bluuebunny/crossref_metadata_2025 huggingface dataset:
Pemetrexed Disodium: A Novel Antifolate Clinically Active Against Multiple Solid Tumors
Authors: Hanauske Axel-R. , Chen Victor , Paoletti Paolo , Niyikiza Clet
Published: August 2004

Pemetrexed disodium (ALIMTA®, “pemetrexed”) is a novel, multi-targeted antifolate that has demonstrated promising clinical activity in a wide variety of solid tumors, including non-small cell lung, breast, mesothelioma, colorectal, pancreatic, gastric, bladder, cervix, and head and neck. Pemetrexed inhibits multiple folate-dependent enzymes involved in both purine and pyrimidine synthesis including thymidylate synthase, dihydrofolate reductase, glycinamide ribonucleotide formyltransferase, and aminoimidazole carboxamide ribonucleotide formyltransferase. As a single agent, pemetrexed exhibits a moderate toxicity profile at a dose of 500 mg/m2 by 10-minute infusion once every 21 days with myelosuppression being the dose-limiting toxicity. Folic acid added to the diet in preclinical studies reduced toxicities while maintaining antitumor activity. Based on this observation and clinical toxicities, folic acid and vitamin B12 dietary supplementation has been recently introduced into all ongoing trials. Studies combining pemetrexed with other active chemotherapeutic agents demonstrate that these combination therapies may become important treatment regimens in a variety of cancer types. Currently, pemetrexed phase III trials are ongoing in mesothelioma and non-small cell lung cancer with future trials planned to explore this unique multitargeted antifolate.
Adjuvant Therapy of Primary Breast Cancer: A Review of Key Findings from the 7th International Conference, St. Gallen, February 2001
Authors: Aapro Matti S.
Published: August 2004

Breast cancer research has developed at a rapid pace over the last decades. Recent discoveries promise to provide individualized treatment options, increased long-term survival for women with breast cancer, and the possibility of moving toward curative intent in the treatment of advanced breast cancer. Age, race, tumor size, histological tumor type, axillary nodal status, standardized pathological grade, and hormone-receptor status are accepted as established prognostic and/or predictive factors for selection of systemic adjuvant treatment of breast cancer. The role of other promising new factors, such as p53 mutations, HER-2 status, plasminogen activator system, histological evidence of vascular invasion, and quantitative parameters of angiogenesis will be determined in ongoing prospective studies. Currently, 5 years' treatment with adjuvant tamoxifen in women with hormone-positive receptor status, is regarded as the optimal duration of treatment. Long-term follow-up on the randomized trials will determine the added benefit of treatment beyond 5 years. Ovarian ablation has shown a reduction in recurrence and death, and the exact role and extent of adjuvant chemotherapy in premenopausal women with hormone-responsive tumors is under discussion. Combination hormonal and chemo-hormonal therapies are also being evaluated. There are no convincing data on the survival impact of tamoxifen as a preventative therapy for breast cancer: longer-term follow-up is required, and the planned meta-analyses in 2005 should help shed light on this issue. Statistically significant benefits have been observed with adjuvant chemotherapy (particularly with anthracycline-containing regimens in premenopausal women) versus no adjuvant chemotherapy. The optimal length of adjuvant anthracycline/cyclophosphamide (AC) regimens needs further evaluation as do randomized comparisons of AC to cyclophosphamide/ doxorubicin/5-fluorouracil (5-FU) and cyclophosphamide/epirubicin/5-FU. Although taxanes promise to provide an additive benefit to adjuvant chemotherapy regimens, the Cancer and Leukemia Group B 9344 and the National Surgical Adjuvant Breast and Bowel Project B-28 studies evaluating paclitaxel in the adjuvant setting have not yet demonstrated statistically significant benefits on disease-free survival and overall survival. In the year 2000, all adjuvant therapy studies conducted by the Co-operative Groups in both node-negative and node-positive disease involve a taxane. High-dose chemotherapy evaluations are still ongoing. The numerous prospective adjuvant therapy trials (hormonal; selective estrogen-receptor modulators; aromatase inhibitors; chemotherapy, involving anthracyclines/taxanes/platinum/trastuzumab; biological factors; elderly women (>70 years); high-risk patients; radiotherapy in 1-3 positive lymph nodes), and neoadjuvant studies might further define the chances to enhance cure rates in the treatment of primary breast cancer.
Lung Cancer
Authors: Evans Tracey L. , Lynch Thomas J.
Published: August 2004

