ONCOLOGY Vol 16 No 8

The 4th Investigators’ Workshop sponsored by The University of Texas M. D. Anderson Cancer Center was held on July 25-29, 2001, in Colorado Springs, Colorado. The purpose of these annual workshops has been to review the latest data on new agents, with a particular focus on the broadly used agent irinotecan (CPT-11, Camptosar).

Cancer Care has published the fourth edition of its handbook-A Helping Hand: The Resource Guide for People With Cancer. The 148-page booklet contains listings and descriptions of organizations that offer a wide variety of services, support, and information for people with cancer. In general, the booklet shows cancer patients what types of help are available to them and where they can find it, both nationally and regionally. Listings include cancer centers, commercial services that offer products of particular interest to people with cancer (such as wigs and prostheses), state pharmaceutical assistance programs, pharmaceutical manufacturers’ indigent drug programs, and useful tips on what to ask when contacting such services.

Handbook of Gynecologic Oncology, edited by Drs. Barakat, Bevers, Gershenson, and Hoskins, is a first-edition clinical handbook formulated primarily for fellows in gynecologic oncology as well as for interested fellows in medical oncology and radiation oncology. The textbook presents concise summaries of the critical issues in the care of gynecologic cancer patients and would also be of interest to residents preparing for their gynecologic oncology rotations, obstetrician/gynecologists, other physicians who care for gynecologic cancer patients, and practicing gynecologic oncologists.

The results of a phase III multicenter trial presented at the 38th annual meeting of the American Society of Clinical Oncology showed for the first time that chemotherapy can improve the survival of patients with advanced hormone-refractory prostate cancer. For the study, researchers compared the effects of vinblastine alone vs vinblastine combined with estramustine (Emcyt).

Now that President Bush has appointed Julie Gerberding to head the Centers for Disease Control and Prevention (CDC), groups like the Trust for America’s Health are urging her to make cancer tracking a priority.

Novartis has submitted marketing applications with health authorities in the United States and Europe, seeking marketing authorization for Gleevec (imatinib mesylate) for the first-line treatment of patients with newly diagnosed Philadelphia chromosome-positive (Ph+) chronic myeloid leukemia (CML).

Women with early-stage breast cancer treated with a docetaxel (Taxotere)-based regimen after surgery had a 32% less chance of developing disease recurrence than did women receiving one of the most effective adjuvant treatments currently available. Results from the Breast Cancer International Research Group (BCIRG) trial 001, the first phase III trial to evaluate docetaxel after breast surgery, were presented at the recent annual meeting of the American Society of Clinical Oncology (ASCO) by the BCIRG.

According to the results of a multinational phase III trial reported at the 38th annual meeting of the American Society of Clinical Oncology (ASCO), the combination of docetaxel (Taxotere) and a platinum compound leads to a significantly better quality of life than the combination of vinorelbine (Navelbine) and cisplatin in chemonaive patients with advanced non-small-cell lung cancer (NSCLC). The combination of vinorelbine and cisplatin is a standard first-line regimen for these patients.

The House corrected some of the problems with the Medicare physician fee formula when it passed its Medicare reform bill at the end of June. That bill also inaugurates a Medicare outpatient drug benefit for seniors.

At the same time that the House was trying to improve physician pay, the "Centers for Medicare and Medicaid Services" (CMS) announced that barring a change in the Medicare statute, the update in calendar 2003 will again be negative.

Rubinstein and colleagues provide an excellent review of mathematical models for estimating breast cancer risk, including the risk of carrying inherited mutations of BRCA1 and BRCA2. Since we and others reviewed early models to predict the likelihood of inherited susceptibility to breast cancer,[1] newer quantitative tools, most notably by Parmigiani and colleagues,[2] have been developed. These models have been made available on CD-ROM, over the Internet, and in other electronic versions that are accessible to most clinicians and researchers. These quantitative resources constitute useful and important aids in genetic counseling.

The past 30 years have seen tremendous advances in the treatment of pediatric leukemia. What was once an invariably fatal diagnosis is now quite curable in close to 80% of cases. Unfortunately for children with acute myelogenous leukemia (AML), most of these developments have been in the treatment of acute lymphoblastic leukemia (ALL); even today, nearly half of all children diagnosed with AML will die of the disease.

In their paper, Schwartz and colleagues review the risk factors for depression and suicide in patients with cancer and argue convincingly that screening for depression can be simply and quickly performed. They also delineate the efficacy and potential adverse effects of psychotherapeutic or psychopharmacologic treatments for these patients. Buttressing the identification and treatment of depression in the cancer patient are vital, ongoing scientific developments that flow from an increased understanding of interactions among the brain, endocrine system, and immune system. This rapidly evolving body of neurobiological knowledge has catalyzed fundamental changes in how we conceptualize depression in cancer patients and has important ramifications regarding the treatment and prevention of depressive syndromes in this setting.

The Cancer Trials Support Unit (CTSU) is a pilot program sponsored by the National Cancer Institute (NCI). The CTSU has two primary functions. It centralizes regulatory support for all adult Cooperative Group trials (phases I- III), thereby reducing duplication among Group members regarding credentialing, compliance with federal regulations, and institutional review board (IRB) activities. It also provides all Group members and select non-Group members with access to phase III treatment trials.

