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

Aptamers as a novel tool for diagnostics and therapy
Summary Aptamers are short single-stranded DNA or RNA oligonucleotides that are capable of binding small molecules, proteins, or nucleotides with high specificity. They show a stable conformation and high binding affinity for their target molecules. There are numerous applications for aptamers in biotechnology, molecular diagnostics and targeted therapy of diseases. Their production is cheap, and they generally display lower immunogenicity than monoclonal antibodies. In the present review, we give an introduction to the preparation of aptamers and provide examples for their use in biotechnology, diagnostics and th...
Source: Investigational New Drugs - February 1, 2015 Category: Drugs & Pharmacology Source Type: research

Biomarker-driven phase 2 study of MK-2206 and selumetinib (AZD6244, ARRY-142886) in patients with colorectal cancer
Conclusion Despite strong scientific rationale and preclinical data, clinical activity was not observed. The desired level of target inhibition was not achieved. Overlapping toxicities limited the ability to dose escalate to achieve exposures likely needed for clinical activity, highlighting the challenges in developing optimal combinations of targeted agents. (Source: Investigational New Drugs)
Source: Investigational New Drugs - February 1, 2015 Category: Drugs & Pharmacology Source Type: research

A phase I and pharmacokinetic study of ganetespib (STA-9090) in advanced hepatocellular carcinoma
Conclusion Ganetespib had a manageable safety profile in patients with advanced HCC who had progressed on at least one line of systemic therapy. The pharmacokinetic profile showed that ganetespib exposure in patients with mild hepatic dysfunction is similar to that seen in patients with normal liver function. Ganetespib showed limited clinical benefit in patients with advanced HCC in this phase I trial. (Source: Investigational New Drugs)
Source: Investigational New Drugs - January 15, 2015 Category: Drugs & Pharmacology Source Type: research

Duodenal ischemia and upper GI bleeding are dose-limiting toxicities of 24-h continuous intra-arterial pancreatic perfusion of gemcitabine following vascular isolation of the pancreatic head: early results from the Regional Chemotherapy in Locally Advanced Pancreatic Cancer (RECLAP) study
Conclusions While technically feasible to treat locally advanced pancreatic ductal adenocarcinoma, prolonged regional pancreatic perfusion with gemcitabine following pancreatic arterial redistribution carries a high risk for gastrointestinal toxicity. Shorter infusion schedules with frequent on treatment evaluations should be considered for future clinical trials. (Source: Investigational New Drugs)
Source: Investigational New Drugs - January 15, 2015 Category: Drugs & Pharmacology Source Type: research

An innovative, multi-arm, complete phase 1b study of the novel anti-cancer agent tasisulam in patients with advanced solid tumors
Conclusions The multi-arm design allowed the efficient determination of the maximum tolerated dose of tasisulam across multiple combinations, and a preliminary characterization of pharmacokinetics, safety, and potential efficacy. Although enrollment into all planned groups was not completed due to termination of compound development, these data support the feasibility of this approach for accelerated cancer drug development, even for drugs with complex pharmacology. (Source: Investigational New Drugs)
Source: Investigational New Drugs - January 15, 2015 Category: Drugs & Pharmacology Source Type: research

The marine natural product microsclerodermin A is a novel inhibitor of the nuclear factor kappa B and induces apoptosis in pancreatic cancer cells
Summary Pancreatic cancer, the 4th leading cause of cancer death in the US, is highly resistant to all current chemotherapies, and its growth is facilitated by chronic inflammation. An important mediator of inflammation is the nuclear factor kappa B (NFκB), a transcription factor that regulates over 500 genes including the regulation of anti-apoptotic proteins, cell cycle progression and cytokine production. NFκB is constitutively activated in pancreatic cancer cells contributing to their resistance to apoptosis and high metastatic potential. Although many small molecules that inhibit NFκB have ...
Source: Investigational New Drugs - January 15, 2015 Category: Drugs & Pharmacology Source Type: research

