Phase 1 dose de-escalation trial of the endogenous folate [6R]-5,10-methylene tetrahydrofolate in combination with fixed-dose pemetrexed as neoadjuvant therapy in patients with resectable rectal cancer
Conclusions The results of this phase 1 study indicate that the estimated minimum tolerated dose of [6R]-MTHF was 100 mg/m2 once weekly in combination with pemetrexed 500 mg/m2. The low toxicity profile of [6R]-MTHF supports its further evaluation as a component of systemic chemotherapy in the management of colon and rectal cancer. (Source: Investigational New Drugs)
Source: Investigational New Drugs - September 15, 2015 Category: Drugs & Pharmacology Source Type: research

Evaluation of cytotoxic activity of titanocene difluorides and determination of their mechanism of action in ovarian cancer cells
Conclusion We anticipate that the presence of substituents on cyclopentadienyl ring(s) might play an important role in modulation of the activity of particular compounds. Titanocene difluorides exert comparable cytotoxic activity as cisplatin and are more efficient in cisplatin-resistant cell lines. Our results suggest potential utilization of these compounds especially in the treatment of cisplatin-resistant tumor cells. (Source: Investigational New Drugs)
Source: Investigational New Drugs - September 15, 2015 Category: Drugs & Pharmacology Source Type: research

Topotecan plus cyclophosphamide in adults with relapsed or refractory pediatric-type sarcoma: a retrospective analysis from the German Sarcoma Medical Oncology Group (AIO)
Conclusions Limited activity was seen in adult pts with refractory or relapsed pediatric-type sarcomas with the regimen which has proven activity in pediatric patients. Adults with refractory small cell sarcoma appear to have a similar dismal outcome as seen in pts with common adult-type histologies; however, a subset of patients has achieved long-lasting remissions on TC resulting in long-term survival. (Source: Investigational New Drugs)
Source: Investigational New Drugs - September 15, 2015 Category: Drugs & Pharmacology Source Type: research

Phase I study of TAS-102 and irinotecan combination therapy in Japanese patients with advanced colorectal cancer
Conclusion The RD was determined to be 50 mg/m2/day of TAS-102 combined with 150 mg/m2 of irinotecan although further investigation to explore optimal regimen is warranted. (Source: Investigational New Drugs)
Source: Investigational New Drugs - September 15, 2015 Category: Drugs & Pharmacology Source Type: research

A pilot study of JI-101, an inhibitor of VEGFR-2, PDGFR-β, and EphB4 receptors, in combination with everolimus and as a single agent in an ovarian cancer expansion cohort
Summary JI-101 is an oral multi-kinase inhibitor that targets vascular endothelial growth factor receptor type 2 (VEGFR-2), platelet derived growth factor receptor β (PDGFR-β), and ephrin type-B receptor 4 (EphB4). None of the currently approved angiogenesis inhibitors have been reported to inhibit EphB4, and therefore, JI-101 has a novel mechanism of action. We conducted a pilot trial to assess the pharmacokinetics (PK), tolerability, and efficacy of JI-101 in combination with everolimus in advanced cancers, and pharmacodynamics (PD), tolerability, and efficacy of JI-101 in ovarian cancer. This was the ...
Source: Investigational New Drugs - September 14, 2015 Category: Drugs & Pharmacology Source Type: research

Severe acute interstitial lung disease in a patient with anaplastic lymphoma kinase rearrangement–positive non–small cell lung cancer treated with alectinib
We report a patient who developed severe acute interstitial lung disease after alectinib treatment. An 86-year-old woman with stage IV lung adenocarcinoma positive for rearrangement of ALK gene was treated with alectinib. On the 215th day after initiation of alectinib administration, she was admitted to our hospital with the symptom of progressive dyspnea. Computed tomography (CT) revealed diffuse ground glass opacities and consolidations in both lungs, and analysis of bronchoalveolar lavage fluid revealed pronounced lymphocytosis. There was no evidence of infection or other specific causes of her condition, and she was th...
Source: Investigational New Drugs - September 4, 2015 Category: Drugs & Pharmacology Source Type: research

