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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.

HERSHEY, Pennsylvania-Elevated levels of common serum biomarkers, including HER2/neu, predict response to hormone therapy among women with advanced breast cancer, according to a study reported by Kim Leitzel, MS, senior research associate in the Experimental Oncology Research Lab, directed by Allan Lipton, MD, at Penn State/Hershey Medical Center, Hershey, Pennsylvania.

ANN ARBOR, Michigan-Giving oral capecitabine (Xeloda) plus IV vinorelbine (Navelbine) in flat doses unadjusted for body surface area (BSA) is a feasible, convenient strategy that has good activity in previously treated metastatic breast cancer, according to results of a phase I/II study. The findings lay the groundwork for investigating a potential flat-dosed, all-oral regimen, according to Anne F. Schott, MD, assistant professor of internal medicine with the University of Michigan Comprehensive Cancer Center at Ann Arbor.

ESSEN, Germany-The combination of capecitabine (Xeloda) plus vinorelbine (Navelbine) is feasible and has a favorable toxicity profile in anthracycline-pretreated or taxane-pretreated advanced breast cancer, according to results of a recent phase I/II study. "The response rate over 50% is very promising," noted Udo Vanhoefer, MD, professor of medicine at University of Essen Medical School in Germany. "We had no alopecia, the incidence of hand-foot syndrome is very low, and the dose density is very high at 90% and very acceptable for this combination."

BERN, Switzerland-The antiestrogen fulvestrant (Faslodex) is an effective and well-tolerated treatment option for women with heavily pretreated, hormone-sensitive advanced breast cancer, according to an interim analysis from an ongoing study by the Swiss Group for Clinical Cancer Research (SAKK), based in Bern, Switzerland. All of the patients in the study had failed both tamoxifen and an aromatase inhibitor, but 11 of 32 patients (34%) had prolonged clinical benefit on fulvestrant 250 mg every 28 days.

EVANSTON, Indiana-Analysis of traditional factors that correlate with choice of mastectomy or breast-conserving surgery failed to explain the significantly higher mastectomy rates in the United States compared to the United Kingdom seen in the international Arimidex (anastrozole), Tamoxifen, Alone or in Combination (ATAC) trial. ATAC investigator Gershon Y. Locker, MD, noted the striking difference "in the mastectomy rates between the two largest accruing nations in ATAC-the United Kingdom with a 42% mastectomy rate and the United States with a 51% mastectomy rate. This is a 21% increased risk of having a mastectomy if enrolled in the United States compared to the United Kingdom."

PHILADELPHIA-T-cell depletion had no clear advantage over immunosuppressive drug therapy in patients receiving a matched, unrelated donor bone marrow transplant, John E. Wagner, MD, reported at the 44th Annual Meeting of the American Society of Hematology (ASH abstract 274).

CHARLOTTE, North Carolina-Dose-intense, dose-dense neoadjuvant docetaxel (Taxotere) /vinorelbine (Navelbine) produced a pathologic complete response rate of 36% in women with locally advanced breast cancer, making the combination among the most active ever tested in this setting, according to investigator Steven A. Limentani, MD. Preliminary study results also suggest the regimen is safe and well tolerated.

CHICAGO-Among patients with intractable and severe pain because of bony metastases, radiofrequency ablation either relieved pain completely or produced a significant reduction in patients’ assessment of pain, according to a study presented at the 88th Scientific Assembly and Annual Meeting of the Radiological Society of North America (RSNA abstract 228VI-p). In this multicenter study of 62 patients with osteolytic metastases, 44% reported they were completely free of pain at some point during the 6 months following radiofrequency ablation, 81% had a 3-point drop in the Brief Pain Inventory (BPI), and 95% had at least a 2-point drop in BPI.

REIMS, France-Results of a French study suggest that oncologists should not underestimate the potential threat posed by local recurrence of ductal carcinoma in situ (DCIS). Reporting on the DCIS experience of 11 French cancer centers, Bruno Cutuli, MD, a radiation oncologist at the Center for Radiotherapy and Oncology at Polyclinique Courlancy in Reims, France, emphasized the importance of optimal initial treatment, close follow-up and definitive treatment after an invasive local recurrence.

HOUSTON-A gene that has been labeled metastasis-associated gene appears to be related to poor disease-free survival. Investigators at Baylor College of Medicine in Houston have produced a polyclonal antibody to metastasis-associated tumor antigen (MTA1)-specific isotopes that may prove useful as a prognostic marker for recurrence.

