Ibrutinib (Imbruvica TM ) potently inhibits ErbB receptor phosphorylation and cell viability of ErbB2-positive breast cancer cells
In this study, we determined the effect of Ibrutinib on breast cancer cells. We demonstrate that Ibrutinib efficiently reduces the phosphorylation of the receptor tyrosine kinases ErbB1, ErbB2 and ErbB3, thereby suppressing AKT and MAPK signaling in ErbB2-positive (ErbB2+) breast cancer cell lines. Treatment with Ibrutinib significantly reduced the viability of ErbB2+ cell lines with IC50 values at nanomolar concentrations, suggesting therapeutic potential of Ibrutinib in breast cancer. Combined treatment with Ibrutinib and the dual PI3K/mTOR inhibitor BEZ235 synergistically reduces cell viability of ErbB2+ breast cancer c...
Source: Investigational New Drugs - November 11, 2014 Category: Drugs & Pharmacology Source Type: research

A phase I trial of pantoprazole in combination with doxorubicin in patients with advanced solid tumors: evaluation of pharmacokinetics of both drugs and tissue penetration of doxorubicin
Conclusion Administration of high doses of pantoprazole in combination with doxorubicin is feasible. The recommended phase II dose of pantoprazole, 240 mg, will be evaluated in combination with docetaxel as first line in patients with castration-resistant prostate cancer. (Source: Investigational New Drugs)
Source: Investigational New Drugs - November 11, 2014 Category: Drugs & Pharmacology Source Type: research

Improved replication efficiency of echovirus 5 after transfection of colon cancer cells using an authentic 5’ RNA genome end methodology
Summary Oncolytic virotherapy is a promising novel form of cancer treatment, but the therapeutic efficiency needs improvement. A potential strategy to enhance the therapeutic effect of oncolytic viruses is to use infectious nucleic acid as therapeutic agent to initiate an oncolytic infection, without administrating infectious viral particles. Here we demonstrate improved viral replication activation efficiency when transfecting cells with 5’ end authentic in vitro transcribed enterovirus RNA as compared to genomic RNA with additional non-genomic 5’ nucleotides generated by conventional cloning methods...
Source: Investigational New Drugs - November 11, 2014 Category: Drugs & Pharmacology Source Type: research

Pneumocystis jirovecii pneumonia under everolimus in two patients with metastatic pancreatic neuroendocrine tumors
Conclusion Everolimus may induce pneumonitis, lymphopenia and opportunistic infections. The time from treatment initiation to opportunistic infection may be short. Risk factors in oncology deserve further identification in order to start prophylaxis without delay. (Source: Investigational New Drugs)
Source: Investigational New Drugs - November 11, 2014 Category: Drugs & Pharmacology Source Type: research

In vitro multifaceted activities of a specific group of novel phosphatidylinositol 3-kinase inhibitors on hotspot mutant PIK3CA
Conclusions Our result shows that the PI3K inhibitors exhibit potent activity on both hotspot mutant and wild type PI3Kα, suggesting they might be used to treat patients with or without PIK3CA mutation when approved. (Source: Investigational New Drugs)
Source: Investigational New Drugs - November 11, 2014 Category: Drugs & Pharmacology Source Type: research

A multicenter phase 1 study of PX-866 and cetuximab in patients with metastatic colorectal carcinoma or recurrent/metastatic squamous cell carcinoma of the head and neck
Conclusion Treatment with PX-866 and cetuximab was tolerated with signs of anti-tumor activity. Further development of this combination is warranted. (Source: Investigational New Drugs)
Source: Investigational New Drugs - November 11, 2014 Category: Drugs & Pharmacology Source Type: research

Phase 2, open-label, 1:1 randomized controlled trial exploring the efficacy of EMD 1201081 in combination with cetuximab in second-line cetuximab-naïve patients with recurrent or metastatic squamous cell carcinoma of the head and neck (R/M SCCHN)
Conclusion: EMD 1201081 was well tolerated combined with cetuximab, but there was no incremental clinical efficacy. (Source: Investigational New Drugs)
Source: Investigational New Drugs - November 11, 2014 Category: Drugs & Pharmacology Source Type: research