Is any one combination therapy for metastatic non-small cell lung cancer (NSCLC) superior to other regimens for metastatic NSCLC? The answer is “probably no.” More than 4,000 patients with advanced NSCLC participated in randomized trials presented at the 37th Annual Meeting of the American Society of Clinical Oncology. TAX326 was the only study in which the investigational arm (cisplatin/docetaxel) showed a statistically significant difference in survival compared with the reference standard (cisplatin/vinorelbine). We did learn, however, that what we administer may make some difference: cisplatin might be superior to carboplatin, and patients treated with nonplatinum chemotherapy regimens have a trend toward poorer survival than those who receive platinum doublets. Although there is still no clear best regimen for advanced NSCLC, we may now know how much chemotherapy to give: a randomized study presented found that four cycles produces as much survival benefit as treating until progression. The most significant abstracts presented at this year's lung cancer session involved the use of novel agents with unique mechanisms of action. The median survival in the large, randomized trials of chemotherapy in advanced NSCLC remains a bleak 9 months. ISIS 3521, an antisense oligonucleotide that targets protein kinase C, was found to produce a near doubling of survival when combined with carboplatin and paclitaxel. OSI-774, an epidermal growth factor receptor tyrosine kinase inhibitor, was shown to have impressive single agent activity in the second-line treatment of lung cancer. The future of lung cancer therapy will involve combining these novel agents with active chemotherapy regimens in an effort to improve outcome.

While we appear to have reached a plateau in what we can accomplish with various combinations of cytotoxic chemotherapy in metastatic NSCLC, in locally-advanced disease new chemotherapy combinations can achieve remarkable results when combined with radiation therapy. The Southwest Oncology Group presented unprecedented phase II data on the use of cisplatin and etoposide with concurrent radiation therapy followed by consolidation docetaxel in patients with stage IIIB NSCLC.
Matrix Metalloproteinase Inhibitors: Current Developments and Future Perspectives
Authors: Hoekstra R. , Eskens F.A.L.M. , Verweij J.
Published: August 2004

Malignant tumors are characterized by invasive growth and metastasis. To facilitate this invasive behavior, the enzymatic breakdown of the extracellular matrix (ECM) is a prerequisite. Many human tumors are characterized by locally increased concentrations of matrix metalloproteinases (MMPs), enzymes that are able to degrade this ECM. A vast number of matrix metalloproteinase inhibitors (MMPIs) have been developed in recent years and after extensive preclinical testing, the results of the first clinical studies with several of these compounds have recently been presented. In this review we will describe some of the basic concepts of the degradation of the ECM, with special emphasis on the role of MMPs in the progression of cancer. Furthermore we will review the results of preclinical and clinical studies with MMPIs and discuss their future perspective.
Changes in Finances, Insurance, Employment, and Lifestyle Among Persons Diagnosed with Hairy Cell Leukemia
Authors: Hounshell Jennie , Tomori Cecilia , Newlin Rebecca , Knox Kirstin , Rundhaugen Lynn , Tallman Martin , Bennett Charles
Published: August 2004

Background. While being cured of cancer generally leads to a life expectancy similar to that of the general population, the extent to which other aspects of life are affected is unknown. To address these concerns, patients with hairy cell leukemia, a cancer with a very high cure rate, were queried about employment, insurance, finances, and lifestyle during and following their treatment.

Methods. Study participants (n = 31) ranging in age from 24 to 73 years at the time of diagnosis (median, 49 years) were surveyed regarding changes in health and life insurance, employment, out-of-pocket medical costs, exercise, diet, and use of mental and alternative health services that occurred during or following hairy cell leukemia treatment.

Results. Following a diagnosis of hairy cell leukemia, 61.3% of the respondents paid for some aspect of medical care in spite of having health insurance coverage at the time of diagnosis. Four respondents (12.9%) could not obtain health insurance following treatment, and the occupational choices of several individuals or their spouses were based in large part on a desire to obtain or maintain comprehensive health insurance. Of the 13 individuals who attempted to purchase life insurance, 10 had difficulty obtaining a policy or were denied coverage. Lifestyle changes were noted by 40% to 60% of respondents, and included reports of more frequent exercise, adoption of a healthier diet, and having a greater appreciation for life, loved ones, and physical health.

Conclusions. While hairy cell leukemia is a highly curable malignancy, cancer survivors' lives and lifestyles are altered substantially after receiving treatment for the illness.
Evaluating the Total Costs of Chemotherapy-Induced Toxicity: Results from a Pilot Study with Ovarian Cancer Patients
Authors: Calhoun Elizabeth A. , Chang Chih-Hung , Welshman Emily E. , Fishman David A. , Lurain John R. , Bennett Charles L.
Published: August 2004

Purpose. While chemotherapy-related toxicities affect cancer patients' activities of daily living and result in large expenditures of medical care for treatment, few studies have assessed the out-of-pocket and indirect costs incurred by patients who experience toxicity. The objective of this study was to evaluate the feasibility of obtaining detailed and comprehensive cost information from patients who experienced neutropenia, thrombocytopenia, or neurotoxicity during treatment.

Methods. Ovarian cancer patients who experienced chemotherapy-associated hematologic or neurologic toxicities were asked to record detailed information about hospitalization, laboratories, physician visits, phone calls, home visits, medication, medical devices, lost productivity, and caregivers. Resource estimates were converted into cost units, with direct medical cost estimates based on hospital cost-accounting data and indirect costs (i.e., productivity loss) on modified labor force, employment, and earnings data.