HOUSTON-The nonsteroidal aromatase inhibitor anastrozole (Arimidex) continues to outperform tamoxifen in every efficacy measurement in the Arimidex, Tamoxifen, Alone or in Combination (ATAC) trial, according to a recent 47-month update. Speaking for the ATAC Trialists’ Group, Aman U. Buzdar, MD, professor of medicine and deputy chairman of the Department of Breast Medical Oncology at The University of Texas M.D. Anderson Cancer Center, Houston, reported that the absolute differences between the two drugs are increasing with time.

INDIANAPOLIS-Adding the antiangiogenesis agent bevacizumab (Avastin) to capecitabine (Xeloda) increases the objective response rate-but not progression-free survival-in women with advanced breast cancer, according to a phase III trial. This was the first randomized trial to report results with an antiangiogenic agent in patients with metastatic disease, according to lead investigator Kathy D. Miller, MD, assistant professor of medicine in the division of hematology/oncology at Indiana University School of Medicine, Indianapolis.

Infections are major causes of morbidityand mortality in patientswith cancer. In certain instances,the malignancy itself can predisposepatients to severe or recurrent infections.For example, acute leukemiamay cause neutropenia and ensuingbacterial or fungal infection. Hypogammaglobulinemiaof chroniclymphocytic leukemia may be complicatedby infections due to encapsulatedbacteria. Patients withHodgkin’s lymphoma may sufferfrom recurrent varicella-zoster infections.Solid tumors may obstruct thelumens of respiratory, digestive, andurinary tracts, leading to bacterial infections.Nevertheless, the principalrisk of infectious complications is relatedto the intensity and duration ofimmunosuppressive chemotherapy.Patients with cancer constitute ahighly varied population, both interms of the underlying malignancyand in terms of their immunosuppression.In addition, a single patientmay have multiple predisposing factors,thus increasing the spectrum oflikely pathogens. When evaluating apatient with cancer for a possible infection,it is essential to develop aconceptual framework of quantitativeand qualitative immune defectsthe patient is likely to have, and thento stratify the risk for specific pathogensin the context of the history,physical exam, and laboratorydata.[1]

Each year, 2.4 million patients in the United States develop healthcare–associated infections (HAIs), requiring treatment at an annualcost of approximately $4.5 billion. HAI is the primary cause of deathin approximately 30,000 patients and contributes to the death of 70,000annually. Oncology patients are more susceptible than other patientsto HAIs due to compromised immune systems, surgery (drains),invasive technology (catheters), and environmental factors. This paperwill review each of these risk factors and discuss preventive steps suchas a predictive index, antibiotic therapy, and infection control practices.

Drs. Guinan, McGuckin, andNowell have nicely reviewedthe risk factors associatedwith increased susceptibility to hospital-acquired infection in oncologypatients and also discussed preventivesteps to attenuate those risks.We agree that patients with malignanciespresent a challenge to thehealth-care provider, as infection willdevelop at some point in almost allcancer patients[1] and may be associatedwith significant mortality.[2]

HOUSTON-Inflammation is a common link between the toxicity of chemotherapy and cancer progression, and the possibility that anti-inflammatory treatments might help both is attracting more research attention. "Cancer is a nonhealing wound with persistent inflammation," Edward H. Lin, MD, said, quoting Harold Dvorak, MD, of Beth Israel Hospital in Boston. Dr. Lin is assistant professor of gastrointestinal medical oncology at the University of Texas M.D. Anderson Cancer Center in Houston.

CHICAGO-Black men with localized prostate cancer do just as well as white men when treated with brachy-therapy alone, William Barrett, MD, said at the 88th Annual Scientific Assembly of the Radiological Society of North America (RSNA abstract 252RO-p).

MELVILLE, New York-ONI is pleased to announce the addition of two new members to its recently created Editorial Advisory Board for Oncology Nursing: Genevieve V. Foley, RN, MSN, OCN, CNAA, and Mary Pazdur, RN, MSN, ANP, AOCN. The two will work with Sharon Krumm, PhD, RN, Editor of Oncology Nursing, and current nursing board members Catherine Coleman, RN, OCN, and Mary McCabe, BSN, MA (see ONI January 2003, page 27).

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.