Pancreatic Cancer

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).

Surgery for cancer carries concerns of tumor dissemination related to tumor manipulation, tumor violation, and wound seeding. Minimally invasive surgery is now standard for several benign conditions, such as symptomatic cholelithiasis and surgical therapy of gastroesophageal reflux. With the minimally invasive surgery explosion of the 1990s, virtually every procedure traditionally performed via laparotomy has been performed successfully with laparoscopic methods, including pancreaticoduodenectomy for cancer. Shortly after the first descriptions of laparoscopic-assisted colectomy, reports of port-site tumor recurrences surfaced, raising concerns of using pneumoperitoneum-based surgery for malignancy. This review covers the development of laparoscopic surgery for cancer. Historical perspectives elucidate factors that helped shape the current state of the art. Theoretical concerns are discussed regarding surgery-induced immune suppression and its potential effects on tumor recurrence with both open and laparoscopic approaches. The concerns of laparoscopic port-site wound metastases are addressed, with a critical evaluation of the literature. Finally, a technical discussion of laparoscopic-assisted resections of hepatic and pancreatic tumors details patient selection, operative approach, and existing data for these operations.

Treatment of metastatic breast cancer is "a book with many chapters, ie, with many opportunities for meaningful intervention, as opposed to pancreatic cancer, for example," Andrew Seidman, MD, said in his discussion of metastatic breast cancer at the Second Annual Advances in Oncology meeting, sponsored by the journal ONCOLOGY.

This supplement to Oncology News International includes more than 15 reportson presentations made at the 41st annual meeting of the American Society of Clinical Oncology.Reviews focus on the use of targeted agents in non–small-cell lung cancer and other solid tumors,evaluating the novel therapies bevacizumab, cetuximab, bortezomib, erlotinib, and gefitinib, aloneand/or in combination with other chemotherapy agents. Continuing medical education credit isavailable by completing a post-test and evaluation online at www.cancernetwork.com/cme.

TORONTO, CANADA-Addingerlotinib (Tarceva) to gemcitabine(Gemzar) increased 1-year survivalby 40% for patients with

BASEL, SWITZERLAND-The combination of gemcitabine(Gemzar)/capecitabine (Xeloda)(GemCap) failed to prolong survivalmore than gemcitabine (Gem) alone,

ANAHEIM, California-Heavy consumption of red meat and processed meats may increase the risk of pancreatic cancer, according to a multiethnic study. The results suggest that carcinogenic substances related to meat preparation, rather than the

Combined-modality positronemissiontomography (PET)–computed tomography (CT) isbecoming the imaging method ofchoice for an increasing number ofoncology indications. The goal of thispaper is to review the evidence-basedliterature justifying PET-CT fusion.The best evidence comes from prospectivestudies of integrated PETCTscans compared to other methodsof acquiring images, with histopathologicconfirmation of disease presenceor absence. Unfortunately, veryfew studies provide this kind of data.Retrospective studies with similarcomparisons can be used to provideevidence favoring the use of integratedPET-CT scans in specific clinicalsituations. Also, inferential conclusionscan be drawn from studies whereclinical rather than pathologic dataare used to establish disease presenceor absence.

HOLLYWOOD, Florida-Smoking not only increases the risk of developing pancreatic cancer but also speeds disease progression, according to Randall E. Brand, MD. In a presentation at the 2005 Gastrointestinal Cancers Symposium (abstract 76), Dr. Brand said that current smokers develop pancreatic cancers about 10 years sooner than nonsmokers. "Smoking at any age has an impact on the age of diagnosis of pancreatic cancer," Dr. Brand said. "To our knowledge, this is the first report that provides compelling evidence for the role of cigarette smoking early in neoplastic transformation of the pancreas."

This special “annual highlights” supplement to Oncology News International (ONI)is a compilation of selected news on important advances in the management ofgastrointestinal cancers over the past year, as reported in ONI. Guest Editor, Dr.James L. Abbruzzese, comments on the reports included herein and discussesdevelopments in the clinical management of GI cancers, with a look at the impactof targeted agents with cytotoxic chemotherapy, first-line and adjuvant therapies foradvanced disease, and the role of statins and COX-2 inhibitors in prevention.

This special “annual highlights” supplement to Oncology News International (ONI)is a compilation of selected news on important advances in the management ofgastrointestinal cancers over the past year, as reported in ONI. Guest Editor, Dr.James L. Abbruzzese, comments on the reports included herein and discussesdevelopments in the clinical management of GI cancers, with a look at the impactof targeted agents with cytotoxic chemotherapy, first-line and adjuvant therapies foradvanced disease, and the role of statins and COX-2 inhibitors in prevention.

Pisters and colleagues from theM. D. Anderson Cancer Centeroffer a state-of-the-art discussionof the staging and treatment ofpancreatic cancer. Their treatise addressesmost of the current issues ofcontroversy surrounding this diseasefrom a largely nonparochial standpoint,and should serve as a primerfor the multidisciplinary approach tothe treatment of pancreatic ductal cancer.Their call for and justification ofregionalization of treatment in patientswith potentially resectable diseaserings true with virtually all nationaland international studies that have examinedthis topic from the aspect ofmorbidity, mortality (and thus survival),duration of hospitalization, andof course in our current economic climate,cost.[1-7] This topic should nolonger be considered controversial.

