Outcomes and prognostic factors for relapsed or refractory lymphoma patients in phase I clinical trials
Conclusion Performance status, LDH, albumin and histological type (tumour aggressiveness) appear to be the most relevant prognostic factors for enrolling Phase I participants with relapsed or refractory lymphoma. 39% of the patients experienced a first high-grade toxic event after the dose-limiting toxicity period, suggesting that the conventional concept of dose-limiting toxicity (designed for chemotherapy) should be redefined in the era of modern cancer therapies. (Source: Investigational New Drugs)
Source: Investigational New Drugs - June 9, 2017 Category: Drugs & Pharmacology Source Type: research

Erratum to: Sarcopenic overweight is associated with early acute limiting toxicity of anti-PD1 checkpoint inhibitors in melanoma patients
(Source: Investigational New Drugs)
Source: Investigational New Drugs - June 9, 2017 Category: Drugs & Pharmacology Source Type: research

Clinical parameters associated with anti-programmed death-1 (PD-1) inhibitors-induced tumor response in melanoma patients
Conclusion A long time lapse from diagnosis to anti-PD-1 initiation and PS 0 are associated with higher sensitivity to anti-PD-1 in melanoma patients. These two clinical features might reflect a potentially intact immune system of the host. (Source: Investigational New Drugs)
Source: Investigational New Drugs - May 31, 2017 Category: Drugs & Pharmacology Source Type: research

A phase II study of antibody-drug conjugate, TAK-264 (MLN0264) in previously treated patients with advanced or metastatic pancreatic adenocarcinoma expressing guanylyl cyclase C
Conclusions TAK-264 demonstrated a manageable safety profile; however, the low efficacy of TAK-264 observed in this study did not support further clinical investigation. (Source: Investigational New Drugs)
Source: Investigational New Drugs - May 19, 2017 Category: Drugs & Pharmacology Source Type: research

Gankyrin as a potential therapeutic target for cancer
AbstractGankyrin is an oncoprotein that plays a central role in the development of cancer. Although researchers have increasingly focused on the relationships of gankyrin with carcinogenesis, metastasis and prognosis of different cancers, the molecular mechanisms are still unclear. In recent years, several interacting partners of gankyrin and cell signaling pathways regulated by gankyrin have been elucidated. In addition, accumulating evidence has indicated the contribution of microRNAs to regulating gankyrin expression in tumor cells. In this review, we summarize the major known roles of gankyrin in cancer cells and highl...
Source: Investigational New Drugs - May 19, 2017 Category: Drugs & Pharmacology Source Type: research

Gilteritinib, a FLT3/AXL inhibitor, shows antileukemic activity in mouse models of FLT3 mutated acute myeloid leukemia
SummaryAdvances in the understanding of the molecular basis for acute myeloid leukemia (AML) have generated new potential targets for treatment. Fms-like tyrosine kinase 3 (FLT3) is one of the most frequently mutated genes in AML and mutations in this gene are associated with poor overall survival. AXL plays a role in the activation of FLT3 and has been implicated in the pathogenesis of AML. The studies reported here evaluated the ability of a novel FLT3/AXL inhibitor, gilteritinib, to block mutated FLT3 in cellular and animal models of AML. Initial kinase studies showed that gilteritinib, a type I tyrosine kinase inhibito...
Source: Investigational New Drugs - May 17, 2017 Category: Drugs & Pharmacology Source Type: research

Ganetespib overcomes resistance to PARP inhibitors in breast cancer by targeting core proteins in the DNA repair machinery
Conclusion These data provide a novel strategy for the treatment of breast cancer with wild type BRCA1 using combination therapy targeting Hsp90 to overcome resistance to PARP inhibitors. (Source: Investigational New Drugs)
Source: Investigational New Drugs - May 5, 2017 Category: Drugs & Pharmacology Source Type: research

Phase II study of lanreotide autogel in Japanese patients with unresectable or metastatic well-differentiated neuroendocrine tumors
Conclusions The efficacy and safety of lanreotide in this study indicated its usefulness as a treatment option for Japanese NET patients. Trial registration: JapicCTI-132,375, JapicCTI-142,698. (Source: Investigational New Drugs)
Source: Investigational New Drugs - May 3, 2017 Category: Drugs & Pharmacology Source Type: research

