Pancreatic Cancer

It is a continuing challenge for oncologists to effectively treatadvanced/metastatic pancreatic and biliary cancer. Both irinotecan(CPT-11, Camptosar) and gemcitabine (Gemzar) have shown activityagainst these diseases with different mechanisms. Preclinical andclinical data also suggest additive or synergistic effects of the combinationof these two agents with few or no overlapping toxicities. Phosphorylationof gemcitabine, a process of intracellular activation of theagent, is dose-rate dependent. It has been suggested that the fixed-doserateinfusion of gemcitabine increases the concentration of intracellulartriphosphate gemcitabine, which in turn may result in more objectiveresponses and longer median survival compared to the standard infusion.This phase I study tests the toxicity of the combination of irinotecanwith fixed-dose-rate infusion of gemcitabine, and determines thedose of the combination for phase II investigation.

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.

DUBLIN, California-Super-Gen Inc. has begun submission of a New Drug Application (NDA) for Orathecin, an oral camptothecin, for the treatment of pancreatic cancer patients who are refractory/resistant to available therapies. The submission will occur on a rolling basis and is ex-pected to be completed by the end of the first quarter of 2003. The submission will contain data on more than 2,700 patients treated under Orathecin study protocols, the company said in a news release.

SEATTLE-Telomerase may be an early biomarker of pancreatobiliary malignancies, and telomerase enzyme immunostaining represents a potential breakthrough in screening for and diagnosing cancer in patients with biliary strictures, Tarun Mullick, MD, said at the president’s plenary session of the 67th Annual Meeting of the American College of Gastroenterology (ACG abstract 3).

Approximately 30,300 people will be diagnosedwith pancreatic cancer in the UnitedStates this year. The 99% mortality rate is thehighest of any cancer, and most patients die within 1year of diagnosis.[1] There are only two drugs approvedas a first-line indication for pancreatic cancerpatients, and treatment options are very limited.These patients have poor prognoses and few options,and must make decisions in short time frames.

Drs. Konner and O’Reilly have provided a thorough review of current perspectives on pancreatic cancer. The disease is lethal, difficult to diagnose in its early stages, and resistant to standard chemotherapy regimens. Surgery can be curative if performed when the tumor is small (< 2 cm), but only a minority of patients have small tumors.

The review by Drs. Konner and O’Reilly addresses a number of important issues in pancreatic cancer. Adenocarcinoma of the pancreas is a devastating disease,[1] not only because it will occur in approximately 30,000 Americans this year, and perhaps 200,000 people worldwide, but also because of its high associated mortality. Pancreatic adenocarcinoma is one of the least treatable and, therefore, most lethal of all cancers. Fully 95% of all patients with an established diagnosis of adenocarcinoma of the pancreas will die of their disease.

Pancreatic cancer is a leading cause of cancer-related mortality. Treatment has limited efficacy, and 5-year survival rates remain less than 5%. Insights from epidemiology and discoveries in molecular genetics have laid

ORLANDO-In a randomized multicenter phase II study of advanced pancreatic carcinoma by the European Organization for Research and Treatment of Cancer (EORTC) Gastrointestinal Cancer Group, the combination of docetaxel (Taxotere) and gemcitabine (Gemzar) was "promising" relative to docetaxel/cisplatin (Platinol), Manfred P. Lutz, MD, of University Hospital, Ulm, Germany, said at the 38th Annual Meeting of the American Society of Clinical Oncology (abstract 498).

KING OF PRUSSIA, Pennsylvania-Protarga, Inc. has received comments from the FDA that allow it to proceed with two separate phase III clinical studies of its new cancer drug Taxoprexin Injection (DHA-pacli-taxel) for the treatment of metastatic melanoma and pancreatic cancer. Taxoprexin is made by linking the fatty acid docosahexaenoic acid (DHA) to paclitaxel, the company said in a news release.

ORLANDO-The combination of pemetrexed (Alimta) and gemcitabine (Gemzar) is active in pancreatic cancer with acceptable toxicity and a promising 32% 1-year survival rate, according to an oral presentation at the 38th Annual Meeting of the American Society of Clinical Oncology (abstract 499).

ORLANDO-The combination of pemetrexed (Alimta) and gemcitabine (Gemzar) is active in pancreatic cancer with acceptable toxicity and a promising 32% 1-year survival rate, according to an oral presentation at the 38th Annual Meeting of the American Society of Clinical Oncology (abstract 499).

Cancer of the pancreas is the fourth leading cause of cancer death in the United States. Of the 28,000 patients diagnosed each year, more than 95% will die of pancreatic cancer. Therefore, the focus of therapy for most patients is palliative care. In fact, the most active single-agent therapy for advanced disease-gemcitabine (Gemzar)-was first compared to fluorouracil (5-FU) with relief of disease symptoms as a primary end point. However, the survival with gemcitabine remains approximately 6 months for advanced disease, and no new agent, either alone or in combination, has exceeded this time frame in phase III study.

Gastroenteropancreatic tumors, although relatively rare, present management problems that may last many years, in comparison with the usually more aggressive adenocarcinomas whose management may encompass a far briefer span of time. In general, 50% of such tumors are insulinomas, while gastrinomas comprise 25%, and nonfunctional tumors 20% VIPomas and glucagonomas are the predominant lesions of the remaining 5%. Clinical diagnosis is usually made on the presence of the classical symptom complex. In uncertain circumstances or covert presentations, the critical diagnostic biochemical test is plasma chromogranin A as well as measurement of the specific peptide.

