St Lukes Cancer Center

Bethlehem, United States

St Lukes Cancer Center

Bethlehem, United States
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Nicholson B.,Penn Medicine | Agarwala S.S.,St Lukes Cancer Center
Journal of Opioid Management | Year: 2011

Analgesics delivered via the oral route of administration (capsules, tablets, or solutions) are most commonly used to treat cancer breakthrough pain (BTP); however, the effectiveness of oral opioids may be limited by slow gastrointestinal absorption and first-pass metabolic effects. Although the limitations presented by oral opioid delivery are acknowledged and formulations and delivery systems that mirror the temporal characteristics of the majority of cancer BTP episodes are available, short-acting oral opioids are the accepted standard of care. The purpose of this review is to provide an overview of the different routes of opioid administration used in the treatment of cancer BTP and briefly discuss the characteristics of different delivery systems. © 2011 Journal of Opioid Management, All Rights Reserved.

Payne S.,Lancaster University | Chan N.,National University of Singapore | Davies A.,St Lukes Cancer Center | Poon E.,Ang Mo Kio Thye Hua Kwan Hospital | And 2 more authors.
The Lancet Oncology | Year: 2012

The burden of cancer in Asia is high; 6·1 million new cases were diagnosed in the continent in 2008, which accounted for 48% of new cases worldwide. Deaths from cancer are expected to continue to rise because of ageing populations and modifiable risk factors such as tobacco and alcohol use, diet, and obesity. Most patients who are diagnosed with cancer in Asia have advanced disease that is not amenable to curative treatment, which means that they are likely to have pain and other symptoms and psychosocial concerns. These burdens vary with the economic and political situation of the different countries and are affected by such factors as an absence of screening programmes, insufficient cancer diagnostic and treatment services (especially in sparsely populated and rural areas), legal restrictions on access to drugs to relieve pain, and a medical culture in which quality-of-life considerations are undervalued in relation to imperatives to treat. These issues could be ameliorated by increased investment in cancer screening, removal of restrictions on prescription of opioids, and improvements in medical education to increase recognition of treatment futility. Supportive, palliative, and end-of-life care offer the potential to enhance quality of life, improve pain control, and reduce suffering for patients with cancer and their families, and to give patients a dignified death. All patients should have access to such care-in resource-rich regions these services should be integrated into oncology services, whereas in resource-poor regions they should be the main focus of treatment. The form of care should depend on the economic circumstances within and across countries, and recommendations are made across four resource classifications (basic to maximal) to take account of the diversity of settings in Asia. © 2012 Elsevier Ltd.

Postow M.A.,Sloan Kettering Cancer Center | Postow M.A.,New York Medical College | Chesney J.,University of Louisville | Pavlick A.C.,New York University | And 20 more authors.
New England Journal of Medicine | Year: 2015

BACKGROUND: In a phase 1 dose-escalation study, combined inhibition of T-cell checkpoint pathways by nivolumab and ipilimumab was associated with a high rate of objective response, including complete responses, among patients with advanced melanoma. METHODS: In this double-blind study involving 142 patients with metastatic melanoma who had not previously received treatment, we randomly assigned patients in a 2:1 ratio to receive ipilimumab (3 mg per kilogram of body weight) combined with either nivolumab (1 mg per kilogram) or placebo once every 3 weeks for four doses, followed by nivolumab (3 mg per kilogram) or placebo every 2 weeks until the occurrence of disease progression or unacceptable toxic effects. The primary end point was the rate of investigator-assessed, confirmed objective response among patients with BRAF V600 wild-type tumors. RESULTS: Among patients with BRAF wild-type tumors, the rate of confirmed objective response was 61% (44 of 72 patients) in the group that received both ipilimumab and nivolumab (combination group) versus 11% (4 of 37 patients) in the group that received ipilimumab and placebo (ipilimumab-monotherapy group) (P<0.001), with complete responses reported in 16 patients (22%) in the combination group and no patients in the ipilimumab-monotherapy group. The median duration of response was not reached in either group. The median progression-free survival was not reached with the combination therapy and was 4.4 months with ipilimumab monotherapy (hazard ratio associated with combination therapy as compared with ipilimumab monotherapy for disease progression or death, 0.40; 95% confidence interval, 0.23 to 0.68; P<0.001). Similar results for response rate and progression-free survival were observed in 33 patients with BRAF mutation-positive tumors. Drug-related adverse events of grade 3 or 4 were reported in 54% of the patients who received the combination therapy as compared with 24% of the patients who received ipilimumab monotherapy. Select adverse events with potential immunologic causes were consistent with those in a phase 1 study, and most of these events resolved with immune-modulating medication. CONCLUSIONS: The objective-response rate and the progression-free survival among patients with advanced melanoma who had not previously received treatment were significantly greater with nivolumab combined with ipilimumab than with ipilimumab monotherapy. Combination therapy had an acceptable safety profile. Copyright © 2015 Massachusetts Medical Society.

