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]

Proposed biosimilar pegfilgrastim (LA-EP2006) compared with reference pegfilgrastim in Asian patients with breast cancer: an exploratory comparison from two Phase III trials.

Future Oncol. 2017 Jul;13(16):1385-1393

Authors: Harbeck N, Gascon P, Jones CM, Nixon A, Krendyukov A, Nakov R, Li Y, Blackwell K

Abstract
AIM: This is a pooled subgroup analysis of Asian patients enrolled in two Phase III confirmatory studies comparing proposed biosimilar LA-EP2006 with reference pegfilgrastim in women receiving chemotherapy for breast cancer.
PATIENTS & METHODS: Women were randomized to LA-EP2006 (n = 90) or reference (n = 84) pegfilgrastim (Neulasta®, Amgen, Inc., CA, USA) for ≤6 cycles of TAC chemotherapy. Primary end point was duration of severe neutropenia during Cycle 1 (number of consecutive days with absolute neutrophil count <0.5 × 109/l) with equivalence confirmed if 95% CIs were within a ±1-day margin.
RESULTS: Mean duration of severe neutropenia (days) in Cycle 1 was 1.36 ± 0.98 (LA-EP2006) versus 1.35 ± 1.06 (reference) (difference 0.01 days; 95% CI: -0.30-0.32, indicating equivalence).
CONCLUSION: LA-EP2006 showed similar clinical efficacy and safety compared with reference pegfilgrastim.

PMID: 28453299 [PubMed - indexed for MEDLINE]

Systematic literature review of efficacy, safety and tolerability outcomes of chemotherapy regimens in patients with metastatic Merkel cell carcinoma.

Future Oncol. 2017 Jun;13(14):1263-1279

Authors: Nghiem P, Kaufman HL, Bharmal M, Mahnke L, Phatak H, Becker JC

Abstract
AIM: Merkel cell carcinoma (MCC) is a rare neuroendocrine, cutaneous malignancy with poor prognosis once metastasized. The aim of this study was to conduct a systematic literature review to assess clinical outcomes associated with chemotherapy regimens in metastatic MCC.
MATERIALS & METHODS: Embase®, MEDLINE®, MEDLINE®-In-Process and CENTRAL were searched for studies published in January 2016.
RESULTS & CONCLUSION: Overall, the literature on chemotherapy in patients with metastatic MCC is sparse, with most studies being case series/reports. Across all studies, response rates ranged from 20 to 61%, with higher response rates in first-line setting (53-61%) versus second-line setting (23-45%). Among responders, duration of response was short (≤8 months) in both first- and second-line settings. There is a need for novel agents that can induce durable responses in metastatic MCC.

PMID: 28350180 [PubMed - indexed for MEDLINE]

All medicines have side effects.

Arch Dis Child. 2016 10;101(10):951-2

Authors: Allegaert K, Choonara I

PMID: 27339166 [PubMed - indexed for MEDLINE]

Personalizing aromatase inhibitor therapy in patients with breast cancer.

Cancer Treat Rev. 2018 Jul 23;70:47-55

Authors: Hamadeh IS, Patel JN, Rusin S, Tan AR

Abstract
BACKGROUND: Aromatase inhibitors are the mainstay of therapy for patients with hormone receptor-positive breast cancer in both adjuvant and metastatic settings. Their use in clinical practice has been challenged by significant inter-individual variability in response and tolerability. Hence, the purpose of this paper is to provide a succinct review of the literature on the genetic factors contributing to this variability.
DESIGN: A systematic search in PUBMED was conducted to identify studies that investigated the association between germline polymorphisms and disposition, clinical response and toxicities of aromatase inhibitors, as well as those evaluating the implications of mutations in ESR1 on clinical response.
RESULTS: Polymorphisms in genes coding for phase I and phase II enzymes (pharmacokinetic genes) significantly modulated exposure to aromatase inhibitors; however, there is a paucity of data linking interindividual variability in drug exposure to clinical response. Furthermore, pharmacogenetic studies interrogating relationship between polymorphisms in CYP19A1 (the target site of aromatase inhibitors, i.e. a pharmacodynamic gene) and response yielded conflicting results. Acquired mutations in ESR1 receptors have been identified as the underlying mechanism of resistance to aromatase inhibitors, and likely predict drug response. Although some pharmacogenetic studies have implicated polymorphisms in CYP19A1 and ESR1 with drug-related side effects, the putative role of these genes in predicting toxicity warrants further validation.
CONCLUSION: Genetic polymorphisms in pharmacokinetic and pharmacodynamic genes appear to influence aromatase inhibitor disposition, response and/or toxicity; however, prospective interventional studies are needed to understand the application of genomics to personalize aromatase inhibitor therapy in breast cancer patients.