Results. Direct medical costs were highest for neutropenia (mean of $7,546/episode), intermediate for thrombocytopenia (mean of $3,268/episode), and lowest for neurotoxicity (mean of $688/episode). Indirect costs relating to patient and caregiver work loss and payments for caregiver support were substantial, accounting for $4,220, $3,834, and $4,282 for patients who developed neurotoxicity, neutropenia, and thrombocytopenia, respectively. The total costs of chemotherapy-related neurotoxicity, neutropenia, and thrombocytopenia were $4,908, $11,830, and $7,550.

Conclusion. Our study has shown that, with the assistance of patients who are experiencing toxicity, estimation of the total costs of cancer-related toxicities is feasible. Indirect costs, while not included in prior estimates of the costs of toxicity studies, accounted for 34% to 86% of the total costs of cancer supportive care.
New Strategies for Prophylactic Platelet Transfusion in Patients with Hematologic Diseases
Authors: Wandt Hannes , Ehninger Gerhard , Gallmeier Walter Michael
Published: August 2004

There is an increasing demand for platelet transfusions due to intensive chemotherapy and blood stem cell or bone marrow transplantation for the treatment of hematologic and oncologic diseases. There has been a long-lasting debate over whether the traditional threshold for prophylactic platelet transfusion of 20,000/μl is really necessary to prevent hemorrhagic complications. During the last 10 years several studies with more than 1,000 patients together have proven the safety of a platelet transfusion trigger of 10,000/μl or even lower when patients are clinically stable without active bleeding. This experience has been mostly gathered in patients with acute leukemia. But this stringent platelet transfusion policy can be used also after blood stem cell and bone marrow transplantation. In stable patients with aplastic anemia and myelodysplasia, prophylactic transfusions should be replaced in most patients by a therapeutic transfusion strategy. Such restrictive platelet transfusion strategies decrease the risk of infectious disease transmission, immunization, and febrile transfusion reactions. Besides reduced hospital visits and a shorter hospital stay for the patients, the costs for platelet transfusions are lowered by 20%-30% compared with traditional transfusion strategies. The decision to administer platelet transfusions should incorporate individual clinical characteristics of the patients and not simply be a reflexive reaction to the platelet count. Further clinical studies are needed to answer the still open question of whether patients with acute leukemia should also be transfused therapeutically rather than prophylactically when they are in stable condition without signs of active bleeding.
The NCI-Ireland Consortium: A Unique International Partnership in Cancer Care
Authors: Johnston Patrick G. , Daly Peter A.
Published: August 2004

The Ireland-Northern Ireland-National Cancer Institute Cancer Consortium was launched in October of 1999, at a conference in Belfast, Northern Ireland, for the development of cancer programs in Ireland and Northern Ireland, where cancer is a significant cause of mortality and morbidity.

Cancer services there have undergone major restructuring as a result of several government reports. Specifically, the National Strategy Document for Cancer proposed that cancer treatment services should be centered around primary care services, regional services, and a national coordinating structure where supra-regional centers would deliver specialist surgery, medical and radiation oncology, rehabilitation, and specialist palliative care. Therefore, this was an opportune time to bring the National Cancer Institute (NCI) on board in a determined effort to redevelop and significantly improve services and outcomes for cancer patients throughout the island.

During the NCI All Ireland Cancer Consortium, initial major goals were established as follows: A) To share best available technology and enhance clinical research; B) conduct joint clinical research studies involving people from all jurisdictions; C) sponsor formal training exchanges for Irish and American scholars in cancer programs in partner institutions; D) implement the use of teleconferencing, telesynergy, and other information technology capabilities to facilitate education, and E) consolidate the Cancer Registries of Ireland and Northern Ireland and learn more about cancer incidence and trends on the entire island. In the past year, significant advances have been made in all these areas.

Plans are already under way for the second NCI All Ireland Cancer Conference which will be held in late 2002 and feature speakers from Ireland, Northern Ireland, the U.S., and other areas. It will be open to all oncologists, researchers, nurses, students, and other health care professionals interested in learning and enhancing cancer care and research.
Complementary, Alternative, Integrative, or Unconventional Medicine?
Authors: Penson Richard T. , Castro Cesar M. , Seiden Michael V. , Chabner Bruce A. , Lynch Thomas J.
Published: August 2004

Shortly before his death in 1995, Kenneth B. Schwartz, a cancer patient at Massachusetts General Hospital (MGH), founded the Kenneth B. Schwartz Center. The Schwartz Center is a non-profit organization dedicated to supporting and advancing compassionate health care delivery, which provides hope to the patient, support to caregivers, and sustenance to the healing process. The center sponsors the Schwartz Center Rounds, a monthly multidisciplinary forum where caregivers reflect on important psychosocial issues faced by patients, their families, and their caregivers, and gain insight and support from fellow staff members.