Momordica Charantia lectin exhibits antitumor activity towards hepatocellular carcinoma
Conclusion Our data show that the natural compound MCL manifests antitumor activities towards HCC and therefore suggest MCL as a promising chemotherapeutic agent. (Source: Investigational New Drugs)
Source: Investigational New Drugs - January 15, 2015 Category: Drugs & Pharmacology Source Type: research

In vitro evaluation of a tetrahydroisoquinoline derivative as a steroid sulfatase inhibitor and a selective estrogen receptor modulator
Summary Selective estrogen receptor modulators (SERMs) are currently in use in the hormonal therapy of breast cancer. In that respect, a new hormone-related approach is the therapeutical inhibition of steroid sulfatase (STS), which converts inactive, sulfated steroids into active hormones. We investigated the potential of 6-EO-14, a non-steroidal STS inhibitor with SERM potential. The latter compound, which exhibits a sulfamate moiety, releases the phenol derivative 8-EO-14 after the irreversible inhibition of STS. STS was inhibited by 6-EO-14 (IC50 = 0.3 μM), but not 8-EO-14, in HEK-293 cel...
Source: Investigational New Drugs - January 15, 2015 Category: Drugs & Pharmacology Source Type: research

Pharmacokinetics and excretion of 14 C-lenvatinib in patients with advanced solid tumors or lymphomas
In conclusion, lenvatinib is rapidly absorbed and extensively metabolized, with subsequent excretion in urine and, more predominantly, in feces. Additionally, lenvatinib showed acceptable safety and preliminary antitumor activity. (Source: Investigational New Drugs)
Source: Investigational New Drugs - January 15, 2015 Category: Drugs & Pharmacology Source Type: research

Successful treatment of Evans syndrome with Tacrolimus
(Source: Investigational New Drugs)
Source: Investigational New Drugs - January 15, 2015 Category: Drugs & Pharmacology Source Type: research

Phase 2 study of CT-322, a targeted biologic inhibitor of VEGFR-2 based on a domain of human fibronectin, in recurrent glioblastoma
This study evaluated CT-322 in an open-label run-in/phase 2 setting to assess its efficacy and safety in recurrent glioblastoma. Eligible patients had 1st, 2nd or 3rd recurrence of glioblastoma with measurable tumor on MRI and no prior anti-angiogenic therapy. The initial CT-322 dose was 1 mg/kg IV weekly, with plans to escalate subsequent patients to 2 mg/kg weekly if tolerated; within each CT-322 dose cohort, patients were randomized to ±irinotecan IV semiweekly. The primary endpoint was 6-month progression-free survival (PFS-6). Sixty-three patients with a median age of 56 were treated, the majority at ...
Source: Investigational New Drugs - January 15, 2015 Category: Drugs & Pharmacology Source Type: research

A phase I open-label study of the safety, tolerability, and pharmacokinetics of pazopanib in combination with irinotecan and cetuximab for relapsed or refractory metastatic colorectal cancer
Conclusions This study provided evidence for the manageable safety profile and feasibility of using the novel triplet combination of pazopanib, irinotecan, and cetuximab in patients with refractory mCRC. Further large-scale Phase II studies are warranted. (Source: Investigational New Drugs)
Source: Investigational New Drugs - January 15, 2015 Category: Drugs & Pharmacology Source Type: research

4,5-Diaryl imidazoles with hydroxamic acid appendages as anti-hepatoma agents
Conclusions The new imidazolyl hydroxamic acids lend themselves as a possible alternative to SAHA in the therapy of HCC. Even more so since similar 4,5-diarylimidazoles lacking only the hydroxamate functionality were previously shown in animal studies to be well tolerated and orally applicable. (Source: Investigational New Drugs)
Source: Investigational New Drugs - January 15, 2015 Category: Drugs & Pharmacology Source Type: research

