Pancreatic Cancer

Erlotinib (Tarceva) is a human epidermal growth factor receptor type 1/epidermal growth factor receptor (HER1/EGFR) tyrosine kinase inhibitor initially approved by the US Food and Drug Administration for the treatment of patients with locally advanced or metastatic non–small-cell lung cancer after failure of at least one prior chemotherapy regimen. In this report, we present the pivotal study that led to the approval of erlotinib in combination with gemcitabine (Gemzar) in patients with locally advanced/metastatic chemonaive pancreatic cancer patients. The combination demonstrated a statistically significant increase in overall survival accompanied by an increase in toxicity. Physicians and patients now have a new option for the treatment of locally advanced/metastatic adenocarcinoma of the pancreas.

Erlotinib (Tarceva) is a human epidermal growth factor receptor type 1/epidermal growth factor receptor (HER1/EGFR) tyrosine kinase inhibitor initially approved by the US Food and Drug Administration for the treatment of patients with locally advanced or metastatic non–small-cell lung cancer after failure of at least one prior chemotherapy regimen. In this report, we present the pivotal study that led to the approval of erlotinib in combination with gemcitabine (Gemzar) in patients with locally advanced/metastatic chemonaive pancreatic cancer patients. The combination demonstrated a statistically significant increase in overall survival accompanied by an increase in toxicity. Physicians and patients now have a new option for the treatment of locally advanced/metastatic adenocarcinoma of the pancreas.

Erlotinib (Tarceva) is a human epidermal growth factor receptor type 1/epidermal growth factor receptor (HER1/EGFR) tyrosine kinase inhibitor initially approved by the US Food and Drug Administration for the treatment of patients with locally advanced or metastatic non–small-cell lung cancer after failure of at least one prior chemotherapy regimen. In this report, we present the pivotal study that led to the approval of erlotinib in combination with gemcitabine (Gemzar) in patients with locally advanced/metastatic chemonaive pancreatic cancer patients. The combination demonstrated a statistically significant increase in overall survival accompanied by an increase in toxicity. Physicians and patients now have a new option for the treatment of locally advanced/metastatic adenocarcinoma of the pancreas.

Inoperable pancreatic adenocarcinoma is a dilemma that oncologists frequently encounter. Only 15% to 20% of patients are diagnosed when cancer of the pancreas is still surgically resectable. However, pancreaticoduodenectomy is the only curative option for this disease and should be offered to all patients who meet resection criteria and do not have significant comorbidities. For inoperable pancreatic cancer, the goals of treatment are to palliate symptoms and prolong life. Improved survival in locally advanced disease has been demonstrated with chemoradiation plus fluorouracil or with gemcitabine (Gemzar) alone. In metastatic disease, single-agent gemcitabine has been associated with improvement in symptoms and survival. Trials combining various chemotherapeutic agents with gemcitabine have not had a significant impact on overall survival, although meta-analyses suggest a small benefit. The targeted agent erlotinib (Tarceva) has shown a modest improvement in overall survival in combination with gemcitabine. This combination is another option for first-line therapy in patients with locally advanced or metastatic disease. Despite these recent advances, survival for patients with inoperable pancreatic cancer continues to be poor. Future investigations need to focus on understanding the molecular nature of this malignancy, with the goal of developing interventions based on this knowledge.

Inoperable pancreatic adenocarcinoma is a dilemma that oncologists frequently encounter. Only 15% to 20% of patients are diagnosed when cancer of the pancreas is still surgically resectable. However, pancreaticoduodenectomy is the only curative option for this disease and should be offered to all patients who meet resection criteria and do not have significant comorbidities. For inoperable pancreatic cancer, the goals of treatment are to palliate symptoms and prolong life. Improved survival in locally advanced disease has been demonstrated with chemoradiation plus fluorouracil or with gemcitabine (Gemzar) alone. In metastatic disease, single-agent gemcitabine has been associated with improvement in symptoms and survival. Trials combining various chemotherapeutic agents with gemcitabine have not had a significant impact on overall survival, although meta-analyses suggest a small benefit. The targeted agent erlotinib (Tarceva) has shown a modest improvement in overall survival in combination with gemcitabine. This combination is another option for first-line therapy in patients with locally advanced or metastatic disease. Despite these recent advances, survival for patients with inoperable pancreatic cancer continues to be poor. Future investigations need to focus on understanding the molecular nature of this malignancy, with the goal of developing interventions based on this knowledge.

