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ONCOLOGY Vol 13 No 12

Off-Label Drug Promotion

The Senate’s only physician, Sen. Bill Frist (R-TN), told FDA Commissioner Jane Henney, MD, that when Congress rewrites the “off-label” drug marketing law, the new version should give physicians more credit for being sophisticated

A three-day interdisciplinary cancer conference will be held March 2 through 4, 2000, at the Best Western Gateway Grand in Gainesville, Florida. The seminar will emphasize the latest advances in radiation therapy techniques and results. It will include refresher courses by senior faculty, panel discussions, and new departmental research results. Visiting Professor will be Professeur Jean-Pierre Gerard, Service de Radiotherapie-Oncologie, Hôpitaux de Lyon, France. Other presentations will be made by clinicians from the Department of Radiation Oncology,University of Florida.

Studies in the first phase of the Early Lung Cancer Action Project (ELCAP), a joint research study with Weill Cornell Medical Center at New York Presbyterian Hospital and New York University Hospital, show that not only can spiral (“helical”) chest computed tomographic (CT) scans detect four times as many lung cancer tumors as conventional chest x-rays, but also the scans find these tumors when they are significantly smaller. Results of these studies (published in the July 10th issue of the Lancet) show that lung cancer patients have a significantly improved chance for long-term survival if the CT scan (which travels completely around the patient’s torso), is used to detect early-stage tumors.

Physician groups are apt to seize on two aspects of the Clintonmedical records privacy proposal, which came out at the end of October and is expected to be finalized in February. The proposal

The Southwest Oncology Group (SWOG) announced the beginning of the first major phase III clinical trial comparing the combination of docetaxel (Taxotere) and estramustine (Emcyt) to the commonly used combination of mitoxantrone (Novantrone) and prednisone in the treatment of advanced, hormone-refractory prostate cancer. Patient enrollment is currently underway, with approximately 660 men being recruited. This trial is being conducted by SWOG and is funded by the National Cancer Institute (NCI) in collaboration with the Cancer and Leukemia Group B (CALGB) and North Central Cancer Treatment Group (NCCTG).

The article by Drs. Labriola and Livingston is the first written collaboration of which I am aware between a doctor of naturopathic medicine and a professor of medicine at a major state university. The authors present a thorough review of the available information on interactions between dietary antioxidants, both natural and supplements, and chemotherapy.

A 15-year study published in the June 1, 1999, issue of Cancer offers further hope to premenopausal breast cancer patients who might want to bear children. According to the study of 520 women £ 40 years old, pregnancy after breast cancer diagnosis and successful treatment does not increase a patient’s risk for recurrence or death from the disease. This is particularly true for women with local disease at diagnosis.

The second edition of Pediatric Hematolgy, edited by the text's original editors, John S. Lilleyman and Ian M. Hann, as well as a new editor, Victor S. Blanchette, completely updates and expands upon the first edition (published in 1992). The new edition grew from 15 to 40 chapters, with contributions by many of the most well-known investigators and clinicians in pediatric hematology in the world. The textbook will especially be of value to practicing clinicians, house staff, and students.

Results of a study conducted by the American Society of Plastic and Reconstructive Surgeons (ASPRS) showed that 84% of women who have had their breast implants removed have replaced them with new implants. In 1998, 32,262 women with breast augmentation had their breast implants removed, and 27,320 of them opted for new implants.

The Federal Trade Commission(FTC) released a consumer alert regarding home-use test kits for the human immunodeficiency virus (HIV). According to the FTC, some of the kits being marketed and sold on the Internet are giving users false information about their HIV status.

The 10th edition of Wintrobe’s Clinical Hematology is a two volume, multiauthored work that spans the ever-expanding discipline of hematology in over 2,600 pages. The book is appropriately introduced by an excellent short chapter written previously by Dr. Wintrobe on “The Diagnostic and Therapeutic Approach to Hematologic Problems.” There follows a valuable series of six chapters totaling 133 pages devoted to laboratory hematology, including blood and bone marrow examination, immunodiagnosis, clinical flow cytometry, cytogenetics, clusters of differentiation, and molecular genetics. These chapters contain ample illustrations, diagrams, tables, and references.

Researchers at the University of California, San Diego, (UCSD) Cancer Center report success inusing a new technology to develop a sustained-release formulation of cytarabine (ara-C). The new formulation, called DepoCyt, produced a significantly better response rate than the standard ara-C formulation in patients with lymphomatous meningitis. Results of the open, multicenter, controlled study were reported at the 35th meeting of the American Society of Clinical Oncology (ASCO).

Premenopausal women with early breast cancer have a significantly better chance of living longer when treated with a chemotherapy regimen that includes epirubicin (Ellence), as opposed to a current standard combination regimen, according to data presented at the 35th meeting of the American Society of Clinical Oncology (ASCO).

The management of patients with clinical stage I nonseminomatous germ-cell tumors is still highly controversial. In a recent survey, urologists and oncologists were asked to state their choice of treatment for patients with clinical stage I nonseminomas who were at high risk for recurrence after orchiectomy. Not surprisingly, urologists chose retroperitoneal lymph node dissection over chemotherapy, while oncologists indicated a preference for adjuvant chemotherapy.[1]

The article by Drs. Dan Labriola and Robert Livingston on possible interactions between dietary antioxidants and chemotherapy, published in the July issue of Oncology (13,1999), is based on a theoretical concern that has proven to be unfounded when actually tested in clinical trials. Contrary to the authors’ assertions, numerous studies, including in vitro experiments, animal trials, and small human trials, have consistently shown an enhancement of tumor kill and patient survival when antioxidants are combined with conventional cancer therapies.