A 48-year-old man is referred for evaluation. He has a history of hypercholesterolemia and obesity. Treatment with cholesterol-lowering medication was associated with elevated liver chemistries. When the elevated liver chemistries persisted

Fujirebio Diagnostics recently announced that its CA 19-9 radioimmunoassay for monitoring of pancreatic cancer patients received marketing clearance from the US Food and Drug Administration (FDA). The CA 19-9 radioimmunoassay is the first

Drs. Ahrendt and Pitt should be congratulated on a comprehensive and well-presented review of the surgical management of pancreatic cancer. Unfortunately, pancreatic cancer continues to be a major cause of cancer-related death. The majority (80%) of patients still present with unresectable locally advanced or metastatic disease.

Adenocarcinoma of the pancreas remains a lethal malignancy: The majority of patients with pancreatic cancer continue to present with advanced disease and die within a year of diagnosis. Despite this grim fact, some progress has been made over the past decade, particularly in the surgical management of patients with resectable and advanced disease. This well-constructed review by Drs. Ahrendt and Pitt succinctly details the advances that have been made and highlights many of the unresolved issues.

It is with great pleasure that I comment on the excellent article authored by Drs. Ahrendt and Pitt, who have provided a well-written, succinct, up-to-date review focusing on adenocarcinoma of the pancreas. The authors introduce the topic, discuss preoperative staging and assessment of resectability, cover the critical issues regarding resectional therapy and palliative surgery, and provide data on the results of such therapy, including mortality, morbidity, and quality-of-life outcomes. Emphasizing the importance of this topic, the authors note that pancreatic cancer is the fifth leading cause of cancer death in the United States.

Pancreatic cancer is the fifth leading cause of cancer death in the United States, with an overall survival rate of 3%. Unfortunately, only a minority of patients present with localized disease amenable to surgical resection.

Drs. Ahrendt and Pitt should be congratulated on a comprehensive and well-presented review of the surgical management of pancreatic cancer. Unfortunately, pancreatic cancer continues to be a major cause of cancer-related death. The majority (80%) of patients still present with unresectable locally advanced or metastatic disease.

Early clinical studies combining irinotecan (CPT-11, Camptosar) and gemcitabine (Gemzar) have yielded encouraging results. Gemcitabine administered via a twice-weekly schedule results in an enhanced radiation-sensitizing effect.

The combination of irinotecan (CPT-11, Camptosar) and gemcitabine (Gemzar) produced a 1-year survival rate of 27%, which is greater than that reported for gemcitabine alone in previous studies in patients with advanced pancreatic cancer (15% and 18% 1-year survival rates, respectively). These study results were published in a recent issue of the Journal of Clinical Oncology (20:1182-1191, 2002).

The multistep process of carcinogenesis, which can take many years, provides many opportunities for intervention to inhibit disease progression. Effective chemoprevention agents may reduce the risk of cancer by inhibiting the initiation stage of carcinoma through induction of apoptosis or DNA repair in cells harboring mutations, or they may act to prevent promotion of tumor growth. Similarly, chemoprevention may entail blocking cancer progression to an invasive phenotype.

Among the most exciting new anticancer products presented at the 2001 ASCO meeting were new drugs that block the epidermal growth factor receptor (EGFR). About 30% to 90% of carcinomas express high levels of EGFR. These include, among others, head and neck cancer, lung cancer, pancreatic cancer, colon cancer, breast cancer, ovarian cancer, and bladder cancer.

Lorus Therapeutics announced recently that it has initiated a phase III trial to evaluate the macrophage activator Virulizin for the treatment of advanced pancreatic cancer. The company will present the results of this trial to the US Food and Drug Administration (FDA) in a new drug application at the completion of the study.

Surgery is still the most important treatment for solid tumors, regardless of the age of the patient. In this article, we discuss the physiology of aging as it relates to risk assessment in the elderly surgical oncology patient. A brief review of the role of surgery in the treatment of breast, colorectal, pancreatic, and gastric cancer is provided, because these solid tumors primarily affect elderly patients.

The article by Drs. Levy and Wiersema is an excellent overview of the indications, technical nuances, and efficacy of endoscopic ultrasound in the diagnosis and staging of pancreatic neoplasms. Endoscopic ultrasonography was introduced into the diagnostic armamentarium for gastroenterology approximately 15 years ago. Although the literature suggests a general increase in the utility and experience with endoscopic ultrasound, the technique remains most effective in the hands of experienced experts like Drs. Levy and Wiersema. Their article is a complete and thorough review of the indications and expected accuracy of the technique when evaluating a variety of different pancreatic lesions.

Two decades have elapsed since publication of the first papers describing the examination of the pancreas via the stomach and the duodenum using an ultrasound probe fixed to an endoscope tip. Initial attempts to image the pancreas in this fashion proved difficult and frustrating, but they were promising enough that instrument makers and gastrointestinal endoscopists persisted in developing increasingly effective devices.

Patients with signs and symptoms suggestive of a pancreatic neoplasm typically undergo initial imaging with transabdominal ultrasound or computed tomography. This evaluation often reveals the presence of a pancreatic mass or fullness.