Impressive and durable response to nivolumab in a patient with metastatic type 2 papillary renal cell carcinoma: On-label but without evidence
We report the case of a woman with recurrent metastatic PRCC who had an impressive therapeutic response to nivolumab with no significant adverse events. She had previously been treated with sunitinib and paz opanib with no response. She showed a remarkable clinical improvement after only the first 2 immunotherapy cycles and subsequent radiographic studies demonstrated a marked decrease in tumor burden. At present, she continues to show a durable benefit after 8 months of treatment. Her tumor had
Source: Investigational New Drugs - May 2, 2017 Category: Drugs & Pharmacology Source Type: research

Phase I study of Nedaplatin, a platinum based antineoplastic drug, combined with nab-paclitaxel in patients with advanced squamous non –small cell lung cancer
Conclusions The combination of NED and nab-PTX was a tolerable and effective regimen and its recommended dose was 100  mg/m2 and 100  mg/m2, respectively, in chemotherapy-naive patients with advanced squamous NSCLC (UMIN000010963). (Source: Investigational New Drugs)
Source: Investigational New Drugs - May 2, 2017 Category: Drugs & Pharmacology Source Type: research

Successful osimertinib rechallenge in a patient with advanced non-small cell lung cancer following osimertinib-induced interstitial lung disease after treatment with nivolumab
(Source: Investigational New Drugs)
Source: Investigational New Drugs - May 2, 2017 Category: Drugs & Pharmacology Source Type: research

The outcome of sorafenib monotherapy on hepatocellular carcinoma with portal vein tumor thrombosis
This study aimed to elucidate the safety and efficacy of sorafenib monotherapy on HCC with macro-vascular invasion (MVI). A total of 415 consecutive advanced HCC patients received sorafenib in our hospital. Patients with only MVI and sorafenib monotherapy were retrospectively enrolled. We enrolled 113 (27.2%) patients, including 56 (49.5%) Vp3 (portal invasion at the first branch) and 57 (50.5%) Vp4. Their median intervals of follow-up and sorafenib-use were 7.8  months and 2.7 months respectively. Using sorafenib, more Vp4 had hepatic decompensation (HD) (37% VS 18.2%,p = 0.028) than Vp3 patients. The ...
Source: Investigational New Drugs - May 2, 2017 Category: Drugs & Pharmacology Source Type: research

A phase I dose-escalation study of Selumetinib in combination with Erlotinib or Temsirolimus in patients with advanced solid tumors
Conclusions MTDs were established for selumetinib in combination with erlotinib or temsirolimus. Overlapping toxicities prevented the escalation of selumetinib to its recommended phase II monotherapy dose of 75  mg BID.Trial registration:ClinicalTrials.gov NCT00600496; registered 8 July 2009. (Source: Investigational New Drugs)
Source: Investigational New Drugs - April 19, 2017 Category: Drugs & Pharmacology Source Type: research

Bis-anthracycline WP760 abrogates melanoma cell growth by transcription inhibition, p53 activation and IGF1R downregulation
SummaryAnthracycline chemotherapeutics, e.g. doxorubicin and daunorubicin, are active against a broad spectrum of cancers. Their cytotoxicity is mainly attributed to DNA intercalation, interference with topoisomerase activity, and induction of double-stranded DNA breaks. Since modification of anthracyclines can profoundly affect their pharmacological properties we attempted to elucidate the mechanism of action, and identify possible molecular targets, of bis-anthracycline WP760 which previously demonstrated anti-melanoma activity at low nanomolar concentrations. We studied the effect of WP760 on several human melanoma cell...
Source: Investigational New Drugs - April 17, 2017 Category: Drugs & Pharmacology Source Type: research

A phase I dose-escalation study of the safety and pharmacokinetics of a tablet formulation of voxtalisib, a phosphoinositide 3-kinase inhibitor, in patients with solid tumors
Conclusions The safety profile of voxtalisib tablets at the MTD in patients with solid tumors was consistent with that observed with voxtalisib capsules. Given the limited activity observed across multiple clinical trials, no further trials of voxtalisib are planned. (Source: Investigational New Drugs)
Source: Investigational New Drugs - April 17, 2017 Category: Drugs & Pharmacology Source Type: research