Ellipticine derivative induces potent cytostatic effect in acute myeloid leukaemia cells
This study provides for the first time detailed cellular information on the potential use of isoellipticines as chemotherapeutic agents. (Source: Investigational New Drugs)
Source: Investigational New Drugs - November 11, 2014 Category: Drugs & Pharmacology Source Type: research

Investigational Aurora A kinase inhibitor alisertib (MLN8237) as an enteric-coated tablet formulation in non-hematologic malignancies: Phase 1 dose-escalation study
Conclusions Alisertib ECT was generally well tolerated in adults with advanced, non-hematologic malignancies. The RP2D is 50 mg BID for 7 d and is being evaluated in ongoing phase 2 studies. (Source: Investigational New Drugs)
Source: Investigational New Drugs - November 11, 2014 Category: Drugs & Pharmacology Source Type: research

Contributions from emerging transcriptomics technologies and computational strategies for drug discovery
Summary Drug discovery involves various steps and is a long process being even more demanding for complex diseases such as cancer. Tumors are ensembles of subpopulations with different mutations, require very specific and effective strategies. Conventional drug screening technologies may not be adequate and efficient anymore. Drug repositioning is a useful strategy to identify new uses for previously failed drugs. High throughput and deep sequencing technologies provide valuable support by yielding enormous amounts of “-omics” data and contribute to understanding the molecular mechanisms responsible f...
Source: Investigational New Drugs - November 11, 2014 Category: Drugs & Pharmacology Source Type: research

Phase I clinical and pharmacokinetic study of ombrabulin (AVE8062) combined with cisplatin/docetaxel or carboplatin/paclitaxel in patients with advanced solid tumors
Conclusions The addition of ombrabulin to standard doses of cisplatin/docetaxel or carboplatin/paclitaxel proved feasible with manageable overlapping toxicities but appears to have limited impact on the efficacy of these doublets. Recommended combination doses are 35 mg/m2 ombrabulin with 75 mg/m2 cisplatin/75 mg/m2 docetaxel or 200 mg/m2 paclitaxel/AUC6 carboplatin, every 3 weeks. (Source: Investigational New Drugs)
Source: Investigational New Drugs - November 11, 2014 Category: Drugs & Pharmacology Source Type: research

The efficacy of Pistacia Terebinthus soap in the treatment of cetuximab-induced skin toxicity
The objective response rate was 100 %, and no delay, dose reduction or discontinuation of CTX treatment due to skin toxicity was necessary. Skin toxicity reoccurred in all patients when patients stopped administering the soap and therefore they used it throughout the cetuximab treatment. Pistacia terebinthus soap seemed to be used safely and effectively in the treatment of skin toxicity induced by Cetuximab. (Source: Investigational New Drugs)
Source: Investigational New Drugs - November 11, 2014 Category: Drugs & Pharmacology Source Type: research

Human uridine phosphorylase-1 inhibitors: a new approach to ameliorate 5-fluorouracil-induced intestinal mucositis
Conclusion Our results bring support to the hUP1 inhibitor strategy as a novel possibility of prevention and treatment of mucositis during the 5-FU chemotherapy, based on the approach of uridine accumulation in plasma and tissues. (Source: Investigational New Drugs)
Source: Investigational New Drugs - November 11, 2014 Category: Drugs & Pharmacology Source Type: research

CG100649, a novel COX-2 inhibitor, inhibits colorectal adenoma and carcinoma growth in mouse models
Summary Nonsteroidal anti-inflammatory drugs (NSAIDs) and selective cyclooxygenase-2 (COX-2) inhibitors (COXIBs) can reduce the risk of developing colorectal cancer (CRC) and are being considered for use as adjuvant therapy for treatment of CRC patients. However, long-term use of most NSAIDs, except aspirin, increases cardiovascular risk, hampering use of these drugs in CRC prevention and possibly for treatment. CG100649 is a new member of the COXIB family, which is proposed to inhibit both COX-2 and carbonic anhydrase-I/-II (CA-I/-II) activity. Using mouse models, we show here that CG100649 inhibits premalignant...
Source: Investigational New Drugs - November 11, 2014 Category: Drugs & Pharmacology Source Type: research