Agarwala S.S.,St Lukes Cancer Center | O'Day S.J.,The Angeles Clinical and Research Institute
Cancer Treatment Reviews | Year: 2011

The current treatment for melanoma with nodal involvement, but without distant metastasis, is surgical excision and lymph node dissection followed by adjuvant therapy. A number of systemic regimens have been evaluated for melanoma patients with a medium or high risk of disease recurrence following surgery. The only agent approved for the adjuvant therapy of melanoma is high-dose interferon (IFN)-α2b, which prolongs relapse-free survival, but its effects on overall survival remain controversial. Its use is also accompanied by significant toxicity. Thus, despite its approval, high-dose IFN-α2b is not always used for the adjuvant therapy of melanoma, particularly in countries other than the United States. Studies aimed at identifying subgroups of patients that have the greatest benefit-to-risk ratio with this regimen are ongoing. Several vaccines have been studied in the adjuvant setting for melanoma, but none has shown superiority to IFN-containing regimens. The GMK ganglioside vaccine, for instance, has actually been shown to be inferior to high-dose IFN-α2b. Therefore, a therapeutic regimen which improves overall survival with a favorable safety profile would be a major advance in the adjuvant therapy of melanoma. One approach that is currently being investigated is the potentiation of antitumour immune responses through blockade of cytotoxic T-lymphocyte antigen-4 (CTLA-4). Here, we provide an overview of the current unmet needs in the adjuvant therapy of melanoma and evaluate the potential of CTLA-4 blockade as a future therapeutic option in this setting. © 2010.

Fecher L.A.,University of Pennsylvania | Agarwala S.S.,St Lukes Cancer Center | Stephen Hodi F.,Dana-Farber Cancer Institute | Weber J.S.,H. Lee Moffitt Cancer Center and Research Institute
Oncologist | Year: 2013

The treatment for metastatic melanoma has evolved significantly in the past few years. Ipilimumab, an immunotherapy, is now in mainstream oncology practice given that it has shown improved overall survival in randomized clinical trials. Other immune modulating agents, such as programmed death receptor-1 and programmed death receptor ligand-1 antibodies, are showing promise in early clinical trials. This manuscript will review ipilimumab and its most common side effects. Immune-related adverse events (irAEs) are important to recognize early,andtheir presentation, timing of onset,and general recommendations for workup and management will be reviewed. Assembling a multidisciplinary team, as well as thorough education of the patient, is recommended to optimize patient care. ©AlphaMed Press 2013.

Agarwala S.S.,St Lukes Cancer Center | Case S.,SciStrategy Communications
Oncologist | Year: 2010

Historically, there have been few treatment options for patients with advanced renal cell carcinoma (RCC) besides immunotherapy with interleukin-2 and interferon (IFN)-α. Targeted therapies have improved clinical outcomes over the past several years. These include the vascular endothelial growth factor receptor (VEGFR) tyrosine kinase inhibitors sunitinib and sorafenib, which inhibit angiogenic signaling in endothelial cells and vascular pericytes predominantly through VEGFR and platelet-derived growth factor receptor β. Also included is the anti-VEGF monoclonal antibody bevacizumab used in combination with IFN-α. These agents mediate their antitumor effects by interfering with the VEGF signaling pathway, thereby inhibiting angiogenesis and causing tumor shrinkage. However, ultimately, most patients develop resistance and experience disease progression during VEGF/VEGFR-targeted therapy, and until the recent approval of the mammalian target of rapamycin (mTOR) inhibitor everolimus (RAD001), there were no agents available with proven activity in this setting. This review describes the clinical development of everolimus in advanced RCC and the rationale for the use of mTOR inhibitors after failure of VEGF/ VEGFR inhibitors. ©AlphaMed Press.