Resistance to immunotherapy: clouds in a bright sky
SummaryTwo major challenges persist for an optimal management of immunotherapy: i) identifying those patients who will benefit from this type of therapy, and ii) determining the biological, cellular and molecular mechanisms that trigger disease progression while on therapy. There is a consensual view in favor of standardizing practices currently used to measure programmed death ligand 1 (PD-L1) expression that relates to innate resistance. The tumor mutation landscape has been widely explored as a potential predictor of treatment efficacy. In contrast, our knowledge is rather limited as concerns the mechanisms sustaining a...
Source: Investigational New Drugs - April 12, 2017 Category: Drugs & Pharmacology Source Type: research

Sarcopenic overweight is associated with early acute limiting toxicity of anti-PD1 checkpoint inhibitors in melanoma patients
SummaryLittle is known on factors predicting toxicity of anti-PD1 checkpoint inhibitors. Sarcopenic obesity is associated with increased acute toxicity of cytotoxic agents and targeted therapies. We explored whether body composition also influenced the occurrence of early acute limiting toxicity (ALT) of anti-PD1 in melanoma patients. This is a monocentric, retrospective study analyzing toxicity outcome in consecutive melanoma patients treated with nivolumab or pembrolizumab. Various parameters linked to the patient or the disease status have been analysed. Body mass index (BMI; kg/m2) and muscle mass using CT were measure...
Source: Investigational New Drugs - April 10, 2017 Category: Drugs & Pharmacology Source Type: research

Phase I trial and pharmacokinetic study of tanibirumab, a fully human monoclonal antibody to vascular endothelial growth factor receptor 2, in patients with refractory solid tumors
Conclusions Treatment with tanibirumab showed a tolerable toxicity profile and modest clinical efficacy in patients with refractory solid tumors. A phase II trial of tanibirumab is ongoing now. (Source: Investigational New Drugs)
Source: Investigational New Drugs - April 8, 2017 Category: Drugs & Pharmacology Source Type: research

Erratum to: First-in-human phase I study of SOR-C13, a TRPV6 calcium channel inhibitor, in patients with advanced solid tumors
(Source: Investigational New Drugs)
Source: Investigational New Drugs - April 7, 2017 Category: Drugs & Pharmacology Source Type: research

New doxorubicin nanocarriers based on cyclodextrins
SummaryPolymeric nanoparticles and fibrin gels (FBGs) are attractive biomaterials for local delivery of a variety of biotherapeutic agents, from drugs to proteins. We combined these different drug delivery approaches by preparing nanoparticle-loaded FBGs characterized by their intrinsic features of drug delivery rate and antiproliferative/apoptotic activities. Inclusion complexes of doxorubicin (DOXO) with oligomeric β-cyclodextrins (oCyD) functionalized with different functional groups were studied. These nanocarriers were able to interact with FBGs as shown by a decreased release rate of DOXO. One of these complexes...
Source: Investigational New Drugs - April 4, 2017 Category: Drugs & Pharmacology Source Type: research

Aplastic anemia in a lung adenocarcinoma patient receiving pemetrexed
SummaryPemetrexed (PEM) is an antimetabolite drug that interferes with enzymes involved in DNA synthesis and also the folate-dependent metabolic processes necessary for DNA replication and homocysteine homeostasis. Continuation maintenance with PEM after induction therapy with PEM plus cisplatin has been the standard form of first-line chemotherapy for advanced non-squamous non-small cell lung cancer. The regimen has a low incidence of bone marrow suppression, and the incidences of anemia, leukopenia, neutropenia and thrombocytopenia exceeding grade 3 are less than 5%. Here we report a 68-year-old Japanese man with stage I...
Source: Investigational New Drugs - March 30, 2017 Category: Drugs & Pharmacology Source Type: research

A phase 1, open label, dose escalation study to investigate the safety, tolerability, and pharmacokinetics of MG1102 (apolipoprotein(a) Kringle V) in patients with solid tumors
Conclusions The safety profile of MG1102 was generally manageable and the toxicities resolved quickly. Potential antitumor activity was observed with 1 unconfirmed PR (60% size reduction). (Source: Investigational New Drugs)
Source: Investigational New Drugs - March 28, 2017 Category: Drugs & Pharmacology Source Type: research

