Safety, tolerability, and pharmacokinetic profile of dabrafenib in Japanese patients with BRAF V600 mutation-positive solid tumors: a phase 1 study
Conclusions Dabrafenib was well tolerated and rapidly absorbed administered as single- or multiple dose. Comparable safety and pharmacokinetic profiles were observed compared with non-Japanese patients. Dabrafenib has promising clinical activity in Japanese patients withBRAF mutated malignant melanoma. (Source: Investigational New Drugs)
Source: Investigational New Drugs - September 7, 2017 Category: Drugs & Pharmacology Source Type: research

Crucial microRNAs and genes in metformin ’s anti-pancreatic cancer effect explored by microRNA-mRNA integrated analysis
SummaryDespite great improvements in surgical procedures and chemotherapy, pancreatic cancer remains one of the most aggressive and fatal human malignancies, with a low 5-year survival rate. Therefore, novel therapeutic strategies for the prevention and treatment of pancreatic cancer are urgently needed. The present study aimed to investigate the mechanisms by which metformin exerts its anticancer effects on the microRNA-mRNA interactions in human pancreatic cancer. Microarray and systematic analyses revealed that the anti-pancreatic cancer effects of metformin were correlated with 3 up-regulated microRNAs and 4 of their t...
Source: Investigational New Drugs - September 5, 2017 Category: Drugs & Pharmacology Source Type: research

Phase I dose escalation and pharmacokinetic study on the nanoparticle formulation of polymeric micellar paclitaxel for injection in patients with advanced solid malignancies
Conclusions PM-paclitaxel showed high MTD without additional toxicity, and exhibited desirable antitumor activity. The recommended dose of PM paclitaxel for phase II study is 300  mg/m2. (Source: Investigational New Drugs)
Source: Investigational New Drugs - September 4, 2017 Category: Drugs & Pharmacology Source Type: research

Phase II basket trial of perifosine monotherapy for recurrent gynecologic cancer with or without PIK3CA mutations
Conclusions Perifosine monotherapy showed good tolerability but expected efficacy was not achieved. Modest efficacy was demonstrated in ovarian cancer patients withPIK3CA mutations and endometrial cancer patients withPIK3CA wild-type; no difference was observed betweenPIK3CA wild-type and mutant in cervical cancer. Absence of PTEN expression may be predictive of clinical efficacy with perifosine monotherapy. (Source: Investigational New Drugs)
Source: Investigational New Drugs - September 2, 2017 Category: Drugs & Pharmacology Source Type: research

Effects of rifampin, itraconazole and esomeprazole on the pharmacokinetics of alisertib, an investigational aurora a kinase inhibitor in patients with advanced malignancies
Conclusions The use of gastric acid reducing agents, strong CYP3A inhibitors or strong metabolic enzyme inducers should be avoided in patients receiving alisertib. (Source: Investigational New Drugs)
Source: Investigational New Drugs - August 30, 2017 Category: Drugs & Pharmacology Source Type: research

Vinblastine and antihelmintic mebendazole potentiate temozolomide in resistant gliomas
SummaryGlioblastoma (GBM) is a very aggressive tumor that has not had substantial therapeutic improvement since the introduction of temozolomide (TMZ) in combination with radiotherapy. Combining TMZ with other chemotherapeutic agents is a strategy that could be further explored for GBM. To search for molecular predictors of TMZ resistance, the TCGA (The Cancer Genome Atlas) database was utilized to assess the impact of specific genes on TMZ response. Patients whose tumors expressed low levels of FGFR3 and AKT2 responded poorly to TMZ. Combination treatment of vinblastine (VBL) plus mebendazole (MBZ) with TMZ was more effec...
Source: Investigational New Drugs - August 29, 2017 Category: Drugs & Pharmacology Source Type: research

Effect of alisertib, an investigational aurora a kinase inhibitor on the QTc interval in patients with advanced malignancies
SummaryAims A primary objective of this study was to investigate the effect of single and multiple doses of alisertib, an investigational Aurora A kinase inhibitor, on the QTc interval in patients with advanced malignancies. The dose regimen used was the maximum tolerated dose which was also the recommended phase 3 dose (50  mg twice daily [BID] for 7 days in 21-day cycles).Methods Patients received a single dose of alisertib (50  mg) on Day 1, and multiple doses of alisertib (50 mg BID) on Days 4 through to the morning of Day 10 of the first cycle of treatment. Triplicate ECGs were collected at interva...
Source: Investigational New Drugs - August 18, 2017 Category: Drugs & Pharmacology Source Type: research