Agarwala S.S.,St Lukes Cancer Center
Expert Review of Anticancer Therapy | Year: 2012

For patients with localized melanoma, excision of the primary tumor, including lymphadenectomy for nodal metastases, is standard treatment. However, patients with large primary tumors (stage IIB and IIC) or stage III melanoma have a relatively poor prognosis owing to the high risk of recurrence. High-dose IFN-α2b and pegylated IFN-α2b (PEG-IFN-α2b) are the only approved options for adjuvant therapy of stage III melanoma, but the lack of comparative data has led to considerable confusion in choosing between these options. In this article, current evidence regarding the pharmacokinetics, efficacy, safety and tolerability of adjuvant PEG-IFN-α2b in patients with melanoma is reviewed, with frequent reference to and comparisons with data using IFN-α2b. Particular focus is given to the pharmacokinetic differences between IFN-α2b and PEG-IFN-α2b and their implications for the treatment of high-risk patients. In addition, emerging evidence suggests that PEG-IFN-α2b therapy may provide clinically significant overall survival benefit for selected high-risk patients. © 2012 2012 Expert Reviews Ltd.

Agarwala S.S.,St Lukes Cancer Center | Ribas A.,Jonsson Comprehensive Cancer Center
Journal of Immunotherapy | Year: 2010

Monoclonal antibodies (mAbs) specific for cytotoxic T lymphocyte-associated antigen 4 (CTLA4) are a novel form of immunotherapy for treatment of patients with advanced cancers. These anti-CTLA4mAbs prevent normal downregulation of the immune system, thus prolonging and enhancing T-cell activation and potentially promoting an antitumor immune response. Clinical studies in patients with advanced cancers have indicated that CTLA4 blockade with mAbs is associated with antitumor activity in a small percentage of patients and has a manageable toxicity profile. The key limitations for broader applicability of this mode of therapy are better definition of the mechanism that leads to tumor rejection and the validation of favorable observations in single-arm studies into prospectively randomized clinical trials. Copyright © 2010 by Lippincott Williams & Wilkins.

The successful management of advanced melanoma remains an unmet need because of a resolutely poor prognosis and therapeutic options with limited effectiveness. Dacarbazine and fotemustine are the only approved chemotherapeutic agents for advanced melanoma, yet neither alone or in combination regimens has been shown to extend survival in randomized clinical trials. The only agent to be approved for advanced melanoma in the US in more than 30 years is high-dose bolus interleukin-2, but its use is associated with high toxicity and cost, and it has also failed to show a survival benefit. Our expanding knowledge of the complex factors and pathways regulating immune function has led to the advent of novel immunotherapeutic agents. Among these are ipilimumab and tremelimumab -fully human, monoclonal antibodies directed against cytotoxic T-lymphocyte antigen-4 (CTLA-4). The pivotal role of CTLA-4 in regulating T-cell function is established, and a series of preclinical studies provided proof-of-concept evidence of the antitumor activity of anti-CLTA-4 antibodies in combination with vaccines or chemotherapy. Subsequently, anti-CTLA-4 antibodies have shown encouraging results in clinical trials in advanced melanoma. Recent progress in the understanding of melanoma genetics and tumorigenesis has led to potential new therapeutic targets. Molecular targeted agents that inhibit the proliferation and survival of metastatic melanoma cells offer potential partners for anti-CTLA-4 antibodies in combined modality regimens. Novel combinations are reviewed in the context of creating an immunosupportive environment in the host. © 2010 Wolters Kluwer Health | Lippincott Williams & Wilkins.

Khelwatty S.A.,Kingston University | Essapen S.,St Lukes Cancer Center | Seddon A.M.,Kingston University | Modjtahedi H.,Kingston University
Frontiers in Bioscience | Year: 2013

Colorectal cancer is one of the leading causes of cancer deaths. At present, anti-epidermal growth factor receptor (EGFR) monoclonal antibodies (mAbs) cetuximab and panitumumab and anti-vascular endothelial growth factor (VEGF) mAb bevacizumab have been incorporated into treatment paradigms for patients with refractory metastatic colorectal cancer. However, many patients simply do not respond to these treatments or eventually acquire resistance following a short course therapy. In this article, we review the literature for studies on the expression patterns, prognostic significance and predictive value of HER (also called erbB) family members and other factors for response to therapy with the HER inhibitors in colorectal cancer. We discuss some of the advances, challenges as well as future opportunities for more effective targeting of the HER receptors using a cocktail of HER inhibitors (e.g. dual and pan HER TKIs, monospecific or bispecific antibodies) in combination with other therapeutic interventions.

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