A novel tetravalent bispecific antibody targeting programmed death 1 and tyrosine-protein kinase Met for treatment of gastric cancer
Conclusion The engagement of the PD-1/PD-L1 blockade to c-Met-overexpressing cancer cells is a promising strategy for the treatment of gastric cancer and potentially other malignancies. (Source: Investigational New Drugs)
Source: Investigational New Drugs - December 4, 2018 Category: Drugs & Pharmacology Source Type: research

Phase I dose-escalation trial of afatinib, an irreversible ErbB family blocker, in combination with gemcitabine or docetaxel in patients with relapsed or refractory solid tumors
Conclusions Afatinib/gemcitabine and afatinib/docetaxel demonstrated manageable safety profiles, with evidence of clinical efficacy at the MTDs. For afatinib/docetaxel, a dose level of afatinib 30  mg/docetaxel 75 mg/m2 produced higher response rates.Trial registration: NCT01251653 (ClinicalTrials.gov). (Source: Investigational New Drugs)
Source: Investigational New Drugs - November 12, 2018 Category: Drugs & Pharmacology Source Type: research

Phase 1b investigation of the MEK inhibitor binimetinib in patients with advanced or metastatic biliary tract cancer
Conclusion Binimetinib was well tolerated and showed promising evidence of activity in patients with BTC. Correlative studies suggested the potential for binimetinib to promote muscle gain in patients with BTC. (Source: Investigational New Drugs)
Source: Investigational New Drugs - November 12, 2018 Category: Drugs & Pharmacology Source Type: research

Acquired resistance to an epidermal growth factor receptor-tyrosine kinase inhibitor (EGFR-TKI) in an uncommon G719S EGFR mutation
Discussion The newly established G719S-GR cell line may be useful for investigating the mechanism underlying the development of AR in the G719X mutation; the loss ofPTEN may be one such mechanism. (Source: Investigational New Drugs)
Source: Investigational New Drugs - November 12, 2018 Category: Drugs & Pharmacology Source Type: research

First-in-human phase I study of the microtubule inhibitor plocabulin in patients with advanced solid tumors
Conclusion The main DLT of plocabulin was PSN, as anticipated for a tubulin-binding agent. Since encouraging antitumor activity was observed, efforts to improve toxicity and to find the RD were planned in other trials evaluating D1&D8 and D1-D3 plus D15-D17 schedules. (Source: Investigational New Drugs)
Source: Investigational New Drugs - November 9, 2018 Category: Drugs & Pharmacology Source Type: research

A phase II trial of gemcitabine, S-1 and LV combination (GSL) therapy in patients with advanced pancreatic cancer
Conclusions In this single center, phase II trial, gemcitabine, S-1 and LV combination therapy was tolerable and can potentially be a treatment option for advanced pancreatic cancer. (Source: Investigational New Drugs)
Source: Investigational New Drugs - November 9, 2018 Category: Drugs & Pharmacology Source Type: research

Phase I/II study evaluating the safety and clinical efficacy of temsirolimus and bevacizumab in patients with chemotherapy refractory metastatic castration-resistant prostate cancer
Conclusions The combination of temsirolimus and bevacizumab showed limited clinical activity in mCRPC patients previously treated with chemotherapy and was associated with significant adverse events (AEs). Transient decrease in CTC levels was independent from PSA response. NCT01083368. (Source: Investigational New Drugs)
Source: Investigational New Drugs - November 7, 2018 Category: Drugs & Pharmacology Source Type: research

Mass balance, routes of excretion, and pharmacokinetics of investigational oral [ 14 C]-alisertib (MLN8237), an Aurora A kinase inhibitor in patients with advanced solid tumors
Conclusions Findings suggest that alisertib is eliminated mainly via feces, consistent with hepatic metabolism and biliary excretion of drug-related material. Further investigation of alisertib pharmacokinetics in patients with moderate-severe hepatic impairment is warranted to inform dosing recommendations in these patient populations. (Source: Investigational New Drugs)
Source: Investigational New Drugs - November 6, 2018 Category: Drugs & Pharmacology Source Type: research

