Investigation of the impact of hepatic impairment on the pharmacokinetics of dacomitinib
Summary Dacomitinib (PF-00299804) is a small-molecule inhibitor of the tyrosine kinases human epidermal growth factor receptor-1 (HER1; epidermal growth factor receptor, EGFR), HER2, and HER4 currently being developed for the treatment of lung cancer with sensitizing mutations in EGFR or refractory to EGFR-directed treatment. Dacomitinib is largely metabolized by the liver through oxidative and conjugative metabolism; therefore, determination of the impact of varying degrees of hepatic impairment on the pharmacokinetics (PK) of dacomitinib was warranted to ensure patient safety. In this phase I, open-label, parall...
Source: Investigational New Drugs - June 6, 2015 Category: Drugs & Pharmacology Source Type: research

Response to: Does the Nerium oleander extract PBI-05204 have potential for pancreatic cancer?
(Source: Investigational New Drugs)
Source: Investigational New Drugs - May 19, 2015 Category: Drugs & Pharmacology Source Type: research

Randomized phase III trial of regorafenib in metastatic colorectal cancer: analysis of the CORRECT Japanese and non-Japanese subpopulations
Conclusion Regorafenib appears to have comparable efficacy in Japanese and non-Japanese subpopulations, with a manageable adverse-event profile, suggesting that this agent could potentially become a standard of care in patients with mCRC. (Source: Investigational New Drugs)
Source: Investigational New Drugs - May 19, 2015 Category: Drugs & Pharmacology Source Type: research

Does the Nerium oleander extract PBI-05204 have potential for pancreatic cancer therapy?
(Source: Investigational New Drugs)
Source: Investigational New Drugs - May 19, 2015 Category: Drugs & Pharmacology Source Type: research

Co-administration of antigen with chemokine MCP-3 or MDC/CCL22 enhances DNA vaccine potency
Abstract We evaluated the utility of chemokine MCP-3 and MDC/CCL22 as molecular adjuvants of DNA vaccines for botulinum neurotoxin serotype A (BoNT/A) in a Balb/c mouse model. Notably, the immunogenicity of the DNA vaccine against BoNT/A was not enhanced using a fusion of the AHc-C antigen with the MCP-3 or MDC/CCL22. Nevertheless, the potency of the DNA vaccine was significantly modulated and enhanced by co-administration of the AHc-C antigen with MCP-3 or MDC/CCL22. This strategy elicited high levels of humoral immune responses and protection against BoNT/A. The enhanced potency was further boosted by co-adminis...
Source: Investigational New Drugs - May 8, 2015 Category: Drugs & Pharmacology Source Type: research

First-in-human, phase I study of elisidepsin (PM02734) administered as a 30-min or as a 3-hour intravenous infusion every three weeks in patients with advanced solid tumors
In conclusion, elisidepsin doses of 1.1 mg/m2 (equivalent to a FD of 2.0 mg) and 11.0 mg FD are the dose levels achieved for further phase II trials testing the 30-min q3wk and 3-h q3wk schedules, respectively. (Source: Investigational New Drugs)
Source: Investigational New Drugs - May 8, 2015 Category: Drugs & Pharmacology Source Type: research

Phase II trial of gemcitabine and tanespimycin (17AAG) in metastatic pancreatic cancer: a Mayo Clinic Phase II Consortium study
Conclusions The lack of clinical activity suggests that targeting Chk1 by inhibiting HSP90 is not important in pancreatic cancer sensitivity to gemcitabine alone. Further studies of HSP90 targeted agents with gemcitabine alone are not warranted. (Source: Investigational New Drugs)
Source: Investigational New Drugs - May 8, 2015 Category: Drugs & Pharmacology Source Type: research