Interest in complementary and alternative medicine (CAM) has grown exponentially in the past decade, fueled by Internet marketing, dissatisfaction with mainstream medicine, and a desire for patients to be actively involved in their health care. There is a large discordance between physician estimates and reported prevalence of CAM use. Many patients do not disclose their practices mainly because they believe CAM falls outside the rubric of conventional medicine or because physicians do not ask. Concern about drug interactions and adverse effects are compounded by a lack of Food and Drug Administration regulation. Physicians need to be informed about CAM and be attuned to the psychosocial needs of patients.
The Development of Camptothecin Analogs in Childhood Cancers
Authors: Bomgaars Lisa , Berg Stacey L. , Blaney Susan M.
Published: August 2004

Camptothecin analogs, agents that target the intranuclear enzyme topoisomerase I, represent a promising new class of anticancer drugs for the treatment of childhood cancer. In preclinical studies, camptothecins, such as topotecan and irinotecan, are highly active against a variety of pediatric malignancies including neuroblastomas, rhabdomyosarcomas, gliomas, and medulloblastomas. In this paper, we review the status of completed and ongoing clinical trials and pharmacokinetic studies of camptothecin analogs in children. These and future planned studies of this novel class of cytotoxic agents are critical to defining the ultimate role of topoisomerase I poisons in the treatment of childhood cancer.
Selected Novel Anticancer Treatments Targeting Cell Signaling Proteins
Authors: Elsayed Yusri A. , Sausville Edward A.
Published: August 2004

Empirical approaches to discovery of anticancer drugs and cancer treatment have made limited progress in the cure of cancer in the last several decades. Recent advances in technology and expanded knowledge of the molecular basis of tumorigenesis and metastasis have provided unique opportunities to design novel compounds that rationally target the abnormal molecular and biochemical signals leading to cancer. Several such novel agents have completed advanced stages in clinical development. The excellent clinical results achieved by some of these compounds are creating new paradigms in management of patients with neoplastic diseases. Clinical development of these agents also raises challenges to the traditional methods of drug evaluation and measurement of efficacy.
Combination Endocrine Therapy in the Management of Breast Cancer
Authors: Boehnke Michaud Laura , Jones Kellie L. , Buzdar Aman U.
Published: August 2004

Combination endocrine therapy has long been sought after as a means to better treat breast cancer. Agents that suppress estrogen production are given with agents that suppress estrogenic activity at the cellular level. Historically, these combinations have resulted in initial improvements in response rates, but relapse-free and overall survival were not significantly improved. Also, the increased toxicity seen with these regimens was limiting. New endocrine therapies with more potent activity and less toxicity have led to a resurgence of this idea in the management of breast cancer. Complete estrogen blockade has been compared with single-agent treatments in many different settings. The endocrine effects of this type of therapy are intriguing, but apparently do not readily predict a clinical advantage. The combination of an aromatase inhibitor and an antiestrogen, despite pharmacokinetic interactions, may prove to be beneficial. Results from ongoing trials are eagerly awaited to further address this question in postmenopausal breast cancer patients. For premenopausal breast cancer patients the options are more complex. Clinical outcomes with leutinizing hormone releasing hormone (LHRH) agonists plus aromatase inhibitors are limited to very small phase II studies and are not clearly superior to single-agent therapy. Clinical data in the metastatic setting with premenopausal patients favor the use of an LHRH agonist with tamoxifen over the use of an LHRH agonist alone. However, a similar comparison with tamoxifen alone is lacking with only one trial including this as a treatment arm. Adjuvant therapy with this combined endocrine approach (LHRH agonist plus antiestrogen) has been more extensively studied, but lacks crucial comparisons necessary for making complex treatment decisions. Hopefully, through investigative diligence and ingenuity this issue can be adequately understood. However, many exciting new agents are on the horizon that offer hope to further advance the progress made to date although further confounding the questions already answered.
Targeting Protein Kinase C: New Therapeutic Opportunities Against High-Grade Malignant Gliomas?
Authors: da Rocha A. B. , Mans D.R.A. , Regner A. , Schwartsmann G.
Published: August 2004

Learning Objectives

After completing this course, the reader should be able to:

Understand protein kinase C (PKC) in signal transduction pathways. Understand protein kinase C (PKC) in tumor cell proliferation and invasion Understand protein kinase C as a potential target in experimental therapies for malignant gliomas.

Access CME test online and receive one hour category 1 credit at CME.TheOncologist.com

A large body of evidence suggests that the abnormal phenotype of neoplastic astrocytes, including their excessive proliferation rate and high propensity to invade surrounding tissues, results from mutations in critical genes involved in key cellular events. These genetic alterations can affect cell-surface-associated receptors, elements of signaling pathways, or components of the cell cycle clock, conferring a gain or a loss of relevant metabolic functions of the cells. The understanding of such phenomena may allow the development of more efficacious forms of cancer treatment. Examples are therapies specifically directed against overexpressed epidermal growth factor receptor, hyperactive Ras, excessively stimulated Raf-1, overproduced ornithine decarboxylase, or aberrantly activated cyclin-dependent kinases. The applicability of some of these approaches is now being assessed in patients suffering from primary malignant central nervous system tumors that are not amenable to current therapeutic modalities. Another potentially useful therapeutic strategy against such tumors involves the inhibition of hyperactive or overexpressed protein kinase C (PKC). This strategy is justified by the decrease in cell proliferation and invasion following inhibition of the activity of this enzyme observed in preclinical glioma models. Thus, interference with PKC activity may represent a novel form of experimental cancer treatment that may simultaneously restrain the hyperproliferative state and the invasive capacity of high-grade malignant gliomas without inducing the expected toxicity of classical cytotoxic agents. Of note, the experimental use of PKC-inhibiting agents in patients with refractory high-grade malignant gliomas has indeed led to some clinical responses. The present paper reviews the current status of the biochemistry and molecular biology of PKC, as well as the possibilities for developing novel anti-PKC-based therapies for central nervous system malignancies.
Localized Adenocarcinoma of the Pancreas: The Rationale for Preoperative Chemoradiation
Authors: Wayne Jeffrey D. , Abdalla Eddie K. , Wolff Robert A. , Crane Christopher H. , Pisters Peter W.T. , Evans Douglas B.
Published: August 2004

