Gastrointestinal Cancer

BIRMINGHAM, Ala-New oral agents being tested in clinical trials for the treatment of colorectal cancer show promise of improving the efficacy of 5-fluorouracil (5-FU) in combination regimens. A review of several agents under study-capecitabine (Xeloda), UFT (a combination of uracil plus ftorafur [Tegafur]), and S-1-was presented by Robert B. Diasio, MD, at a clinical investigators’ workshop.

NEW ORLEANS-A meta-analysis of two independent phase III randomized multicenter studies “further strengthens the conclusion that the combination of irinotecan (CPT-11, Camptosar)/fluorouracil (5-FU)/leucovorin represents a new reference standard in the first-line treatment of patients with metastatic colorectal cancer,” said Leonard Saltz, MD, associate attending physician, Division of Solid Tumor Oncology, Memorial Sloan-Kettering Cancer Center.

PHILADELPHIA-“Most people would agree that standard-of-care for frontline treatment of advanced colorectal cancer (CRCA) should now be irinotecan (Camptosar) plus 5-fluorouracil/leucovorin (5-FU/LV),” stated Daniel G. Haller, MD, at an investigators’ workshop sponsored by the University of Texas M. D. Anderson Cancer Center and Pharmacia Oncology. As the basis for this assessment, Dr. Haller of the University of Pennsylvania Cancer Center in Philadelphia, cited presentations made earlier this year.

NEW ORLEANS-New data demonstrate that the recently approved combination of irinotecan (Camptosar), 5-fluorouracil (5-FU), and leucovorin (LV) in-creases overall survival when used as first-line therapy in patients with metastatic colorectal cancer, without a significant increase in side effects.

VILLEJUIF, France-Infusions of oxaliplatin, 5-fluorouracil (5-FU), and leucovorin (LV) timed to circadian rhythms are better tolerated and have better anticancer activity in patients with metastatic colorectal cancer than the same drugs infused traditionally at a constant rate, said Francis Lévi, MD, PhD, chairman of the International Organization for Cancer Chronotherapy in the Department of Medical Oncology, Hôpital Paul Brousse, Villejuif, France.

SAN DIEGO-Virtual colonoscopy is an accurate screening tool for colorectal cancer in lesions greater than 10 mm with good patient tolerance, Richard J. Farrell, MD, said at the American Gastroenterological Association meeting held during the Digestive Disease Week conference.

FLINT, Michigan-The debate continues on the use of sentinel lymph node (SLN) mapping in colon cancer. How many nodes need to be analyzed to improve the outcome for this patient group? The current thought is the more nodes harvested, the better the predictive value, and Dr. Thomas LeVoyer made the case that removing more nodes yields a better survival benefit.

BOSTON-Interim results from an ongoing multicenter study suggest that an irinotecan (Camptosar) dosing regimen of every 3 weeks for patients with 5-fluorouracil (5-FU)-refractory colorectal cancer may be associated with a lower incidence of grade 3-4 late diarrhea when compared to a four-times-a-week schedule. The results were presented at the 36th ASCO Annual Meeting.

PHILADELPHIA-Nearly 45% of all cases of colon cancer have lymph node involvement. Surgical resection is the gold standard of treatment, with adjuvant chemotherapy used in an attempt to improve survival in patients with late-stage disease, but the outlook is often dismal.

NEDLANDS, Australia-If the implications of an Australian study are validated in further prospective studies, microsatellite instability (MSI) could potentially predict those patients with Dukes’ C and possibly Dukes’ B colorectal cancer who will respond best to chemotherapy.

LOS ANGELES-A new angiogenesis signaling inhibitor called SU5416 can be safely used with 5-fluorouracil (5-FU) and leucovorin to treat metastatic colorectal cancer, according to results presented at the 36th annual meeting of the American Society of Clinical Oncology (ASCO).

LONDON-Early trial results from the Royal Marsden GI Collaborators, in the United Kingdom, show that 12 weeks of protracted venous infusion 5-fluorouracil (PVI 5-FU) results in the same efficacy as 6 months of bolus 5-FU for colorectal cancer. This results in less toxicity and impairment of quality of life (QOL).

Laparoscopic colorectal surgery is being utilized increasingly for benign diseases. Recent published series have proven that morbidity and mortality from laparoscopic procedures are superior to those seen after traditional open

SAN DIEGO-“More awareness for colorectal cancer can save lives,” Today Show anchor Katie Couric said via live satellite feed to attendees of the American Gastroenterological Association (AGA) plenary session, held during the Digestive Disease Week conference.

FORT LAUDERDALE, Fla-More patients are candidates for sphincter-saving operations under the revised National Comprehensive Cancer Network (NCCN) practice guidelines for rectal cancer.