The effect of paclitaxel and nab-paclitaxel in combination with anti-angiogenic therapy in breast cancer cell lines
Summary Taxanes represent a treatment of choice for metastatic breast cancer. Their combination with bevacizumab improved response rate and progression-free survival. We studied in vitro the effect on cell survival of the combination of either paclitaxel or nab-paclitaxel with bevacizumab and we investigated the biological factors involved in the response to treatments. We used two breast cancer cell lines, MCF7 (ER+/HER2-) and MDA-MB-231 (ER-/HER2-), co-cultured with or without HUVEC cells. We analysed cell survival by MTT test, VEGF secretion by ELISA and VEGFR, SPARC, MDR1 expression by western blot. Doses of b...
Source: Investigational New Drugs - May 7, 2015 Category: Drugs & Pharmacology Source Type: research

A phase 1 study with dose expansion of the CDK inhibitor dinaciclib (SCH 727965) in combination with epirubicin in patients with metastatic triple negative breast cancer
Conclusion, The combination of dinaciclib and epirubicin is associated with substantial toxicities and does not appear to be an effective treatment option for TNBC. (Source: Investigational New Drugs)
Source: Investigational New Drugs - May 7, 2015 Category: Drugs & Pharmacology Source Type: research

A phase II study of bevacizumab with modified OPTIMOX1 as first-line therapy for metastatic colorectal cancer: the TCOG-GI 0802 study
Conclusions Bevacizumab plus mFOLFOX6 was well tolerated, and patients could continue chemotherapy for longer than with conventional FOLFOX regimens. This regimen might be an effective treatment option for patients with metastatic colorectal cancer. (Source: Investigational New Drugs)
Source: Investigational New Drugs - May 5, 2015 Category: Drugs & Pharmacology Source Type: research

Pharmacokinetic assessment of dacomitinib (pan-HER tyrosine kinase inhibitor) in patients with locally advanced head and neck squamous cell carcinoma (LA SCCHN) following administration through a gastrostomy feeding tube (GT)
Conclusion Compared with oral dosing of intact immediate release (IR) tablets, GT administration resulted in 34 % reduction in Cmax and 33–44 % decrease in AUC (all p
Source: Investigational New Drugs - May 5, 2015 Category: Drugs & Pharmacology Source Type: research

Phase 1 dose escalation trial of ilorasertib, a dual Aurora/VEGF receptor kinase inhibitor, in patients with hematologic malignancies
Conclusions Ilorasertib exhibited acceptable safety and pharmacokinetics at or below the recommended phase 2 dose, displayed evidence of dual Aurora kinase and VEGF receptor kinase inhibition, and activity in AML. (Source: Investigational New Drugs)
Source: Investigational New Drugs - May 2, 2015 Category: Drugs & Pharmacology Source Type: research

Phase I study of ipilimumab in phased combination with paclitaxel and carboplatin in Japanese patients with non-small-cell lung cancer
Conclusions The recommended dose of ipilimumab in phased combination with PTX and CBDCA in Japanese patients with NSCLC was identified as 10 mg/kg. The safety profile was consistent with the previously defined AE profile. (Source: Investigational New Drugs)
Source: Investigational New Drugs - May 1, 2015 Category: Drugs & Pharmacology Source Type: research

AZD3514, an oral selective androgen receptor down-regulator in patients with castration-resistant prostate cancer – results of two parallel first-in-human phase I studies
Conclusion AZD3514 has moderate anti-tumour activity in pts with advanced CRPC but with significant levels of nausea and vomiting. However, anti-tumour activity as judged by significant PSA declines, objective responses and durable disease stabilisations, provides the rationale for future development of SARD compounds. (Source: Investigational New Drugs)
Source: Investigational New Drugs - April 29, 2015 Category: Drugs & Pharmacology Source Type: research

A first-in-human phase I trial of LY2780301, a dual p70 S6 kinase and Akt Inhibitor, in patients with advanced or metastatic cancer
This study suggests a dose of LY2780301 500 mg QD for future studies. (Source: Investigational New Drugs)
Source: Investigational New Drugs - April 24, 2015 Category: Drugs & Pharmacology Source Type: research