Improvements in the clinical staging of testicular cancer may permit the identification of clinical stage I patients at low risk of harboring metastatic disease, who could be spared treatment and observed only. Both retrospective, single-institution studies and studies of unselected, consecutive patients have confirmed that vascular invasion, lymphatic invasion, and percentage of embryonal carcinoma are predictive of metastasis in patients with low-stage nonseminoma. Whether patients with these risk factors have a worse outcome if managed with surveillance, rather than with aggressive therapy, is unclear. Low MIB-1 staining (which identifies the Ki-67 antigen) in conjunction with a low percentage of embryonal carcinoma in the testicular specimen appears to be predictive of a low probability of metastasis. Computed tomography (CT) is a useful staging tool. A new prognostic classification system for seminomas and nonseminomas was recently developed by an international consensus conference. Laparoscopic retroperitoneal lymphadenectomy appears to be a feasible staging tool with acceptable short-term morbidity. Whether laparoscopic lymph node dissection is equivalent to the open procedure when used as a therapeutic modality is not yet known. At present, laparoscopy should be used only in selected patients in a study setting. Primary chemotherapy is not recommended currently because it has not yet been proven to be superior in patients with high-risk clinical stage I nonseminoma and can cause significant long-term sequelae.[ONCOLOGY 13(12):1689-1694, 1999]

Endometrial carcinoma is the most common gynecologic malignancy in the United States. Most cases are diagnosed at an early stage. However, the outcome for women diagnosed with advanced-stage disease remains poor. The etiology of most endometrial carcinomas stems from the effects of excess estrogen, whether this comes from exogenous or endogenous sources. Differences in epidemiology and presentation suggest the existence of two forms of endometrial cancer: those related to and those unrelated to hormonal stimulation. Most women with endometrial cancer present with abnormal uterine bleeding; endometrial sampling is essential to exclude endometrial carcinoma in such patients. Endometrial cancer is surgically staged, and staging usually includes a hysterectomy and bilateral salpingo-oophorectomy. Lymphadenectomy also should be performed in selective cases to better assess disease spread and to evaluate the need for adjuvant therapy. Adjuvant treatment may include the use of radiation, progestins, or cytotoxic chemotherapeutic agents. Several clinical trials are underway to compare these treatment modalities, as well as to determine the optimal combination of active chemotherapeutic agents, such as doxorubicin, platinum agents, and paclitaxel (Taxol). [ONCOLOGY 13(12):1665-1675, 1999]

We commend Chen et al for their comprehensive review of the evaluation and treatment of endometrial cancer. As the authors state, endometrial cancer is the most common gynecologic malignancy in the United States. Fortunately, it is also one of the most curable. The majority of women with endometrial cancer are treated by surgery alone; primary radiation therapy is generally reserved for patients with unacceptable risks of surgical morbidity. In this commentary, we will address several areas of current controversy.

Autologous hematopoietic stem- cell transplantation has become an accepted therapy for some patients with Hodgkin’s disease and non-Hodgkin’s lymphoma. Convincing evidence for a graft-vs-lymphoma effect has led to increasing use of allogeneic transplantation in these patients. Dr. Winter has written an excellent overview of transplantation in the lymphomas. She has focused on several areas of controversy and described results of randomized trials.

The number of new cases of Hodgkin’s disease and non-Hodgkin’s lymphoma diagnosed and treated each year are increasing. Although human immunodeficiency virus (HIV) infection and toxins in the environment and workplace may be responsible for the development of these diseases in some patients, explanations for this increase remain elusive. Lymphoid malignancies continue to be among the most responsive to chemotherapy and radiation therapy, however, and a sizeable percentage of affected patients are cured after primary therapy.

High-dose therapy with hematopoietic progenitor-cell transplantation plays a key role in the treatment of Hodgkin’s disease and the non-Hodgkin’s lymphomas. First and foremost, transplantation is used as a salvage treatment for those who relapse or do not achieve a complete remission with first-line chemotherapy. Carefully selected patients with poor prognostic features may benefit from the incorporation of high-dose therapy and transplant into their initial treatment programs. Despite a myriad of trials, many pivotal questions regarding the appropriate application of high-dose therapy with transplantation to the lymphoid malignancies remain unsettled, including the role of allogeneic transplantation and the optimal timing of transplant for patients with poor prognostic indicators. Phase III studies are required to address these issues; these trials will demand the active commitment of concerned transplanters and referring hematologists and oncologists. Although autologous transplantation has been the preferred approach for the majority of patient subgroups, new approaches to allogeneic transplantation that have diminished toxicity may pave the way for a greater role for allogeneic grafting in the lymphoid diseases. [ONCOLOGY 13(12):1635-1645, 1999]

Pain Medication Bill

Looks like Congress will pass a bill that makes it clear that physicians can prescribe pain medication for terminally ill patients, including those with cancer, without running afoul of the Drug Enforcement Administration (DEA). The DEA has charge of the

Experienced authors Richard Foster and Craig Nichols providea thoughtful, state-of-the-art discussion of current controversies in the management of testicular cancer. Present cure rates illustrate that significant diagnostic, chemotherapeutic, and surgical advances made over the past century have transformed testicular cancer from a once uniformly fatal disease into a tremendous oncologic success story.

Smoking-once a socially accepted behavior-is the leading preventable cause of death and disability in the United States. During the first decades of the 20th century, lung cancer was rare; however, as cigarette smoking became increasingly popular, first among men and later among women, the incidence of lung cancer became epidemic (Figure 1).