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Textbook of Medical Oncology, 2nd EditionIn this day of encyclopedic oncology texts, frequently updated online reference sites, and literature searches at the click of a button, is there a place for a basic medical oncology textbook? The second edition of the Textbook of Medical Oncology, edited by Drs. Cavalli, Hansen, and Kaye, is approximately 50% longer than the first edition, due in large part to the inclusion of newer therapeutic approaches.
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Stereotactic Body Radiation TherapyStereotatic body radiation therapy (SBRT) is a rapidly evolving cancertreatment method in which concepts and techniques previously developedfor brain tumor radiosurgery are adapted to eradicate tumorselsewhere in the body. The spatial accuracy, conformality, and steepradiation dose gradients of radiosurgery, which have been critical to itssuccess in the treatment of intracranial tumors, are applied in SBRT totreat a variety of extracranial tumors. Early results demonstrate excellentresponse rates and low toxicity with a variety of hypofractionateddose regimens and localization/immobilization techniques. This articleprovides an overview of the rationale and results of SBRT for specificindications, descriptions of some methods of treatment delivery, anddiscussion of potential areas of future investigation.
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Persistence of Lymphedema Reduction After Noninvasive Complex Lymphedema TherapyWe treated 119 consecutive patients with lymphedema with complex lymphedema therapy (CLT). Lymphedema reductions after CLT averaged 62.6% in the 56 patients with one affected arm and 68.6% in the 38 patients with
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Chronic Myelogenous Leukemia: Update on Biology and TreatmentChronic myelogenous leukemia (CML) is a myeloproliferative disorder that follows a characteristic clinical course in which a chronic phase of variable duration precedes an accelerated, and ultimately blastic, phase,
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Perspectives on Salvage Therapy for Non–Small-Cell Lung CancerPlatinum-based chemotherapy offers a modest survival advantage overbest supportive care in chemotherapy-naive patients with a good performancestatus and advanced/metastatic non–small-cell lung cancer(NSCLC). Despite the survival benefit associated with first-line chemotherapy,the majority of patients will experience relapse or disease progression.In clinical practice, an increasing number of patients maintaina good performance status after first-line treatment and are eligible forfurther treatments. Docetaxel (Taxotere) at 75 mg/m2 given once every3 weeks has been the standard of care for second-line chemotherapy sincethe year 2000. Pemetrexed (Alimta) is a novel multitargeted antifolateagent with single-agent activity in first- and second-line treatment ofNSCLC. A large phase III study comparing docetaxel to pemetrexed insecond-line therapy demonstrated that pemetrexed is equally active andless toxic than docetaxel. Based on these results, pemetrexed is a reasonablesecond-line chemotherapy option for patients with recurrent, advancedNSCLC. Progress made in the field of molecular biology has led to theidentification of drugs active against specific cellular targets. Gefitinib(Iressa) and erlotinib (Tarceva) are both orally active tyrosine kinase inhibitorsof the epidermal growth factor receptor. Phase II and III trialshave demonstrated that these agents are active particularly in a subgroupof patients with specific biologic characteristics. Both drugs have beenapproved for the treatment of pretreated NSCLC. Other drugs, such ascetuximab (Erbitux) and bevacizumab (Avastin) have shown promisingactivity in NSCLC and are currently being tested in clinical trials.
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Pemetrexed in Gastric CancerGastric cancer is a major clinical challenge, with poor overall prognosisand limited life expectancy for patients with advanced disease.Even with surgery and other modalities, palliation is often difficult.Improvement of response rates has evolved with the development ofstandard regimens and those incorporating newer chemotherapy agents,such as oral fluoropyrimidines, the taxanes, camptothecins, novel platinums(eg, oxaliplatin [Eloxatin]), and antifolates (eg, pemetrexed[Alimta]). Ongoing trials with these regimens aim toward improvingsurvival, as well as improving the safety profile. It is hoped that in conjunctionwith molecular research in the pathogenesis of gastric cancerand development of targeted therapies in this disease, these trial datamight lead to the evolution of treatment strategies that could prove effective.