A phase I study of VS-6063, a second-generation focal adhesion kinase inhibitor, in patients with advanced solid tumors
Conclusions VS-6063 has an acceptable safety profile. Treatment-related adverse events were mild to moderate, and reversible. The recommended phase II fasting dose of VS-6063 is 425 mg b.i.d. (Source: Investigational New Drugs)
Source: Investigational New Drugs - September 4, 2015 Category: Drugs & Pharmacology Source Type: research

Long term exposure to antiangiogenic therapy, bevacizumab, induces osteonecrosis
Conclusions With an incidence of 4 out of 1000 patients osteonecrosis is a rare side effect of anti-angiogenic agent. With the increasing utilisation and duration of exposure of anti-VEGF therapy some rare side effect due to chronic ischemia may appear. The clinician should be aware about uncommon symptoms. (Source: Investigational New Drugs)
Source: Investigational New Drugs - August 27, 2015 Category: Drugs & Pharmacology Source Type: research

BRAF-mutated clear cell sarcoma is sensitive to vemurafenib treatment
We report a patient with a metastatic relapse of clear cell sarcoma, whose tumor harbored BRAF V600E mutation. Standard chemotherapy with doxorubicin and ifosfamide failed to slow the disease progression. Subsequent administration of vemurafenib (960 mg twice a day) resulted in complete tumor response after 8 weeks of treatment. Literature data on the use of vemurafenib and dabrafenib in non-melanoma BRAF-mutated tumors are reviewed. (Source: Investigational New Drugs)
Source: Investigational New Drugs - August 19, 2015 Category: Drugs & Pharmacology Source Type: research

Ulcerative colitis in a patient with non-small-cell lung cancer receiving bevacizumab
Summary Bevacizumab, a humanized monoclonal antibody against vascular endothelial growth factor, is anticipated to prolong survival with inhibition of angiogenesis in patients with non-small-cell lung cancer. Rare life-threatening adverse events affecting the digestive tract have been reported, such as gastrointestinal hemorrhage and bowel perforation. A 62-year-old Japanese woman who was diagnosed as having stage IIIB (cT4N2M0) lung adenocarcinoma received chemotherapy with bevacizumab, pemetrexed and carboplatin every 3 weeks for four cycles, which resulted in a partial response, and then continued with mai...
Source: Investigational New Drugs - August 17, 2015 Category: Drugs & Pharmacology Source Type: research

Phase I trial of combination of FOLFIRI and pasireotide, a somatostatin analogue, in advanced gastrointestinal malignancies
This study aimed to evaluate the maximum tolerated dose (MTD) of pasireotide in combination with standard FOLFIRI (5-fluorouracil, leucovorin and irinotecan) regimen in patients with gastrointestinal malignancies. Methods This was a phase 1, 3 + 3 design, open-label dose escalation study conducted in sequential cohorts to determine the MTD of pasireotide in combination with FOLFIRI. All patients had gastrointestinal malignancies and were previously treated. Sixteen patients enrolled in five dose cohorts at pasireotide doses of 40, 60, 80, 100 and 120 mg were evaluated for safety and tolerability of the c...
Source: Investigational New Drugs - August 15, 2015 Category: Drugs & Pharmacology Source Type: research

Chloroquine inhibits the malignant phenotype of glioblastoma partially by suppressing TGF-beta
Conclusion These results suggest that CQ, alone or as an adjuvant therapeutic, could be used to inhibit the GBM malignant phenotype and could benefit GBM afflicted patients. (Source: Investigational New Drugs)
Source: Investigational New Drugs - August 14, 2015 Category: Drugs & Pharmacology Source Type: research

Subcellular localization of anthracyclines in cultured rat cardiomyoblasts as possible predictors of cardiotoxicity
In this study, we compared the cellular uptake, intracellular localization and cytotoxicity of two groups of anthracycline derivatives in cultured H9c2(2-1) rat cardiomyoblasts. The first group consisted of doxorubicin (DOX) and two of its derivatives containing a formamidino group (–N = CH–N
Source: Investigational New Drugs - August 14, 2015 Category: Drugs & Pharmacology Source Type: research