Cytotoxic flavonoids and isoflavonoids from Erythrina sigmoidea towards multi-factorial drug resistant cancer cells
Conclusions Compounds from Erythrina sigmoidea and mostly 6α-hydroxyphaseollidin are potential antiproliferative natural products that deserve more investigations to develop novel anticancer drugs against sensitive and otherwise drug-resistant phenotypes. (Source: Investigational New Drugs)
Source: Investigational New Drugs - November 11, 2014 Category: Drugs & Pharmacology Source Type: research

A phase I study of the histone deacetylase (HDAC) inhibitor entinostat, in combination with sorafenib in patients with advanced solid tumors
Abstract Based on preclinical data demonstrating cytotoxic synergy between sorafenib and entinostat, a phase I study of this combination was conducted in patients with advanced solid tumors. Enrollment followed the traditional “3 + 3” dose escalation scheme. Entinostat was given orally once every 2 weeks, starting at a dose of 4 mg and escalating to 6 and 10 mg every 2 weeks. Sorafenib was administered as a continuous oral dose, escalating from 200 to 400 mg twice daily. A treatment cycle was 28 days. A total of 31 patients with advanced solid tumors were enr...
Source: Investigational New Drugs - November 5, 2014 Category: Drugs & Pharmacology Source Type: research

Dual antiangiogenic inhibition: a phase I dose escalation and expansion trial targeting VEGF-A and VEGFR in patients with advanced solid tumors
Conclusions Combination sorafenib and bevacizumab was well-tolerated and demonstrated antitumor activity in heavily pretreated patients with advanced solid tumors. (Source: Investigational New Drugs)
Source: Investigational New Drugs - November 4, 2014 Category: Drugs & Pharmacology Source Type: research

Role of the lean body mass and of pharmacogenetic variants on the pharmacokinetics and pharmacodynamics of sunitinib in cancer patients
Conclusions This study indicates that LBM and drug monitoring may be helpful in the management of sunitinib-treated patients. (Source: Investigational New Drugs)
Source: Investigational New Drugs - October 25, 2014 Category: Drugs & Pharmacology Source Type: research

Phase I/II study with ruthenium compound NAMI-A and gemcitabine in patients with non-small cell lung cancer after first line therapy
Conclusion NAMI-A administered in combination with gemcitabine is only moderately tolerated and less active in NSCLC patients after first line treatment than gemcitabine alone. (Source: Investigational New Drugs)
Source: Investigational New Drugs - October 25, 2014 Category: Drugs & Pharmacology Source Type: research

Identification of cellular and molecular factors determining the response of cancer cells to six ergot alkaloids
In conclusion, the cytotoxicity of ergot alkaloids is not involved in classical mechanisms of drug resistance opening the possibility to bypass resistance and to treat otherwise drug-resistant and refractory tumors. The modes of action are multifactorial, which is a typical feature of many natural compounds. (Source: Investigational New Drugs)
Source: Investigational New Drugs - October 25, 2014 Category: Drugs & Pharmacology Source Type: research

BYL719, a selective inhibitor of phosphoinositide 3-Kinase α, enhances the effect of selumetinib (AZD6244, ARRY-142886) in KRAS-mutant non-small cell lung cancer
Conclusion Taken together, these data suggest that combination treatment with selumetinib and BYL719 is a promising therapeutic approach to overcoming resistance to MEK inhibitors. (Source: Investigational New Drugs)
Source: Investigational New Drugs - October 25, 2014 Category: Drugs & Pharmacology Source Type: research

Phase I dose-escalation study evaluating safety, tolerability and pharmacokinetics of MEDI-573, a dual IGF-I/II neutralizing antibody, in Japanese patients with advanced solid tumours
Conclusions MEDI-573 is well tolerated at the doses investigated. (Source: Investigational New Drugs)
Source: Investigational New Drugs - October 25, 2014 Category: Drugs & Pharmacology Source Type: research

