Lowell Anthony - Academia.edu (original) (raw)

Papers by Lowell Anthony

BMC Cancer, 2021

Background Neuroendocrine tumors, although relatively rare in incidence, are now the second most ... more Background Neuroendocrine tumors, although relatively rare in incidence, are now the second most prevalent gastrointestinal neoplasm owing to indolent disease biology. A small but significant sub-group of neuroendocrine tumor patients suffer from diarrhea. This is usually secondary to carcinoid syndrome but can also be a result of short gut syndrome, bile acid excess or iatrogenic etiologies. Recently, an amino acid based oral rehydration solution (enterade® Advanced Oncology Formula) was found to have anti-diarrheal properties in preclinical models. Methods A retrospective chart review of all NET patients treated with enterade® AO was performed after IRB approval. Results Ninety-eight NET patients who had received enterade® AO at our clinic from May 2017 through June 2019 were included. Patients ( N = 49 of 98) with follow up data on bowel movements (BMs) were included for final analysis. Eighty-four percent of patients (41/49) had fewer BMs after taking enterade® AO and 66% (27/4...

JCO oncology practice, 2020

The role of clinical researchers is vital to cancer progress. The teaching, research, and leaders... more The role of clinical researchers is vital to cancer progress. The teaching, research, and leadership roles that academic oncologists hold need to be accounted for and appropriately compensated. National metrics are currently inexistent, but are necessary to move the oncology research field forward. Clinical research and routine clinical care must be harmoniously integrated without competing. This article reviews the national landscape of clinical cancer research and proposes a call for action.

Carcinogenesis, 2013

Carcinoid tumors are rare neuroendocrine tumors (NETs) that are increasing in incidence. Mutation... more Carcinoid tumors are rare neuroendocrine tumors (NETs) that are increasing in incidence. Mutation and altered expression of Wnt/β-catenin signaling components have been described in many tumors but have not been well-studied in NETs. Here, we observed accumulation of β-catenin in the cytoplasm and/or nucleus in 25% of clinical NET tissues. By mutational analysis, the mutations of β-catenin (I35S) and APC (E1317Q, T1493T) were identified in NET cells and the tissues. Expression of representative Wnt inhibitors was absent or markedly decreased in BON, a human pancreatic carcinoid cell line; treatment with 5-aza-2′-deoxycytidine (5-aza-CdR) increased expression levels of the Wnt inhibitors. Methylation analyses demonstrated that CpG islands of SFRP-1 and Axin-2 were methylated, whereas the promoters of DKK-1, DKK-3 and WIF-1 were unmethylated in four NET cells. Aberrant methylation of SFRP-1 was particularly observed in most of clinical NET tissues. In addition, the repression of these unmethylated genes was associated with histone H3 lysine 9 dimethylation (H3K9me2) in BON cells. Together, 5-aza-CdR treatment inhibited cell proliferation and decreased the protein levels of H3K9me2 and G9a. Moreover, a novel G9a inhibitor, UNC0638, suppressed BON cell proliferation through inhibition of Wnt/β-catenin pathway. Overexpression of the inhibitory genes, particularly SFRP-1 and WIF-1 in BON cells, resulted in suppression of anchorage-independent growth and inhibition of tumor growth in mice. Our findings suggest that aberrant Wnt/β-catenin signaling, through either mutations or epigenetic silencing of Wnt antagonists, contributes to the pathogenesis and growth of NETs and have important clinical implications for the prognosis and treatment of NETs.

Investigational New Drugs, 2014

Rare Tumors

Large cell neuroendocrine carcinomas (LCNEC) are rare, aggressive high-grade neuroendocrine neopl... more Large cell neuroendocrine carcinomas (LCNEC) are rare, aggressive high-grade neuroendocrine neoplasms within the neuroendocrine cell lineage spectrum. This manuscript provides a detailed review of published literature on LCNEC of gynecological origin. We performed a PubMed search for material available on gynecologic LCNEC. We analyzed 104 unique cases of gynecologic LCNECs, of which 45 were cervical primary, 45 were ovarian, 13 were uterine, and 1 was vaginal. A total of 45 cases of cervical LCNEC were identified with a median age of 36 years. Median overall survival was 16 months. We identified 45 ovarian LCNEC cases in the published literature with a median age of 54 years. Median overall survival was 8 months. 13 LCNEC cases of uterine origin were identified; 12 out of 13 were of endometrial origin and the median age was 71 years. The majority of patients presented with Stage III/IV disease (stages I–IV were 31%, 8%, 38%, and 23%, respectively). Gynecologic LCNEC is an aggressiv...