Learning Objectives

After completing this course, the reader should be able to:

Define the radiologic (CT) criteria that determine whether a pancreatic neoplasm is surgically resectable, locally advanced, or metastatic. Explain why it is difficult to conduct clinical trials of adjuvant or neoadjuvant therapy in resectable pancreatic cancer. Review the advantages and disadvantages of preoperative versus postoperative adjuvant therapy for patients with pancratic adenocarcinoma.

Access CME test online and receive one hour category 1 credit at CME.TheOncologist.com

Pancreatic adenocarcinoma is the fifth leading cause of cancer-related death in the U.S. In spite of advancements in surgical treatment, nearly 80% of patients thought to have localized pancreatic cancer die of recurrent or metastatic disease when treated with surgery alone. Therefore, efforts to alter the patterns of recurrence and improve survival for patients with pancreatic cancer currently focus on the delivery of systemic therapy and irradiation before or after surgery. Postoperative adjuvant therapy appears to improve median survival. However, more than one-fourth of patients do not complete planned adjuvant therapy due to surgical complications or a delay in postoperative recovery of performance status. Utilizing a preoperative (neoadjuvant) approach, overall treatment time is reduced, a greater proportion of patients receive all components of therapy, and patients with rapidly progressive disease are spared the side effects of surgery as metastatic disease may be found at restaging following chemoradiation (prior to surgery).

This paper examines the factors pertinent to clinical trial design for resectable pancreatic cancer, and carefully reviews the existing data supporting adjuvant and neoadjuvant therapy for potentially resectable disease.
Adenoviral Gene Therapy
Authors: Vorburger Stephan A. , Hunt Kelly K.
Published: August 2004

Learning Objectives

After completing this course, the reader should be able to:Understand the advantages and disadvantages of recombinant adenoviral vectors for gene delivery.Review the current biological strategies employed in clinical trials utilizing adenoviral mediated gene therapy for cancer.Understand modifications that may improve the utility of adenoviral vectors for gene therapy approaches.

Access CME test online and receive one hour category 1 credit at CME.TheOncologist.com

As of May 2001, 532 gene therapy protocols had been approved for evaluation in clinical trials; however, only five of those had been evaluated in phase III clinical trials. Among the most commonly used vectors for the delivery of genetic material into human cells are the adenoviruses. Remarkable progress has been made with these vectors in the last decade, but some shortcomings continue to challenge investigators. The newly acquired knowledge of the adenoviral life cycle and the positive outcomes from phase II clinical trials have led to the application of vectors engineered to selectively target tumor tissue under controlled promoters.
The Cardiotoxic Potential of the 5-HT3 Receptor Antagonist Antiemetics: Is There Cause for Concern?
Authors: Keefe Deborah L.
Published: August 2004

Purpose. To review and evaluate the potential cardiac effects of 5-HT3 antiemetic treatment in patients who may be predisposed to cardiac complications resulting from malignancy, cytotoxic oncologic regimens, or preexisting comorbid conditions.

Design. A literature review was conducted on the negative cardiovascular effects of chemotherapeutic agents, and, more specifically, on the cardiac interactions of the 5-HT3 receptor antagonists commonly used to treat chemotherapy-induced nausea and vomiting.

Results. Clinical studies in healthy subjects have reported electrocardiograph changes following administration of 5-HT3 receptor antagonists. However, there are limited data on the use of 5-HT3 antiemetics when administered with cardiotoxic chemotherapy. Nonetheless, the development of significant electrocardiograph changes with some agents may indicate a potential for significant cardiac effects in patients, particularly those who may be predisposed to cardiac complication.

Conclusions. As the predicted human life span increases, clinicians will be treating a larger, older oncology population. Because two of the most common major comorbidities are cardiovascular related, we need to be acutely aware of the toxic effects of chemotherapy, as well as the possible cardiac interaction of supportive agents, specifically the 5-HT3 antiemetics. Until more data are made available, the best antiemetic option for patients receiving emetogenic and cardiotoxic chemotherapy may be the agent with the fewest apparent cardiac effects.
Development of the Proteasome Inhibitor PS-341
Authors: Adams Julian
Published: August 2004

