potential DDIs were only followed, and only 5% of patients developed AEs in which the implication of DDIs could not be excluded.

PMID: 28994141 [PubMed - indexed for MEDLINE]

Regulatory Factors Influencing Usage of Retinal Pharmaceuticals: A Look Both Home and Abroad.

Am J Ophthalmol. 2016 09;169:xiv-xvi

Authors: Croft DE, Wykoff CC, Michels S, Chakravarthy U, Cruess AF

PMID: 27485923 [PubMed - indexed for MEDLINE]

The Prevalence of Hydroxychloroquine Retinopathy and Toxic Dosing, and the Role of the Ophthalmologist in Reducing Both.

Am J Ophthalmol. 2016 06;166:ix-xi

Authors: Browning DJ

PMID: 27133016 [PubMed - indexed for MEDLINE]

Emotional Consequences of Finasteride: Fool's Gold.

Am J Mens Health. 2018 Jan;12(1):90-95

Authors: Ganzer CA, Jacobs AR

Abstract
Androgenetic alopecia, the gradual, progressive loss of hair frequently results in psychological despair, in part related to changes in self-image. Current androgenetic alopecia treatments are limited to hair transplantation and medications that inhibit dihydrotestosterone, a potent androgen associated with follicular micronization. Users of finasteride, which prevents dihydrotestosterone production, report serious physical and emotional adverse effects, collectively known as post-finasteride syndrome. Psychiatric illnesses and personality traits, specifically neuroticism influence emotional well-being. Limited research exists exploring the psychological corollaries of post-finasteride syndrome and preexisting Axis I and Axis II mental health conditions. The aim of this study was to explore how having a preexisting personal and/or familial history of a psychiatric diagnosis and certain personality traits may influence anxiety and depression among finasteride users. Participants in this online survey completed the Beck Depression Inventory, the Beck Anxiety Inventory, and Ten-Item Personality Inventory. An important finding in this study was that almost 57% ( n = 97) of men reported a psychiatric diagnosis and 28% ( n = 27) had a first-degree relative with a mental health disorder, of this group 17 only had a family history. Nearly 50% of the men surveyed reported clinically significant depression as evidenced by Beck Depression Inventory score and 34% experienced anxiety on the Beck Anxiety Inventory. There were no statistically significant trends in personality traits reported. Results provide evidence on the need to screen for psychiatric history and counseling patients about the potential psychological consequences of finasteride. Prescribing clinicians should carefully weigh the risk/benefit ratio with these patients.

PMID: 26868914 [PubMed - indexed for MEDLINE]

A phase I study to assess afatinib in combination with carboplatin or with carboplatin plus paclitaxel in patients with advanced solid tumors.

Cancer Chemother Pharmacol. 2018 Aug 07;:

Authors: O'Brien MER, Sarker D, Bhosle J, Thillai K, Yap TA, Uttenreuther-Fischer M, Pemberton K, Jin X, Wiebe S, de Bono J, Spicer J

Abstract
PURPOSE: Afatinib, an irreversible ErbB family blocker, has demonstrated preclinical antitumor activity with chemotherapy.
METHODS: As part of a phase I trial in patients with advanced solid tumors (NCT00809133; 3 + 3 dose-escalation design), we determined the maximum tolerated dose (MTD) of afatinib with carboplatin (A/C) or with carboplatin plus paclitaxel (A/C/P). Starting doses: afatinib 20 mg/day, carboplatin AUC6 (A/C) with paclitaxel 175 mg/m2 (A/C/P) (chemotherapy: Day 1 of 21-day cycles). The primary objective was to determine the MTDs; safety, pharmacokinetics and antitumor activity were also evaluated.
RESULTS: Thirty-eight patients received A/C (n = 12) or A/C/P (n = 26). No dose-limiting toxicities (DLTs) were reported with A(20 mg)/C(AUC6). One patient experienced DLT in the A(40 mg)/C(AUC6) cohort (grade 3 acneiform rash); A(40 mg)/C(AUC6) was determined as the recommended phase II dose (RP2D) for A/C. Two patients each had DLTs with A(20 mg/day)/C(AUC6)/P(175 mg/m2): fatigue, infection, diarrhea, small intestine hemorrhage, dehydration, renal impairment, neutropenic sepsis (n = 1), mucositis (n = 1); A(40 mg)/C(AUC5)/P(175 mg/m2): febrile neutropenia (n = 1), mucositis, fatigue (n = 1); and A(30 mg)/C(AUC5)/P(175 mg/m2): stomatitis (n = 1), mucositis (n = 1). No DLT was observed with A(20 mg)/C(AUC5)/P(175 mg/m2), determined as the RP2D for A/C/P. The most frequent drug-related adverse events were (A/C; A/C/P): rash (75%; 73%), fatigue (67%; 69%), and diarrhea (58%; 88%). Drug plasma concentrations were similar between cycles, suggesting no drug-drug interactions. Objective response rates in these heavily pretreated patients were A/C, 3/12 (25%); A/C/P, 5/26 (19%).
CONCLUSIONS: Afatinib 40 mg/day (approved monotherapy dose) with carboplatin AUC6, and afatinib 20 mg/day with carboplatin AUC5 and paclitaxel 175 mg/m2 demonstrated manageable safety and antitumor activity. Afatinib > 20 mg/day in the triple combination was not well tolerated.

