Gastrointestinal Cancer

NASHVILLE, Tennessee-Regimens that contain oxaliplatin (Eloxatin) as well as irintoecan (CPT-11, Camptosar) and fluorouracil (5-FU)/ leucovorin have produced prolonged survival of 18 to 21 months in patients with advanced colorectal cancer and should be considered for first-line therapy, according to Mace L. Rothenberg, MD. Dr. Rothenberg, who is professor of medicine at Vanderbilt-Ingram Cancer Center, Nashville, Tennessee, reviewed the current status of oxaliplatin-based regimens.

SEATTLE-Regular use of non-steroidal anti-inflammatory drugs (NSAIDs) and aspirin lowers the relative risk of colorectal cancer by an overall rate of 24%, according to a study presented at the 67th Annual Scientific Meeting of the American College of Gastroenterology (abstract 12). The rate rises to 32% when aspirin/NSAIDs are used for more than 2 years.

TAEJON, Korea-In a study from Korea of patients with locally advanced rectal cancer, preoperative capecitabine (Xeloda) with leucovorin given concurrently with radiotherapy resulted in primary tumor downstaging and nodal downstaging, reported Jun-Sang Kim, MD, of Chungnam National University, Taejon, and colleagues.

SEATTLE-Having at least one follow-up colonoscopy within 5 years of a diagnosis of nonmetastatic colorectal cancer decreased the mortality risk by 40%, according to a study presented at the 67th Annual Scientific Meeting of the American College of Gastroenterology (president’s plenary session abstract 11).

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).

Radiation therapy alone is an adequate treatment for some patients with rectal cancer, according to a study published in a recent issue of the International Journal of Radiation Oncology, Biology, Physics (54:142-149, 2002).

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-One in four patients with resected rectal cancer who later underwent surgical salvage for recurrence at a single site were still alive at 5 years, according to a subanalysis of a large, randomized Intergroup study presented at the 38th Annual Meeting of the American Society of Clinical Oncology (abstract 507). "Approximately 27% of the patients have long-term survival and appear to be cured," said Michael J. O’Connell, MD, director, Allegheny Cancer Center, Allegheny General Hospital, Pittsburgh.

The US Senate Health, Education, Labor, and Pensions Committee has passed the Eliminate Colorectal Cancer Act (S.710), legislation introduced by Sen. Jesse Helms (R-NC) and Sen. Edward M. Kennedy (D-Mass). The bill, with the companion

ORLANDO-A phase III clinical trial of first-line therapy in advanced colorectal cancer showed improved progression-free survival (PFS) for weekly infusional FUFOX-fluorouracil/folinic acid (5-FU/FA)/oxaliplatin (Eloxatin)-compared with the Mayo bolus 5-FU/FA (leucovorin in the United States) regimen, Axel Grothey, MD, University of Halle, Halle, Germany, said at the American Society of Clinical Oncology 38th Annual Meeting (abstract 512).

ORLANDO-Delivering Selective Internal Radiation Therapy (SIRT) via radioactive microspheres (SIR-Spheres) significantly increased response to treatment and time to progression in a small cohort of patients receiving chemotherapy for advanced colorectal cancer liver metastases.

ORLANDO-Treatment of unre-sectable hepatocellular carcinoma (HCC) with 90-yttrium-embedded glass micro-spheres (TheraSphere, MDS Nordion) appears to be safe, effective, and less toxic than the alternative, transarterial che-moembolization (TACE).

Malignant small bowel tumors are extremely rare, accounting for 0.1% to 0.3% of all malignancies. Fewer than 2,400 new cases of small bowel malignancy are reported in the United States each year.[1] Malignant tumors, which account for about two-thirds of all primary small bowel tumors, consist of four primary subtypes: adenocarcinoma, carcinoid tumor, lymphoma, and sarcoma (or gastrointestinal [GI] stromal tumor). Each malignancy is characterized by unique predisposing factors, anatomy, and biology. The prevalence, pattern, and relevance of both regional lymph node and distant metastases differ. As a result, the study of malignant small bowel tumors, taken as an aggregate, is fraught with difficulty.

Small bowel adenocarcinoma is a relatively rare malignancy. Only limited information is available on the incidence, prognosis, and role of chemotherapy in the treatment of this disease. We present a review of currently

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.