Edward Garmey - Academia.edu (original) (raw)

Papers by Edward Garmey

Patient Education and Counseling, 2007

Objective-To determine uptake and socio-demographics predictors of acceptance of voluntary counse... more Objective-To determine uptake and socio-demographics predictors of acceptance of voluntary counseling and testing (VCT) among post-partum women in Botswana.

Clinical advances in hematology & oncology: H&O

Prostate cancer is the most common cancer occurring among men in the United States. In spite of t... more Prostate cancer is the most common cancer occurring among men in the United States. In spite of the disease's favorable prognosis, approximately 30,000 U.S. men develop incurable metastatic disease each year, making prostate cancer the second-leading cause of cancer-related deaths among men in the United States. Although hormone-based therapies generally result in rapid responses, virtually all patients ultimately develop androgen-independent progressive disease. It is among these men with hormone-refractory prostate cancer (HRPC) that the role of chemotherapy continues to be investigated. To date, three drugs (estramustine, mitoxantrone, and docetaxel) have been approved by the US Food and Drug Administration (FDA) for first-line chemotherapy in HRPC, with other agents and combinations now under evaluation in ongoing clinical trials. Patients whose tumors progress through first-line chemotherapy have limited treatment options available to them and less than half of all men with HRPC will receive any second-line chemotherapy. To date, only one phase III randomized clinical trial has been completed in this setting and no therapies are FDA-approved. We review here the entirety of phase II and III data evaluating chemotherapy agents in second-line HRPC.

European Journal of Cancer Supplements, 2009

European Journal of Cancer Supplements, 2010

Poster Session -Toxicology-side effects from the known hUPP1 structure. This high resolution stru... more Poster Session -Toxicology-side effects from the known hUPP1 structure. This high resolution structure revealed unequivocally the presence of an intramolecular disulfide bridge that repositions a critical, active-site, phosphate-coordinating arginine residue (Arg100) to a location that does not support catalysis of the enzyme's phosphorolytic activity. Consistent with this structural finding, in vitro comparison of mammalian UPP1 and UPP2 activity reveals a substantial sensitivity to oxidative inactivation in the latter isoform. Together these results demonstrate that UPP2 is intracellularly controlled by a redox mechanism that could be exploited to inactivate the enzyme and therefore limit the activation of Capecitabine in the liver and other organs expressing this UPP isoform.

The Oncologist, 2011

Expression of the receptor tyrosine kinase c-MET (MET, mesenchymal-epithelial transition factor) ... more Expression of the receptor tyrosine kinase c-MET (MET, mesenchymal-epithelial transition factor) in many cancers, and its participation in multiple signal transduction pathways involved in malignant tumor growth, suggest a wide therapeutic potential for MET inhibition in human cancer. Here we describe the discovery and early clinical development of ARQ 197, a novel, selective, non-ATP-competitive inhibitor of MET. Phase I studies demonstrate that ARQ 197 has a predictable pharmacokinetics and favorable safety profile, making it a potentially ideal partner for combination with cytotoxic chemotherapies and targeted anticancer agents. Results from phase I and phase II trials demonstrate preliminary evidence of anticancer activity. New data from a global phase II randomized trial comparing a combination of ARQ 197 plus erlotinib with erlotinib/placebo, in endothelial growth factor receptor inhibitor-naïve patients with locally advanced/ metastatic non-small cell lung cancer, demonstrate improvement in progression-free and overall survival with combined therapy. Results were especially pronounced for patients with non-squamous lung cancer histologies, and in particular molecularly defined subgroups including KRAS mutations. These and other data from ARQ 197 clinical trials in hepatocellular, germ-cell, pancreatic (in combination with gemcitabine), and colorectal (in combination with cetuximab and irinotecan) cancers further highlight the potential role of ARQ 197 in existing and emerging anticancer therapeutic regimens. The Oncologist 2011;16:788 -799

Patient Education and Counseling, 2007

Objective-To determine uptake and socio-demographics predictors of acceptance of voluntary counse... more Objective-To determine uptake and socio-demographics predictors of acceptance of voluntary counseling and testing (VCT) among post-partum women in Botswana.

Journal of Pediatric Surgery, 2010

Background: Catheter-related bloodstream infections remain costly with no simple prevention. We r... more Background: Catheter-related bloodstream infections remain costly with no simple prevention. We report preliminary results of a phase I trial of ethanol-lock administration to prevent mediport catheterrelated bloodstream infections in children. Methods: Twelve patients receiving intravenous antibody treatments for neuroblastoma were enrolled. On 4 days of each 5-day antibody cycle, 70% ethanol was administered instead of heparin to dwell in each patient's mediport overnight. We used clinical monitoring/questionnaires to assess symptoms and measured blood ethanol levels and liver functions. Patients were tracked for positive blood cultures. Time to infection for ethanol-lock-treated patients was compared with historical controls. Results: We administered 123 ethanol-locks. No adverse symptoms attributable to ethanol occurred; one patient's urticaria worsened. Blood ethanol levels averaged 11 mg/dL. The study was voluntarily suspended after 3 patients' catheters became occluded, 1 of which fractured. A positive blood culture occurred in 1 (8%) of 12 patients, but suspension of the study precluded statistical power to detect impact on time to infection.