Phase 1 study of APTO-253 HCl, an inducer of KLF4, in patients with advanced or metastatic solid tumors
Conclusion APTO-253 was well tolerated at the Phase 2 recommended dose and produced evidence of antitumor activity in the form of stable disease in patients with advanced solid tumors. Based on the drug levels achieved and the lower frequency of treatment-emergent adverse events encountered, 229 mg/m2 was selected as the recommended Phase 2 dose. Overall APTO-253 was found to be well tolerated and to have favorable pharmacokinetics, and treatment was associated with stable disease in 5 of 21 (24 %) of patients with far advanced solid tumors. (Source: Investigational New Drugs)
Source: Investigational New Drugs - August 14, 2015 Category: Drugs & Pharmacology Source Type: research

A phase I/Ib study of trametinib (GSK1120212) alone and in combination with gemcitabine in Japanese patients with advanced solid tumors
Conclusions Trametinib monotherapy was tolerable in Japanese patients with cancer. However, the combination of trametinib plus gemcitabine carried a higher risk as compared with monotherapy, during which no ILD was observed. (ClinicalTrials.gov number, NCT01324258.) (Source: Investigational New Drugs)
Source: Investigational New Drugs - August 11, 2015 Category: Drugs & Pharmacology Source Type: research

In vitro and in vivo toxicity of 5-FdU-alendronate, a novel cytotoxic bone-seeking duplex drug against bone metastasis
Conclusion The coupling of an amino-bisphosphonate with an antimetabolite via an N-alkyl-bonding offers a new strategy for the preparation of amino-bisphosphonates conjugates with a cancer cell-specific, efficacious cytotoxic bone-targeting potential along with a reduced systemic toxicity. The innovative duplex drug 5-FdU-ale therefore warrants further clinical investigation. (Source: Investigational New Drugs)
Source: Investigational New Drugs - July 5, 2015 Category: Drugs & Pharmacology Source Type: research

Dose-finding study of hepatic arterial infusion of irinotecan-based treatment in patients with advanced cancers metastatic to the liver
Conclusions HAI irinotecan in combination with bevacizumab; oxaliplatin plus bevacizumab; or cetuximab plus bevacizumab was safe and may be a treatment option for selected patients with advanced cancer and liver involvement. (Source: Investigational New Drugs)
Source: Investigational New Drugs - July 5, 2015 Category: Drugs & Pharmacology Source Type: research

Generation and tumor recognition properties of two human monoclonal antibodies specific to cell surface anionic phospholipids
Summary Phosphatidylserine (PS) and other anionic phospholipids, which become exposed on the surface of proliferating endothelial cells, tumor cells and certain leukocytes, have been used as targets for the development of clinical-stage biopharmaceuticals. One of these products (bavituximab) is currently being investigated in Phase 3 clinical trials. There are conflicting reports on the ability of bavituximab and other antibodies to recognize PS directly or through beta-2 glycoprotein 1, a serum protein that is not highly conserved across species. Here, we report on the generation and characterization of two full...
Source: Investigational New Drugs - July 5, 2015 Category: Drugs & Pharmacology Source Type: research

A phase II study of the HDAC inhibitor SB939 in patients with castration resistant prostate cancer: NCIC clinical trials group study IND195
Summary Background SB939 is a potent oral inhibitor of class 1, 2, and 4 histone deacetylases (HDACs). These three HDAC classes are highly expressed in castration resistant prostate cancer (CRPC) and associated with poor clinical outcomes. We designed a phase II study of SB939 in men with metastatic CRPC. Methods Patients received SB939 60 mg on alternate days three times per week for 3 weeks on a 4-week cycle. Primary endpoints were PSA response rate (RR) and progression-free survival (PFS). Secondary endpoints included objective response rate and duration; overall survival; circulating...
Source: Investigational New Drugs - July 5, 2015 Category: Drugs & Pharmacology Source Type: research