Phase II study of the Multikinase inhibitor of angiogenesis, Linifanib, in patients with metastatic and refractory colorectal cancer expressing mutated KRAS
Conclusion Despite observing zero responses, a majority of patients had stable disease and eight patients had stable disease lasting longer than 5  months. These results suggest that linifanib has some anti-tumor activity inKRAS mutant metastatic and refractory CRC. (Source: Investigational New Drugs)
Source: Investigational New Drugs - March 28, 2017 Category: Drugs & Pharmacology Source Type: research

MPT0B002, a novel microtubule inhibitor, downregulates T315I mutant Bcr-Abl and induces apoptosis of imatinib-resistant chronic myeloid leukemia cells
In this study, we evaluated its effects on the proliferation, cell cycle, and apoptosis of K562 CML cells and BaF3 cells expressing either wild-type Bcr-Abl (BaF3/p210) or T315I-mutated Bcr-Abl (BaF3/T315I). MPT0B002 inhibited cell viability in a dose-dependent manner in these cells but did not affect the proliferation of human umbilical vein endothelial cells. It disrupted tubulin polymerization and arrested cell cycle at the G2/M phase. Treatment with MPT0B002 induced apoptosis, and this induction was associated with increased levels of cleaved caspase-3 and cleaved PARP. Furthermore, MPT0B002 can downregulate both Bcr-A...
Source: Investigational New Drugs - March 27, 2017 Category: Drugs & Pharmacology Source Type: research

Imaging and clinicopathological features of nivolumab-related cholangitis in patients with non-small cell lung cancer
Conclusions Nivolumab-related cholangitis is associated with distinct imaging and clinicopathological features that distinguish it from acute cholangitis of common etiologies and other immune-related cholangitis. Further studies are warranted to establish the optimal management of patients with this irAE. (Source: Investigational New Drugs)
Source: Investigational New Drugs - March 20, 2017 Category: Drugs & Pharmacology Source Type: research

Phase I trial of the oral smoothened inhibitor sonidegib in combination with paclitaxel in patients with advanced solid tumors
Conclusions The combination of sonidegib and paclitaxel is tolerable and evidence of antitumor activity was identified. The RP2D of sonidegib was 800 mg in combination with paclitaxel 80mg/m2. (Source: Investigational New Drugs)
Source: Investigational New Drugs - March 20, 2017 Category: Drugs & Pharmacology Source Type: research

Effects of histone deacetylase inhibitory prodrugs on epigenetic changes and DNA damage response in tumor and heart of glioblastoma xenograft
SummaryThe histone deacetylase (HDAC) inhibitory prodrugs of butyric (AN7) and valproic (AN446) acids, which release the active acids upon metabolic degradation, were studied examining their differential effects on the viability, HDAC inhibitory activity and the DNA damage response (DDR), in glioblastoma cell and normal human astrocytes (NHAs). In xenografts of glioblastoma, AN7 or AN446 given or the combination of each of them with Dox augmented the anticancer activity of Dox and protected the heart from its toxicity. In order to determine the processes underlying these opposing effects, the changes induced by these treat...
Source: Investigational New Drugs - March 17, 2017 Category: Drugs & Pharmacology Source Type: research

Human mass balance study and metabolite profiling of 14 C-niraparib, a novel poly(ADP-Ribose) polymerase (PARP)-1 and PARP-2 inhibitor, in patients with advanced cancer
This study evaluates the absorption, metabolism and excretion (AME) of14C –niraparib, administered to six patients as a single oral dose of 300 mg with a radioactivity of 100 μCi. Total radioactivity (TRA) in whole blood, plasma, urine and faeces was measured using liquid scintillation counting (LSC) to obtain the mass balance of niraparib. Moreover, metabolite profi ling was performed on selected plasma, urine and faeces samples using liquid chromatography – tandem mass spectrometry (LC-MS/MS) coupled to off-line LSC. Mean TRA recovered over 504 h was 47.5% in urine and 38.8% in faeces, indic...
Source: Investigational New Drugs - March 16, 2017 Category: Drugs & Pharmacology Source Type: research

A randomized, open-label, multicenter, phase II study evaluating the efficacy and safety of BTH1677 (1,3 –1,6 beta glucan; Imprime PGG) in combination with cetuximab and chemotherapy in patients with advanced non-small cell lung cancer
Conclusions BTH1677 combined with cetuximab/carboplatin/paclitaxel was well tolerated and improved ORR as first-line treatment in patients with advanced NSCLC. Future patient selection by biomarker status may further improve efficacyClinicalTrials.gov Identifier: NCT00874848 (Source: Investigational New Drugs)
Source: Investigational New Drugs - March 16, 2017 Category: Drugs & Pharmacology Source Type: research