Journal of Clinical Oncology, 2011

Purpose c-MET (MET) receptor activation is associated with poor prognosis and epidermal growth fa... more Purpose c-MET (MET) receptor activation is associated with poor prognosis and epidermal growth factor receptor (EGFR) tyrosine kinase inhibitor (TKI) resistance in non-small-cell lung cancer (NSCLC). This global, randomized phase II trial examined erlotinib plus tivantinib (ARQ 197; ArQule, Woburn, MA), a novel MET inhibitor.

Journal of Clinical Oncology, 2008

We examined the rate of increase in the body mass index (BMI; kg/m 2 ) after final height attainm... more We examined the rate of increase in the body mass index (BMI; kg/m 2 ) after final height attainment in survivors of acute lymphoblastic leukemia (ALL) and a noncancer comparison group.

Clinical cancer research : an official journal of the American Association for Cancer Research, Jan 15, 2015

Increased tumor hypoxia and hence elevated hypoxia-inducible factor-1α (HIF1α) is thought to limi... more Increased tumor hypoxia and hence elevated hypoxia-inducible factor-1α (HIF1α) is thought to limit the efficacy of vascular endothelial growth factor (VEGF) pathway-targeting drugs by upregulating adaptive resistance genes. One strategy to counteract this is to combine antiangiogenic drugs with agents able to suppress HIF1α. One such possibility is the investigational drug CRLX101, a nanoparticle-drug conjugate (NDC) containing the payload camptothecin, a known topoisomerase-I poison. CRLX101 was evaluated both as a monotherapy and combination with bevacizumab in a preclinical mouse model of advanced metastatic ovarian cancer. These preclinical studies contributed to the rationale for undertaking a phase II clinical study to evaluate CRLX101 monotherapy in patients with advanced platinum-resistant ovarian cancer. Preclinically, CRLX101 is highly efficacious as a monotherapy when administered at maximum-tolerated doses. Furthermore, chronic low-dose CRLX101 with bevacizumab reduced b...

Patient Education and Counseling, 2007

Objective-To determine uptake and socio-demographics predictors of acceptance of voluntary counse... more Objective-To determine uptake and socio-demographics predictors of acceptance of voluntary counseling and testing (VCT) among post-partum women in Botswana.

Clinical advances in hematology & oncology: H&O

Prostate cancer is the most common cancer occurring among men in the United States. In spite of t... more Prostate cancer is the most common cancer occurring among men in the United States. In spite of the disease's favorable prognosis, approximately 30,000 U.S. men develop incurable metastatic disease each year, making prostate cancer the second-leading cause of cancer-related deaths among men in the United States. Although hormone-based therapies generally result in rapid responses, virtually all patients ultimately develop androgen-independent progressive disease. It is among these men with hormone-refractory prostate cancer (HRPC) that the role of chemotherapy continues to be investigated. To date, three drugs (estramustine, mitoxantrone, and docetaxel) have been approved by the US Food and Drug Administration (FDA) for first-line chemotherapy in HRPC, with other agents and combinations now under evaluation in ongoing clinical trials. Patients whose tumors progress through first-line chemotherapy have limited treatment options available to them and less than half of all men with HRPC will receive any second-line chemotherapy. To date, only one phase III randomized clinical trial has been completed in this setting and no therapies are FDA-approved. We review here the entirety of phase II and III data evaluating chemotherapy agents in second-line HRPC.

European Journal of Cancer Supplements, 2009

European Journal of Cancer Supplements, 2010

Poster Session -Toxicology-side effects from the known hUPP1 structure. This high resolution stru... more Poster Session -Toxicology-side effects from the known hUPP1 structure. This high resolution structure revealed unequivocally the presence of an intramolecular disulfide bridge that repositions a critical, active-site, phosphate-coordinating arginine residue (Arg100) to a location that does not support catalysis of the enzyme's phosphorolytic activity. Consistent with this structural finding, in vitro comparison of mammalian UPP1 and UPP2 activity reveals a substantial sensitivity to oxidative inactivation in the latter isoform. Together these results demonstrate that UPP2 is intracellularly controlled by a redox mechanism that could be exploited to inactivate the enzyme and therefore limit the activation of Capecitabine in the liver and other organs expressing this UPP isoform.