Phase II study of tivantinib (ARQ 197) in patients with metastatic triple-negative breast cancer
Conclusion This study represents the first evaluation of tivantinib for the treatment of metastatic triple-negative breast cancer. These results suggest that single agent tivantinib is well tolerated, but did not meet prespecified statistical targets for efficacy. (Source: Investigational New Drugs)
Source: Investigational New Drugs - July 1, 2015 Category: Drugs & Pharmacology Source Type: research

P-glycoprotein and breast cancer resistance protein restrict the brain penetration of the CDK4/6 inhibitor palbociclib
Conclusion Thus, the brain penetration of palbociclib is restricted by P-gp and BCRP, which may restrict the efficacy against GBM and DIPG. Moreover, preclinical studies with this agent should be conducted at a more clinically relevant dose level. (Source: Investigational New Drugs)
Source: Investigational New Drugs - June 30, 2015 Category: Drugs & Pharmacology Source Type: research

Differential nucleobase protection against 5-fluorouracil toxicity for squamous and columnar cells: implication for tissue function and oncogenesis
Conclusion The directed application of the normal nucleobase uracil to the squamous cells of the oral mucosa and palms and soles together with the delivery of the normal nucleobase adenine to the columnar cells of the GI tract may enable the safe delivery of higher 5FU dose intensity. These results also suggest a feature of tissue function where squamous cells grow largely by recycling overlying tissue cell components. Columnar cells use absorbed surface nutrients for de novo growth. A disruption of this tissue function can result in growth derived from an underlying nutrient source. That change would also cause the l...
Source: Investigational New Drugs - June 30, 2015 Category: Drugs & Pharmacology Source Type: research

Cytotoxicity of anthraquinones from the roots of Pentas schimperi towards multi-factorial drug-resistant cancer cells
Conclusions Anthraquinones from Pentas schimperi and mostly 1 and 2 are potential cytotoxic natural products that deserve more investigations to develop novel antineoplastic drugs against multifactorial drug resistant cancers. (Source: Investigational New Drugs)
Source: Investigational New Drugs - June 27, 2015 Category: Drugs & Pharmacology Source Type: research

Antitumor activity of a rhenium (I)-diselenoether complex in experimental models of human breast cancer
Summary Rhenium (I)-diselenother (Re-diselenoether) is a water soluble metal-based compound, combining one atom of rhenium and two atoms of selenium. This compound has been reported to exhibit marked activities against several solid tumor cell lines. We now disclose an improved synthesis of this complex. The Re-diselenoether showed a potent inhibitory effect on MDA-MB231 cell division in vitro, which lasted when the complex was no longer present in the culture. Re-diselenoether induced a remarkable reduction of the volume of the primitive breast tumors and of the pulmonary metastases without clinical signs of toxi...
Source: Investigational New Drugs - June 25, 2015 Category: Drugs & Pharmacology Source Type: research

Targeting the plasma membrane of neoplastic cells through alkylation: a novel approach to cancer chemotherapy
Conclusion Despite these compelling data, preliminary clinical trials for plasma membrane-directed agents have yet to be considered. Therefore, this review is intended for academics and clinicians to postulate a novel approach of chemotherapy; altering critical malignant cell signaling at the plasma membrane surface through alkylation, thereby inducing irreversible changes to functions needed for cell survival. (Source: Investigational New Drugs)
Source: Investigational New Drugs - June 23, 2015 Category: Drugs & Pharmacology Source Type: research

Three-dimensional and co-culture models for preclinical evaluation of metal-based anticancer drugs
Conclusion Taken together, our results demonstrate the advantages of spheroid-based assays and underline the necessity of using different experimental models for reliable preclinical investigations assessing and better predicting the anticancer potential of new compounds. (Source: Investigational New Drugs)
Source: Investigational New Drugs - June 21, 2015 Category: Drugs & Pharmacology Source Type: research

Phase I study of the mTOR inhibitor ridaforolimus and the HDAC inhibitor vorinostat in advanced renal cell carcinoma and other solid tumors
Conclusions The combination of ridaforolimus and vorinostat was tolerable at the recommended phase II dose. Two patients with papillary RCC experienced prolonged disease stabilization, thus further study of combined HDAC and mTOR inhibition in this population is warranted. (Source: Investigational New Drugs)
Source: Investigational New Drugs - June 20, 2015 Category: Drugs & Pharmacology Source Type: research