Blood

Currently available IV iron agents pose substantial safety and practical challenges to effective ... more Currently available IV iron agents pose substantial safety and practical challenges to effective management of iron deficiency anemia. Iron dextran administration requires a test dose and carries the risk of anaphylaxis. Non-dextran-containing IV iron agents (iron sucrose and ferric gluconate) do not require a test dose nor have this safety issue, but pose some practical challenges. These agents are FDA approved only for chronic kidney disease indications and require repeated administration of small doses (125 mg of iron as ferric gluconate over 10 minutes, 200 mg of iron as iron sucrose over 2–5 minutes, or 300–400 mg of iron as iron sucrose over 1.5 to 2.5 h). Accordingly, in a multicenter, randomized, blinded, placebo-controlled, crossover trial we assessed the safety of iron carboxymaltose, a new, investigational non-dextran IV iron complex that allows for rapid administration of high doses of iron. Five-hundred and eighty four (584) iron deficiency anemia patients received eith...

American Journal of Gastroenterology

Journal of Gastrointestinal Oncology

Ochsner Journal

Background: Checkpoint inhibitors have transformed the treatment of cancer in adults. This class ... more Background: Checkpoint inhibitors have transformed the treatment of cancer in adults. This class of drugs has demonstrated encouraging results in various malignancies such as metastatic melanoma, bladder cancer, renal cancer, and non-small cell lung carcinoma. However, researchers have only begun investigating the effectiveness and tolerability of checkpoint inhibitors in pediatric patients. Methods: We conducted a review of PubMed indexed literature and clinicaltrials.gov using combinations of the keywords checkpoint, inhibitor, pediatric, CTLA-4 (cytotoxic T lymphocyte antigen-4), PD-1 (programmed cell death-1), and PD-L1 (programmed cell death receptor-1 ligand) to find every recently completed and ongoing trial evaluating checkpoint inhibitors in patients younger than 21 years old. Pertinent articles and clinical trials discussing the role of immune checkpoint inhibitors in the pediatric population were selected for final analysis and manuscript citation. Results: This review presents an overview of the cellular mechanisms involved in checkpoint inhibition and of studies evaluating checkpoint inhibitors in humans. The review also details results and side effects from studies conducted with pediatric patients, current pediatric clinical trials, and future implications. Conclusion: Immune checkpoint inhibitors have the potential to further therapeutic advances in pediatric oncology; however, we need more clinical trials and combination drug strategies targeted toward pediatric cancers.

Anticancer research, 2018

Combination nab-paclitaxel/gemcitabine (AG) is superior to gemcitabine in patients with metastati... more Combination nab-paclitaxel/gemcitabine (AG) is superior to gemcitabine in patients with metastatic pancreatic cancer (PC). There are limited data for AG in borderline resectable (BR) or locally advanced pancreatic cancer (LAPC). Herein, we report our experience with neoadjuvant AG for BR/LAPC in patients ineligible for FOLFIRINOX. This retrospective series, included patients with BR/LAPC who received AG as neoadjuvant therapy for 3-4 months followed by radiation, then re-evaluation for surgery. Between 10/2013-2/2018, 32 patients (22 BR, 10 LAPC) were treated with this approach. Median age was 70 years. Nine patients were converted to resectability by imaging; six had R0 resections (19%), five (16%) achieved a partial response and 24 (75%) had stable disease. In this small series, the R0 resection rate and response rate were 19% and 16% respectively. These data suggest that neoadjuvant AG may be an alternate option for patients ineligible for FOLFIRINOX.