CUDC-907, a dual HDAC and PI3K inhibitor, reverses platinum drug resistance
SummaryPlatinum (Pt)-based anticancer drugs are the mainstay of treatment for solid cancers. However, resistance to Pt drugs develops rapidly, which can be caused by overexpression of multidrug resistance transporters and activation of DNA repair. CUDC-907 is a potent molecular targeted anticancer agent, rationally designed to simultaneously inhibit histone deacetylase (HDAC) and phosphatidylinositol 3-kinase (PI3K). We investigated the potentiation effect of CUDC-907 on Pt drugs in resistant cancer cells. ABCC2 stably-transfected HEK293 cells and two pairs of parental and Pt-resistant cancer cell lines were used to test f...
Source: Investigational New Drugs - August 17, 2017 Category: Drugs & Pharmacology Source Type: research

First-in-human study of the epichaperome inhibitor PU-H71: clinical results and metabolic profile
Conclusions PU-H71 was well tolerated at the doses administered during this study (10 to 470  mg/m2/day), with no dose limiting toxicities. (Source: Investigational New Drugs)
Source: Investigational New Drugs - August 12, 2017 Category: Drugs & Pharmacology Source Type: research

Germline BRCA mutations in Asian patients with pancreatic adenocarcinoma: a prospective study evaluating risk category for genetic testing
Conclusion Personal or family history of breast or ovarian cancers is a feasible, cost-effective risk categorization for screening germlineBRCA mutations in Asian PDAC patients as 10% of this population had the pathogenic mutation herein. Future validation from a large, prospective cohort is needed. (Source: Investigational New Drugs)
Source: Investigational New Drugs - August 7, 2017 Category: Drugs & Pharmacology Source Type: research

Synthesis, characterization, and evaluation of Cd[L-proline] 2 , a novel histone deacetylase inhibitor that induces epigenetic modification of histone deacetylase isoforms in A549 cells
SummaryHistone deacetylases (HDACs) play an important role in the epigenetic regulation of gene expression through their effects on the compact chromatin structure. In clinical studies, several classes of histone deacetylase inhibitors (HDACi) have demonstrated potent anticancer activities with metal complexes. Hence, we synthesized cadmium –proline complexes using both the D- and L-isomers of proline and evaluated their biological activities by observing the efficiency of their inhibition of HDAC activity, ability to reduce the expression of HDAC isoforms in A549 cells and effect on apoptosis. The synthesized compou...
Source: Investigational New Drugs - August 3, 2017 Category: Drugs & Pharmacology Source Type: research

Addition of an antiangiogenic therapy, bevacizumab, to gemcitabine plus oxaliplatin improves survival in advanced biliary tract cancers
Conclusion In mBTC, the addition of bevacizumab to GEMOX increased the progression-free survival and was associated with manageable toxicity. These data pave the way for further evaluation of antiangiogenic agents in mBTC. (Source: Investigational New Drugs)
Source: Investigational New Drugs - August 1, 2017 Category: Drugs & Pharmacology Source Type: research

A Phase I study to determine safety, pharmacokinetics, and pharmacodynamics of ANF-RHO ™, a novel PEGylated granulocyte colony-stimulating factor, in healthy volunteers
SummaryPatients receiving pegfilgrastim (Neulasta ®) for the treatment of neutropenia can experience bone pain following the injections required to achieve effective neutrophil levels. The safety, pharmacokinetic (PK), and pharmacodynamic (PD) profiles of ANF-RHO™, a novel pegylated granulocyte colony stimulating factor, were assessed in a rando mized, controlled, double-blind Phase 1 clinical study in healthy volunteers. Subjects received a single subcutaneous dose of ANF-RHO over a range of 6 doses (5–50 μg/kg), placebo (saline), or the recommended clinical dose of pegfilgrastim administered at th...
Source: Investigational New Drugs - July 28, 2017 Category: Drugs & Pharmacology Source Type: research