The Oncologist, 2011

Expression of the receptor tyrosine kinase c-MET (MET, mesenchymal-epithelial transition factor) ... more Expression of the receptor tyrosine kinase c-MET (MET, mesenchymal-epithelial transition factor) in many cancers, and its participation in multiple signal transduction pathways involved in malignant tumor growth, suggest a wide therapeutic potential for MET inhibition in human cancer. Here we describe the discovery and early clinical development of ARQ 197, a novel, selective, non-ATP-competitive inhibitor of MET. Phase I studies demonstrate that ARQ 197 has a predictable pharmacokinetics and favorable safety profile, making it a potentially ideal partner for combination with cytotoxic chemotherapies and targeted anticancer agents. Results from phase I and phase II trials demonstrate preliminary evidence of anticancer activity. New data from a global phase II randomized trial comparing a combination of ARQ 197 plus erlotinib with erlotinib/placebo, in endothelial growth factor receptor inhibitor-naïve patients with locally advanced/ metastatic non-small cell lung cancer, demonstrate improvement in progression-free and overall survival with combined therapy. Results were especially pronounced for patients with non-squamous lung cancer histologies, and in particular molecularly defined subgroups including KRAS mutations. These and other data from ARQ 197 clinical trials in hepatocellular, germ-cell, pancreatic (in combination with gemcitabine), and colorectal (in combination with cetuximab and irinotecan) cancers further highlight the potential role of ARQ 197 in existing and emerging anticancer therapeutic regimens. The Oncologist 2011;16:788 -799

Patient Education and Counseling, 2007

Objective-To determine uptake and socio-demographics predictors of acceptance of voluntary counse... more Objective-To determine uptake and socio-demographics predictors of acceptance of voluntary counseling and testing (VCT) among post-partum women in Botswana.

Journal of Pediatric Surgery, 2010

Background: Catheter-related bloodstream infections remain costly with no simple prevention. We r... more Background: Catheter-related bloodstream infections remain costly with no simple prevention. We report preliminary results of a phase I trial of ethanol-lock administration to prevent mediport catheterrelated bloodstream infections in children. Methods: Twelve patients receiving intravenous antibody treatments for neuroblastoma were enrolled. On 4 days of each 5-day antibody cycle, 70% ethanol was administered instead of heparin to dwell in each patient's mediport overnight. We used clinical monitoring/questionnaires to assess symptoms and measured blood ethanol levels and liver functions. Patients were tracked for positive blood cultures. Time to infection for ethanol-lock-treated patients was compared with historical controls. Results: We administered 123 ethanol-locks. No adverse symptoms attributable to ethanol occurred; one patient's urticaria worsened. Blood ethanol levels averaged 11 mg/dL. The study was voluntarily suspended after 3 patients' catheters became occluded, 1 of which fractured. A positive blood culture occurred in 1 (8%) of 12 patients, but suspension of the study precluded statistical power to detect impact on time to infection.

Journal of Clinical Oncology, 2011

Purpose c-MET (MET) receptor activation is associated with poor prognosis and epidermal growth fa... more Purpose c-MET (MET) receptor activation is associated with poor prognosis and epidermal growth factor receptor (EGFR) tyrosine kinase inhibitor (TKI) resistance in non-small-cell lung cancer (NSCLC). This global, randomized phase II trial examined erlotinib plus tivantinib (ARQ 197; ArQule, Woburn, MA), a novel MET inhibitor.

Journal of Clinical Oncology, 2008

We examined the rate of increase in the body mass index (BMI; kg/m 2 ) after final height attainm... more We examined the rate of increase in the body mass index (BMI; kg/m 2 ) after final height attainment in survivors of acute lymphoblastic leukemia (ALL) and a noncancer comparison group.

Clinical cancer research : an official journal of the American Association for Cancer Research, Jan 15, 2015

Increased tumor hypoxia and hence elevated hypoxia-inducible factor-1α (HIF1α) is thought to limi... more Increased tumor hypoxia and hence elevated hypoxia-inducible factor-1α (HIF1α) is thought to limit the efficacy of vascular endothelial growth factor (VEGF) pathway-targeting drugs by upregulating adaptive resistance genes. One strategy to counteract this is to combine antiangiogenic drugs with agents able to suppress HIF1α. One such possibility is the investigational drug CRLX101, a nanoparticle-drug conjugate (NDC) containing the payload camptothecin, a known topoisomerase-I poison. CRLX101 was evaluated both as a monotherapy and combination with bevacizumab in a preclinical mouse model of advanced metastatic ovarian cancer. These preclinical studies contributed to the rationale for undertaking a phase II clinical study to evaluate CRLX101 monotherapy in patients with advanced platinum-resistant ovarian cancer. Preclinically, CRLX101 is highly efficacious as a monotherapy when administered at maximum-tolerated doses. Furthermore, chronic low-dose CRLX101 with bevacizumab reduced b...