SAN FRANCISCO-RhuMAb VEGF (recombinant humanized monoclonal antibody to vascular endothelial cell growth factor) in combination with 5-fluorouracil/leucovorin chemotherapy (5-FU/LV) is well tolerated and may increase response rates and prolong time to disease progression in previously untreated metastatic colorectal cancer, as compared with 5-FU/LV alone.

SAN DIEGO-It has been suggested that laparoscopic surgical techniques may increase malignant cell spread, due primarily to peritoneal insufflation. A study conducted at the Colorectal Cancer Unit, Institut de Malalties Digestives, Hospital Clinic, Barcelona, Spain, has found that the type of surgery is not a determining factor in colorectal cancer spread.

NCI Colorectal Cancer Group Outlines a Decade of Research Goals

SAN DIEGO-Despite the egalitarian nature of health maintenance organizations (HMOs), minority and low-income patients enrolled in such plans may not receive the same colorectal cancer surveillance care as whites and higher income patients.

The article, “Management of Hepatocellular Carcinoma,” by Drs. Nakakura and Choti, is an excellent, comprehensive overview of the treatment modalities used for one of the most challenging cancers. The thoroughness of this review underscores the current frustration of the clinician in the management of this disease and the inadequacies of available therapies. The authors list more than 17 treatments for the various stages of this disease. However, if any one of the therapies mentioned offered cure to a majority of patients, there would be little need for more review articles or randomized controlled trials. There are few cancers that command such a vast array of differing therapies from so many different specialties.

Hepatocellular carcinoma (HCC) is responsible for a significant amount of morbidity and mortality throughout the world. In many countries, including the United States, a definite increase in the incidence of HCC has been

As Drs. Nakakura and Choti point out, the incidence of hepatocellular carcinoma (HCC) is rising in many countries including the United States, mainly as the result of a steady increase in hepatitis C infections. Unfortunately, it now seems that the hepatitis C virus is more carcinogenic than the hepatitis B virus, judging from the frequency with which HCC develops among patients with hepatitis C- vs hepatitis B-induced cirrhosis.[1] Numerous studies have demonstrated changes in various oncogenes and tumor suppressor genes, but no consistent sequence of genetic changes has emerged similar to the adenoma-carcinoma sequence in colon cancer.

Hepatocellular carcinoma (HCC) is the most common solid organ tumor worldwide. In recent decades, diagnosis and treatment of this cancer has evolved significantly. The article by Drs. Nakakura and Choti summarizes many of the advances in this field, delineates the current evidence-based treatment options, and defines promising areas for future study.

AstraZeneca has announced the launch of a new website that will help keep researchers and physicians up to date on

NEW ORLEANS-A prospective study in colorectal cancer patients has found that sentinel lymph node (SLN) mapping correctly predicts the presence or absence of nodal metastases, with a very low incidence of skip metastases (disease in a non-SLN), as it does in melanoma and breast cancer.

Patients with metastatic colorectal cancer may benefit from therapy with the oral anticancer agent capecitabine

WASHINGTON-Pharmacia & Upjohn’s Camptosar (irinotecan) has won FDA approval for use as a first-line agent in metastatic colorectal cancer, in combination with fluorouracil (5-FU) and leucovorin. [See ONI April 2000, page 3 for the ODAC review.] The agent was approved as a follow-up colorectal cancer treatment in 1996.

Microsatellite Instability Linked to Longer Colon Cancer Survival

Damjanov and Meropol review the status of several oral fluoropyrimidine drugs that are currently undergoing clinical testing for the treatment of colorectal cancer. Meta-analysis indicates an 8% improvement in the overall response rate and a survival advantage of 0.8 months with infusional vs bolus fluorouracil (5-FU)-arguably small differences. The incidence of grade 3-4 diarrhea, mucositis, and myelosuppression is < 10% with infusional 5-FU, although hand-foot syndrome is commonly associated with this therapy. The prevailing strategy for the development of oral 5-FU drugs employs multiple daily dosing for periods of 2 to 4 weeks followed by a 1- or 2-week break in order to mimic the protracted infusional schedule.UFT

The article by Damjanov and Meropol elegantly outlines the rationale behind the preclinical development of several potential new oral chemotherapy options for patients with advanced colorectal carcinoma and the available data from clinical trials in advanced colorectal cancer that evaluated the activity and safety of these agents. The authors relate the history of fluorinated pyrimidine therapy in colorectal cancer and the pharmacologic challenges to delivering effective oral therapy in a such a way that the chemistry behind the processes becomes readily intelligible. They note that the erratic absorption and blood levels associated with orally administered fluorouracil (5-FU) led to the current approaches to oral therapy.