Pazopanib with low fat meal (PALM) in advanced renal cell carcinoma
SummaryBackground Pazopanib is approved for metastatic renal cell carcinoma (RCC). We assessed the safety and efficacy of pazopanib with a low fat meal (LFM):
Source: Investigational New Drugs - November 5, 2018 Category: Drugs & Pharmacology Source Type: research

A phase I study of the vascular endothelial growth factor inhibitor Vatalanib in combination with Pemetrexed disodium in patients with advanced solid tumors
Conclusion The combination of vatalanib with pemetrexed disodium was feasible, but not well tolerated. The modest efficacy results are consistent with other results obtained from combinations of chemotherapy and a large number of VEGF tyrosine kinase inhibitors. This combination should not be developed further unless predictive biomarkers can be identified. (Source: Investigational New Drugs)
Source: Investigational New Drugs - October 31, 2018 Category: Drugs & Pharmacology Source Type: research

Lurbinectedin (PM01183), a selective inhibitor of active transcription, effectively eliminates both cancer cells and cancer stem cells in preclinical models of uterine cervical cancer
Conclusions Lurbinectedin is highly effective on uterine cervical cancer because it eliminates CSCs, and lurbinectedin is a promising agent to overcome platinum resistance in cervical cancer. (Source: Investigational New Drugs)
Source: Investigational New Drugs - October 30, 2018 Category: Drugs & Pharmacology Source Type: research

The bispecific anti-CD3  × anti-CD155 antibody mediates T cell immunotherapy for human prostate cancer
SummaryExpression of CD155 differs between tumor and normal tissues, and high expression of this molecule can promote tumor metastasis. Here, we investigate whether CD155 can serve as a target for T cell-mediated immunotherapy of human prostate cancer. We first demonstrate that prostate cancer cells, including PC-3, PC-3  M, and LNCAP cells, express CD155 at high levels. Next, the specific cytotoxic activity of activated T cells (ATCs) armed with a novel anti-CD3 × anti-CD155 bispecific antibody (CD155Bi-Ab) against tumor cells was evaluated by flow cytometry, lactate dehydrogenase assay (LDH), and ELI...
Source: Investigational New Drugs - October 29, 2018 Category: Drugs & Pharmacology Source Type: research

A novel humanized anti-PD-1 monoclonal antibody potentiates therapy in oral squamous cell carcinoma
In this study, the role of our novel mAb was tested in the treatment of OSCC in vitro and in vivo. We found that our novel mAb can significantly augment T cell mediated cytokine secretion, target cellular lytic and apoptotic abilities, and inhibit tumor growth and inflammation in vivo. The PD-L1 blockade was accompanied by the inhibition of AKT and ERK1/2, thus suggesting that the PD-L1/PD-1 signaling pathway may play an important immunopreventive role in the tumorigenic properties of OSCC cells by modulating the AKT and ERK1/2 pathways. Additionally, PD-L1 staining was observed both in human OSCC tissues and normal oral m...
Source: Investigational New Drugs - October 27, 2018 Category: Drugs & Pharmacology Source Type: research

Chemotherapy in pregnancy: exploratory study of the effects of paclitaxel on the expression of placental drug transporters
Discussion Paclitaxel modulates the expression of placental drug transporters involved in the disposition of various anticancer agents. Further studies will be needed to assess the impact of repeated or prolonged exposure to paclitaxel on the expression and function of placental drug transporters. (Source: Investigational New Drugs)
Source: Investigational New Drugs - October 26, 2018 Category: Drugs & Pharmacology Source Type: research

Advanced development of ErbB family-targeted therapies in osteosarcoma treatment
SummaryOsteosarcoma (OS) is the most common primary aggressive and malignant bone tumor. Newly diagnostic OS patients benefit from the standard therapy including surgical resection plus radiotherapy and neoadjuvant chemotherapy (MAP chemotherapy: high-dose methotrexate, doxorubicin and cisplatin). However, tumor recurrence and metastasis give rise to a sharp decline of the 5-year overall survival rate in OS patients. Little improvement has been made for decades, urging the development of more effective therapeutic approaches. ErbB receptor family including EGFR, HER2, HER3 and HER4, being important to the activation of PI3...
Source: Investigational New Drugs - October 24, 2018 Category: Drugs & Pharmacology Source Type: research