Phase 1 study of the investigational Aurora A kinase inhibitor alisertib (MLN8237) in East Asian cancer patients: pharmacokinetics and recommended phase 2 dose
Conclusion The MTD/RP2D of alisertib in East Asian patients (30 mg BID) was lower than in Western patients (50 mg BID), consistent with higher systemic exposures in the East Asian population. Alisertib was generally well tolerated and showed signs of antitumor activity in East Asian cancer patients. (Source: Investigational New Drugs)
Source: Investigational New Drugs - June 19, 2015 Category: Drugs & Pharmacology Source Type: research

Multicenter phase II study of the AKT inhibitor MK-2206 in recurrent or metastatic nasopharyngeal carcinoma from patients in the mayo phase II consortium and the cancer therapeutics research group (MC1079)
Conclusion The study was terminated due to the limited activity observed in this heavily pre-treated group of patients. Further studies are needed to elucidate the optimal way of selecting patients for AKT inhibitors. (Source: Investigational New Drugs)
Source: Investigational New Drugs - June 19, 2015 Category: Drugs & Pharmacology Source Type: research

Phase I study of the heat shock protein 90 (Hsp90) inhibitor onalespib (AT13387) administered on a daily for 2 consecutive days per week dosing schedule in patients with advanced solid tumors
This study followed an accelerated titration design with a starting dose of 20 mg/m2/dose and a standard 3 + 3 dose escalation design for dose level 4 (120 mg/m2/dose) and above. Additional patients were enrolled at the RP2D with mandatory paired tumor biopsies to assess modulation of 210 client proteins using reverse phase protein array analysis. Thirty-one patients were treated; RP2D was established at 160 mg/m2/dose on the QDx2/week schedule. Common toxicities were gastrointestinal, hepatic, and hematologic. Pharmacokinetic profile was linear and plasma levels increased proportionally with d...
Source: Investigational New Drugs - June 18, 2015 Category: Drugs & Pharmacology Source Type: research

First-in-human study of the toxicity, pharmacokinetics, and pharmacodynamics of CG200745, a pan-HDAC inhibitor, in patients with refractory solid malignancies
Conclusions CG200745 can be safely administered at effective dose levels that inhibit HDAC in PBMCs and tumor tissue. Although MTD was not reached, further escalation was not performed because acetylated histone H4 plateaued at dose levels higher than 51 mg/m2. Additional phase II trials are recommended at 250 mg/m2. (Source: Investigational New Drugs)
Source: Investigational New Drugs - June 16, 2015 Category: Drugs & Pharmacology Source Type: research

Amidation inhibitors 4-phenyl-3-butenoic acid and 5-(acetylamino)-4-oxo-6-phenyl-2-hexenoic acid methyl ester are novel HDAC inhibitors with anti-tumorigenic properties
In this report, we show that PBA also increases the acetylation levels of selected histone subtypes in a dose and time dependent manner, an effect that is attributable to the inhibition of histone deacetylase (HDAC) enzymes. Comparison studies with the known HDAC inhibitor suberoylanilide hydroxamic acid (SAHA) using high resolution two-dimensional polyacrylamide gels and Western analysis provide evidence that PBA acts as an HDAC inhibitor within cells. PBA and a more potent amidation inhibitor, 5-(acetylamino)-4-oxo-6-phenyl-2-hexenoic acid methyl ester (AOPHA-Me), inhibit HDAC enzymes in vitro at micromolar concentration...
Source: Investigational New Drugs - June 13, 2015 Category: Drugs & Pharmacology Source Type: research

Phase II study of saracatinib (AZD0530) in patients with previously treated metastatic colorectal cancer
Conclusion Saracatinib is a novel oral Src kinase inhibitor that was well tolerated but failed to meet its primary endpoint of improvement in 4 month progression-free survival as a single agent in previously treated metastatic colorectal cancer patients. (Source: Investigational New Drugs)
Source: Investigational New Drugs - June 12, 2015 Category: Drugs & Pharmacology Source Type: research

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