Inoperable pancreatic adenocarcinoma is a dilemma that oncologists frequently encounter. Only 15% to 20% of patients are diagnosed when cancer of the pancreas is still surgically resectable. However, pancreaticoduodenectomy is the only curative option for this disease and should be offered to all patients who meet resection criteria and do not have significant comorbidities. For inoperable pancreatic cancer, the goals of treatment are to palliate symptoms and prolong life. Improved survival in locally advanced disease has been demonstrated with chemoradiation plus fluorouracil or with gemcitabine (Gemzar) alone. In metastatic disease, single-agent gemcitabine has been associated with improvement in symptoms and survival. Trials combining various chemotherapeutic agents with gemcitabine have not had a significant impact on overall survival, although meta-analyses suggest a small benefit. The targeted agent erlotinib (Tarceva) has shown a modest improvement in overall survival in combination with gemcitabine. This combination is another option for first-line therapy in patients with locally advanced or metastatic disease. Despite these recent advances, survival for patients with inoperable pancreatic cancer continues to be poor. Future investigations need to focus on understanding the molecular nature of this malignancy, with the goal of developing interventions based on this knowledge.

In a prospective case-control study, individuals in the lowest quartile of circulating insulin-like growth factor binding protein -1 (IGFBP-1) had a twofold greater risk of developing pancreatic cancer than those in the three highest quartiles

Using two novel light-scattering techniques to detect optical markers of pancreatic cancer, researchers have shown for the first time the efficacy of a new approach to detecting the disease without biopsy or direct visualization of the organ

An experimental gene therapy targeting pancreatic cancer reduced or eradicated tumors, inhibited metastasis, and prolonged survival in experiments in two mouse models, and did so with very limited toxicity.

A 72-year-old man is referred for evaluation of abnormal liver chemistries. He has a history of unresectable pancreatic cancer (adenocarcinoma of the head).

Very small pancreatic cystic tumors are safe to observe, rather than treat, in patients with no symptoms and no radiographic features associated with malignancy, according to a study of patients with neoplasms less than 3 cm in size.

Avalon initiates phase II trial of AVN944 in pancreatic cancer

The appearance of a rash in cancer patients treated with erlotinib (Tarceva) is strongly associated with longer survival, according to researchers from the drug's developer, OSI Pharmaceuticals

BRIDGEWATER, New Jersey—Enzon Pharmaceuticals, Inc.'s PEG-SN38, a novel polyethyleneglycol-SN38 conjugate, resulted in significant tumor growth inhibition in mice resistant to irinotecan (Camptosar) (a 25% decrease in tumor volume) and outperformed irinotecan when given as a second-round therapy to mice initially sensitive to irinotecan, the company said in a news release. The data were presented at the American Association for Cancer Research 2007 meeting (abstract 1494). Additionally, PEG-SN38 demonstrated long-lasting anti-tumor activity in mouse models of human breast and pancreatic cancers, the company said.

Study results published by the Journal of Clinical Oncology show that adding erlotinib (Tarceva) to gemcitabine (Gemzar) chemotherapy significantly improves survival by 22% in patients with advanced pancreatic cancer.

ImClone and Bristol-Myers Squibb announced that a phase III study of cetuximab (Erbitux) plus gemcitabine (Gemzar) in patients with locally advanced unresectable or metastatic pancreatic cancer did not meet its primary endpoint of improving overall survival.

Despite attempted curative resection of localized adenocarcinoma of the pancreas, most patients experience a recurrence and die of their disease. The Gastrointestinal Tumor Study Group, European Organisation for Research and Treatment of Cancer, and European Study Group for Pancreatic Cancer trials have suggested the benefit of adjuvant therapy. However, the relatively few randomized trials available have not established a definite standard of care due to study limitations. Although these trials, and the recently published Charité Onkologie (CONKO)-001 trial, have shown a definite advantage of adjuvant chemotherapy, the most effective chemotherapy and the role of radiation therapy remain unclear. This review will discuss the data available from reported trials of adjuvant and neoadjuvant therapy in pancreatic cancer, address the issues leading to the ongoing controversies, and consider future directions for clinical trials.