Corticosteroid switch in heavily pre-treated castration-resistant prostate cancer patients progressed on abiraterone acetate plus prednisone
SummaryThe aim of this retrospective study is to evaluate the activity and safety of a steroidal switch from prednisone to dexamethasone in patients with advanced, heavily pre-treated, castration-resistant prostate cancer (CRPC) who progressed on abiraterone acetate. Treatment consisted of oral daily abiraterone plus dexamethasone (0.5 mg once daily) administered until disease progression or unacceptable toxicity. Thirty-six patients were evaluated: all men underwent a prior treatment with enzalutamide. A PSA decrease ≥50% was observed in 11% of patients; median progression-free survival was 10.8 weeks (95% CI: 9.2&ndas...
Source: Investigational New Drugs - October 22, 2018 Category: Drugs & Pharmacology Source Type: research

Antitumor evaluation of novel phenothiazine derivatives that inhibit migration and tubulin polymerization against gastric cancer MGC-803 cells
SummaryTwo novel series of 1,2,3-triazole −phenothiazine hybrids and dithiocarbamate−phenothiazine hybrids were designed and synthesized by molecular hybridization strategy. Their antiproliferative activity against three gastric cancer cell lines (MKN28, MGC-803 and MKN45) were evaluated. Among them, hybrid13h displayed the most potent inhibitory activity against gastric cancer MGC-803 cells with an IC50 value of 1.2  μM. Hybrid13h could inhibit migration by regulating the expression level of N-cadherin, E-cadherin, Vimentin, and actived-MMP2. Furthermore, it could regulate wnt/ β-catenin signaling...
Source: Investigational New Drugs - October 22, 2018 Category: Drugs & Pharmacology Source Type: research

Correction to: Phase I study combining the aurora kinase a inhibitor alisertib with mFOLFOX in gastrointestinal cancer
The authors would like to note that the investigator affiliations have been corrected to reflect the actual affiliations of each author. The authors would also like to note an amendment to the first name of the second author. Nilo Azad was changed to reflect the full name of the author, which is Nilofer S. Azad as shown above. The original article has been corrected. (Source: Investigational New Drugs)
Source: Investigational New Drugs - October 18, 2018 Category: Drugs & Pharmacology Source Type: research

Relationship between expression of XRCC1 and tumor proliferation, migration, invasion, and angiogenesis in glioma
In this study, we investigated whether XRCC1 plays a role in glioma pathogenesis. Using the tissue microarray technology, we found that XRCC1 expression is significantly decreased in glioma compared with tumor adjacent normal brain tissue (P 
Source: Investigational New Drugs - October 17, 2018 Category: Drugs & Pharmacology Source Type: research

Prognostic factors in patients with metastatic or recurrent pancreatic cancer treated with first-line nab -paclitaxel plus gemcitabine: implication of inflammation-based scores
Conclusion Among the inflammation based prognostic scores, mGPS was a reliable prognostic indicator that could stratify survival outcomes in patients with recurrent or mPC who received AG as first-line chemotherapy. (Source: Investigational New Drugs)
Source: Investigational New Drugs - October 16, 2018 Category: Drugs & Pharmacology Source Type: research

Second-line chemotherapy in patients with advanced or recurrent biliary tract cancer: a single center, retrospective analysis of 294 cases
SummaryPurpose The survival benefit of first-line chemotherapy (CT1) for biliary tract cancer (BTC) is now established but the role of second-line chemotherapy (CT2) has not been fully elucidated yet.Methods Consecutive advanced BTC patients receiving CT1 between 2000 and 2016 were retrospectively studied. We investigated the safety and efficacy of CT2, prognostic factors for residual survival after CT1, and explored subgroups who would benefit from CT2.Results Among 294 patients receiving CT1 for advanced BTC, CT2 was given in 139 patients (47%). CT2 provided a response rate of 4%, a disease control rate of 52%, a median ...
Source: Investigational New Drugs - October 15, 2018 Category: Drugs & Pharmacology Source Type: research

Canadian Cancer Trials Group (CCTG) IND215: A phase Ib study of Selumetinib in patients with untreated advanced or metastatic NSCLC who are receiving standard chemotherapy regimens
Conclusion Selumetinib at a dose of 75  mg b.i.d continuously can be safely combined with paclitaxel and carboplatin or pemetrexed and cisplatin in patients with advanced or metastatic NSCLC. This trial provided the dose for the regimens used in a randomized phase II trial in NSCLC (CCTG IND.219). (Source: Investigational New Drugs)
Source: Investigational New Drugs - October 13, 2018 Category: Drugs & Pharmacology Source Type: research