Lung cancer and β-glucans: review of potential therapeutic applications
SummaryThe potential of natural substances with immunotherapeutic properties has long been studied. β-glucans, a cell wall component of certain bacteria and fungi, potentiate the immune system against microbes and toxic substances. Moreover, β-glucans are known to exhibit direct anticancer effects and can suppress cancer proliferation through immunomodulatory pathways. Mortality of lung cancer has been alarmingly increasingly worldwide; therefore, treatment of lung cancer is an urgent necessity. Numerous researchers are now dedicated to using β-glucans as a therapy for lung cancer. In the present a...
Source: Investigational New Drugs - March 16, 2017 Category: Drugs & Pharmacology Source Type: research

Prognostic and predictive value of circulating tumor cells and CXCR4 expression as biomarkers for a CXCR4 peptide antagonist in combination with carboplatin-etoposide in small cell lung cancer: exploratory analysis of a phase II study
Conclusions In patients with ED-SCLC, baseline CXCR4 expression in tumor tissue was not prognostic of survival or predictive of LY2510924 treatment response. Baseline CXCR4+ CTCs ≥7% was prognostic of shorter PFS. CTC count ≥6 at baseline and after 1 cycle of treatment were prognostic of shorter PFS and OS. (Source: Investigational New Drugs)
Source: Investigational New Drugs - March 15, 2017 Category: Drugs & Pharmacology Source Type: research

Diclofenac sex-divergent drug-drug interaction with Sunitinib: pharmacokinetics and tissue distribution in male and female mice
SummaryCoadministration of diclofenac and sunitinib, tyrosine kinase inhibitor, led to sex-divergent pharmacokinetic drug-drug interaction outcomes. Male and female mice were administered 60  mg/kg PO sunitinib alone (control groups) or with 30 mg/kg PO diclofenac. Sunitinib concentration in plasma, brain, kidney and liver were determined by HPLC and non-compartmental pharmacokinetic parameters calculated. In male mice, diclofenac decreased AUC0 →∞ 38% in plasma (p 
Source: Investigational New Drugs - March 11, 2017 Category: Drugs & Pharmacology Source Type: research

Risk of hypertension with ramucirumab-based therapy in solid tumors: data from a literature based meta-analysis
SummaryRamucirumab is a monoclonal antibody against Vascular Endothelial Growth Factor Receptor-2 (VEGFR-2) approved for the treatment of several solid tumours. As shown in recent trials results, new-onset hypertension is one of the most frequent adverse events associated with ramucirumab therapy. Recent studies looked at the quantification of the risk of hypertension in patients receiving other anti-angiogenesis medications. We conducted a meta-analysis of randomized clinical trials with the aim to investigate the incidence and quantify the risk of new-onset hypertension of any grade in patients treated with ramucirumab. ...
Source: Investigational New Drugs - March 11, 2017 Category: Drugs & Pharmacology Source Type: research

Metabolic carbonyl reduction of anthracyclines — role in cardiotoxicity and cancer resistance. Reducing enzymes as putative targets for novel cardioprotective and chemosensitizing agents
SummaryAnthracycline antibiotics (ANT), such as doxorubicin or daunorubicin, are a class of anticancer drugs that are widely used in oncology. Although highly effective in cancer therapy, their usefulness is greatly limited by their cardiotoxicity. Possible mechanisms of ANT cardiotoxicity include their conversion to secondary alcohol metabolites (i.e. doxorubicinol, daunorubicinol) catalyzed by carbonyl reductases (CBR) and aldo-keto reductases (AKR). These metabolites are suspected to be more cardiotoxic than their parent compounds. Moreover, overexpression of ANT-reducing enzymes (CBR and AKR) are found in many ANT-resi...
Source: Investigational New Drugs - March 10, 2017 Category: Drugs & Pharmacology Source Type: research

Phase Ib study of the mitochondrial inhibitor ME-344 plus topotecan in patients with previously treated, locally advanced or metastatic small cell lung, ovarian and cervical cancers
Conclusions The combination of ME-344 10  mg/kg weekly and topotecan 4 mg/m2 was tolerable, however, the degree of anti-cancer activity does not support further investigation of the combination in unselected patients with SCLC, ovarian and cervical cancers. (Source: Investigational New Drugs)
Source: Investigational New Drugs - March 10, 2017 Category: Drugs & Pharmacology Source Type: research