Over the last decade, the critical role of the proteasome in cell-cycle regulation has become increasingly apparent. The proteasome, a multicatalytic protease present in all eukaryotic cells, is the primary component of the protein degradation pathway of the cell. By degrading regulatory proteins (or their inhibitors), the proteasome serves as a central conduit for many cellular regulatory signals and, thus, is a novel target for therapeutic drugs. PS-341 is a small molecule that is a potent and selective inhibitor of the proteasome. In vitro and mouse xenograft studies of PS-341 have shown antitumor activity in a variety of tumor types, including myeloma, chronic lymphocytic leukemia, prostate cancer, pancreatic cancer, and colon cancer, among others. Although PS-341 rapidly leaves the vascular compartment, a novel pharmacodynamic assay has shown that inhibition of proteasome—the biologic target—is dose dependent and reversible. These studies provided the rationale for a twice-weekly dosing schedule employed in ongoing clinical studies. Phase I trials in a variety of tumor types have shown PS-341 to be well tolerated, and phase II trials in several hematologic malignancies and solid tumor types are now in progress. Efficacy and safety data from the most advanced of these, a phase II multicenter trial in myeloma, will be available in early 2002.
The Cancer Patient and Quality of Life
Authors: Bottomley Andrew
Published: August 2004

Over the last decade, clinicians have accepted that while survival and disease-free survival are critical factors for cancer patients, overall quality-of-life is fundamental. This review considers recent developments in the field of quality of life, oncological challenges and future directions.
Comparable Efficacy of Epoetin Alfa for Anemic Cancer Patients Receiving Platinum- and Nonplatinum-Based Chemotherapy: A Retrospective Subanalysis of Two Large, Community-Based Trials
Authors: Glaspy John , Degos Laurent , Dicato Mario , Demetri George D.
Published: August 2004

Learning Objectives

After completing this course, the reader will be able to:

Understand the etiology, symptoms, and impact (as reported by patients) of cancer- and chemotherapy-associated anemia. Recognize the clinical evidence supporting the efficacy of epoetin alfa in reducing transfusion requirements, increasing hemoglobin levels, and improving quality-of-life in anemic cancer patients receiving platinum- versus nonplatinum-based chemotherapy. Identify potential prognostic factors for responsiveness to epoetin alfa.

Access and take the CME test online and receive one hour of AMA PRA category 1 credit at CME.TheOncologist.com

Background. Data from two large, community-based clinical trials that evaluated the efficacy of epoetin alfa in anemic cancer patients receiving chemotherapy were retrospectively analyzed to determine if clinical outcomes were different depending on whether chemotherapy was platinum- or nonplatinum-based.

Patients and Methods. Patients received epoetin alfa 150-300 IU/kg (Glaspy: Study 1; n = 2,342) or 10,000-20,000 IU (Demetri: Study 2; n = 2,370) s.c. three times each week for 4 months. Efficacy end points were changes in transfusion requirements, hemoglobin (Hb) levels, and quality of life (QOL). A total of 4,298 out of 4,712 patients (platinum-based, n = 1,601; nonplatinum-based, n = 2,697), who both received chemotherapy and had available data, were eligible for this retrospective analysis.

Results. Baseline characteristics across groups were comparable with few exceptions, which were anticipated in view of the characteristics of the two different chemotherapy types. Decreases in transfusion requirements after 2, 3, and 4 months were significant, regardless of chemotherapy type. Mean increases in Hb level from baseline to final evaluation ranged from 1.6 g/dl to 2.0 g/dl across study groups and were significant, regardless of chemotherapy type. QOL, as measured by the Linear Analog Scale Assessment (LASA), improved significantly by 20%-43%, regardless of chemotherapy type, and improvements were associated with increases in Hb. Epoetin alfa was well tolerated in both studies, regardless of chemotherapy type.

Conclusion. Treatment of anemic cancer patients with epoetin alfa results in significant reduction in transfusion requirements, increase in Hb levels, and improvements in QOL, regardless of whether the chemotherapy is platinum- or nonplatinum-based.
The Effect of Nonmalignant Systemic Disease on Tolerance to Radiation Therapy
Authors: Chon Brian H. , Loeffler Jay S.
Published: August 2004

Purpose. Some patients with nonmalignant systemic diseases, like collagen vascular disease (CVD), hypertension, diabetes mellitus, and inflammatory bowel disease (IBD), tolerate radiation therapy poorly. Although the mechanisms of each of these disease processes are different, they share a common microvessel pathology that is potentially exacerbated by radiotherapy. This article reviews and evaluates available data examining the effects of these benign disease processes on radiation tolerance.

Methods. We conducted a thorough review of the Anglo-American medical literature from 1960 to 2001 on the effects of radiotherapy on CVD, hypertension, diabetes mellitus, and IBD.

Results. Fifteen studies were identified that examined the effects of radiation therapy for cancer in patients with CVDs. Thirteen of 15 studies documented greater occurrences of acute and late toxicities (range 7%-100%). Higher rates of complications were noted especially for nonrheumatoid arthritis CVDs. Nine studies evaluated the effects of hypertension and diabetes on radiation tolerance. All nine studies documented higher rates of late toxicities than in a “control” group (range 34%-100%). When patients had both diabetes and hypertension, the risk of late toxicities was even higher. Six studies examined radiation tolerance of patients with IBD irradiated to the abdomen and pelvis. Five of these six studies showed greater occurrences of acute and late toxicities for patients with IBD, even with precautionary measures like reduced fraction size and volume and patient immobilization (13%-29%).