Erratum to: Effect of simvastatin plus cetuximab/irinotecan for KRAS mutant colorectal cancer and predictive value of the RAS signature for treatment response to cetuximab
(Source: Investigational New Drugs)
Source: Investigational New Drugs - January 15, 2015 Category: Drugs & Pharmacology Source Type: research

Chemotherapy with cytochalasin congeners in vitro and in vivo against murine models
Conclusion Taken together, it appears that cytochalasins have unique antineoplastic activity that could potentiate a novel class of chemotherapeutic agents. (Source: Investigational New Drugs)
Source: Investigational New Drugs - January 7, 2015 Category: Drugs & Pharmacology Source Type: research

Chemotherapy in vivo against M109 murine lung carcinoma with cytochalasin B by localized, systemic, and liposomal administration
Abstract Cytochalasin B is a potentially novel microfilament-directed chemotherapeutic agent that prevents actin polymerization, thereby inhibiting cytokinesis. Although cytochalasin B has been extensively studied in vitro, only limited data are available to assess its in vivo potential. Cytochalasin B was administered to Balb/c mice challenged i.d. with M109 murine lung carcinoma to determine whether the agent could affect an established i.d. tumor when the compound is administered s.c. in the region of the i.d. tumor, but not in direct contact with it. Cytochalasin B was also administered either i.p. or s.c. at ...
Source: Investigational New Drugs - January 5, 2015 Category: Drugs & Pharmacology Source Type: research

Phase 1/2 study of orteronel (TAK-700), an investigational 17,20-lyase inhibitor, with docetaxel–prednisone in metastatic castration-resistant prostate cancer
Summary Background: Docetaxel–prednisone (DP) is an approved therapy for metastatic castration-resistant prostate cancer (mCRPC). Orteronel (TAK-700) is an investigational, selective, non-steroidal inhibitor of 17,20-lyase, a key enzyme in androgenic hormone production. This phase 1/2 study evaluated orteronel plus DP in mCRPC patients. Methods: Adult men with chemotherapy-naïve mCRPC, serum prostate-specific antigen (PSA) ≥5 ng/mL, and serum testosterone
Source: Investigational New Drugs - January 4, 2015 Category: Drugs & Pharmacology Source Type: research

Pharmacokinetic, pharmacodynamic and biomarker evaluation of transforming growth factor-β receptor I kinase inhibitor, galunisertib, in phase 1 study in patients with advanced cancer
Conclusion Based on the PK, PD, and biomarker evaluations, the intermittent administration of galunisertib at 300 mg/day is safe for future clinical investigation. (Source: Investigational New Drugs)
Source: Investigational New Drugs - December 22, 2014 Category: Drugs & Pharmacology Source Type: research

A phase 1 dose escalation study of BI 831266, an inhibitor of Aurora kinase B, in patients with advanced solid tumors
Conclusion The MTD of BI 831266 was not reached because of early trial termination. BI 831266 demonstrated a generally manageable safety profile and signs of antitumor activity in some patients’ solid tumors. (Source: Investigational New Drugs)
Source: Investigational New Drugs - December 22, 2014 Category: Drugs & Pharmacology Source Type: research

Phase I study of the novel Cdc2/CDK1 and AKT inhibitor terameprocol in patients with advanced leukemias
Conclusion Terameprocol can be safely administered to advanced leukemia patients, sufficient drug exposure was obtained and clinical activity and biomarker modulation were observed. (Source: Investigational New Drugs)
Source: Investigational New Drugs - December 18, 2014 Category: Drugs & Pharmacology Source Type: research

Phase II trial of combination therapy of gemcitabine plus anti-angiogenic vaccination of elpamotide in patients with advanced or recurrent biliary tract cancer
Conclusion Gemcitabine and elpamotide combination therapy was tolerable and had a moderate antitumor effect. For future development of therapies, it will be necessary to optimize the target population for which therapeutic effects could be expected. (Source: Investigational New Drugs)
Source: Investigational New Drugs - December 13, 2014 Category: Drugs & Pharmacology Source Type: research