Preclinical combination therapy of the investigational drug NAMI-A + with doxorubicin for mammary cancer
Conclusions The combined therapy of NAMI-A with doxorubicin synergizes on lung metastasis in a preclinical mouse model. The combination therapy at the maximum tolerated doses of the two drugs is toxic. Hence, this combination is not suitable for clinical studies using maximum tolerated doses. (Source: Investigational New Drugs)
Source: Investigational New Drugs - October 23, 2014 Category: Drugs & Pharmacology Source Type: research

Novel benzoxazines as inhibitors of angiogenesis
In this study, we screened eight novel benzoxazine inhibitors of both PI3K isoforms and the related DNA-PK, for their anti-angiogenic effects. Our findings identified the novel benzoxazine (7, 8 (substituted)-2-morpholino-benz (1,3) oxazine: LTUSI122) to be non-toxic at concentrations up to 5 μM, while exhibiting significant inhibition of various aspects of angiogenesis including endothelial proliferation, migration and tube formation. The molecular mechanisms were examined using an angiogenesis array, revealing inhibition of several proliferative and migratory angiogenic factors, including VEGFR, MMP, IL-8, uPAR a...
Source: Investigational New Drugs - October 23, 2014 Category: Drugs & Pharmacology Source Type: research

A phase Ib study of linsitinib (OSI-906), a dual inhibitor of IGF-1R and IR tyrosine kinase, in combination with everolimus as treatment for patients with refractory metastatic colorectal cancer
Conclusions The MTD of OSI-906 and everolimus was 50 mg BID and 5 mg QD, respectively. No indications of clinical activity were observed in refractory mCRC patients. (Source: Investigational New Drugs)
Source: Investigational New Drugs - October 22, 2014 Category: Drugs & Pharmacology Source Type: research

A phase I trial of combination trastuzumab, lapatinib, and bevacizumab in patients with advanced cancer
Conclusions Combination trastuzumab, lapatinib, and bevacizumab was well-tolerated and demonstrated antitumor activity in heavily pretreated patients with advanced malignancy. (Source: Investigational New Drugs)
Source: Investigational New Drugs - October 18, 2014 Category: Drugs & Pharmacology Source Type: research

A multicenter phase 1 study of γ -secretase inhibitor RO4929097 in combination with capecitabine in refractory solid tumors
Conclusions The recommended phase 2 dose is capecitabine 1,000 mg/m2 orally twice daily on days 1 through 14 with RO4929097 20 mg orally once daily on days 1–3, 8–10 and 15–17 with a 21 day cycle. Clinical benefit was observed in cervical and colon cancer. Autoinduction of RO4929097 was seen both with increasing cycle number and increasing dose. Plasma concentrations of RO4929097 were above those needed for Notch inhibition. (Source: Investigational New Drugs)
Source: Investigational New Drugs - October 16, 2014 Category: Drugs & Pharmacology Source Type: research

A phase II trial of bevacizumab plus temsirolimus in patients with advanced hepatocellular carcinoma
Conclusion This first-line HCC trial evaluating the BEV/TEM doublet reports an ORR of 19 % and OS of 14 months which is favorable but requires further study at a more optimized dose and schedule. (Source: Investigational New Drugs)
Source: Investigational New Drugs - October 16, 2014 Category: Drugs & Pharmacology Source Type: research

Phase 1 trial of tivantinib in combination with sorafenib in adult patients with advanced solid tumors
Conclusions The combination treatment could be administered at full standard single-agent doses in all patients except those with HCC, where tivantinib was lowered to 240 mg BID. Preliminary evidence of anticancer activity was observed in patients with RCC, HCC, and melanoma, including patients refractory to sorafenib and/or other anti-VEGF pathway therapies. The combination treatment has therapeutic potential in treating a variety of solid tumors. (Source: Investigational New Drugs)
Source: Investigational New Drugs - October 8, 2014 Category: Drugs & Pharmacology Source Type: research

Pharmacology, immunogenicity, and efficacy of a novel pegylated recombinant Erwinia chrysanthemi-derived L-asparaginase
Summary Bacterial L-asparaginase (ASNase), hydrolyzing L-asparagine (Asn), is an indispensable component used in the treatment of acute lymphoblastic leukemia (ALL) and certain lymphoma entities. Native Erwinia chrysanthemi-derived ASNase (n-crisantaspase) has been approved as a second-line drug for treating patients exhibiting allergy syndromes to native and pegylated Escherichia coli-derived ASNase (EC-ASNase). However, it still induces hypersensitivity in at least 17 % of treated patients. In the present study, we investigated the pharmacological activity, immunogenicity and anti-leukemic activity of a ne...
Source: Investigational New Drugs - September 25, 2014 Category: Drugs & Pharmacology Source Type: research

