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BETHESDA, Maryland-Cell signaling pathways offer many potential targets for antitumor therapies, but hitting those targets is proving more difficult than researchers had anticipated, according to John J. Wright, MD, PhD. He is senior clinical investigator, Investigational Drug Branch, Cancer Therapy Evaluation Program, at the National Cancer Institute in Bethesda, Maryland.

PHILADELPHIA-Preoperative chemoradiotherapy with irinotecan (CPT-11, Camptosar), fluorouracil (5-FU), and radiation showed a significant ability to downsize rectal adenocarcinomas and is being studied further in clinical trials, Edith P. Mitchell, MD, reported. Due to problems associated with the central venous access required for continuous infusion 5-FU, capecitabine (Xeloda) is being substituted for 5-FU in ongoing studies. Dr. Mitchell is clinical professor of medicine at Thomas Jefferson University in Philadelphia.

ROCHESTER, Minnesota-Summarizing cooperative group approaches to adjuvant treatment of colorectal cancer, Charles Erlichman, MD, noted: "Treatment for stage II colon cancer remains controversial. Treatment for stage III colon cancer should be fluorouracil (5-FU)/leucovorin. Treatment for stage III rectal cancer should be radiation plus fluorouracil/leucovorin. The results of three-drug regimens are pending, as are data on the role of COX-2 inhibitors and of targeted agents such as epidermal growth factor receptor (EGFR) or tyrosine kinase inhibitors." Dr. Erlichman is professor of oncology, Mayo Clinic, Rochester, Minnesota.

PHILADELPHIA-Bevacizumab (Avastin), a monoclonal antibody against vascular endothelial growth factor (VEGF), was well tolerated in preliminary analyses of two Eastern Cooperative Oncology Group (ECOG) studies, according to Bruce J. Giantonio, MD, assistant professor of medicine, University of Pennsylvania Medical Center, Philadelphia.

NEW YORK-By tinkering with both dosage and scheduling, researchers are hoping to shift the balance of benefits over toxicity in patients treated with irinotecan/fluorouracil/leucovorin (IFL). Variations being tried include moving to a day 1, day 8 schedule every 21 days with day 15 as a rest day, and reducing starting doses for particular patient groups, David H. Ilson, MD, PhD, reported. Dr. Ilson is associate attending physician at Memorial Sloan-Kettering Cancer Center and assistant professor of medicine at Weill Medical College of Cornell University in New York.

PHILADELPHIA-Chemotherapy patients whose hemoglobin (Hb) drops below 9 g/dL are typically treated with recombinant human erythropoietin, but those whose anemia is in the 10 to 12 g/dL range are typically not given hematopoietic support.

PHILADELPHIA-Early results of a phase II trial of sequential fludarabine (Fludara)/alemtuzumab (Campath) therapy in patients with high-risk chronic lymphocytic leukemia (CLL) are encouraging in that the monoclonal antibody appears to improve the rate of flu-darabine-induced responses, Dr. Kanti R. Rai said at the 44th Annual Meeting of the American Society of Hematology (abstract 772). This study is one of several Cancer and Leukemia Group B (CALGB) trials investigating the combination of fludarabine, an effective single-agent therapy for CLL, with various antineoplastic monoclonal antibody agents.

SAN ANTONIO-ILEX Oncology, Inc. has launched the first ILEX-sponsored study of Campath (alemtuzumab) in patients with CD52-antigen-positive relapsing or refractory non-Hodgkin’s lymphoma (NHL). Campath is a humanized monoclonal antibody directed against the CD52 antige

PHILADELPHIA-A four-cycle regimen of simultaneous combined flu-darabine (Fludara) and alemtuzumab (Campath) (FLUCAM) was effective in patients with relapsed or refractory B-cell chronic lymphocytic leukemia (CLL), according to a poster presentation at the 44th Annual Meeting of the American Society of Hematology (abstract 3169). [See page 42 for another ASH presentation on these two agents in CLL.]

NEW YORK-"Chemotherapy-induced diarrhea remains a serious clinical problem, but newer guidelines may improve the clinical outcome for this syndrome," Scott Wadler, MD, said. He is head of the solid tumor service at Cornell University’s Weill Medical College in New York.

PITTSBURGH-Attempts to conduct randomized comparative trials of preoperative vs postoperative therapy for rectal cancer have been largely unsuccessful in the United States. Many surgeons have already decided which approach they are committed to and will not randomize patients to the alternate approach, according to Roy E. Smith, MD. As director of medical affairs and oversight for the National Surgical Adjuvant Breast and Bowel Project (NSABP) Foundation in Pittsburgh, Dr. Smith has had experience in NSABP’s efforts to get comparative trials off the ground.