Survival outcome and prognostic model of patients with colorectal cancer on phase 1 trials
SummaryBackground Patients with metastatic colorectal cancer (mCRC) who progress on standard therapies may be eligible for phase I trials. To better delineate the risk-benefit ratio, we assessed toxicities, clinical outcomes and prognostic factors.Methods Records of mCRC patients on phase I trials at our institution over 18  years were reviewed. Univariable (UVA) and multivariable analyses (MVA) were undertaken and a prognostic model developed.Results There were 187 enrollments on 37 phase I trials. Median age was: 59 (29 –83) years and number of prior therapies: 3 (0–8). The clinical benefit rate (CBR): r...
Source: Investigational New Drugs - October 12, 2018 Category: Drugs & Pharmacology Source Type: research

A phase II study of imatinib mesylate and letrozole in patients with hormone receptor-positive metastatic breast cancer expressing c-kit or PDGFR- β
Conclusion The combination of imatinib mesylate and letrozole is well tolerated but appears to have limited efficacy in the treatment of hormone receptor-positive metastatic breast cancer. (Source: Investigational New Drugs)
Source: Investigational New Drugs - October 11, 2018 Category: Drugs & Pharmacology Source Type: research

Phase I/II study of everolimus combined with mFOLFOX-6 and bevacizumab for first –line treatment of metastatic colorectal cancer
Conclusions Everolimus plus mFOLFOX-6  + bevacizumab is tolerable and demonstrated preliminary efficacy for first-line mCRC. Further studies are warranted in PTEN deficiency. (Source: Investigational New Drugs)
Source: Investigational New Drugs - October 10, 2018 Category: Drugs & Pharmacology Source Type: research

Phase 1 trial of enzalutamide in combination with gemcitabine and nab-paclitaxel for the treatment of advanced pancreatic cancer
Conclusions Enzalutamide 160  mg daily in combination with gemcitabine and nab-paclitaxel can be safely administered with no unexpected toxicities. We also noticed preliminary signals of efficacy with this combination. (Source: Investigational New Drugs)
Source: Investigational New Drugs - October 9, 2018 Category: Drugs & Pharmacology Source Type: research

Safety and efficacy of immune checkpoint inhibitors for end-stage renal disease patients undergoing dialysis: a retrospective case series and literature review
We report our experience with ICI administration to three ESRD patients undergoing hemodialysis. One of the patients had a partial response for several months; however, the other patients had a stable disease while undergoing dialysis. The toxicity was tolerable; however, one patient developed grade 2 pneumonitis. A literature review of other rarely reported cases of hemodialysis revealed that 10 out of 13 patients had a partial response or complete response; in addition, grade 3 or grade 4 immune-related adverse events occurred in 3 patients. ESRD combined with dialysis may not be a contraindication for the use of ICIs. I...
Source: Investigational New Drugs - October 8, 2018 Category: Drugs & Pharmacology Source Type: research

A phase 1, dose-escalation study of PF-06664178, an anti-Trop-2/Aur0101 antibody-drug conjugate in patients with advanced or metastatic solid tumors
Conclusion PF-06664178 showed toxicity at high dose levels with modest antitumor activity. Neutropenia, skin rash and mucosal inflammation were dose limiting toxicities. Findings from this study may potentially aid in future antibody drug conjugate design and trials. (Source: Investigational New Drugs)
Source: Investigational New Drugs - October 1, 2018 Category: Drugs & Pharmacology Source Type: research

First-in-human phase I dose escalation study of MK-8033 in patients with advanced solid tumors
Conclusion MK-8033 was well tolerated with no significant toxicity issues, albeit with limited clinical activity. Unfortunately, the company decided to discontinue further clinical development of MK-8033. (Source: Investigational New Drugs)
Source: Investigational New Drugs - October 1, 2018 Category: Drugs & Pharmacology Source Type: research