Journal of oncology, 2018

Incidence of low grade well-differentiated neuroendocrine tumors (NET) is on the rise. The North ... more Incidence of low grade well-differentiated neuroendocrine tumors (NET) is on the rise. The North American Neuroendocrine Tumor Society estimates that the United States has more than 150,000 gastroenteropancreatic NET patients. About 10% of metastatic NETs can be unknown primary, and due to their rarity, dedicated treatment algorithms and regimens are not defined. Combination of capecitabine and temozolomide (CAPTEM) is one of the systemic treatments used in gastroenteropancreatic NETs. We explored clinical activity of CAPTEM in NET of unknown primary. . Retrospective review of NET of unknown primary managed at the University of Kentucky over the past five years (2012-2016). . 56 patients with NET of unknown primary were identified; 12 patients were treated with CAPTEM. Median progression-free survival on CAPTEM in grade II and grade III NET of unknown primary was 10.8 and 7 months, respectively. Six patients showed reduction in metastatic tumor volume at three-month CT scan. Three p...

Oncotarget, Jan 10, 2018

Neuroendocrine tumors (NETs) have a low incidence but relatively high prevalence. Over the last t... more Neuroendocrine tumors (NETs) have a low incidence but relatively high prevalence. Over the last three decades, the incidence of NETs has risen 6-fold in the United States. We conducted an observational study to compare the incidence of NETs reported to the Kentucky Cancer Registry (KCR) versus that reported to Surveillance, Epidemiology, and End Results Program (SEER). We also provide a systematic review of the state of neuroendocrine tumors worldwide, and compare the available global and local published data. KCR and SEER databases were queried for NET cases between 1995 and 2015. A detailed literature review of epidemiological data for various nations worldwide summarize epidemiological data from various countries. KCR recorded 6179 individuals with newly diagnosed NETs between 1995 and 2015. Between 1995-2012, the incidence of NETs in KCR increased from 3.1 to 7.1 per 100,000 cases, while it increased from 3.96 to 6.61 in the SEER database. The incidence rates in both KCR and SEE...

Clinical therapeutics, Jan 30, 2018

In the placebo-controlled Phase III TELESTAR (Telotristat Etiprate for Somatostatin Analogue Not ... more In the placebo-controlled Phase III TELESTAR (Telotristat Etiprate for Somatostatin Analogue Not Adequately Controlled Carcinoid Syndrome) trial, the oral tryptophan hydroxylase inhibitor telotristat ethyl significantly reduced bowel movement (BM) frequency during a 12-week, double-blind treatment period in 135 patients with metastatic neuroendocrine tumors with carcinoid syndrome and ≥4 BMs per day. Patients (mean [SD] age, 63.5 [8.9] years; mean [SD] body mass index, 24.9 [4.9] kg/m) received placebo, telotristat ethyl 250 mg, or telotristat ethyl 500 mg 3 times per day (TID) in addition to somatostatin analogue therapy. Weight loss is associated with uncontrolled carcinoid syndrome and may be associated with reduced survival. Assessment of the occurrence of weight change ≥3% at week 12 was prespecified in the statistical analysis plan. In 120 patients with weight data available, weight gain ≥3% was observed in 2 of 39 patients (5.1%) taking placebo TID, 7 of 41 (17.1%) taking tel...

Oncotarget, Jan 6, 2018

This unique case series and review of literature suggests that immune checkpoint inhibitors may h... more This unique case series and review of literature suggests that immune checkpoint inhibitors may have clinical activity in neuroendocrine tumors. Summarize advances of immuno-oncology in neuroendocrine tumors with the help of a case series. Case series and review of literature. The patients were treated with immune checkpoint inhibitors (pembrolizumab or nivolumab). Life expectancy, quality of life, disease progression. Maximum durable response of 16 months in one of the patients so far. All patients showed improvement in quality of life before disease progression. Two out of four are still on therapy. None of the patients experienced immune checkpoint inhibitor associated side-effects. All patients had failed standard of care therapy prior to the initiation of immune checkpoint inhibitors and were on the verge of hospice. Immune checkpoint inhibitors have revolutionized cancer management and the last 5 years have seen a rapid expansion in the indications for this class of drug. Neur...