Preclinical analyses and phase I evaluation of LY2603618 administered in combination with Pemetrexed and cisplatin in patients with advanced cancer
Summary LY2603618 is an inhibitor of checkpoint kinase 1 (CHK1), an important regulator of the DNA damage checkpoints. Preclinical experiments analyzed NCI-H2122 and NCI-H441 NSCLC cell lines and in vitro/in vivo models treated with pemetrexed and LY2603618 to provide rationale for evaluating this combination in a clinical setting. Combination treatment of LY2603618 with pemetrexed arrested DNA synthesis following initiation of S-phase in cells. Experiments with tumor-bearing mice administered the combination of LY2603618 and pemetrexed demonstrated a significant increase of growth inhibition of NCI-H2122 (H2122)...
Source: Investigational New Drugs - September 25, 2014 Category: Drugs & Pharmacology Source Type: research

Novel antitumour indole alkaloid, Jerantinine A, evokes potent G2/M cell cycle arrest targeting microtubules
Summary Natural products play a pivotal role in the treatment of cancer; identification of compounds such as taxanes and the vinca alkaloids were seminal landmarks in natural product drug discovery. Jerantinine A, a novel Aspidosperma alkaloid isolated from plant species Tabernaemontana corymbosa, was previously reported to possess cytotoxic activity against vincristine-resistant nasopharyngeal carcinoma cells and is therefore an ideal candidate for biological investigation. Furthermore, Tabernaemontana corymbosa, has been placed in the endangered list of threatened species by the International Union for Conserva...
Source: Investigational New Drugs - September 25, 2014 Category: Drugs & Pharmacology Source Type: research

In vitro and in vivo characterisation of ASP9521: a novel, selective, orally bioavailable inhibitor of 17β-hydroxysteroid dehydrogenase type 5 (17βHSD5; AKR1C3)
Conclusions ASP9521 is a potent, selective, orally bioavailable AKR1C3 inhibitor. (Source: Investigational New Drugs)
Source: Investigational New Drugs - September 25, 2014 Category: Drugs & Pharmacology Source Type: research

Phase II trial of bortezomib plus doxorubicin in hepatocellular carcinoma (E6202): a trial of the Eastern Cooperative Oncology Group
Conclusions The combination of doxorubicin and bortezomib was well-tolerated in patients with hepatocellular carcinoma, but the primary endpoint was not met. Exploratory analyses of markers of proteasome inhibition suggest a possible prognostic and predictive role and should be explored further in tumor types for which bortezomib is efficacious. (Source: Investigational New Drugs)
Source: Investigational New Drugs - September 25, 2014 Category: Drugs & Pharmacology Source Type: research

Preclinical characterization of the CDK4/6 inhibitor LY2835219: in-vivo cell cycle-dependent/independent anti-tumor activities alone/in combination with gemcitabine
We present the identification and characterization of a potent CDK4/6 inhibitor, LY2835219. LY2835219 inhibits CDK4 and CDK6 with low nanomolar potency, inhibits Rb phosphorylation resulting in a G1 arrest and inhibition of proliferation, and its activity is specific for Rb-proficient cells. In vivo target inhibition studies show LY2835219 is a potent inhibitor of Rb phosphorylation, induces a complete cell cycle arrest and suppresses expression of several Rb-E2F-regulated proteins 24 hours after a single dose. Oral administration of LY2835219 inhibits tumor growth in human tumor xenografts representing different hist...
Source: Investigational New Drugs - September 25, 2014 Category: Drugs & Pharmacology Source Type: research