Although in centers where pancreatectomy is performed frequently,associated morbidity and mortality rates have improved, long-term outcomesin pancreatic adenocarcinoma patients remain poor when surgeryis the sole therapeutic modality. The impact of adjuvant chemotherapyon survival in patients with localized pancreatic cancer remainsincompletely defined. The European Study Group for Pancreatic Cancer(ESPAC)-1 trial has suggested that overall survival rates are superiorwhen chemotherapy is added to surgery, even when regimens believedto be relatively ineffective in the treatment of advanced diseaseare used. The role of radiotherapy given with chemotherapy is alsounresolved, but chemoradiation continues to receive consideration inthe multimodality approach to localized pancreatic cancer. Enhancedcollaboration and increased involvement by pancreatic surgeons havehelped in the recruitment of pancreatic cancer patients for large-scalerandomized clinical trials in Europe and the United States. Many newerchemotherapeutic agents with efficacy in gastrointestinal cancers haveyet to be investigated in the adjuvant and neoadjuvant settings.

Drs. Pisters, Wolff, Crane, andEvans have provided an excellentoverview of contemporaryapproaches to staging, surgicalmanagement, and treatment ofpatients with potentially resectablepancreatic cancer. Given the impressiveadvances in our understandingof the biology and genetics of pancreaticcancer, we would agree thatcurrent opportunities for progressagainst this malignancy are encouraging.The reality, however, is thatmortality rates still exceed 95%.While the article addresses the clinicalmanagement of patients with operablepancreatic cancer, this subsetof patients constitutes only 10% to15% of all patients with the disease.This group as well as patients withlocally advanced and metastatic diseaseare in need of new and innovativetreatment strategies. In thisreview, we will highlight several ofthe points made by the authors.

Pancreatic cancer is the fifth leading cause of cancer death in the United States.In the year 2005, an estimated 32,180 new cases will be diagnosed, and 31,800deaths will be ascribed to this cancer.

Unresectable pancreatic cancer has few therapeutic options and adismal prognosis. Cyclooxygenase-2 (COX-2) expression is increasedat the RNA and protein levels in most human pancreatic cancers. Thepurpose of this trial was to determine whether the addition of a COX-2inhibitor to chemotherapy was beneficial. To date, 11 patients with inoperablepancreatic cancer have been treated with the combination ofgemcitabine (Gemzar), irinotecan (Camptosar), and celecoxib(Celebrex) at 400 mg orally twice daily. Encouraging pain relief, improvementin performance status, and decreases in CA 19-9 andcarcinoembryonic antigen levels have been observed.

From the results of recent studies, it is likely that multimodality therapy with chemotherapy and radiation treatment may improve the overall outcome of locally advanced upper gastrointestinal (GI) malignancies, including esophageal, gastric, pancreatic, and biliary tract carcinomas. However, more effective, more optimal, and less toxic chemotherapy regimen(s) with concomitant radiotherapy are needed beyond the concurrent continuous-infusion fluorouracil (5-FU) with radiation that is commonly applied in general practice. Epirubicin (Ellence), cisplatin, and irinotecan (Camptosar) are all active cytotoxic chemotherapy agents in upper GI cancers. Two phase I studies were designed to test the tolerability of the combination of radiotherapy with infusional 5-FU, epirubicin, and cisplatin (ECF) or 5-FU, irinotecan, and epirubicin (EIF) in the treatment of locally advanced upper GI malignancies.

Single-agent gemcitabine (Gemzar) is the standard of chemotherapyfor advanced pancreatic cancer, with no phase III trials to date havingshown significantly improved survival with gemcitabine-based combinationsvs single-agent treatment. The multitargeted antifolate agentpemetrexed (Alimta) shows synergistic effects in vitro in combinationwith gemcitabine, and activity and good tolerability when used as singleagenttreatment in advanced pancreatic cancer. In a phase II trial inpatients with advanced pancreatic cancer, the combination ofgemcitabine at 1,250 mg/m2 on days 1 and 8 plus pemetrexed at 500mg/m2 on day 8 after gemcitabine every 21 days resulted in a mediansurvival of 6.5 months and a 1-year survival rate of 29%. Neutropeniawas the primary toxicity, with grade 4 toxicity in 51% of patients. Thepromising results of this trial prompted the initiation of a phase IIItrial comparing gemcitabine at 1,000 mg/m2 on days 1, 8, and 15 every28 days vs the 21-day gemcitabine/pemetrexed regimen given with vitaminsupplementation in patients with pancreatic cancer. The primaryoutcome measure was overall survival, with secondary measures includingresponse rate, progression-free survival, and quality of life.While an increase in response and time to progression was reported forthe gemcitabine/pemetrexed combination, there were no significantdifferences in survival between treatment arms.

The 30 reports in this special supplement to Oncology News International represent highlights of ongoing major clinical trials and new research presented at ASCO 2004 regarding state-of-the-art chemotherapeutic management of gastrointestinal and other cancers. Important developments in capecitabine as adjuvant therapy, novel targeted agents, and new combinations are discussed.

WASHINGTON-The 2004 US Surgeon General’s report on the health risks of smoking adds five cancers to the list of diseases caused by cigarettes-acute myeloid leukemia, and stomach, pancreatic, cervical, and kidney cancers. Other newly