PMID: 30088048 [PubMed - as supplied by publisher]

Study protocol of a phase II clinical trial (KSCC1501A) examining oxaliplatin + S-1 for treatment of HER2-negative advanced/recurrent gastric cancer previously untreated with chemotherapy.

BMC Cancer. 2018 01 08;18(1):57

Authors: Saeki H, Emi Y, Oki E, Tokunaga S, Kakeji Y, Akagi Y, Baba H, Baba E, Maehara Y, Kyushu Study group of Clinical Cancer (KSCC)

Abstract
BACKGROUND: Oxaliplatin + S-1 is a recognized treatment regimen in Japan, but there are no Japanese clinical data on an oxaliplatin dose of 130 mg/m2. The current research involves a single-arm, prospective, phase II clinical trial to examine the efficacy and safety of oxaliplatin + S-1 with an oxaliplatin dose of 130 mg/m2 to treat HER2-negative advanced/recurrent gastric cancer previously untreated with chemotherapy in Japan.
METHODS/DESIGN: The primary endpoint of this trial will be the response rate, and the secondary endpoints will be the safety profile of oxaliplatin + S-1, progression-free survival, the response rate in subjects under the age of 75, overall survival, time to treatment failure, duration of treatment, time to failure of strategy, and dose intensity. The threshold response rate is 45% and the expected response rate is 60%. Assuming that a one-tailed score test will be performed with an α of 0.05, 68 patients are needed to ensure a statistical power of 80%. Planned enrollment is 70 subjects and the total duration of this trial is expected to be 3 years.
DISCUSSION: Since replacing cisplatin with oxaliplatin should provide the same level of therapeutic efficacy while limiting adverse events and simplifying treatment, oxaliplatin + S-1 may be increasingly used to treat gastric cancer in Japan. Verifying the efficacy and safety of oxaliplatin + S-1 with an oxaliplatin dose of 130 mg is an important task that the current trial has set out to achieve.
TRIAL REGISTRATION: The protocol was registered at the website of the University Hospital Medical Information Network (UMIN), Japan (protocol ID UMIN000017550) on May 29, 2015. The details are available at the following web address: http://www.umin.ac.jp/ctr/ .

PMID: 29310611 [PubMed - indexed for MEDLINE]

Immune-mediated thrombocytopenia and hypothyroidism in a lung cancer patient treated with nivolumab.

Immunotherapy. 2018 Feb;10(2):85-91

Authors: Jotatsu T, Oda K, Yamaguchi Y, Noguchi S, Kawanami T, Kido T, Satoh M, Yatera K

Abstract
Patients treated with immune checkpoint inhibitors can develop various immunological complications; however, few cases of immune thrombocytopenia occurring in association with the administration of these agents have so far been reported. We herein report the case of a 62-year-old Japanese man with non-small-cell lung cancer who developed immune thrombocytopenia and hypothyroidism during nivolumab therapy. After the second administration of the drug, his peripheral blood platelet count rapidly decreased to 1.6 × 104/μl with a petechial rash and symptoms associated with a low thyroid function. Nivolumab-induced immune thrombocytopenia and hypothyroidism were suspected based on the presence of platelet-associated IgG, an increased level of autoantibodies to thyroglobulin and thyroid peroxidase and an enlarged thyroid gland. The patient eventually made a full recovery after treatment with oral prednisolone and levothyroxine. Further investigations and the accumulation of data are necessary to elucidate the precise mechanisms underlying the autoimmune responses that occur in patients treated with immune checkpoint inhibitors.

PMID: 29260625 [PubMed - indexed for MEDLINE]

The safety profile of Polyoxidonium in daily practice: results from postauthorization safety study in Slovakia.