Breast and ovarian carcinomas pose major public health problems in most Western countries. Countless attempts have been made to better understand a patient’s lifetime risk of breast cancer. The most significant etiologic risk is increasing age, followed by family history. In addition, hormonal and reproductive factors-ie, early menarche and later age at menopause, nulliparity (and, therefore, a greater number of ovulations over the patient’s lifetime), and late age at first pregnancy (greater than age 30 years)-also increase a patient’s breast cancer risk.

The use of intensive therapy over a brief period of time has produced dramatic improvements in outcome for pediatric patients with acute myelogenous leukemia (AML), as has been demonstrated in studies by the major cooperative groups in the United States and Europe. Still, despite high-intensity chemotherapy and bone marrow transplantation, only about half of the children diagnosed with AML are cured. Future improvements are unlikely to come from further increases in chemotherapy intensity. Alternative approaches, such as risk-directed therapy based on different prognostic criteria; differentiation therapy with all-trans-retinoic acid (ATRA, Vesanoid), arsenic trioxide (Trisenox), or azacytidine; and immunotherapy with monoclonal antibodies, tumor vaccines, or cytokines may lead to further advances. [ONCOLOGY 16:1057-1070, 2002]

Depression is a common but treatable condition among cancer patients. Screening for depression can be done simply and effectively, and a variety of practical treatment strategies are available. Numerous factors should be

Because irinotecan (CPT-11, Camptosar) is a topoisomerase I inhibitor with a broad spectrum of antitumor clinical activity, we investigated its activity in relapsed or refractory non-Hodgkin’s lymphomas (NHLs). Irinotecan at 300 mg/m² IV was administered every 21 days with intensive loperamide management of diarrhea.

Women at increased risk of breast cancer have important opportunities for early detection and prevention. There are, however, serious drawbacks to the available interventions. The magnitude of breast cancer risk is a crucial factor in the optimization of medical benefit when considering the efficacy of risk-reduction methods, the adverse effects of intervention, and economic and quality-of-life outcomes. Breast cancer risk assessment has become increasingly quantitative and is amenable to computerization. The assembly of risk factor information into practical, quantitative models for clinical and scientific use is relatively advanced for breast cancer, and represents a paradigm for broader risk management in medicine. Using a case-based approach, we will summarize the major breast cancer risk assessment models, compare and contrast their utility, and illustrate the role of genetic testing in risk management. Important considerations relevant to clinical oncology practice include the role of risk assessment in cancer prevention, the logistics of implementing risk assessment, the ramifications of conveying risk information with limited genetic counseling, and the mechanisms for genetics referral. Medical professionals can embrace new preventive medicine techniques more effectively by utilizing quantitative methods to assess their patients’ risks. [ONCOLOGY 16:1082-1099, 2002]

The hepatic metabolism and biliary secretion of irinotecan (CPT-11, Camptosar) and metabolites is complex and involves cytochrome P450 isoenzymes, carboxylesterases, glucuronosyltransferase, and the ATP-dependent export pumps MRP-2 and MXR. Enzyme-inducing antiepileptic drugs (EIAEDs) such as phenytoin and carbamazepine are known to induce several of the metabolic pathways relevant to ininotecan’s elimination. The North American Brain Tumor Consortium phase I study is designed to determine the maximum tolerated dose and pharmacokinetics of irinotecan given every 3 weeks to patients who are receiving EIAEDs.

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.

Both irinotecan (CPT-11, Camptosar) and epirubicin (Ellence) are significant chemotherapeutic agents that are used in the management of many different cancers. Each agent works through the inhibition of topoisomerases, and inhibition of topoisomerases I and II may possibly result in significant clinical synergy. This phase I clinical study represents an investigation of the first combination of irinotecan and epirubicin in patients with advanced cancer.

Irinotecan and mitomycin (Mutamycin) possess significant single-agent activity against several tumor types, and mitomycin activates topoisomerase I, the cellular target of irinotecan. We conducted a phase I dose-escalation study of irinotecan and mitomycin in 37 evaluable patients with solid tumors. Antitumor responses included 2 complete responses, 5 partial responses, 10 minor responses, and a CA 19-9 tumor marker response.

The authors present an excellent review of prostate-specific antigen (PSA), bringing us up to date on the large body of information that has been collected since this marker came into clinical use in the mid-1980s. It is hard to believe that we have had this tool for nearly 20 years. Much has been learned.

This is a well-written and timely review of a topic that has recently become both complex to urologists and confusing to nonurologists. The authors discuss the physiology of prostate-specific antigen (PSA) and its role in a variety of clinical situations, highlighting the areas of proven utility and identifying areas of controversy.

Despite the impact of prostate-specific antigen (PSA) testing on the detection and management of prostate cancer, controversy about its usefulness as a marker of disease activity continues. This review, based on a

Improvement in pediatric acute myelogenous leukemia (AML) over the past 30 years has been only modest. Although rates of complete remission induction have climbed steadily to 85% or 90%, cure rates remain in the 50% to 60% range. These figures may inspire envy from medical oncologists treating adults with AML, but they lag far behind the successes in treating pediatric acute lymphocytic leukemia (ALL).