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Reassessments of ESAs for Cancer Treatment in the US and EuropeAnemia is a widely prevalent complication among cancer patients. At the time of diagnosis, 30% to 40% of patients with non-Hodgkin lymphoma or Hodgkin lymphoma and up to 70% of patients with multiple myeloma are anemic; rates are higher among persons with myelodysplastic syndromes. Among patients with solid cancers or lymphomas, up to half develop anemia following chemotherapy. For almost 2 decades, erythropoiesis-stimulating agents (ESAs) were the primary treatment for cancer-related anemia. However, reassessments of benefits and risks of ESAs for cancer-associated anemia have occurred internationally. We reviewed guidelines and notifications from regulatory agencies and manufacturers, reimbursement policies, and utilization for ESAs in the cancer and chronic kidney disease settings within the United States, Europe, and Canada. In 2008 the US Food and Drug Administration (FDA) restricted ESAs from cancer patients seeking cure. Reimbursement is limited to hemoglobin levels < 10 g/dL. In the United States, ESA usage increased 340% between 2001 and 2006, and decreased 60% since 2007. The European Medicines Agency (EMEA) recommended that ESA benefits do not outweigh risks. In Europe between 2001 and 2006, ESA use increased 51%; since 2006, use decreased by 10%. In 2009, Canadian manufacturers recommended usage based on patient preferences. In Canada in 2007, approximately 20% of anemic cancer patients received ESAs, a 20% increase since 2004. In contrast to Europe, where ESA use has increased over time, reassessments of ESA-associated safety concerns in the United States have resulted in marked decrements in ESA use among cancer patients.
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Multiple Myeloma: Role of Allogeneic TransplantationIn this article, Pandit and Vesole present a focused overview of allogeneic transplantation for multiple myeloma. Additionally, this article addresses the challenges of allogeneic transplantation, including continued relapse and treatment-related toxicity and mortality.
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Anthracycline and Trastuzumab in Breast Cancer TreatmentThis study was designed to evaluate the cardiac safety of the combined treatment of HER2-positive metastaticbreast cancer patients with trastuzumab (Herceptin) plus epirubicin and cyclophosphamide (EC) incomparison with EC alone in HER2-negative metastatic breast cancer patients. Patients included those withmetastatic breast cancer without any prior anti-HER2 treatment, anthracycline therapy, or any other chemotherapyfor metastatic disease. This was a nonrandomized, prospective, dose-escalating, multicenter, openlabel,phase II study in Germany. A control group of 23 patients received EC 90/600 mg/m2 3-weekly for sixcycles (EC90 alone). A total of 26 HER2-positive patients were treated with trastuzumab, or H (2 mg/kg weeklyafter an initial loading dose of 4 mg/kg), and EC 60/600 mg/m2 3-weekly for six cycles (EC60+H); another 25HER2-positive patients received H and EC 90/600 mg/m2 3-weekly for six cycles. Asymptomatic reductions inleft ventricular ejection fraction (LVEF) of more than 10% points were detected in 12 patients (48%) treatedwith EC60 + H and in 14 patients (56%) treated with EC90 + H vs 6 patients (26%) in the EC90 alone cohort.LVEF decreases to < 50% occurred in one patient in the EC60+H cohort and in two patients in the EC90+Hcohort during the H monotherapy. No cardiac event occurred in the cohort with EC90 alone. The overallresponse rates for EC60+H and EC90+H were >60%, vs 26% for EC90 alone. The interim results of this studysuggest the cardiac safety of the combination of H with EC may be greater than that of H with AC (doxorubicin[Adriamycin]/cyclophosphamide); however, studies in larger numbers of patients are warranted. The combinationregimen revealed promising efficacy.
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Improving the Therapeutic Ratio in Hodgkin Lymphoma Through the Use of Proton TherapyThis review addresses the rationale and evidence for-and the challenges, cost implications, and future development of-proton therapy as an important part of the treatment strategy in Hodgkin lymphoma.
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T-Cell Therapy Produced Prolonged Remission in Relapsed Pediatric ALLIn this video from the 2014 ASH Meeting, Dr. Grupp discusses data from a trial using CAR T-cell therapy in children and young adults with relapsed, treatment-resistant ALL.
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Management of Follicular Lymphoma in the Up-Front and Relapsed SettingsA number of recent treatment advances in the management of follicular lymphoma (FL), including the introduction of the anti-CD20 monoclonal antibody rituximab, have effectively shifted the primary therapeutic goal away from palliation and avoidance of toxicity toward the more proactive objective of extending survival. This paper reviews recent practice patterns in the broad context of the published findings from major phase III randomized trials; it documents potential gaps between trial results and actual practice, and the implications of these for continuing education of oncologists. Forty-three US-based community oncologists participated in a cross-sectional case survey during which 40 documented their management of 186 patients with newly diagnosed FL and 133 patients with relapsed FL, all of whom were treated after January 1, 2008. The findings from this initiative indicate that the majority of these patients did not have any major symptoms at presentation. Additionally, tolerance of and response to treatment, regardless of the regimen employed, were similar across the different age groups studied (<65, 65-74, ≥75 years). Therapies selected by the physicians surveyed in both the up-front and the relapsed settings broadly corresponded to the evidence-based published literature and were supported by treatment guidelines. In addition, a change in the proportional use of bendamustine/rituximab (BR) in the up-front treatment of FL from 2008 to 2010 was observed, suggesting that community oncologists are rapidly incorporating pivotal clinical trial results when deciding on individual patient management strategies.