Despite attempted curative resection of localized adenocarcinoma of the pancreas, most patients experience a recurrence and die of their disease. The Gastrointestinal Tumor Study Group, European Organisation for Research and Treatment of Cancer, and European Study Group for Pancreatic Cancer trials have suggested the benefit of adjuvant therapy. However, the relatively few randomized trials available have not established a definite standard of care due to study limitations. Although these trials, and the recently published Charité Onkologie (CONKO)-001 trial, have shown a definite advantage of adjuvant chemotherapy, the most effective chemotherapy and the role of radiation therapy remain unclear. This review will discuss the data available from reported trials of adjuvant and neoadjuvant therapy in pancreatic cancer, address the issues leading to the ongoing controversies, and consider future directions for clinical trials.

Despite attempted curative resection of localized adenocarcinoma of the pancreas, most patients experience a recurrence and die of their disease. The Gastrointestinal Tumor Study Group, European Organisation for Research and Treatment of Cancer, and European Study Group for Pancreatic Cancer trials have suggested the benefit of adjuvant therapy. However, the relatively few randomized trials available have not established a definite standard of care due to study limitations. Although these trials, and the recently published Charité Onkologie (CONKO)-001 trial, have shown a definite advantage of adjuvant chemotherapy, the most effective chemotherapy and the role of radiation therapy remain unclear. This review will discuss the data available from reported trials of adjuvant and neoadjuvant therapy in pancreatic cancer, address the issues leading to the ongoing controversies, and consider future directions for clinical trials.

Curcumin, an ingredient in the dietary spice turmeric (see box), may be useful in treating pancreatic cancer, according to two groups of investigators who presented their work at the Society for Integrative Oncology Third International Conference.

An investigational therapeutic vaccine (GVAX immunotherapy) given with chemotherapy and radiation therapy following surgery for pancreatic cancer appears to improve survival for these difficult-to-treat patients

Cell Genesys, Inc, announced follow-up data from a phase II clinical trial of GVAX immunotherapy for pancreatic cancer in 60 patients with operable pancreatic cancer who received the immunotherapy after surgical resection of their tumor and adjuvant radiation and chemotherapy.

Mutation of palladin, a cytoskeletal gene that controls cell shape and motility, and overexpression of palladin protein are implicated in both familial and sporadic forms of pancreatic cancer, respectively, and explain the typical nuclear disarray seen histologically in patients with the disease

A panel of 10 biomarkers found in the blood may prove to be useful in detecting asymptomatic pancreatic cancer, according to researchers at the University of Pittsburgh School of Medicine. "With median survival rates of 6 to 12 months, early detection of pancreatic cancer is crucial to patient survival, but there has been no way to diagnose it early before symptoms occur," Anna E. Lokshin, PhD, associate professor of medicine and pathology, said at the American Association of Cancer Research's Frontiers in Cancer Prevention Research meeting

Results from Oncolytics Biotech's phase I trial of Reolysin, its oncolytic reovirus, show stable disease in 7 of 32 patients with advanced or metastatic solid tumors refractory to standard therapy or for which no curative standard therapy exists. Dr. Timothy Yap of The Institute of Cancer Research, Sutton, UK, presented the study at the 18th EORTC-NCI-AACR Symposium on Molecular Targets and Cancer Therapeutics

An innovative cancer agent called PHA-739358, which inhibits one of the aurora proteins, has shown indications of potential benefit in 7 of 36 patients (19.4%) with advanced or metastatic solid tumors who participated in a phase I dosing and toxicity study, Dutch researchers reported at the EORTC-NCI-AACR Symposium on Molecular Targets and Cancer Therapeutics

The science supporting molecularly targeted therapies for the treatment of patients with solid tumors continues to evolve. Nurses are challenged to understand cell signaling, molecular targeting, and the mechanism of action of targeted agents. Two cell signal transduction pathways regulate the development, proliferation, and metastasis of solid tumors: the human epidermal growth factor (HER) receptor pathway and the vascular endothelial growth factor (VEGF) receptor pathway. Several novel pharmacologic agents with distinct indications and methods of administration target the HER and VEGF molecular pathways.

A study comparing two experimental regimens with standard 30-minute gemcitabine (Gemzar) infusions for advanced pancreatic cancer found temporary improvements in tumor response, but no survival benefit

Nationally, the rate of in-hospital mortality associated with pancreatectomy for pancreatic cancer and other neoplasms has decreased in recent years

Salinosporamide A, a novel proteasome inhibitor, enhances the effectiveness of conventional chemotherapy and molecular therapy combinations in pancreatic cancer, new preclinical data show. Lead author James C. Cusack, Jr., MD, presented findings from a set of experiments with the novel agent at the 2006 Gastrointestinal Cancers Symposium (abstract 93).