LEXINGTON, Kentucky-Inadequate surgical resection is emerging as a major cause of recurrence in rectal cancer, and most such recurrences could be prevented by use of sharp mesorectal excision (SME) rather than blunt dissection, according to Alfred M. Cohen, MD. Dr. Cohen, director of the Lucille P. Markey Cancer Center at the University of Kentucky in Lexington, reviewed state-of-the-art rectal cancer surgery.

NEW HAVEN, Connecticut-Capecitabine (Xeloda) was developed as an oral tumor-activated alternative to fluorouracil (5-FU) and now appears set to replace that agent in some combination regimens for colorectal cancer according to Edward Chu, MD. Dr. Chu reported that phase II trials suggest that either capecitabine/oxaliplatin (Eloxatin) or capecitabine/irinotecan (CPT-11, Camptosar) might be effective replacements for 5-FU-based regimens. Dr. Chu is professor of medicine and pharmacology at Yale University School of Medicine and associate director of the Yale Cancer Center, New Haven, Connecticut.

WASHINGTON-The 107th Congress, by general agreement, will not enter the history books as a major contributor to medical and health policy. However, legislation it failed to pass serves as a prologue to some of the issues the new 108th Congress will consider during the next 2 years, said Susan Erickson, acting director of the National Cancer Institute’s (NCI) Office of Policy Analysis and Response. "We will probably continue to see these themes, no matter what specific pieces of legislation come back," she said at a meeting of the National Cancer Advisory Board.

BOSTON-Oncologists should screen cancer patients and survivors routinely for fatigue and attempt to treat those who complain of exhaustion that rest does not relieve, according to two speakers at the 14th international meeting of the Multinational Association for Supportive Care in Cancer (MASCC) and International Association for Oral Oncology.

NANTES, France-Most ongoing European trials in colorectal cancer are either comparing bolus fluorouracil (5-FU)/leucovorin to infusional 5-FU/leucovorin regimens or comparing infusional 5-FU/leucovorin to combinations with either irinotecan (CPT-11, Camptosar) or oxaliplatin (Eloxatin), according to Jean-Yves Douillard, MD, PhD. He is professor of medical oncology and head of the department of medical oncology at Centre Rene Gauducheau, University of Nantes, France.

PALM BEACH, Florida-What is the best method for administering fluorouracil (5-FU)? Should it be given as a continuous intravenous infusion, as often done in Europe? Or should 5-FU be administered as an intravenous bolus, as typically done by American physicians, at least partly to avoid the need for central venous access and pump devices.

NEW YORK-In phase I trials, AMGN-0007, a new compound to prevent bone metastasis, decreased bone resorption markers to the same extent as the bisphosphonate pamidronate (Aredia), Allan Lipton, MD, professor of medicine, Milton S. Hershey Medical Center, Pennsylvania State University, reported at the Chemotherapy Foundation Symposium XX.

SANTA MONICA, California-Vascular endothelial growth factor (VEGF) offers a number of sites for therapeutic targeting and is thought to play an important role in human cancers. Several angiogenesis inhibitors that work through effects on VEGF are under development, but one that failed in a phase III study may offer important insights for investigators developing this new area of anticancer therapy according to Lee S. Rosen, MD. Dr. Rosen, who was involved in research on the tyrosine kinase inhibitor SU5416, is director of developmental therapeutics, Cancer Institute Medical Group, Santa Monica, California.

PORTLAND, Oregon-Median survival for patients with advanced colorectal cancer treated with front-line regimens that include irinotecan (CPT-11,Camptosar) or oxaliplatin (Eloxatin) is approaching 3 years. "That is an absolutely remarkable figure to me," said Charles D. Blanke, MD, in a review of new approaches to colorectal cancer treatment. Dr. Blanke is director of the gastrointestinal malignancies program at the Oregon Health Sciences University Cancer Institute in Portland.

For several decades, the nutritional deterioration ofpatients diagnosed with cancer has been recognized,and attempts have been made to prevent orreverse it. However, with all the advancements intechnology and medicine, it is somewhat surprisingto find that little has altered in the approach or themanagement of cancer patients suffering from acompromised nutritional status or altered metabolismdue to either the treatment or the disease process.