Oncotarget, Jan 6, 2018

Large cell neuroendocrine carcinomas (LCNEC) are a group of rare high grade neuroendocrine tumors... more Large cell neuroendocrine carcinomas (LCNEC) are a group of rare high grade neuroendocrine tumors that often behave clinically like small cell carcinoma (SCLC) and are treated as such. No major advancement in the management of these tumors has occurred in the last 30 years. We present a case series of three cases from Markey Cancer center along with a review of 13 published cases in the literature wherein immune-checkpoint inhibitors were utilized in the management of LCNEC. Immune-checkpoint inhibitors might have clinical activity in LCNEC. Role of immune-checkpoint inhibitors should be explored in prospective LCNEC clinical trials. We summarize current evidence regarding use of immune checkpoint inhibitors in the treatment of LCNEC.

Endocrine-related cancer, Jan 12, 2018

Telotristat ethyl, a tryptophan hydroxylase inhibitor, was efficacious and well tolerated in the ... more Telotristat ethyl, a tryptophan hydroxylase inhibitor, was efficacious and well tolerated in the Phase 3 TELESTAR study in patients with carcinoid syndrome (CS) experiencing ≥4 bowel movements per day (BMs/day) while on somatostatin analogs (SSAs). TELECAST, a Phase 3 companion study, assessed safety and efficacy of telotristat ethyl in patients with CS (diarrhea, flushing, abdominal pain, nausea, or elevated urinary 5-hydroxyindoleacetic acid [u5-HIAA]) with <4 BMs/day on SSAs (or ≥1 symptom or ≥4 BMs/day if not on SSAs) during a 12-week double-blind treatment period followed by a 36-week open-label extension (OLE). The primary safety and efficacy endpoints were incidence of treatment-emergent adverse events (TEAEs) and percent change from baseline in 24-hour u5-HIAA at Week 12. Patients (N=76) were randomly assigned (1:1:1) to receive placebo or telotristat ethyl 250 mg or 500 mg 3 times per day (tid); 67 continued receiving telotristat ethyl 500 mg tid during the OLE. Through ...

BMC Cancer, 2021

Background Neuroendocrine tumors, although relatively rare in incidence, are now the second most ... more Background Neuroendocrine tumors, although relatively rare in incidence, are now the second most prevalent gastrointestinal neoplasm owing to indolent disease biology. A small but significant sub-group of neuroendocrine tumor patients suffer from diarrhea. This is usually secondary to carcinoid syndrome but can also be a result of short gut syndrome, bile acid excess or iatrogenic etiologies. Recently, an amino acid based oral rehydration solution (enterade® Advanced Oncology Formula) was found to have anti-diarrheal properties in preclinical models. Methods A retrospective chart review of all NET patients treated with enterade® AO was performed after IRB approval. Results Ninety-eight NET patients who had received enterade® AO at our clinic from May 2017 through June 2019 were included. Patients ( N = 49 of 98) with follow up data on bowel movements (BMs) were included for final analysis. Eighty-four percent of patients (41/49) had fewer BMs after taking enterade® AO and 66% (27/4...

JCO oncology practice, 2020

The role of clinical researchers is vital to cancer progress. The teaching, research, and leaders... more The role of clinical researchers is vital to cancer progress. The teaching, research, and leadership roles that academic oncologists hold need to be accounted for and appropriately compensated. National metrics are currently inexistent, but are necessary to move the oncology research field forward. Clinical research and routine clinical care must be harmoniously integrated without competing. This article reviews the national landscape of clinical cancer research and proposes a call for action.