PMID: 30086432 [PubMed - as supplied by publisher]

Strategies for Recognizing and Managing Immune-Mediated Adverse Events in the Treatment of Hodgkin Lymphoma with Checkpoint Inhibitors.

Oncologist. 2018 Aug 06;:

Authors: Vardhana S, Cicero K, Velez MJ, Moskowitz CH

Abstract
The programmed death-1 (PD-1) receptor checkpoint inhibitors nivolumab and pembrolizumab represent an important therapeutic advance in the treatment of relapsed or refractory classical Hodgkin lymphoma (cHL). Clinical trials have shown substantial therapeutic activity and an acceptable safety profile in heavily pretreated patients, resulting in U.S. Food and Drug Administration approval of nivolumab for the treatment of cHL that has relapsed or progressed after either autologous hematopoietic cell transplantation (auto-HCT) and brentuximab vedotin treatment or three or more lines of systemic therapy (including auto-HCT), and of pembrolizumab for adult or pediatric patients with refractory cHL or cHL that has relapsed after three or more prior therapies. Mechanistically, anti-PD-1 therapy prevents inhibitory signaling through PD-1 receptors on T cells, thereby releasing a 'block' to antitumor T-cell responses. However, this disinhibition can also lead to inappropriate T-cell activation and responses against healthy tissues, resulting in immune-mediated adverse events (IMAEs) that affect a number of organ systems. The skin, gastrointestinal, hepatic, and endocrine systems are most commonly involved, typically resulting in rash, colitis, abnormal liver enzyme levels, and thyroiditis, respectively. Notably, pneumonitis is a potentially fatal complication of checkpoint inhibitor immunotherapy. Hematologic oncologists who treat cHL with PD-1 immune checkpoint inhibitors should monitor patients for IMAEs, as early recognition and treatment can rapidly reduce morbidity and mortality. This review focuses on IMAEs during the treatment of relapsed or refractory cHL with nivolumab and pembrolizumab.
IMPLICATIONS FOR PRACTICE: This article highlights the importance of monitoring for immune-mediated adverse events (IMAEs) in patients with Hodgkin lymphoma (HL) who receive anti-programmed death-1 (anti-PD-1) therapy, with particular attention given to the recognition and management of such events. The risk of individual IMAEs differs between patients with HL and those with solid tumors, as prior treatments may predispose certain organ systems to specific IMAEs. Accurate and prompt diagnosis of IMAEs is essential for optimal management, allowing PD-1 inhibitor therapy to be restarted in order to maintain disease control. Potential difficulties, such as distinguishing disease progression from pneumonitis, or colitis from diarrhea, are highlighted to raise clinical awareness.

PMID: 30082490 [PubMed - as supplied by publisher]

Phase I Study of the Investigational Aurora A Kinase Inhibitor Alisertib plus Rituximab or Rituximab/vincristine in Relapsed/refractory Aggressive B-cell Lymphoma.

Clin Cancer Res. 2018 Aug 06;:

Authors: Kelly KR, Friedberg JW, Park SI, McDonagh KT, Hayslip J, Persky D, Ruan J, Puvvada S, Rosen PJ, Padmanabhan Iyer S, Stefanovic A, Bernstein SH, Weitman S, Karnad AB, Monohan G, VanderWalde A, Mena R, Schmelz M, Spier C, Groshen S, Venkatakrishnan K, Zhou X, Sheldon-Waniga E, Leonard EJ, Mahadevan D

Abstract
PURPOSE: The aurora A kinase inhibitor alisertib demonstrated single-agent clinical activity and preclinical synergy with vincristine/rituximab in B-cell non-Hodgkin's lymphoma (B-NHL). This phase I study aimed to determine the safety and recommended phase II dose (RP2D) of alisertib in combination with rituximab ± vincristine in patients with relapsed/refractory aggressive B-NHL.
EXPERIMENTAL DESIGN: Patients with relapsed/refractory, diffuse, large, or other aggressive B-NHL received oral alisertib 50 mg BID days 1-7, plus IV rituximab 375 mg/m2 on day 1, for up to eight 21-day cycles (MR). Patients in subsequent cohorts (3+3 design) received increasing doses of alisertib (30 mg starting dose; 10 mg increments) BID days 1-7 plus rituximab and vincristine (1.4 mg/m2 [maximum 2 mg] days 1, 8) for 8 cycles (MRV). Patients benefiting could continue single-agent alisertib beyond 8 cycles. Cell-of-origin and MYC/BCL2 immunohistochemistry was performed on available archival tissue.
RESULTS: Forty-five patients participated. The alisertib RP2D for MR was 50 mg BID. For MRV (n = 32) the RP2D was determined as 40 mg BID (1 DLT at 40 mg; 2 DLTs at 50 mg). Drug-related adverse events were reported in 89% of patients, the most common was neutropenia (47%). Seven patients had complete responses (CRs), seven had partial responses (PRs); 9/20 (45%) patients at the MRV RP2D responded (4 CRs, 5 PRs), all with non-germinal center B-cell (GCB) DLBCL.
CONCLUSIONS: The combination of alisertib 50 mg BID plus rituximab or alisertib 40 mg BID plus rituximab and vincristine was well tolerated and demonstrated activity in non-GCB DLBCL.