Activity of the polyamine-vectorized anti-cancer drug F14512 against pediatric glioma and neuroblastoma cell lines.
Summary The poor prognosis of children with high-grade glioma (HGG) and high-risk neuroblastoma, despite multidisciplinary therapeutic approaches, demands new treatments for these indications. F14512 is a topoisomerase II inhibitor containing a spermine moiety that facilitates selective uptake by tumor cells via the Polyamine Transport System (PTS) and increases topoisomerase II poisoning. Here, F14512 was evaluated in pediatric HGG and neuroblastoma cell lines. PTS activity and specificity were evaluated using a fluorescent spermine-coupled probe. The cytotoxicity of F14512, alone or in combination with ionizing...
Source: Investigational New Drugs - September 25, 2014 Category: Drugs & Pharmacology Source Type: research

Pharmacokinetic/Pharmacodynamic modeling of abexinostat-induced thrombocytopenia across different patient populations: application for the determination of the maximum tolerated doses in both lymphoma and solid tumour patients
Conclusions The PKPD model was able to predict thrombocytopenia following abexinostat administration in both patient populations. A model-based approach to determine the recommended dose in phase I trials is preferable due to the imprecision of the 3 + 3 design. (Source: Investigational New Drugs)
Source: Investigational New Drugs - September 25, 2014 Category: Drugs & Pharmacology Source Type: research

A phase I clinical trial of navitoclax, a targeted high-affinity Bcl-2 family inhibitor, in combination with gemcitabine in patients with solid tumors
Conclusions: The combination of navitoclax 325 mg with gemcitabine 1,000 mg/m2 was generally well tolerated and exhibited a favorable safety profile in patients with advanced solid tumors. (Source: Investigational New Drugs)
Source: Investigational New Drugs - September 25, 2014 Category: Drugs & Pharmacology Source Type: research

Rituximab for treating CD20+ prostate cancer with generalized lymphadenopathy: a case report and review of the literature
We report a case of advanced prostate cancer presenting with generalized lymphadenopathy that expressed CCR7 and CD20. CCR7 expression in prostate cancer has been previously reported only once; the expression of CD20 has not been reported before. Rituximab therapy was initiated in this case and resulted in a significant biochemical response. This unique metastatic and biochemical pattern may signify a distinct subtype of prostate cancer that may be amenable to treatment with anti-CD20 antibodies. (Source: Investigational New Drugs)
Source: Investigational New Drugs - September 25, 2014 Category: Drugs & Pharmacology Source Type: research

A phase I study of decitabine with pegylated interferon α-2b in advanced melanoma: impact on DNA methylation and lymphocyte populations
Conclusions The response to this combination regimen was characterized by significant myelosuppression, particularly neutropenia. Although disappointing efficacy and slow accrual led to early closure of the trial, hypomethylation showed pharmacodynamic evidence of a therapeutic effect of decitabine at all dose levels. (Source: Investigational New Drugs)
Source: Investigational New Drugs - September 25, 2014 Category: Drugs & Pharmacology Source Type: research

Effects of the combination of TRC105 and bevacizumab on endothelial cell biology
In this report, we evaluated the effects of TRC105 on primary human umbilical vascular endothelial cells (HUVEC) as a single agent and in combination with bevacizumab. As single agents, both TRC105 and bevacizumab efficiently blocked HUVEC tube formation, and the combination of both agents achieved even greater levels of inhibition. We further assessed the effects of each drug on various aspects of HUVEC function. While bevacizumab was observed to inhibit HUVEC viability in nutrient-limited medium, TRC105 had little effect on HUVEC viability, either alone or in combination with bevacizumab. Additionally, both drugs inhibit...
Source: Investigational New Drugs - September 25, 2014 Category: Drugs & Pharmacology Source Type: research

In vitro 3D colon tumor penetrability of SRJ09, a new anti-cancer andrographolide analog
In conclusion, SRJ09 successfully penetrated through DLD-1 MCL by diffusion and emerged as a potential candidate to be developed as a clinically viable anti-colon cancer drug. (Source: Investigational New Drugs)
Source: Investigational New Drugs - September 25, 2014 Category: Drugs & Pharmacology Source Type: research