Anti-invasive effects of CXCR4 and FAK inhibitors in non-small cell lung carcinomas with mutually inactivated p53 and PTEN tumor suppressors
In this study, we first examined the invasive characteristics of NSCLC cells with suppressed p53 and PTEN activity using wound healing, gelatin degradation and invasion assays. Further, changes in the expression of CXCR4 and FAK were evaluated by RT-qPCR and Western Blot analysis. Finally, we tested the ability of CXCR4 and FAK inhibitors (WZ811 and PF-573228, respectively) to suppress the migratory and invasive potential of p53/PTEN deficient NSCLC cells, in vitro and in vivo using metastatic models of human NSCLC. Our results showed that cells with mutually inactive p53 and PTEN have significantly increased invasive pote...
Source: Investigational New Drugs - July 22, 2017 Category: Drugs & Pharmacology Source Type: research

Induction of accelerated senescence by the microtubule-stabilizing agent peloruside A
SummaryChemotherapeutic agents can induce accelerated senescence in tumor cells, an irreversible state of cell cycle arrest. Paclitaxel, a microtubule-stabilizing agent used to treat solid tumors of the breast, ovary, and lung and discodermolide, another stabilizing agent from a marine sponge, induce senescence in cultured cancer cells. The aim of this study was to determine if the microtubule-stabilizing agent peloruside A, a polyketide natural product from a marine sponge, can induce accelerated senescence in a breast cancer cell line MCF7. Doxorubicin, a DNA-damaging agent, paclitaxel, and discodermolide were used as po...
Source: Investigational New Drugs - July 22, 2017 Category: Drugs & Pharmacology Source Type: research

Copper (II) complexes of bidentate ligands exhibit potent anti-cancer activity regardless of platinum sensitivity status
SummaryInsensitivity to platinum, either through inherent or acquired resistance, is a major clinical problem in the treatment of many solid tumors. Here, we explored the therapeutic potential of diethyldithiocarbamate (DDC), pyrithione (Pyr), plumbagin (Plum), 8-hydroxyquinoline (8-HQ), clioquinol (CQ) copper complexes in a panel of cancer cell lines that differ in their sensitivity to platins (cisplatin/carboplatin) using a high-content imaging system. Our data suggest that the copper complexes were effective against both platinum sensitive (IC50 ~ 1 μM platinum) and insensitive (IC50 >  5&...
Source: Investigational New Drugs - July 21, 2017 Category: Drugs & Pharmacology Source Type: research

Feasibility of olanzapine, multi acting receptor targeted antipsychotic agent, for the prevention of emesis caused by continuous cisplatin- or ifosfamide-based chemotherapy
Conclusion A 2.5  mg/day dosage of olanzapine is sufficient to prevent from CINV in Japanese patients receiving continuous five-day chemotherapy. A dose of 10 mg/day, which is recommended by international CINV guidelines, is also tolerated. If CINV is not controlled by an initial dose of 2.5 mg/day of olanzapine, dosage escalation is encouraged. Future studies should compare olanzapine with aprepitant. (Source: Investigational New Drugs)
Source: Investigational New Drugs - July 21, 2017 Category: Drugs & Pharmacology Source Type: research

Phase I dose escalation study of NMS-1286937, an orally available Polo-Like Kinase 1 inhibitor, in patients with advanced or metastatic solid tumors
Conclusions This study successfully identified the MTD and DLTs for NMS-1286937 and characterized its safety profile. (Source: Investigational New Drugs)
Source: Investigational New Drugs - July 20, 2017 Category: Drugs & Pharmacology Source Type: research

Erratum to: A phase I dose-escalation study of Selumetinib in combination with Erlotinib or Temsirolimus in patients with advanced solid tumors
(Source: Investigational New Drugs)
Source: Investigational New Drugs - July 5, 2017 Category: Drugs & Pharmacology Source Type: research

Safety and effectiveness of eribulin in Japanese patients with locally advanced or metastatic breast cancer: a post-marketing observational study
Conclusions The safety and effectiveness profile of eribulin was consistent with prior studies. Eribulin had a favorable risk-benefit balance when used in real-world clinical settings. (Source: Investigational New Drugs)
Source: Investigational New Drugs - June 29, 2017 Category: Drugs & Pharmacology Source Type: research

Chemotherapy-induced cardiomyopathy caused by Pemetrexed
We describe the case of a patient with advanced lung cancer and cardiomyopathy due to pemetrexed. A 59-year-old woman visited our hospital, and we found abnormal findings on a chest radiograph. She was diagnosed as having stage IV lung adenocarcinoma. Chemotherapy with cisplatin and pemetrexed every 3  weeks was initiated. After four cycles of chemotherapy, maintenance chemotherapy with pemetrexed was administered every 3 weeks. During the seventeenth cycle of pemetrexed, she had shortness of breath in her daily life. A chest radiograph showed an enlarged cardiothoracic ratio (66%), and the tra nsthoracic echocar...
Source: Investigational New Drugs - June 28, 2017 Category: Drugs & Pharmacology Source Type: research