Conclusion. The majority of published studies documented lower radiation tolerance for patients who have CVD, diabetes mellitus, hypertension, and IBD. This may reflect a publication bias, as the majority of these studies are retrospective with small numbers of patients and use different scoring scales for complications. These factors may contribute to an overestimation of true radiation-induced morbidity. Although the paucity of data makes precise estimates difficult, a subset of patients, in particular, those with active CVD, IBD, or a combination of uncontrolled hypertension with type I diabetes, is likely to be at higher risk. Future prospective trials need to document these disease entities when reporting treatment-related complications and also must monitor toxicities associated with quiescent versus active IBD and CVD, type I versus type II diabetes, and levels of hypertension (controlled versus uncontrolled) matched for radiation-specific treatment sites, field size, fractionation, and total dose.
Osteogenic Sarcoma Presenting with Lung Metastasis
Authors: Staddon Arthur P. , Lackman Richard , Robinson Keith , Shrager Joseph B. , Warhol Michael
Published: August 2004

Learning Objectives

After completing this course, the reader will be able to:

Understand the multimodality treatments needed for the best outcome in patients with osteogenic sarcoma. Understand the selection criteria for resecting pulmonary metastases. Identify the appropriate work-up and follow-up of patients with osteogenic sarcoma.

Access and take the CME test online and receive one hour of AMA PRA category 1 credit at CME.TheOncologist.com

A patient with osteogenic sarcoma presenting with lung metastases is discussed with attention to appropriate diagnosis, staging, and treatment. Multimodality treatment options using chemotherapy, orthopedic surgery and thoracic surgery are presented. Physical medicine and rehabilitation evaluation and treatment are included. Current research options are discussed.
Between Parent and Child: Negotiating Cancer Treatment in Adolescents
Authors: Penson Richard T. , Rauch Paula K. , McAfee Steve L. , Cashavelly Barbara J. , Clair-Hayes Kathy , Dahlin Constance , Green Kara M. , Chabner Bruce A. , Lynch Thomas J.
Published: August 2004

Learning Objectives

After completing this course, the reader will be able to:

Understand the epidemiology and paradigms of care for adolescents with cancer. Understand the impact of cancer on patient, family, and health care team. Identify appropriate responses to different developmental stages and preferences in style of care. Foster compassionate care.

Access and take the CME test online and receive one hour of AMA PRA category 1 credit in Risk Management at CME.TheOncologist.com

Shortly before his death in 1995, Kenneth B. Schwartz, a cancer patient at Massachusetts General Hospital, founded the Kenneth B. Schwartz Center. The Schwartz Center is a non-profit organization dedicated to supporting and advancing compassionate health care delivery, which provides hope to the patient, support to caregivers, and sustenance to the healing process. The center sponsors the Schwartz Center Rounds, a monthly multidisciplinary forum where caregivers reflect on important psychosocial issues faced by patients, their families, and their caregivers, and gain insight and support from fellow staff members.

Cancer in adolescents presents an extra dynamic of psychosocial complexity. The case of a 19-year-old woman with acute myelocytic leukemia is discussed. Her disease was refractory to allogeneic transplantation, and she died with severe graft-versus-host disease. Ms. P and her mother established very different relationships with the team which supported them through the transitions in her care, and Ms. P was able to die at home, with hospice care. The personal connection with the team enabled a degree of positive adjustment through the nightmare of loss. The epidemiology of cancer in adolescents and paradigms of care are reviewed. Psychosocial aspects of adolescence, opportunities for personal growth and support, and the challenge of end-of-life care are discussed.
Interpreting Measures of Treatment Effect in Cancer Clinical Trials
Authors: Case L. Douglas , Kimmick Gretchen , Paskett Electra D. , Lohman Kurt , Tucker Robert
Published: August 2004

The efficacy of a new cancer regimen is usually assessed by analyzing outcomes such as tumor response and overall survival. Many publications summarizing results of cancer clinical trials report measures such as odds ratios and hazard ratios, as these are the estimators of treatment effect obtained from regression models used to analyze the data. However, these measures are sometimes misinterpreted, as they are not necessarily familiar to many readers. The most common mistake is to interpret both measures as relative risks, an interpretation that can lead to an incorrect impression of the impact of the treatment on response and survival.
Carcinoma of the Anus: Strategies in Management
Authors: Esiashvili Natia , Landry Jerome , Matthews Richard H.
Published: August 2004

Learning Objectives

After completing this course, the reader will be able to:Appreciate the evolution of methods of managing anal carcinomas and appropriate selection of modalities to employ in various situations at the present time.Understand methods of integrating chemotherapy and radiation to achieve desirable outcomes.Understand considerations in choice of chemotherapy agents and radiation doses.

Access and take the CME test online and receive one hour of AMA PRA category 1 credit at CME.TheOncologist.com

The management of anal cancer underwent an interesting transformation over the last two decades. Prior to this period, the standard definitive treatment for carcinoma of the anal canal was abdominal-perineal resection, which necessitated a permanent colostomy. The organ preservation concept appeared following the discovery of a high complete response rate from preoperative combined chemoradiation prior to abdominal-perineal resection.