PMID: 30082475 [PubMed - as supplied by publisher]

Prediction of Effective Drug Combinations by an Improved Naïve Bayesian Algorithm.

Int J Mol Sci. 2018 Feb 05;19(2):

Authors: Bai LY, Dai H, Xu Q, Junaid M, Peng SL, Zhu X, Xiong Y, Wei DQ

Abstract
Drug combinatorial therapy is a promising strategy for combating complex diseases due to its fewer side effects, lower toxicity and better efficacy. However, it is not feasible to determine all the effective drug combinations in the vast space of possible combinations given the increasing number of approved drugs in the market, since the experimental methods for identification of effective drug combinations are both labor- and time-consuming. In this study, we conducted systematic analysis of various types of features to characterize pairs of drugs. These features included information about the targets of the drugs, the pathway in which the target protein of a drug was involved in, side effects of drugs, metabolic enzymes of the drugs, and drug transporters. The latter two features (metabolic enzymes and drug transporters) were related to the metabolism and transportation properties of drugs, which were not analyzed or used in previous studies. Then, we devised a novel improved naïve Bayesian algorithm to construct classification models to predict effective drug combinations by using the individual types of features mentioned above. Our results indicated that the performance of our proposed method was indeed better than the naïve Bayesian algorithm and other conventional classification algorithms such as support vector machine and K-nearest neighbor.

PMID: 29401735 [PubMed - indexed for MEDLINE]

Phase I clinical study of brentuximab vedotin (SGN-35) involving children with recurrent or refractory CD30-positive Hodgkin's lymphoma or systemic anaplastic large cell lymphoma: rationale, design and methods of BV-HLALCL study: study protocol.

BMC Cancer. 2018 02 01;18(1):122

Authors: Sekimizu M, Iguchi A, Mori T, Koga Y, Kada A, Saito AM, Horibe K

Abstract
BACKGROUND: Hodgkin's lymphoma (HL) and anaplastic large-cell lymphoma (ALCL) are the two most common tumors expressing CD30. Internationally, a clinical study that is being conducted involving adults with recurrent or refractory HL or ALCL suggests efficacy of brentuximab vedotin (SGN-35). Pediatric patients should be given medicines that have been appropriately evaluated for their use. In the past, however, new approved drugs have been used for pediatric patients without the confirmation of safety and efficacy in pediatric patients. Therefore, it is important to examine the safety and efficacy of SGN-35 in Japanese children.
METHODS: Phase I clinical study of SGN-35 involving children with recurrent or refractory CD30-positive Hodgkin's lymphoma or systemic anaplastic large cell lymphoma (BV-HLALCL study) is being conducted for pediatric patients in order to evaluate the safety, feasibility and preliminary clinical effectiveness of brentuximab vedotin. SGN-35 is intravenously administered on Day 1 of each cycle (21 days/cycle). The dose of SGN-35 is calculated based on the body weight at the baseline. The primary endpoint is dose limiting toxicity and incidence of adverse events. The secondary endpoints are pharmacokinetics, response rate, complete remission rate, response duration, progression-free survival and event-free survival. The reduction rate of tumor will be calculated according to revised response criteria for malignant lymphoma for measurable tumor. Six pediatric patients will be enrolled in this study.
DISCUSSION: This study aims to expand indication of SGN-35 in Japan by assessing its safety and efficacy in pediatric patients.
TRIAL REGISTRATION: JMACCT ID: JMA-IIA00229 . Registered on 17 Nov 2015.

PMID: 29390984 [PubMed - indexed for MEDLINE]

Adjuvant treatment of resectable biliary tract cancer with cisplatin plus gemcitabine: A prospective single center phase II study.