Carcinogenesis, 2013

Carcinoid tumors are rare neuroendocrine tumors (NETs) that are increasing in incidence. Mutation... more Carcinoid tumors are rare neuroendocrine tumors (NETs) that are increasing in incidence. Mutation and altered expression of Wnt/β-catenin signaling components have been described in many tumors but have not been well-studied in NETs. Here, we observed accumulation of β-catenin in the cytoplasm and/or nucleus in 25% of clinical NET tissues. By mutational analysis, the mutations of β-catenin (I35S) and APC (E1317Q, T1493T) were identified in NET cells and the tissues. Expression of representative Wnt inhibitors was absent or markedly decreased in BON, a human pancreatic carcinoid cell line; treatment with 5-aza-2′-deoxycytidine (5-aza-CdR) increased expression levels of the Wnt inhibitors. Methylation analyses demonstrated that CpG islands of SFRP-1 and Axin-2 were methylated, whereas the promoters of DKK-1, DKK-3 and WIF-1 were unmethylated in four NET cells. Aberrant methylation of SFRP-1 was particularly observed in most of clinical NET tissues. In addition, the repression of these unmethylated genes was associated with histone H3 lysine 9 dimethylation (H3K9me2) in BON cells. Together, 5-aza-CdR treatment inhibited cell proliferation and decreased the protein levels of H3K9me2 and G9a. Moreover, a novel G9a inhibitor, UNC0638, suppressed BON cell proliferation through inhibition of Wnt/β-catenin pathway. Overexpression of the inhibitory genes, particularly SFRP-1 and WIF-1 in BON cells, resulted in suppression of anchorage-independent growth and inhibition of tumor growth in mice. Our findings suggest that aberrant Wnt/β-catenin signaling, through either mutations or epigenetic silencing of Wnt antagonists, contributes to the pathogenesis and growth of NETs and have important clinical implications for the prognosis and treatment of NETs.

Investigational New Drugs, 2014

Rare Tumors

Large cell neuroendocrine carcinomas (LCNEC) are rare, aggressive high-grade neuroendocrine neopl... more Large cell neuroendocrine carcinomas (LCNEC) are rare, aggressive high-grade neuroendocrine neoplasms within the neuroendocrine cell lineage spectrum. This manuscript provides a detailed review of published literature on LCNEC of gynecological origin. We performed a PubMed search for material available on gynecologic LCNEC. We analyzed 104 unique cases of gynecologic LCNECs, of which 45 were cervical primary, 45 were ovarian, 13 were uterine, and 1 was vaginal. A total of 45 cases of cervical LCNEC were identified with a median age of 36 years. Median overall survival was 16 months. We identified 45 ovarian LCNEC cases in the published literature with a median age of 54 years. Median overall survival was 8 months. 13 LCNEC cases of uterine origin were identified; 12 out of 13 were of endometrial origin and the median age was 71 years. The majority of patients presented with Stage III/IV disease (stages I–IV were 31%, 8%, 38%, and 23%, respectively). Gynecologic LCNEC is an aggressiv...

Blood

Currently available IV iron agents pose substantial safety and practical challenges to effective ... more Currently available IV iron agents pose substantial safety and practical challenges to effective management of iron deficiency anemia. Iron dextran administration requires a test dose and carries the risk of anaphylaxis. Non-dextran-containing IV iron agents (iron sucrose and ferric gluconate) do not require a test dose nor have this safety issue, but pose some practical challenges. These agents are FDA approved only for chronic kidney disease indications and require repeated administration of small doses (125 mg of iron as ferric gluconate over 10 minutes, 200 mg of iron as iron sucrose over 2–5 minutes, or 300–400 mg of iron as iron sucrose over 1.5 to 2.5 h). Accordingly, in a multicenter, randomized, blinded, placebo-controlled, crossover trial we assessed the safety of iron carboxymaltose, a new, investigational non-dextran IV iron complex that allows for rapid administration of high doses of iron. Five-hundred and eighty four (584) iron deficiency anemia patients received eith...