A phase 1b dose expansion study of the pan-class I PI3K inhibitor buparlisib (BKM120) plus carboplatin and paclitaxel in PTEN deficient tumors and with dose intensified carboplatin and paclitaxel
Conclusion The addition of buparlisib to high dose carboplatin and paclitaxel was not tolerable. The combination did not reveal significant clinical activity amongst a small and heterogenous group of PTEN deficient tumors, (Source: Investigational New Drugs)
Source: Investigational New Drugs - March 9, 2017 Category: Drugs & Pharmacology Source Type: research

Phase 1b trial of proteasome inhibitor carfilzomib with irinotecan in lung cancer and other irinotecan-sensitive malignancies that have progressed on prior therapy (Onyx IST reference number: CAR-IST-553)
Conclusions Irinotecan and carfilzomib were well tolerated, with common toxicities of fatigue, thrombocytopenia and neutropenic fever. Objective clinical response was 19% (one confirmed partial response (PR) in small cell lung cancer (SCLC) and two unconfirmed); stable disease (SD) was 6% for a disease control rate (DCR) of 25%. The recommended phase II dose was carfilzomib 20/36  mg/m2 and irinotecan125  mg/m2. The phase II evaluation is ongoing in relapsed small cell lung cancer. (Source: Investigational New Drugs)
Source: Investigational New Drugs - February 16, 2017 Category: Drugs & Pharmacology Source Type: research

Phase I trial of MEK 1/2 inhibitor pimasertib combined with mTOR inhibitor temsirolimus in patients with advanced solid tumors
Conclusions The RP2D was not defined and the pimasertib plus temsirolimus combination investigated did not warrant further study. (Source: Investigational New Drugs)
Source: Investigational New Drugs - February 13, 2017 Category: Drugs & Pharmacology Source Type: research

Phase II study of the antibody-drug conjugate TAK-264 (MLN0264) in patients with metastatic or recurrent adenocarcinoma of the stomach or gastroesophageal junction expressing guanylyl cyclase C
Conclusions TAK-264 demonstrated a manageable safety profile in this patient population. The stage I interim analysis did not support continuation to stage II of the study. (Source: Investigational New Drugs)
Source: Investigational New Drugs - February 11, 2017 Category: Drugs & Pharmacology Source Type: research

Erratum to: Zebrafish phenotypic screen identifies novel Notch antagonists
(Source: Investigational New Drugs)
Source: Investigational New Drugs - February 10, 2017 Category: Drugs & Pharmacology Source Type: research

State-dependent block of voltage-gated sodium channels by the casein-kinase 1 inhibitor IC261
Conclusion and Implications IC261 inhibits sodium channels at a similar concentration necessary to reduce CK1 δ/ε activity by 50% (IC50 value 1  μM). Thus, inhibition of sodium channels might contribute to the antitumor activity of IC261. (Source: Investigational New Drugs)
Source: Investigational New Drugs - February 6, 2017 Category: Drugs & Pharmacology Source Type: research

Phase 1 study of narnatumab, an anti-RON receptor monoclonal antibody, in patients with advanced solid tumors
This study assessed safety, maximum tolerated dose (MTD), pharmacokinetics, pharmacodynamics, and efficacy of narnatumab in patients with advanced solid tumors.Methods Narnatumab was administered intravenously weekly at 5, 10, 15, or 20 mg/kg or every 2 weeks at 15, 20, 30, or 40 mg/kg in 4-week cycles.Results Thirty-nine patients were treated, and 1 dose-limiting toxicity (DLT) (grade 3 hyponatremia, 5 mg/kg) was reported. The most common narnatumab-related adverse events (AEs) were fatigue (20.5%) and decreased appetite, diarrhea, nausea, and vomiting (10.3% each). Except for 2 treatment-related grade 3 AEs (hyponatremia...
Source: Investigational New Drugs - February 4, 2017 Category: Drugs & Pharmacology Source Type: research