Phase I combination of pazopanib and everolimus in PIK3CA mutation positive/PTEN loss patients with advanced solid tumors refractory to standard therapy
Conclusion Combination treatment with pazopanib and everolimus was well tolerated and demonstrated activity in solid tumors. Further exploration of this combination and molecular correlation with treatment outcomes is warranted. (Source: Investigational New Drugs)
Source: Investigational New Drugs - April 24, 2015 Category: Drugs & Pharmacology Source Type: research

Pharmacokinetic drug-drug interaction study of the angiopoietin-1/angiopoietin-2-inhibiting peptibody trebananib (AMG 386) and paclitaxel in patients with advanced solid tumors
Conclusions This study showed no evidence of clinically meaningful PK interaction between paclitaxel and trebananib. (Source: Investigational New Drugs)
Source: Investigational New Drugs - April 21, 2015 Category: Drugs & Pharmacology Source Type: research

Screening and biological evaluation of myricetin as a multiple target inhibitor insulin, epidermal growth factor, and androgen receptor; in silico and in vitro
This study is a concerted effort to explore the potent and specific multi-targeted inhibitor against RTKs and AR\ER employing molecular docking approach. IR, IGF1R, EGFR, VEGFR1, VEGFR2, and AR\ER were chosen as a protein and natural compounds as a ligand. Molecular docking procedure followed by using Maestro 9.6 (Schrödinger Inc). All natural compounds were docked with the X-ray crystal structures of selected proteins by employing grid-based ligand docking with energetics Maestro 9.6. IBS natural compounds docked with each selected protein molecules by using GLIDE high throughput virtual screening. On the basis of Gs...
Source: Investigational New Drugs - April 19, 2015 Category: Drugs & Pharmacology Source Type: research

A phase 1 study of ABT-806 in subjects with advanced solid tumors
Conclusions ABT-806 has unique pharmacokinetic and safety profiles. Toxicities were infrequent and typically low grade at the RP2D. Linear ABT-806 pharmacokinetics suggest lack of significant binding to wild-type EGFR in normal tissues. (Source: Investigational New Drugs)
Source: Investigational New Drugs - April 17, 2015 Category: Drugs & Pharmacology Source Type: research

Sorafenib treatment in Child–Pugh A and B patients with advanced hepatocellular carcinoma: safety, efficacy and prognostic factors
Conclusion It is possible that not only Child–Pugh score 5 and 6 but also 7 patients are eligible for future clinical trials with sorafenib or similar drugs. Various survival predictors identified in this study might be considered as stratification factor. Although both MVI and EHM is a phenotype of advanced HCC, MVI should be discriminated from EHM because of the prognostic impact on survival in sorafenib-treated advanced HCC patients. (Source: Investigational New Drugs)
Source: Investigational New Drugs - April 12, 2015 Category: Drugs & Pharmacology Source Type: research

The efficacy of amrubicin on central nervous system metastases originating from small-cell lung cancer: a case series of eight patients
Conclusions The results of this study suggest that amrubicin is active in patients with CNS metastases originating from SCLC. (Source: Investigational New Drugs)
Source: Investigational New Drugs - April 7, 2015 Category: Drugs & Pharmacology Source Type: research

The FLT3 and PDGFR inhibitor crenolanib is a substrate of the multidrug resistance protein ABCB1 but does not inhibit transport function at pharmacologically relevant concentrations
Conclusions Thus ABCB1 expression confers resistance to crenolanib and likely limits crenolanib penetration of the central nervous system, but crenolanib at therapeutic concentrations should not alter cellular exposure to ABC protein substrate chemotherapy drugs. (Source: Investigational New Drugs)
Source: Investigational New Drugs - April 1, 2015 Category: Drugs & Pharmacology Source Type: research

Phase 1 study of the oral histone deacetylase inhibitor abexinostat in patients with Hodgkin lymphoma, non-Hodgkin lymphoma, or chronic lymphocytic leukaemia
Conclusion Abexinostat has manageable toxicity and induced some durable complete and partial responses in B-cell lymphoma or chronic lymphocytic leukaemia. Our results suggest most favourable responses in patients with follicular lymphoma, though further research would be needed to confirm this finding. (Source: Investigational New Drugs)
Source: Investigational New Drugs - April 1, 2015 Category: Drugs & Pharmacology Source Type: research