Phase Ib study evaluating safety and clinical activity of the anti-HER3 antibody lumretuzumab combined with the anti-HER2 antibody pertuzumab and paclitaxel in HER3-positive, HER2-low metastatic breast cancer
Conclusions Combination treatment with lumretuzumab, pertuzumab and paclitaxel was associated with a high incidence of diarrhea. Despite the efforts to alter dosing, the therapeutic window remained too narrow to warrant further clinical development. Trial registration: onClinicalTrials.gov with the identifier NCT01918254 first registered on 3rd July 2013. (Source: Investigational New Drugs)
Source: Investigational New Drugs - October 1, 2018 Category: Drugs & Pharmacology Source Type: research

Proteasome inhibition and mechanism of resistance to a synthetic, library-based hexapeptide
Conclusion 4A6 is a novel specific inhibitor of the β5 subunit-associated chymotrypsin-like proteasome activity. Further exploration of 4A6 as a lead compound for development as a novel proteasome-targeted drug is warranted. (Source: Investigational New Drugs)
Source: Investigational New Drugs - October 1, 2018 Category: Drugs & Pharmacology Source Type: research

Crizotinib-induced simultaneous multiple cardiac toxicities
SummaryCrizotinib is a receptor tyrosine kinase inhibitor that has several targets, including c-ros oncogene 1 and the MET proto-oncogene. Considering its known cardiac toxicity, bradycardia is often investigated following treatment with crizotinib. Our patients had bradycardia, QT prolongation, ventricular rhythm, ventricular fibrillation, and pericarditis simultaneously. The cardiotoxicity of crizotinib can sometimes be simultaneous; thus, intensive observation is needed. (Source: Investigational New Drugs)
Source: Investigational New Drugs - October 1, 2018 Category: Drugs & Pharmacology Source Type: research

Survival and tolerance to sorafenib in Child-Pugh B patients with hepatocellular carcinoma: a prospective study
SummarySorafenib has been widely used to treat unresectable hepatocellular carcinoma (HCC) but most studies have been done in Child-Pugh A (CP-A) patients with well-preserved liver function. We evaluated the overall survival (OS) and tolerance to sorafenib in a large cohort of Child-Pugh B (CP-B) HCC patients as compared to CP-A HCC patients. We prospectively studied 130 patients with advanced HCC who started sorafenib between January 2011 and December 2015. Patients were classified as CP-A (n = 65) or CP-B (n = 65). The average OS for all 130 patients was 10 months. CP-A patients had a med...
Source: Investigational New Drugs - October 1, 2018 Category: Drugs & Pharmacology Source Type: research

The concomitant use of lapatinib and paracetamol - the risk of interaction
SummaryLapatinib is a tyrosine kinase inhibitor used for the treatment of breast cancer. Paracetamol is an analgesic commonly applied to patients with mild or moderate pain and fever. Cancer patients are polymedicated, which involves high risk of drug interactions during therapy. The aim of the study was to assess the interaction between lapatinib and paracetamol in rats. The rats were divided into three groups of eight animals in each. One group received lapatinib + paracetamol (IL  + PA), another group received lapatinib (IIL), whereas the last group received paracetamol (IIIPA). A single dose of lapatinib ...
Source: Investigational New Drugs - October 1, 2018 Category: Drugs & Pharmacology Source Type: research

Comparison of published and unpublished phase I clinical cancer trials: an analysis of the CliniclTrials.gov database
SummaryIntroduction The role of phase I cancer trials is constantly evolving and they are increasingly being used in ‘go/no’ decisions in drug development. As a result, there is a growing need to ensure trials are published when completed. There are limited data on the publication rate and the factors associated with publication in phase I trials.Methods The ClinicalTrials.gov database was searched for completed adult phase I cancer trials with reported results. PubMed was searched for matching publications published prior to April 1, 2017. Logistic regression was used to identify factors associated with unpubl...
Source: Investigational New Drugs - October 1, 2018 Category: Drugs & Pharmacology Source Type: research