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Expertise of Genetic Counselors ClarifiedIn his article, "Genetic Testing for Cancer Susceptibility: Challenges for Creators of Practice Guide-lines" [11(11A):171-176, 1997], Henry Greely, JD, provides a comprehensive review of the complex issues that patients consider when deciding
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ACR Appropriateness Criteria® Recurrent Hodgkin LymphomaBy combining the most recent medical literature and expert opinion, this revised guideline can aid clinicians in the complex decision-making associated with the management of recurrent Hodgkin lymphoma.
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Nutrition During and After Cancer TherapyIn 2008, roughly 1.44 million Americans were diagnosed with cancer,[1] and accordingly were labeled as “cancer survivors.” Fortunately, for roughly 65% of those who were newly diagnosed, this label will expand to encompass issues of long-term survivorship and health maintenance.[2] Extended cancer survivorship is a relatively new concept. In the past, most people who were diagnosed with the disease did not survive it. While longer survival times are a measure of success, the dark side of this victory is that a substantial proportion of these survivors will experience recurrence or second cancers. In addition, many more will go on to develop comorbid conditions such as cardiovascular disease (CVD), diabetes, or osteoporosis, which often kill or debilitate survivors at much higher rates than the cancer itself.[3,4]
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The "Epidemic" of Breast Cancer in the U.S.--Determining the FactorsBreast cancer incidence rates in the United States rose by 24% between 1973 and 1991. Mortality during this period, however, remained stable. Both the 5-year relative survival rate and the rates of in situ and stage I
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Is There a Role for Dose-Intensive Chemotherapy With Stem Cell Rescue in Breast Cancer?Over the past decade, high-dose chemotherapy with autologous bone marrow and/or peripheral blood rescue has been increasingly used to treat women with breast cancer. Laboratory and clinical studies have shown that dose intensity may be important in treating selected patients with breast cancer. Initial phase I studies showed good response rates of short durations. Further trials in metastatic disease with high-dose chemotherapy and stem cell rescue earlier in the treatment course had been encouraging. However, the optimal timing of high-dose chemotherapy remains a question. In addition, randomized trials in high-risk early-stage breast cancer have completed accrual. Technologic improvements in stem cell procurement and hematopoietic growth factors have contributed to decreased morbidity and mortality. This review will discuss the role of such therapy in the treatment of women with breast cancer. [ONCOLOGY 16:1643-1656, 2002]
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Intraperitoneal Chemotherapy for Advanced Epithelial Ovarian Cancer: Many Questions, Much Promise…In 2006, after a third consecutive large-scale US phase III trial conducted by the Gynecologic Oncology Group (GOG) confirmed that use of intraperitoneal (IP) chemotherapy in optimally resected stage III epithelial ovarian cancer results in superior overall survival (OS) and/or progression-free survival (PFS),[
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Paclitaxel and UFT Plus Oral Calcium Folinate in Pretreated Metastatic Breast CancerThis phase I study was designed to determine the maximum tolerated dose (MTD) and dose-limiting side effects of combination treatment with paclitaxel (Taxol) and UFT (uracil and tegafur in a 4:1 molar ratio) plus oral
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Physical Activity Across the Cancer ContinuumIn our commentary, we will address ways to consider this research across the cancer continuum, with a focus on the cancer survivor, highlighting some of the challenges in interpreting the research evidence for translation into clinical practice and noting some research gaps.
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Uterine Sarcomas: The Latest Approaches for These Rare but Potentially Deadly TumorsIn this review we discuss preoperative diagnosis and the role of pathology, and we summarize the current literature regarding the management of uterine sarcomas.
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Paclitaxel as First-Line Treatment for Metastatic Breast CancerWhen administered as a single agent in pretreated patients with advanced breast cancer, paclitaxel (Taxol) exhibits remarkable antitumor activity. This trial was undertaken to compare paclitaxel with standard
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Genetics of Colorectal CancerApproximately 6% of colorectal cancers can be attributed to recognizable heritable germline mutations. Familial adenomatous polyposis is an autosomal dominant syndrome classically presenting with hundreds to thousands of adenomatous colorectal polyps that are caused by mutations in the APC gene.