Pharmacokinetic study of aldoxorubicin in patients with solid tumors
Conclusions Our findings support dosing and administration schemas used in an ongoing phase 3 clinical study of aldoxorubicin in soft tissue sarcoma, and phase 2 clinical studies in small cell lung cancer, glioblastoma, and Kaposi’s sarcoma. (Source: Investigational New Drugs)
Source: Investigational New Drugs - April 1, 2015 Category: Drugs & Pharmacology Source Type: research

Infected complex renal cysts during crizotinib therapy in a patient with non–small cell lung cancer positive for ALK rearrangement
Summary Crizotinib is the first clinically available tyrosine kinase inhibitor that targets anaplastic lymphoma kinase (ALK) and is associated with the development of complex renal cysts. We now describe a 39-year-old woman who developed infected complex renal cysts during crizotinib treatment. After 10 months of such treatment, she presented with a high fever and low back pain. Computed tomography findings were consistent with complex renal cysts and perilesional inflammation. Interventions including cyst drainage and antibiotic administration contributed to diagnosis and management of the infected cysts. (...
Source: Investigational New Drugs - April 1, 2015 Category: Drugs & Pharmacology Source Type: research

A phase I study of farletuzumab, a humanized anti-folate receptor α monoclonal antibody, in patients with solid tumors
Summary Farletuzumab is a humanized monoclonal antibody against folate receptor α (FRA). The purpose of the study is to assess safety and tolerability, the pharmacokinetic (PK) profile, and preliminary antitumor effect. Patients with ovarian cancer (OC) or FRA-expressing solid tumors who are resistant to standard treatments were eligible for the study. After single-dose administration for PK assessment, farletuzumab was administered by intravenous injection, repeating every week until disease progression. Dose-limiting toxicities (DLTs) were defined as grade 4 hematological and grade 3/4 nonhematological to...
Source: Investigational New Drugs - April 1, 2015 Category: Drugs & Pharmacology Source Type: research

Inhibition of human vascular endothelial cell migration and capillary-like tube formation by the microtubule-stabilizing agent peloruside A
In this study, the effects of peloruside A on endothelial cell processes important for angiogenesis were assessed in comparison to docetaxel. Both peloruside A and docetaxel potently inhibited the proliferation of human umbilical vein endothelial cells, with IC50 values of 1.4 and 1.7 nM, respectively. Peloruside also potently blocked endothelial cell migration during wound closure and the three-dimensional organization of the endothelial cells into capillary-like tubes. In the wound scratch assay, peloruside A inhibited wound recovery with an IC50 of 6.3 nM after 18 h. Docetaxel was approximately 3-fold mor...
Source: Investigational New Drugs - March 30, 2015 Category: Drugs & Pharmacology Source Type: research

Xilonix, a novel true human antibody targeting the inflammatory cytokine interleukin-1 alpha, in non-small cell lung cancer
Conclusion Xilonix was well tolerated, with gains in LBM and improvement in symptoms suggesting a clinically important response. Although not statistically significant, the survival outcomes observed for patients with and without prior anti-EGFR therapy raises intriguing questions about the potential synergy of IL-1α blockade and anti-EGFR therapy. Further study for this agent in NSCLC is warranted. (Source: Investigational New Drugs)
Source: Investigational New Drugs - March 30, 2015 Category: Drugs & Pharmacology Source Type: research

Phase I and pharmacokinetics/pharmacodynamics study of the MEK inhibitor RO4987655 in Japanese patients with advanced solid tumors
Abstract RO4987655 is an oral and selective inhibitor of MEK, a key enzyme of the mitogen-activated protein kinase (MAPK) signaling pathway. This phase I dose-escalation study of RO4987655 in Japanese patients with advanced solid tumors aimed to determine maximum tolerated dose (MTD) and to evaluate safety, pharmacokinetics (PK), pharmacodynamics (PD), and anti-tumor activity. Patients received a single dose of RO4987655 (1, 2, 4, 5, or 6.5 mg) followed by continuous once-daily dosing (1, 2, or 4 mg QD) or twice-daily dosing (4, 5, or 6.5 mg BID) in 28-day cycles. A 3 + 3 dose-escalati...
Source: Investigational New Drugs - March 27, 2015 Category: Drugs & Pharmacology Source Type: research