Immunotherapy. 2018 Feb;10(2):131-137

Authors: Pružinec P, Chirun N, Sveikata A

Abstract
AIM: This study assessed the safety of Polyoxidonium® 6 mg lyophilisate for solution for injection in routine practice with a special focus on signs or symptoms of potential adverse renal effects.
MATERIALS & METHODS: A local, multicenter, prospective, open-label, noninterventional, uncontrolled postauthorization safety study was conducted in 15 healthcare centers in Slovakia. Adult patients who received commercially available Polyoxidonium 6 mg lyophilisate for solution for injection as a part of their routine care were observed for one cycle of treatment, consisting of five or ten injections. For safety assessment, adverse events were monitored with a special focus on signs or symptoms of potential adverse renal effects. At the end of the study, investigators and subjects rated the overall tolerance of Polyoxidonium treatment as well as improvement. Data collection was based on the review of medical records and routine examination of subjects.
RESULTS: In total, 502 subjects were enrolled and 498 (99.2%) subjects completed the study. 19 (3.8%) subjects experienced a total of 34 adverse events. Only one (0.1%) subject experienced eight adverse drug reactions (ADRs): restlessness, fatigue, feeling hot (n = 2), pyrexia (n = 3) and asthenia. There were no renal ADRs or serious ADRs. At the end of the study, both investigators and subjects very positively rated global tolerability and global improvement.
CONCLUSION: Polyoxidonium was well tolerated in the heterogenous population of patients, mostly with chronic recurrent bacterial or viral infections. No renal ADRs were reported in this postauthorization safety study, which was designed with a special focus on identifying potential adverse renal effects.

PMID: 29260620 [PubMed - indexed for MEDLINE]

An updated review of the JAK1/2 inhibitor (ruxolitinib) in the Philadelphia-negative myeloproliferative neoplasms.

Future Oncol. 2018 Jan;14(2):137-150

Authors: Curto-Garcia N, Harrison CN

Abstract
Ruxolitinib (Rux), a JAK1/2 inhibitor, has been approved for patients with myelofibrosis and in polycythemia vera with inadequate response/intolerance to hydroxycarbamide. Studies have demonstrated that Rux improves disease-related symptoms and splenomegaly. A late emerging observation from two Phase III trials was that Rux was associated with survival advantage in comparison with placebo or other available therapies in myelofibrosis. Important data suggest that for polycythemia vera Rux improved control of blood counts. Main hematological side effects are anemia and thrombocytopenia predominantly at the beginning of the treatment. Some studies and case reports highlighted potential risks of nonmelanoma skin cancers and increased risk of infection including reactivation of hepatitis B, tuberculosis or herpes zoster infections after Rux treatment.

PMID: 29056075 [PubMed - indexed for MEDLINE]

The PAZOREAL noninterventional study to assess effectiveness and safety of pazopanib and everolimus in the changing metastatic renal cell carcinoma treatment landscape.

Future Oncol. 2017 Jul;13(17):1463-1471

Authors: Goebell PJ, Doehn C, Grüllich C, Grünwald V, Steiner T, Ehneß R, Welslau M

Abstract
VEGFR and mTOR inhibitors are broadly used in metastatic renal cell carcinoma (mRCC) therapy, and sequential first-line pazopanib (VEGFR inhibitor) and second-line everolimus (mTOR inhibitor) is a standard treatment option. Nivolumab and lenvatinib/everolimus combination was recently approved in Europe for use in mRCC after previous therapy. Prospective routine data on sequential therapy including nivolumab and/or lenvatinib are missing. This is a prospective, noninterventional study, which evaluates the effectiveness, tolerability, safety and quality of life following 450 patients with mRCC starting either on pazopanib as first-line therapy or third-line everolimus plus/minus lenvatinib following nivolumab. Adults with histologically confirmed mRCC of any subtype, who have a life expectancy of at least 6 months, are eligible.

PMID: 28523933 [PubMed - indexed for MEDLINE]

Venetoclax for the treatment of patients with chronic lymphocytic leukemia.

Future Oncol. 2017 Jun;13(14):1223-1232

Authors: Crombie J, Davids MS

Abstract
Venetoclax is a potent, selective inhibitor of BCL-2, a key regulator of the intrinsic pathway of apoptosis. In preclinical studies, venetoclax bound to BCL-2 with high affinity and rapidly induced apoptosis in chronic lymphocytic leukemia (CLL) cells. In early-phase clinical trials in CLL, venetoclax treatment led to tumor lysis syndrome in some patients with a large tumor burden, but this risk was subsequently mitigated by a revised study design that included lower initial dosing with intrapatient dose ramp up and close tumor lysis syndrome monitoring and prophylaxis. Other toxicities, such as neutropenia and gastrointestinal adverse events, were manageable. Venetoclax monotherapy resulted in durable and deep responses in patients with relapsed, refractory CLL, including for those with deletion 17p, leading to the approval of venetoclax by the US FDA for relapsed or refractory deletion 17p CLL, and recently to additional approvals in Europe and Canada. Trials also suggest that venetoclax induces deeper and more durable responses when used in combination with rituximab, and combination studies with other agents are ongoing. Phase III trials are also underway, and will provide data on the efficacy and safety of venetoclax in combination with monoclonal antibodies and targeted therapies in larger patient populations.

PMID: 28492339 [PubMed - indexed for MEDLINE]