American Journal of Gastroenterology

Journal of Gastrointestinal Oncology

Ochsner Journal

Background: Checkpoint inhibitors have transformed the treatment of cancer in adults. This class ... more Background: Checkpoint inhibitors have transformed the treatment of cancer in adults. This class of drugs has demonstrated encouraging results in various malignancies such as metastatic melanoma, bladder cancer, renal cancer, and non-small cell lung carcinoma. However, researchers have only begun investigating the effectiveness and tolerability of checkpoint inhibitors in pediatric patients. Methods: We conducted a review of PubMed indexed literature and clinicaltrials.gov using combinations of the keywords checkpoint, inhibitor, pediatric, CTLA-4 (cytotoxic T lymphocyte antigen-4), PD-1 (programmed cell death-1), and PD-L1 (programmed cell death receptor-1 ligand) to find every recently completed and ongoing trial evaluating checkpoint inhibitors in patients younger than 21 years old. Pertinent articles and clinical trials discussing the role of immune checkpoint inhibitors in the pediatric population were selected for final analysis and manuscript citation. Results: This review presents an overview of the cellular mechanisms involved in checkpoint inhibition and of studies evaluating checkpoint inhibitors in humans. The review also details results and side effects from studies conducted with pediatric patients, current pediatric clinical trials, and future implications. Conclusion: Immune checkpoint inhibitors have the potential to further therapeutic advances in pediatric oncology; however, we need more clinical trials and combination drug strategies targeted toward pediatric cancers.

Anticancer research, 2018

Combination nab-paclitaxel/gemcitabine (AG) is superior to gemcitabine in patients with metastati... more Combination nab-paclitaxel/gemcitabine (AG) is superior to gemcitabine in patients with metastatic pancreatic cancer (PC). There are limited data for AG in borderline resectable (BR) or locally advanced pancreatic cancer (LAPC). Herein, we report our experience with neoadjuvant AG for BR/LAPC in patients ineligible for FOLFIRINOX. This retrospective series, included patients with BR/LAPC who received AG as neoadjuvant therapy for 3-4 months followed by radiation, then re-evaluation for surgery. Between 10/2013-2/2018, 32 patients (22 BR, 10 LAPC) were treated with this approach. Median age was 70 years. Nine patients were converted to resectability by imaging; six had R0 resections (19%), five (16%) achieved a partial response and 24 (75%) had stable disease. In this small series, the R0 resection rate and response rate were 19% and 16% respectively. These data suggest that neoadjuvant AG may be an alternate option for patients ineligible for FOLFIRINOX.

Journal of oncology, 2018

Incidence of low grade well-differentiated neuroendocrine tumors (NET) is on the rise. The North ... more Incidence of low grade well-differentiated neuroendocrine tumors (NET) is on the rise. The North American Neuroendocrine Tumor Society estimates that the United States has more than 150,000 gastroenteropancreatic NET patients. About 10% of metastatic NETs can be unknown primary, and due to their rarity, dedicated treatment algorithms and regimens are not defined. Combination of capecitabine and temozolomide (CAPTEM) is one of the systemic treatments used in gastroenteropancreatic NETs. We explored clinical activity of CAPTEM in NET of unknown primary. . Retrospective review of NET of unknown primary managed at the University of Kentucky over the past five years (2012-2016). . 56 patients with NET of unknown primary were identified; 12 patients were treated with CAPTEM. Median progression-free survival on CAPTEM in grade II and grade III NET of unknown primary was 10.8 and 7 months, respectively. Six patients showed reduction in metastatic tumor volume at three-month CT scan. Three p...

Oncotarget, Jan 10, 2018

Neuroendocrine tumors (NETs) have a low incidence but relatively high prevalence. Over the last t... more Neuroendocrine tumors (NETs) have a low incidence but relatively high prevalence. Over the last three decades, the incidence of NETs has risen 6-fold in the United States. We conducted an observational study to compare the incidence of NETs reported to the Kentucky Cancer Registry (KCR) versus that reported to Surveillance, Epidemiology, and End Results Program (SEER). We also provide a systematic review of the state of neuroendocrine tumors worldwide, and compare the available global and local published data. KCR and SEER databases were queried for NET cases between 1995 and 2015. A detailed literature review of epidemiological data for various nations worldwide summarize epidemiological data from various countries. KCR recorded 6179 individuals with newly diagnosed NETs between 1995 and 2015. Between 1995-2012, the incidence of NETs in KCR increased from 3.1 to 7.1 per 100,000 cases, while it increased from 3.96 to 6.61 in the SEER database. The incidence rates in both KCR and SEE...