Phase II study of DFP-10917, a deoxycytidine analog, given by 14-day continuous intravenous infusion for chemotherapy-refractory advanced colorectal cancer
SummaryBackground DFP-10917 is a cytotoxic deoxycytidine analogue that causes DNA fragmentation, G2/M –phase arrest, and apoptosis. This agent has been shown to have antitumor activity against colorectal cancer (CRC) in preclinical studies and to be tolerable in patients. The purpose of our phase II trial was to evaluate the safety, efficacy and pharmacogenomics of DFP-10917 as well as DNA damage studies in patients with advanced CRC refractory to cytotoxic chemotherapy.Methods In this single-arm, Simon two-stage, phase II trial, patients with chemotherapy-refractory advanced CRC received 2.0  mg/m2/day DFP-1091...
Source: Investigational New Drugs - October 1, 2018 Category: Drugs & Pharmacology Source Type: research

SMER28 is a mTOR-independent small molecule enhancer of autophagy that protects mouse bone marrow and liver against radiotherapy
In this study, we investigated the effect of the mTOR-independent small molecule enhancer of autophagy (SMER28) on mouse liver autophagy and post-irradiation recovery of mouse bone marrow and liver. SMER28 enhanced the autophagy flux and improved the survival of normal hepatocytes. This effect was specific for normal cells because SMER28 had no protective effect on hepatoma or other cancer cell line survival in vitro. In vivo subcutaneous administration of SMER28 protected mouse liver and bone marrow against radiation damage and facilitated survival of mice after lethal whole body or abdominal irradiation. These findings o...
Source: Investigational New Drugs - October 1, 2018 Category: Drugs & Pharmacology Source Type: research

Successful oral desensitization with osimertinib following osimertinib-induced fever and hepatotoxicity: a case report
In conclusion, oral desensitization may be a useful method in treating hepatotoxicity and drug fever caused by osimertinib. (Source: Investigational New Drugs)
Source: Investigational New Drugs - October 1, 2018 Category: Drugs & Pharmacology Source Type: research

A phase I trial to determine safety and pharmacokinetics of ASLAN002, an oral MET superfamily kinase inhibitor, in patients with advanced or metastatic solid cancers
Conclusions ASLAN-002 is well tolerated at 300  mg BID and is the recommended dose for future phase II studies (RP2D). Clinical Trials Registry Number:NCT01721148. (Source: Investigational New Drugs)
Source: Investigational New Drugs - October 1, 2018 Category: Drugs & Pharmacology Source Type: research

Oral Metronomic Vinorelbine (OMV) in elderly or pretreated patients with advanced non small cell lung cancer: outcome and pharmacokinetics in the real world
Conclusions OMV produced non-negligible survival in patients and also showed stable long-term blood concentrations. The schedule of 20 –30 mg every other day without interruption gave good tolerability and clinical benefit. (Source: Investigational New Drugs)
Source: Investigational New Drugs - October 1, 2018 Category: Drugs & Pharmacology Source Type: research

Nab-paclitaxel maintenance therapy following carboplatin + nab-paclitaxel combination therapy in chemotherapy na ïve patients with advanced non-small cell lung cancer: multicenter, open-label, single-arm phase II trial
Conclusions Although statistically significance was not demonstrated presumably due to a limited transition rate from induction to maintenance phase, nab-PTX was suggested to be a useful treatment option following the induction therapy with nab-PTX in patients with advanced NSCLC. (Source: Investigational New Drugs)
Source: Investigational New Drugs - October 1, 2018 Category: Drugs & Pharmacology Source Type: research

GLP overexpression is associated with poor prognosis in Chronic Lymphocytic Leukemia and its inhibition induces leukemic cell death
Conclusion Taken together, these results indicate that GLP is associated with a worse prognosis in CLL, and that the inhibition of GLP/G9a influences CLL cell viability. Altogether, the present data demonstrate that these methyltransferases can be potential markers for disease progression, as well as a promising epigenetic target for CLL treatment and the prevention of disease evolution. (Source: Investigational New Drugs)
Source: Investigational New Drugs - October 1, 2018 Category: Drugs & Pharmacology Source Type: research

A phase 1 study of PARP-inhibitor ABT-767 in advanced solid tumors with BRCA1/2 mutations and high-grade serous ovarian, fallopian tube, or primary peritoneal cancer
Conclusions ABT-767 had an acceptable safety profile up to the established RP2D of 400  mg BID and dose-proportional PK. Patients withBRCA1 or BRCA2 mutation, HRD positivity, and platinum sensitivity were more sensitive to ABT-767. (Source: Investigational New Drugs)
Source: Investigational New Drugs - October 1, 2018 Category: Drugs & Pharmacology Source Type: research