Association of an aurora kinase a ( AURKA ) gene polymorphism with progression-free survival in patients with advanced urothelial carcinoma treated with the selective aurora kinase a inhibitor alisertib
Conclusion In patients who received alisertib for advanced or metastatic urothelial carcinoma, longer progression-free survival was observed in carriers of the minor allele A of rs2273535 inAURKA than in patients who were homozygous for the major allele T. This finding, based on a small pilot trial, warrants further investigation. (Source: Investigational New Drugs)
Source: Investigational New Drugs - February 3, 2017 Category: Drugs & Pharmacology Source Type: research

A phase II study of carboplatin plus weekly paclitaxel with bevacizumab for elderly patients with non-squamous non-small-cell lung cancer (NEJ016)
Conclusion Carboplatin plus weekly paclitaxel with bevacizumab is a feasible, effective first-line regimen for elderly non-small cell lung cancer patients. (UMIN00006622). (Source: Investigational New Drugs)
Source: Investigational New Drugs - February 1, 2017 Category: Drugs & Pharmacology Source Type: research

First-in-human phase I study of SOR-C13, a TRPV6 calcium channel inhibitor, in patients with advanced solid tumors
Conclusion SOR-C13 was safe and tolerated up to 6.2  mg/kg. The Maximal Tolerated Dose (MTD) was not established. Stable disease suggested antitumor activity. (Source: Investigational New Drugs)
Source: Investigational New Drugs - February 1, 2017 Category: Drugs & Pharmacology Source Type: research

ProCAID: a phase I clinical trial to combine the AKT inhibitor AZD5363 with docetaxel and prednisolone chemotherapy for metastatic castration resistant prostate cancer
SummaryBackground Docetaxel and prednisolone chemotherapy (DP) extends survival in metastatic castration resistant prostate cancer (mCRPC). However, emergent clinical resistance is almost inevitable. AKT pathway activation is highly prevalent in mCRPC contributing to disease progression and DP resistance. AZD5363 is a potent oral pan-AKT inhibitor with pre-clinical data indicating activity in mCRPC and synergy with docetaxel.Methods This phase I trial was to determine an AZD5363 recommended phase II dose (RP2D) for combination with DP. Eligibility criteria included chemotherapy naive mCRPC, PSA or radiographic disease prog...
Source: Investigational New Drugs - February 1, 2017 Category: Drugs & Pharmacology Source Type: research

Surveillance of protocol deviations in Japanese oncology registration trials: a single institute experience
Conclusion This study showed the number and detail responsible factors of protocol deviations. Our findings support to distinguish between the measures to reduce the serious deviations and to reduce the overall number of deviations. (Source: Investigational New Drugs)
Source: Investigational New Drugs - February 1, 2017 Category: Drugs & Pharmacology Source Type: research

Metabolism and disposition of the anticancer quinolone derivative vosaroxin, a novel inhibitor of topoisomerase II
SummaryBackground Vosaroxin is a first-in-class anticancer quinolone derivative that is being investigated for patients with relapsed or refractory acute myeloid leukemia (AML). The primary objective of this study was to quantitatively determine the pharmacokinetics of vosaroxin and its metabolites in patients with advanced solid tumors.Methods This mass balance study investigated the pharmacokinetics (distribution, metabolism, and excretion) of vosaroxin in cancer patients after a single dose of 60  mg/m2 14C –vosaroxin, administered as short intravenous injection. Blood, urine and feces were collected over 168...
Source: Investigational New Drugs - January 31, 2017 Category: Drugs & Pharmacology Source Type: research

Phase I/II study of docetaxel combined with resminostat, an oral hydroxamic acid HDAC inhibitor, for advanced non-small cell lung cancer in patients previously treated with platinum-based chemotherapy
Conclusion In Japanese NSCLC patients previously treated with platinum-based chemotherapy, DR therapy did not improve PFS compared with docetaxel alone and increased toxicity. (Source: Investigational New Drugs)
Source: Investigational New Drugs - January 30, 2017 Category: Drugs & Pharmacology Source Type: research

Gemcitabine and S-1 versus gemcitabine and cisplatin treatment in patients with advanced biliary tract cancer: a multicenter retrospective study
Conclusion This study demonstrates that GS and GC are similar with regard to their safety and efficacy in patients with advanced BTC. GS could serve as an alternative treatment for advanced BTC as a first-line chemotherapy. (Source: Investigational New Drugs)
Source: Investigational New Drugs - January 26, 2017 Category: Drugs & Pharmacology Source Type: research