Urolithins impair cell proliferation, arrest the cell cycle and induce apoptosis in UMUC3 bladder cancer cells
SummaryEllagitannins have been gaining attention as potential anticancer molecules. However, the low bioavailability of ellagitannins and their extensive metabolization in the gastrointestinal tract into ellagic acid and urolithins suggest that the health benefits of consuming ellagitannins rely on the direct effects of their metabolites. Recently, chemopreventive and chemotherapeutic activities were ascribed to urolithins. Nonetheless, there is still a need to screen and evaluate the selectivity of these molecules and to elucidate their cellular mechanisms of action. Therefore, this work focused on the antiproliferative e...
Source: Investigational New Drugs - June 20, 2017 Category: Drugs & Pharmacology Source Type: research

Decorin gene upregulation mediated by an adeno-associated virus vector increases intratumoral uptake of nab-paclitaxel in neuroblastoma via inhibition of stabilin-1
This study sought to investigate the effects of increased decorin (DCN) expression on the intratumoral uptake of nab-paclitaxel as a potential novel approach to NB. Correlation between the clinical characteristics of neuroblastoma and the expression of DCN, secreted protein acidic and rich in cysteine (SPARC) and stabilin-1 was evaluated. The anticancer effect of recombinant adeno-associated virus-DCN (rAAV-DCN) was assessed in vivo and in vitro. And the effect of rAAV-DCN on the intratumoral uptake of paclitaxel was also studied in neuroblastoma-grafted nude mice. Overall, 12.5%, 17.7%, and 71.9% of the tumors stained pos...
Source: Investigational New Drugs - June 20, 2017 Category: Drugs & Pharmacology Source Type: research

Phase II study of Amrubicin monotherapy in elderly or poor-risk patients with extensive disease of small cell lung cancer
Conclusions The results of the present study suggest that amrubicin could be considered as a viable treatment option for chemotherapy-naive elderly or poor-risk patients with ES-SCLC (Clinical trial registration number: UMIN000011055www.clinicaltrials.gov). (Source: Investigational New Drugs)
Source: Investigational New Drugs - June 20, 2017 Category: Drugs & Pharmacology Source Type: research

A case of nivolumab-related cholangitis and literature review: how to look for the right tools for a correct diagnosis of this rare immune-related adverse event
SummaryAnti-programmed cell death-1 (PD-1) monoclonal antibodies, such as nivolumab, used for the treatment of several tumors, can trigger effector T-cells against tumor- and self-antigens, leading to the occurrence of different immune-related adverse events. Among them, liver injuries are rare and usually transient. To date, only four cases of immune-related cholangitis in non-small cell lung cancer (NSCLC) patients have been described during nivolumab treatment. Here, we describe laboratory tests, imaging and liver biopsy features that confirm this diagnosis as opposed to other forms of autoimmune liver disease; neverthe...
Source: Investigational New Drugs - June 20, 2017 Category: Drugs & Pharmacology Source Type: research

A phase Ib study of everolimus combined with metformin for patients with advanced cancer
Conclusion The combination of everolimus and metformin is poorly tolerated in patients with advanced cancer. The pharmacokinetic interaction between everolimus and metformin may have implications for diabetic cancer patients that are treated with these drugs. Our results advocate for future clinical trials with combinations of other mTOR inhibitors and biguanides. (Source: Investigational New Drugs)
Source: Investigational New Drugs - June 15, 2017 Category: Drugs & Pharmacology Source Type: research

Osimertinib reactivated immune-related colitis after treatment with anti-PD1 antibody for non-small cell lung cancer
We reported a case of relapsing immune-related colitis (initially caused by nivolumab) following osimertinib therapy for lung adenocarcinoma. A 45-year-old female who had never smoked was diagnosed with adenocarcinoma of the lung and underwent surgical resection. Four years after surgical resection, she was diagnosed with recurrent disease and was eventually treated with nivolumab as third-line therapy. One month after the completion of nivolumab therapy, the patient reported abdominal pain and frequent diarrhea. We diagnosed immune-related colitis and started oral prednisolone. However, the steroid therapy was ineffective...
Source: Investigational New Drugs - June 10, 2017 Category: Drugs & Pharmacology Source Type: research

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