Phase I trial of volasertib, a Polo-like kinase inhibitor, plus platinum agents in solid tumors: safety, pharmacokinetics and activity
Conclusions Volasertib plus cisplatin or carboplatin at full single-agent doses was generally manageable and demonstrated activity in heavily pretreated patients with advanced solid tumors. (Source: Investigational New Drugs)
Source: Investigational New Drugs - March 21, 2015 Category: Drugs & Pharmacology Source Type: research

Acknowledgement of Reviewers 2013
(Source: Investigational New Drugs)
Source: Investigational New Drugs - March 19, 2015 Category: Drugs & Pharmacology Source Type: research

Phase 1 study of ixazomib, an investigational proteasome inhibitor, in advanced non-hematologic malignancies
Conclusions In patients with solid tumors, ixazomib was associated with a manageable safety profile, limited antitumor activity, and evidence of downstream proteasome inhibition effects. (Source: Investigational New Drugs)
Source: Investigational New Drugs - March 18, 2015 Category: Drugs & Pharmacology Source Type: research

Convection-enhancement delivery of platinum-based drugs and Lipoplatin TM to optimize the concomitant effect with radiotherapy in F98 glioma rat model
In conclusion, CED increased the accumulation of platinum drugs in tumor, reduced the toxicity, and resulted in a higher median survival time. The best treatment was obtained in animals treated with carboplatin and irradiated 24 h later. (Source: Investigational New Drugs)
Source: Investigational New Drugs - March 18, 2015 Category: Drugs & Pharmacology Source Type: research

Phase I study of the anti-MET antibody onartuzumab in patients with solid tumors and MET-positive lung cancer
Summary Onartuzumab is a monovalent, humanized, monoclonal antibody that showed significant survival benefits in combination with erlotinib in MET-positive non-small-cell lung cancer (NSCLC) in pre-specified subgroup analyses of a randomized phase II study. We conducted a two-stage, open-label, multicenter, phase I study of onartuzumab in Japanese patients. Stage 1 investigated the safety, tolerability, pharmacokinetics (PK), and recommended dose of onartuzumab in patients with solid tumors, and Stage 2 determined the safety, tolerability, and PK of onartuzumab plus erlotinib in patients with MET-positive NSCLC. N...
Source: Investigational New Drugs - March 18, 2015 Category: Drugs & Pharmacology Source Type: research

Acknowledgement of Reviewers 2014
(Source: Investigational New Drugs)
Source: Investigational New Drugs - March 15, 2015 Category: Drugs & Pharmacology Source Type: research

Clinical outcomes in 66 patients with advanced gastric cancer treated in phase I trials: the NCCHE experience
Conclusion Phase I trials of patients with AGC was acceptably feasible with some efficacy signal. Our results suggest that phase I trials might be one treatment option for patients with AGC when conventional therapies fail. (Source: Investigational New Drugs)
Source: Investigational New Drugs - March 15, 2015 Category: Drugs & Pharmacology Source Type: research

A phase I open-labeled, single-arm, dose-escalation, study of dichloroacetate (DCA) in patients with advanced solid tumors
Conclusions The RP2D of oral DCA is 6.25 mg/kg BID. Toxicities will require careful monitoring in future trials. (Source: Investigational New Drugs)
Source: Investigational New Drugs - March 12, 2015 Category: Drugs & Pharmacology Source Type: research

