Gastrointestinal Cancer

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).

ROCKVILLE, Maryland-The United States Food and Drug Administration has approved Eloxatin (oxaliplatin for injection, Sanofi-Synthelabo) in combination with infusional fluorouracil (5-FU) and leucovorin (LV) for the treatment of colorectal cancer that has recurred or become worse following initial therapy with irinotecan (Camptosar) plus bolus 5-FU and LV. The agency granted approval in 7 weeks, the fastest review ever for a cancer drug.

Sanofi-Synthelabo recently announced that its platinum-based drug oxaliplatin (Eloxatin) has been approved by the US Food and Drug Administration (FDA) for use in combination with infusional fluorouracil (5-FU)/leucovorin in advanced colorectal cancer patients whose disease has recurred or progressed after bolus 5-FU/leucovorin plus irinotecan (CPT-11, Camptosar) therapy. The FDA approval is based on the response rate and improved time to tumor progression observed in an ongoing trial. Data that demonstrate a clinical benefit, such as improvement in disease-related symptoms or an increase in survival are not yet available.

Patients with advanced colorectal cancer who received the FOLFOX4 regimen (fluorouracil [5-FU], leucovorin, oxaliplatin [Eloxatin]) responded significantly better to treatment, had fewer severe side effects, and lived months longer than did patients

ORLANDO-In a phase II study, 63% of patients with unresectable and/or metastatic gastrointestinal stromal tumors (GISTs) responded to treatment with imatinib mesylate (Gleevec), and after a median of 15 months of follow-up, 73% of patients remain in the study, Margaret von Mehren, MD, reported at the 38th Annual Meeting of the American Society of Clinical Oncology (abstract 1608). Results at 9 months of follow-up were recently published (N Engl J Med 347:472-478, 2002).

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 chimeric mono-clonal antibody cetuximab (Erbitux, also known as C225, ImClone Systems) has modest single-agent activity in irinotecan (Camptosar)-refractory colorectal cancer expressing epidermal growth factor receptor (EGFR), researchers said at the American Society of Clinical Oncology 38th Annual Meeting (abstract 504).

Hepatocellular carcinoma (HCC) is the third most frequent cause of cancer death worldwide, causing 549,000 deaths in 2000-10% of all cancer deaths. There are strong etiologic associations with hepatitis C, hepatitis B, alcohol, other causes of cirrhosis, and dietary aflatoxins. The US incidence of HCC is 2.4/100,000 persons/year and rising due to the increased prevalence of hepatitis C.[1] After the current cohort of patients infected with the chronic hepatitis C virus passes, there will likely be a continued increase in the US incidence of HCC due to increasing rates of obesity-related nonalcoholic steatohepatitis, which causes many cases of "cryptogenic cirrhosis."

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.

LOS ANGELES-PET/CT fusion imaging can improve the diagnostic certainty and localization of colorectal cancer, compared with PET alone, according to a retrospective review presented at the 49th Annual Meeting of the Society of

ORLANDO-Adjuvant fluorouracil (5-FU)-based chemotherapy for stage II-III colon cancer has been associated with a trend toward decreased survival for patients whose tumors show high-frequency microsatellite instability (MSI-H). This

Recent trials have established the IFL combination (fluorouracil [5-FU], leucovorin, and irinotecan [CPT-11, Camptosar]) as a new standard first-line therapy for patients with metastatic colorectal cancer. Median survival for such patients treated with IFL still ranges from approximately 14 to 18 months, however, underscoring the need for new agents with novel mechanisms of action.

ORLANDO-Combination therapy with irinotecan (CPT-11, Camptosar) and capecitabine (Xeloda) has the potential to become a mainstay of treatment for colorectal cancer, according to David J. Kerr, MD, Rhodes Professor of Therapeutics and Clinical Pharmacology and director of the National Translational Cancer Research Network, Oxford University

LONDON, Ontario-A Canadian study is evaluating the safety and efficacy of single-agent capecitabine(Xeloda) among patients with advanced colorectal cancer deemed unsuitable for more aggressive treatment with bolus fluorouracil (5-FU)/leucovorin/irinotecan (also known as CPT-11, Camptosar).

ROCHESTER, Minnesota-An interim analysis of the North American Intergroup Study N9741 suggests that oxaliplatin (Eloxatin, investigational in the United States) plus infusional fluorouracil (5-FU)/leucovorin (FOLFOX) may be the new standard of care for patients with metastatic colorectal cancer.

PORTLAND, Oregon-In a phase II trial of patients with unresectable or metastatic colorectal cancer, celecoxib (Celebrex) given with irinotecan (CPT-11, Camptosar), fluorouracil (5-FU), and leucovorin (IFL) appears to reduce toxicity, Charles D. Blanke, MD, associate professor of medicine, Oregon Health & Science University, said at the 38th Annual Meeting of the American Society of Clinical Oncology (abstract 505).

OXFORD, UK-The combination of capecitabine (Xeloda) and irinotecan (Camptosar) appears to be an effective, easy-to-use, and well-tolerated treatment for patients with metastatic colorectal cancer, according to results of a phase I/II trial conducted by British and Dutch researchers.

DETROIT-A phase II trial of capecitabine (Xeloda) plus oxaliplatin (Eloxatin, investigational in the United States) supports European data suggesting that the combination is active in advanced colorectal cancer, and with manageable toxicity.

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

Imatinib mesylate (Gleevec) has a lasting effect on advanced gastrointestinal stromal tumors (GISTs), while greatly reducing

ORLANDO-Compared with the standard first-line chemotherapy treatment for advanced colorectal cancer, patients treated with the FOLFOX4 regimen containing the investigational agent oxaliplatin lived longer and had fewer side effects.

A study published in the journal Cancer (94:2327-2332, 2002) suggests that African-Americans who have colon cancer and live in poverty are at much greater risk of dying from the disease.

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.

Preoperative or postoperative pelvic radiation plus concurrent fluorouracil-based chemotherapy is standard adjuvant treatment for patients with T3 and/or N1/2 rectal cancer. Newer chemotherapeutic regimens have been developed for the treatment of patients with metastatic disease.

The US National Cancer Institute Gastrointestinal Intergroup has contributed to the development of chemotherapy and radiation regimens for the treatment of stage II and III rectal cancer. The first Intergroup trial demonstrated improvement in relapse-free and overall survival for patients who received protracted venous infusion fluorouracil (5-FU) with radiation compared to those treated with bolus 5-FU.