The organ preservation method of treatment rapidly gained popularity and ultimately saved a large number of patients from undergoing abdominal-perineal resection and colostomy. Chemoradiation treatment itself subsequently went through an evolutionary process. Several studies have sought to define the optimal chemotherapeutic regimen as well as radiation treatment dose and fractionation. Ongoing studies attempt to define an optimal treatment regimen that yields a higher cure rate while minimizing toxicity. We review the etiology, epidemiology, and treatment regimens for anal cancer.
Assessing a Decade of Progress in Cancer Control
Authors: Andersen LeAnn D. , Remington Patrick , Trentham-Dietz Amy , Reeves Mathew
Published: August 2004

The age-adjusted death rate from cancer peaked in the U.S. in 1990, and has declined steadily since then. We assess reasons for this progress by examining trends in cancer mortality by age, gender, and cause, using underlying cause mortality data from the Centers for Disease Control. Mortality rates for 2000 were estimated using models based on 1979 through 1997 mortality data. Indirect standardization was used to calculate the expected number of cancer deaths in 2000, by age, gender, and cause, assuming that the rates in 1990 had not changed. In the U.S. in 2000, there were an estimated 500,000 deaths from cancer; 64,000 (12.7%) fewer than expected, with 51,900 fewer cancer deaths among men and 12,200 fewer deaths among women. The decline in deaths among men resulted from fewer deaths from lung cancer (20,800), colon cancer (6,700), and prostate cancer (12,900). The decline in deaths among women resulted from fewer deaths from breast cancer (11,100) and colon cancer (4,200), but there were more deaths from lung cancer (6,500). Among women over the age of 75, 5,000 more died of cancer than expected. Declines in lung, prostate, and colon cancer deaths among men and breast and colon cancer among women account for 86% of the recent decline in cancer deaths over the past decade.
A Phase II Study of Intravenous Navelbine and Doxorubicin Combination in Previously Untreated Advanced Breast Carcinoma
Authors: Pawlicki M. , Rolski J. , Zaluski J. , Siedlecki P. , Ramlau C. , Tomzak P.
Published: August 2004

Purpose. The combination of vinorelbine and doxorubicin, two very active drugs in metastatic breast cancer, has demonstrated impressive results in terms of efficacy, at the price of cardiac toxicity (10% grades 2-4) due to the cumulative dose of doxorubicin delivered. This study was designed to divide the dose of doxorubicin into two administrations (day 1 and 8) in order to reduce the toxicity profile, while keeping the same level of efficacy.

Patients and Methods. Thirty-eight chemotherapy-naïve metastatic breast cancer patients entered into the study and were treated with vinorelbine, 25 mg/m2, and doxorubicin, 25 mg/m2, both on days 1 and 8, every 3 weeks. Thirty-seven patients were evaluable for efficacy and 38 for tolerance; 71% of the patients presented with visceral metastases.

Results. Patients received a median of seven cycles and 94.9% of the intended dose intensity of both drugs. Grade 3-4 neutropenia was reported in 10% of cycles. Alopecia was reported in 89.5% of the patients, and grade 2 nausea/vomiting in 9.3% of the cycles. Grade 1-2 cardiac toxicity was noted in 23.7% of the patients. The objective response rate of the patients was 78.4% (nearly 81% for patients with visceral metastases); the median duration of response was 11.6 months, the median survival 21.6 months, and the 1-year survival 75.2%.

Conclusion. This schedule of vinorelbine/doxorubicin represents an active and well-tolerated combination.
Unique Features of the Mode of Action of ET-743
Authors: D'Incalci Maurizio , Erba Eugenio , Damia Giovanna , Galliera Emanuela , Carrassa Laura , Marchini Sergio , Mantovani Roberto , Tognon Gianluca , Fruscio Robert , Jimeno José , Faircloth Glynn T.
Published: August 2004

This paper describes the current knowledge of the primary mode of action of a natural product, ecteinascidin 743 (ET-743), derived from the marine tunicate Ecteinascidia turbinata. ET-743 was initially selected for preclinical development because of its potent antitumor activity observed against several human solid tumor types. In vitro, the drug is cytotoxic in the nanomolar range, and in the case of some very sensitive cell lines, in the picomolar range. The large potency differences observed among several solid tumor types indicate that this compound possesses some tumor selectivity, but the molecular basis of these differential effects remains to be elucidated. The present studies were undertaken to evaluate the mechanism of action of ET-743 in this context. The available information on ET-743 binding to DNA and its effects on transcriptional regulation point to a unique behavior of this drug, as it independently affects specific gene transcription in a promoter-dependent way. In addition, ET-743 shows a peculiar pattern of selectivity in cells with different defects in their DNA-repair pathways. These results highlight a unique property of ET-743, possibly explaining why it possesses antitumor activity against tumors that are refractory to standard anticancer drugs, all of which certainly act by mechanisms that are different from that of ET-743.