Safety, tolerability, and pharmacokinetics of single and multiple doses of intravenous cixutumumab (IMC-A12), an inhibitor of the insulin-like growth factor-I receptor, administered weekly or every 2 weeks in patients with advanced solid tumors
Conclusions: Cixutumumab was associated with favorable safety and PK profiles. A dosing regimen of 10 mg/kg every 2 weeks was recommended for subsequent disease-focused clinical trials. (Source: Investigational New Drugs)
Source: Investigational New Drugs - March 6, 2015 Category: Drugs & Pharmacology Source Type: research

3,4′,5- trans -Trimethoxystilbene; a natural analogue of resveratrol with enhanced anticancer potency
Summary Resveratrol is a phytoalexin produced by many plant species as a defence mechanism. Over the last decade, this polyphenol has been reported to be active against multiple targets associated with chronic disorders. However, its poor pharmacokinetic profile, as well as multiple discrepancies related to its in vitro and in vivo profile, has resulted not only on the study of suitable delivery systems, but the use of resveratrol derivatives. In this regard, the 3,4′,5-trans-trimethoxystilbene (TMS), a natural analogue of resveratrol, has emerged as a strong candidate. TMS has an enhanced anticancer profile...
Source: Investigational New Drugs - February 27, 2015 Category: Drugs & Pharmacology Source Type: research

A phase 1 study of the sachet formulation of the oral dual PI3K/mTOR inhibitor BEZ235 given twice daily (BID) in patients with advanced solid tumors
Conclusions The recommended dose of BEZ235 administered BID as an oral sachet formulation is 300 mg BID. Toxicities seen have been reported for other dual PI3K/mTOR inhibitors. (Source: Investigational New Drugs)
Source: Investigational New Drugs - February 25, 2015 Category: Drugs & Pharmacology Source Type: research

Phase I and pharmacokinetic study of the novel anthracycline derivative 5-imino-13-deoxydoxorubicin (GPX-150) in patients with advanced solid tumors
Conclusions GPX-150 administered every 21 days has an acceptable side effect profile and no cardiotoxicity was observed. Further investigation is needed to determine the efficacy of GPX-150 in anthracycline-sensitive malignancies. (Source: Investigational New Drugs)
Source: Investigational New Drugs - February 21, 2015 Category: Drugs & Pharmacology Source Type: research

Phase-I dose finding and pharmacokinetic study of the novel hydrophilic camptothecin ST-1968 (namitecan) in patients with solid tumors
Conclusions: This study demonstrates clinical safety, favourable pharmacokinetics and preliminary antitumor activity of the novel hydrophilic camptothecin analogue namitecan in patients with heavily pretreated solid malignancies, when given either on a 2 out of 3 weeks or 3-weekly regimen. (Source: Investigational New Drugs)
Source: Investigational New Drugs - February 19, 2015 Category: Drugs & Pharmacology Source Type: research

The oncolytic virus, pelareorep, as a novel anticancer agent: a review
Summary Pelareorep (REOLYSIN®) is an investigational new drug, a proprietary formulation consisting of a live, replication-competent, naturally occurring Reovirus Type 3 Dearing strain. Through several preclinical studies it was determined that reovirus can exhibit profound cytotoxic effects on cancer cells predominantly with an activated RAS-signalling pathway. Moreover, it was discovered that reoviruses can “hitchhike” on peripheral blood mononuclear cells and dendritic cells, thereby evading neutralizing antibodies of the host immune system. Cell carriage, targeted delivery, triggering host immu...
Source: Investigational New Drugs - February 19, 2015 Category: Drugs & Pharmacology Source Type: research

First-in-human phase 1 study of filanesib (ARRY-520), a kinesin spindle protein inhibitor, in patients with advanced solid tumors
Conclusion Filanesib provided exposures with acceptable tolerability and evidence of target-specific pharmacodynamic effects. (Source: Investigational New Drugs)
Source: Investigational New Drugs - February 17, 2015 Category: Drugs & Pharmacology Source Type: research