BMC Cancer. 2018 01 11;18(1):72

Authors: Siebenhüner AR, Seifert H, Bachmann H, Seifert B, Winder T, Feilchenfeldt J, Breitenstein S, Clavien PA, Stupp R, Knuth A, Pestalozzi B, Samaras P

Abstract
BACKGROUND: Biliary tract cancer (BTC) is a dismal disease, even after curative intent surgery. We conducted this prospective, non-randomized phase II study to evaluate the feasibility and efficacy of cisplatin and gemcitabine as adjuvant treatment in patients with resected BTC.
METHODS: Patients initially received gemcitabine 1000 mg/m2 alone on days 1, 8 and 15 every 28-days for a total of six cycles (single agent cohort), and after protocol amendment a combination therapy with gemcitabine 1000 mg/m2 and cisplatin 25 mg/m2 on days 1 and 8 was administered every 21 days for a total of eight cycles (combined regimen cohort). Treatment was planned to start within eight weeks after curative intent resection. Adverse events, disease-free survival and overall survival were assessed.
RESULTS: Overall 30 patients were enrolled in the study from August 2008 and last patient was enrolled at 2nd December 2014. The follow-up of the patients ended at 31st December 2016. The first 9 patients received single-agent gemcitabine. The interim analysis met the predefined feasibility criteria and, from September 2010 on, the second group of 21 patients received the combination of cisplatin plus gemcitabine. In the single-agent cohort with gemcitabine the median relative dose intensity (RDI) was 100% (IQR 88.3-100). Patients treated with the combination cisplatin-gemcitabine received an overall median RDI of 100% (IQR 50-100) for cisplatin and 100% (IQR 75-100) for gemcitabine respectively. The most significant non-hematological adverse events (grade 3 or 4) were fatigue (20%), infections during neutropenia (10%), and two cases of biliary sepsis (7%). Abnormal liver function was seen in 10% of the patients. One patient died due to infectious complications during treatment with cisplatin and gemcitabine. The median disease-free survival (DFS) was 14.9 months (95% CI 0-33.8) with a corresponding 3-year DFS of 43.1 ± 9.1%. The median overall survival (OS) was 40.6 months (95% CI 18.8-62.3) with a 3-year OS of 55.7 ± 9.2%. No statistically significant differences in survival were seen between the two treatment cohorts.
CONCLUSION: Adjuvant chemotherapy with gemcitabine with or without cisplatin was well tolerated and resulted in promising survival of the patients.
TRIAL REGISTRATION: The study was retrospectively registered on 25th June 2009 at clinicaltrials.gov ( NCT01073839 ).

PMID: 29325521 [PubMed - indexed for MEDLINE]

Expectations, concerns, and needs of patients who start drugs for chronic conditions. A prospective observational study among community pharmacies in Serbia.

Eur J Gen Pract. 2018 Dec;24(1):19-25

Authors: Vučićević KM, Miljković BR, Golubović BC, Jovanović MN, Vezmar Kovačević SD, Ćulafić MD, Kovačević MM, de Gier JJ

Abstract
BACKGROUND: During the initiation of treatment of a chronic disease, patients may have varying interests, expectations, concerns, and reasons to stop treatment, influencing compliance with prescribed treatment. Thus, healthcare professionals are expected to integrate these needs into medicines management.
OBJECTIVES: To determine what information is important to patients; assess predictors of patients' interests, expectations, concerns, reasons to stop therapy; evaluate drug-related problems following initiation of therapy and summarize how pharmacists resolve them during patient-pharmacist counselling.
METHODS: In 2014, a four-month study was performed in Serbian community pharmacies, as part of the Pharmaceutical Care Quality Indicators Project led by the European Directorate for the Quality of Medicines & Healthcare. Seventy community pharmacists were asked to participate in the study. Pharmacists recruited adult patients who consented to participate in the study and who initiated treatment, lasting at least six months. Patients completed an open-ended questions form. After two-to-four weeks, a patient-pharmacist consultation was performed.
RESULTS: Forty-four community pharmacists (response rate 62.9%) sent back the completed forms from 391 patients (response rate 67.1%). The total number of dispensed drugs was 403. In terms of drug safety, 29.4% of patients sought information, 32.5% expressed concerns, and 28.1% of patients cited it as a reason to discontinue treatment. During the first weeks of therapy, 18% of patients experienced practical problems, while 27.3% reported adverse drug reactions.
CONCLUSION: Safety issues are a major focus of patients' prescribed new medicines for long-term treatment.

PMID: 29164957 [PubMed - indexed for MEDLINE]