As Dr. Raghavan has emphasizedin his excellent overviewof the current therapyfor testis cancer, it is critical that thesuccess of therapy for this diseasenot be compromised by a desire toavoid the complications of therapy.We would wholeheartedly agree withhis assertion that modifications intherapy must be introduced with athoughtful and structured approachto minimize the risk to efficacy.

The Department of Health and Human Services (HHS) has createda unified advisory committee on human immunodeficiency virus(HIV) and sexually transmitted diseases (STD) by merging twoexisting groups. The new committee brings together the AdvisoryCommittee for HIV Prevention at the Centers for Disease Control andPrevention (CDC) and the AIDS Advisory Committee at the HealthResources and Services Administration (HRSA). The two groups havemet jointly on several occasions during the last 2 years, and all currentmembers of the two bodies will serve on the new CDC/HRSA AdvisoryCommittee on HIV and STD Prevention and Treatment.

A6-year prostate cancer research plan released by the NationalInstitutes of Health (NIH) contains a detailed outline of theNational Cancer Institute’s (NCI) future strategy for dealingwith the disease, which includes a shift in the standard treatment modelfrom seek-and-destroy to target-and-control.

In a recent study, Wolfe and others interviewed 103parents of children who had died from cancer.[1]Approximately 80% of these children suffered anorexia,or loss of appetite. Over 35% of parents identifiedanorexia as a cause of distress for their child whena physician failed to recognize it. Wolfe and othersconcluded,"greater attention to symptomcontrol.…might ease…suffering." In adults, the syndromeof cancer anorexia/weight loss is no lesspervasive, and no less distressing. Anorexia is one ofthe most deleterious symptoms, surpassed only bypain and fatigue.[2] The majority of adults withadvanced cancer suffer from it toward the end of life.Among all cancer patients-regardless of age orcancer type-"greater attention to [the anorexia/weightloss syndrome]…might ease…suffering."

The management of germ cell tumors has advanced dramatically,with cure rates approaching 90% to 95%. Treatment of stage I/Aseminomas generally includes orchiectomy and adjuvant radiotherapy.Treatment of stage I/A nonseminomatous germ cell tumors involvesorchiectomy followed by retroperitoneal lymph node dissection oractive surveillance. One of the major advances has been the introductionof cisplatin-based chemotherapy for metastatic disease and thedevelopment of a system of risk attribution. The logical managementof any patient with curable disease is to provide curative therapy andthen follow the patient in a structured manner, to diagnose and treatany complications in a timely manner.

Despite many therapeutic options for chronic lymphocytic leukemia(CLL), the disease remains incurable. Since monoclonal antibodiesand recombinant toxins that bind surface antigens expressed on themalignant lymphocytes have been developed, targeted therapy hasbecome a vital option in treating CLL. Rituximab (Rituxan), a chimerichuman-mouse anti-CD20 antibody, and alemtuzumab (Campath), ahumanized anti-CD52 monoclonal antibody, have both shown activityin CLL-as single agents and in combination with conventionalchemotherapy. The possibility of combining antibodies has beenexplored as well, with some efficacy. In this review, we discuss theclinical data on the activity of commercially available antibodies inCLL, both as monotherapy and in combination with other agents.

Palliative care, previously viewed by many as anend-of-life movement, is now recognized as anapproach whose principles should infuse the care ofall patients with a chronic illness throughout the fullcourse of that illness. For example, the World HealthOrganization (WHO) has redefined palliative care asfollows:

WASHINGTON-The Department of Health and Human Service (HHS) has created a unified advisory committee on HIV and sexually transmitted diseases (STD) by merging two existing groups. The new committee brings together the Advisory Committee for HIV Prevention at the Centers for Disease Control and Prevention (CDC) and the AIDS Advisory Committee at the Health Resources and Services Administration (HRSA). The two groups have met jointly on several occasions during the last 2 years, and all current members of the two bodies will serve on the new CDC/HRSA Advisory Committee on HIV and STD Prevention and Treatment.

BETHESDA, Maryland-Two medical facilities have received the first grants awarded by the National Cancer Institute’s Cooperative Planning Grant for Cancer Disparities Research Partnerships (CDRP). The 5-year, $27 million program provides support for radiation oncology clinical research at institutions that have not traditionally participated in NCI-sponsored studies. The two grants, totaling more than $2.5 million, went to the Rapid City Regional Hospital in South Dakota ($1,404,486), which serves a largely Native American population, and the Mercy Health Center, Laredo, Texas ($1,120,013), which serves a largely Hispanic community.