Combretastatin A-4 derived imidazoles show cytotoxic, antivascular, and antimetastatic effects based on cytoskeletal reorganisation
Conclusions We deem the new imidazoles promising drug candidates for combination regimens with antiangiogenic VEGFR inhibitors. (Source: Investigational New Drugs)
Source: Investigational New Drugs - February 13, 2015 Category: Drugs & Pharmacology Source Type: research

Preliminary efficacy, safety, pharmacokinetics, pharmacodynamics and quality of life study of pegylated recombinant human arginase 1 in patients with advanced hepatocellular carcinoma
This study was designed to evaluate the efficacy, safety profile, pharmacokinetics, pharmacodynamics and quality of life of pegylated recombinant human arginase 1 (Peg-rhAgr1) in patients with advanced hepatocellular carcinoma (HCC). Patients were given weekly doses of Peg-rhAgr1 (1600 U/kg). Tumour response was assessed every 8 weeks using RECIST 1.1 and modified RECIST criteria. A total of 20 patients were recruited, of whom 15 were deemed evaluable for treatment efficacy. Eighteen patients (90 %) were hepatitis B carriers. Median age was 61.5 (range 30–75). Overall disease control rate was 13 %, wit...
Source: Investigational New Drugs - February 10, 2015 Category: Drugs & Pharmacology Source Type: research

Axitinib plasma pharmacokinetics and ethnic differences
Summary Axitinib, a potent and selective tyrosine kinase inhibitor of vascular endothelial growth factor receptors 1, 2, and 3, showed improved progression-free survival over sorafenib in patients previously treated for advanced renal cell carcinoma in the AXIS trial. Although a few studies had established the efficacy and safety of axitinib in Asian patients, additional evaluation was necessary to obtain regulatory approval in several Asian countries, especially in light of ethnic differences that are known to exist in genetic polymorphisms for metabolizing enzymes such as cytochrome P450 (CYP) 3A5, CYP2C19 and&n...
Source: Investigational New Drugs - February 8, 2015 Category: Drugs & Pharmacology Source Type: research

Phase 1b study of the oral gemcitabine ‘Pro-drug’ LY2334737 in combination with capecitabine in patients with advanced solid tumors
Conclusions No drug interactions or unexpected toxicities were observed in US patients when LY2334737 at doses up to 40 mg/day was administered QD in combination with capecitabine BID; the maximum tolerated dose was not reached. (Source: Investigational New Drugs)
Source: Investigational New Drugs - February 2, 2015 Category: Drugs & Pharmacology Source Type: research

Acetylamine derivative of diospyrin, a plant-derived binaphthylquinonoid, inhibits human colon cancer growth in Nod -Scid mice
Summary Anticancer activity of diospyrin and its derivatives (1–5) was evaluated against thirteen human cell lines. Compared to diospyrin (1), the acetylamine derivative (4) exhibited increase in cytotoxicity, particularly in HT-29 colon cancer cells, showing GI50 values of 33.90 and 1.96 μM, respectively. Also, enhanced toxicity was observed when cells, pre-treated with compound 4, were exposed to radiation. In vivo assessment of 4 was undertaken on tumour-bearing Nod-Scid mice treated at 4 mg/kg/day. Significant reduction in relative tumour volume (~86–91 %) was observed during the...
Source: Investigational New Drugs - February 1, 2015 Category: Drugs & Pharmacology Source Type: research

Phase 1 combination study of Eribulin mesylate with trastuzumab for advanced or recurrent human epidermal growth factor receptor 2 positive breast cancer
Summary Eribulin mesylate (Halaven®) is a novel inhibitor of microtubule dynamics that has demonstrated a survival benefit in patients with locally recurrent or metastatic breast cancer who previously received at least two chemotherapeutic regimens including an anthracycline and a taxane. Although trastuzumab is indicated for patients with human epidermal growth factor receptor 2 positive (HER2+) breast cancer, a phase 1 study to evaluate tolerability/safety of eribulin mesylate with trastuzumab has not been conducted. Therefore, a study of eribulin mesylate in combination with trastuzumab was conducted to ev...
Source: Investigational New Drugs - February 1, 2015 Category: Drugs & Pharmacology Source Type: research