Clinical therapeutics, Jan 30, 2018

In the placebo-controlled Phase III TELESTAR (Telotristat Etiprate for Somatostatin Analogue Not ... more In the placebo-controlled Phase III TELESTAR (Telotristat Etiprate for Somatostatin Analogue Not Adequately Controlled Carcinoid Syndrome) trial, the oral tryptophan hydroxylase inhibitor telotristat ethyl significantly reduced bowel movement (BM) frequency during a 12-week, double-blind treatment period in 135 patients with metastatic neuroendocrine tumors with carcinoid syndrome and ≥4 BMs per day. Patients (mean [SD] age, 63.5 [8.9] years; mean [SD] body mass index, 24.9 [4.9] kg/m) received placebo, telotristat ethyl 250 mg, or telotristat ethyl 500 mg 3 times per day (TID) in addition to somatostatin analogue therapy. Weight loss is associated with uncontrolled carcinoid syndrome and may be associated with reduced survival. Assessment of the occurrence of weight change ≥3% at week 12 was prespecified in the statistical analysis plan. In 120 patients with weight data available, weight gain ≥3% was observed in 2 of 39 patients (5.1%) taking placebo TID, 7 of 41 (17.1%) taking tel...

Oncotarget, Jan 6, 2018

This unique case series and review of literature suggests that immune checkpoint inhibitors may h... more This unique case series and review of literature suggests that immune checkpoint inhibitors may have clinical activity in neuroendocrine tumors. Summarize advances of immuno-oncology in neuroendocrine tumors with the help of a case series. Case series and review of literature. The patients were treated with immune checkpoint inhibitors (pembrolizumab or nivolumab). Life expectancy, quality of life, disease progression. Maximum durable response of 16 months in one of the patients so far. All patients showed improvement in quality of life before disease progression. Two out of four are still on therapy. None of the patients experienced immune checkpoint inhibitor associated side-effects. All patients had failed standard of care therapy prior to the initiation of immune checkpoint inhibitors and were on the verge of hospice. Immune checkpoint inhibitors have revolutionized cancer management and the last 5 years have seen a rapid expansion in the indications for this class of drug. Neur...

Oncotarget, Jan 6, 2018

Large cell neuroendocrine carcinomas (LCNEC) are a group of rare high grade neuroendocrine tumors... more Large cell neuroendocrine carcinomas (LCNEC) are a group of rare high grade neuroendocrine tumors that often behave clinically like small cell carcinoma (SCLC) and are treated as such. No major advancement in the management of these tumors has occurred in the last 30 years. We present a case series of three cases from Markey Cancer center along with a review of 13 published cases in the literature wherein immune-checkpoint inhibitors were utilized in the management of LCNEC. Immune-checkpoint inhibitors might have clinical activity in LCNEC. Role of immune-checkpoint inhibitors should be explored in prospective LCNEC clinical trials. We summarize current evidence regarding use of immune checkpoint inhibitors in the treatment of LCNEC.

Endocrine-related cancer, Jan 12, 2018

Telotristat ethyl, a tryptophan hydroxylase inhibitor, was efficacious and well tolerated in the ... more Telotristat ethyl, a tryptophan hydroxylase inhibitor, was efficacious and well tolerated in the Phase 3 TELESTAR study in patients with carcinoid syndrome (CS) experiencing ≥4 bowel movements per day (BMs/day) while on somatostatin analogs (SSAs). TELECAST, a Phase 3 companion study, assessed safety and efficacy of telotristat ethyl in patients with CS (diarrhea, flushing, abdominal pain, nausea, or elevated urinary 5-hydroxyindoleacetic acid [u5-HIAA]) with <4 BMs/day on SSAs (or ≥1 symptom or ≥4 BMs/day if not on SSAs) during a 12-week double-blind treatment period followed by a 36-week open-label extension (OLE). The primary safety and efficacy endpoints were incidence of treatment-emergent adverse events (TEAEs) and percent change from baseline in 24-hour u5-HIAA at Week 12. Patients (N=76) were randomly assigned (1:1:1) to receive placebo or telotristat ethyl 250 mg or 500 mg 3 times per day (tid); 67 continued receiving telotristat ethyl 500 mg tid during the OLE. Through ...