The novel kinase inhibitor EMD1214063 is effective against neuroblastoma
Conclusions Treatment of neuroblastoma tumor cells with EMD1214063 inhibits HGF-induced c-Met phosphorylation and results in cell death. EMD1214063 treatment is also effective in reducing tumor growth in vivo. EMD1214063 therefore represents a novel therapeutic agent for neuroblastoma, and further preclinical studies of EMD1214063 are warranted. (Source: Investigational New Drugs)
Source: Investigational New Drugs - September 25, 2014 Category: Drugs & Pharmacology Source Type: research

Targeting DNA repair with combination veliparib (ABT-888) and temozolomide in patients with metastatic castration-resistant prostate cancer
This study assessed the efficacy and safety of low dose oral PARP inhibitor veliparib (ABT-888) and temozolomide (TMZ) in docetaxel-pretreated patients with metastatic castration-resistant prostate cancer (mCRPC) in a single-arm, open-label, pilot study. Patients with mCRPC progressing on at least one docetaxel-based therapy and prostate specific antigen (PSA) ≥ 2 ng/mL were treated with veliparib 40 mg twice daily on days 1–7 and TMZ once daily (150 mg/m2/day cycle 1; if well tolerated then 200 mg/m2/day cycle 2 onwards) on days 1–5 q28 days. Patients received 2 (me...
Source: Investigational New Drugs - September 25, 2014 Category: Drugs & Pharmacology Source Type: research

A phase I safety and pharmacokinetic study of ABT-263 in combination with carboplatin/paclitaxel in the treatment of patients with solid tumors
Summary Bcl-2 family proteins are the key regulators of the intrinsic apoptotic pathway, controlling the point-of no-return and setting the threshold to engage the death machinery in response to chemical damage. Bcl-2 proteins have emerged as attractive targets for anti-cancer drug development. Navitoclax is a selective, potent, orally bioavailable, small molecule Bcl-2 inhibitor. Primary endpoints assessed the safety and pharmacokinetic (PK) interactions between navitoclax in combination with carboplatin/paclitaxel or paclitaxel alone in patients with solid tumors The study comprised two arms, one a combination ...
Source: Investigational New Drugs - September 25, 2014 Category: Drugs & Pharmacology Source Type: research

Gemcitabine and oxaliplatin chemotherapy for advanced hepatocellular carcinoma after failure of anti-angiogenic therapies
Summary Background Sorafenib is the only systemic treatment that has shown a significant benefit in overall survival (OS) and in progression-free survival (PFS) in advanced hepatocellular carcinoma (HCC) patients. No standard of care currently exists for second-line treatment. The association of Gemcitabine-Oxaliplatine (GEMOX) has shown efficacy in the first-line setting. The aim of this study was to evaluate the efficacy of GEMOX after failure of at least one line of anti-angiogenic (AA) therapy. Patient and methods We performed a multicenter retrospective analysis of advanced HCC patients that rece...
Source: Investigational New Drugs - September 25, 2014 Category: Drugs & Pharmacology Source Type: research

Phase I study on the safety, pharmacokinetic profile, and efficacy of the combination of TSU-68, an oral antiangiogenic agent, and S-1 in patients with advanced hepatocellular carcinoma
Conclusion The recommended dose for advanced HCC should be 400 mg/day TSU-68 and 100 mg/day S-1 for 4 weeks followed by 2-week rest. (Source: Investigational New Drugs)
Source: Investigational New Drugs - September 25, 2014 Category: Drugs & Pharmacology Source Type: research

Atypical reversible posterior leukoencephalopathy syndrome (RPLS) induced by cediranib in a patient with metastatic rectal cancer
Conclusion RPLS is a rare, but serious, clinicoradiologic syndrome which has been described as an adverse effect of many anti-angiogenic agents and should also be considered in patients on cediranib who present with neurologic symptoms along with vasogenic edema seen on MRI. If RPLS is suspected, cediranib should be discontinued and blood pressure should be aggressively controlled. (Source: Investigational New Drugs)
Source: Investigational New Drugs - September 25, 2014 Category: Drugs & Pharmacology Source Type: research

The use of everolimus to reverse tamoxifen resistance in men with metastatic breast cancer: a case report
(Source: Investigational New Drugs)
Source: Investigational New Drugs - September 25, 2014 Category: Drugs & Pharmacology Source Type: research