Phase II randomized, double-blind, placebo-controlled study of tivantinib in men with asymptomatic or minimally symptomatic metastatic castration-resistant prostate cancer (mCRPC)
Conclusions Tivantinib has mild toxicity and improved PFS in men with asymptomatic or minimally symptomatic mCRPC. (Source: Investigational New Drugs)
Source: Investigational New Drugs - October 1, 2018 Category: Drugs & Pharmacology Source Type: research

Preclinical investigation of a potent geranylgeranyl diphosphate synthase inhibitor
SummaryGeranylgeranyl diphosphate synthase (GGDPS) is the enzyme in the isoprenoid biosynthesis pathway that catalyzes the synthesis of the 20-carbon isoprenoid GGPP, which serves as the isoprenoid donor for protein geranylgeranylation reactions. Rab proteins mediate vesicle trafficking within the cell and their activity is dependent on geranylgeranylation. Our prior work has demonstrated that agents that disrupt Rab geranylgeranylation disrupt monoclonal protein trafficking in myeloma cells, resulting in induction of the unfolded protein response pathway and apoptosis. VSW1198 is a potent GGDPS inhibitor with measurable c...
Source: Investigational New Drugs - October 1, 2018 Category: Drugs & Pharmacology Source Type: research

Post-progression survival following second-line chemotherapy in patients with advanced pancreatic cancer previously treated with gemcitabine: a meta-analysis
This study aimed to improve the understanding of the impact of PPS on OS in this setting.Methods Databases were searched to identify randomized controlled trials (RCTs) in the salvage setting. We evaluated relationships between OS and PFS, PPS, and other variables.Results Totally, 17 RCTs with 3253 patients were identified. Median OS was strongly and moderately associated with median PPS and PFS, respectively (r = 0.913;p 
Source: Investigational New Drugs - October 1, 2018 Category: Drugs & Pharmacology Source Type: research

The in vitro assessment of dipyridophenazine complexes in H-ras oncogene transformed rat embryo fibroblast 5RP7 cell line
Conclusions These findings show that dpzz and its complexes can be studied as novel alternative chemotherapeutics in cancer treatment. (Source: Investigational New Drugs)
Source: Investigational New Drugs - October 1, 2018 Category: Drugs & Pharmacology Source Type: research

SMER28 is a mTOR-independent small molecule enhancer of autophagy that protects mouse bone marrow and liver against radiotherapy
In this study, we investigated the effect of the mTOR-independent small molecule enhancer of autophagy (SMER28) on mouse liver autophagy and post-irradiation recovery of mouse bone marrow and liver. SMER28 enhanced the autophagy flux and improved the survival of normal hepatocytes. This effect was specific for normal cells because SMER28 had no protective effect on hepatoma or other cancer cell line survival in vitro. In vivo subcutaneous administration of SMER28 protected mouse liver and bone marrow against radiation damage and facilitated survival of mice after lethal whole body or abdominal irradiation. These findings o...
Source: Investigational New Drugs - September 12, 2018 Category: Drugs & Pharmacology Source Type: research

A phase I trial to determine safety and pharmacokinetics of ASLAN002, an oral MET superfamily kinase inhibitor, in patients with advanced or metastatic solid cancers
Conclusions ASLAN-002 is well tolerated at 300  mg BID and is the recommended dose for future phase II studies (RP2D). Clinical Trials Registry Number:NCT01721148. (Source: Investigational New Drugs)
Source: Investigational New Drugs - September 12, 2018 Category: Drugs & Pharmacology Source Type: research

Nab-paclitaxel maintenance therapy following carboplatin + nab-paclitaxel combination therapy in chemotherapy na ïve patients with advanced non-small cell lung cancer: multicenter, open-label, single-arm phase II trial
Conclusions Although statistically significance was not demonstrated presumably due to a limited transition rate from induction to maintenance phase, nab-PTX was suggested to be a useful treatment option following the induction therapy with nab-PTX in patients with advanced NSCLC. (Source: Investigational New Drugs)
Source: Investigational New Drugs - September 12, 2018 Category: Drugs & Pharmacology Source Type: research