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PSA Testing: Don't toss the baby out with the bathwater: Readers respond to “Two major studies add fuel to fire of PSA controversy,” April 2009, Cancer Care Practice & Policy, page 8.PSA is the most important biomarker in a common malignancy. I will continue to test men starting at age 35 if there is a family history of prostate or breast cancer. Depending on the vitality of the individual, I will continue with PSA testing for the duration of the man’s health.
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Prophylactic Surgery in Hereditary Breast/Ovarian Cancer SyndromeDrs. Levine and Gemignani havecomposed an excellent comprehensivereview of the issuessurrounding prophylactic surgeryin patients at high risk for breast andovarian cancer. Their article focuseson the role of BRCA1/2 mutations inthe risk of developing hereditary breastand ovarian cancer and the data supportingrisk reduction in mutation carriersundergoing prophylactic surgery.
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Reversing the Surgical Stigma for Small-Cell Lung CancerJust as in recent years attitudes and treatment therapies have changed regarding non–small-cell lung cancer (NSCLC), it is time that the same occur for its small-cell counterpart. Although treatment for advanced-stage small-cell lung cancer (SCLC) is fairly standardized, there remain a number of controversies that have yet to be clarified by evidence-based data.
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Docetaxel vs Doxorubicin in Metastatic Breast Cancer Resistant to Alkylating ChemotherapySingle-agent docetaxel (Taxotere) has been shown to be highly active in metastatic breast cancer, with an overall response rate of 47%, median time to progression of 4 months, and survival of 10 months when administered as
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Imaging Prostate Cancer: Current and Future ApplicationsVarious treatment options are available for adenocarcinoma of the prostate-the most common malignant neoplasm among men in the United States. To select an optimum management strategy, we must be able to identify an organ-confined disease (in which local therapy such as surgery or radiation may be beneficial) vs prostate cancer beyond the confines of the gland (for which other treatment approaches may be more appropriate). At present, no standard imaging modality can by itself reliably diagnose and/or stage adenocarcinoma of the prostate. Standard transrectal ultrasound, magnetic resonance imaging (MRI), computed tomography, bone scans, and plain x-ray are not sufficiently reliable when used alone. Fortunately, advances in imaging technology have led to the development of several promising modalities. These modalities include color and power Doppler ultrasonography, ultrasound contrast agents, intermittent and harmonic ultrasound imaging, MR contrast imaging, MRI with fat suppression, MRI spectroscopy, three-dimensional MRI spectroscopy, elastography, and radioimmunoscintigraphy. These newer imaging techniques appear to improve the yield of prostate cancer detection and staging, but are limited in availability and thus require further validation. This article reviews the status of current imaging modalities for prostate cancer and identifies emerging imaging technologies that may improve the diagnosis and staging of this disease. [ONCOLOGY 15(3):325-342, 2001]
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Commentary (Sahebi/Forman): The Role of Hematopoietic Stem Cell Transplantation in Myelodysplastic SyndromeDrs. Thompson and Luger have written a thoughtful and comprehensive review of the therapeutic options and issues facing physicians caring for patients with myelodysplastic syndrome (MDS). In our commentary, we would like to highlight and expand on several areas of their analysis.
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p53 Tumor Suppressor Gene Therapy for CancerGene therapy has the potential to provide cancer treatments based on novel mechanisms of action with potentially low toxicities. This therapy may provide more effective control of locoregional recurrence in diseases like non–small-cell lung cancer (NSCLC) as well as systemic control of micrometastases. Despite current limitations, retroviral and adenoviral vectors can, in certain circumstances, provide an effective means of delivering therapeutic genes to tumor cells. Although multiple genes are involved in carcinogenesis, mutations of the p53 gene are the most frequent abnormality identified in human tumors. Preclinical studies both in vitro and in vivo have shown that restoring p53 function can induce apoptosis in cancer cells. High levels of p53 expression and DNA-damaging agents like cisplatin (Platinol) and ionizing radiation work synergistically to induce apoptosis in cancer cells. Phase I clinical trials now show that p53 gene replacement therapy using both retroviral and adenoviral vectors is feasible and safe. In addition, p53 gene replacement therapy induces tumor regression in patients with advanced NSCLC and in those with recurrent head and neck cancer. This article describes various gene therapy strategies under investigation, reviews preclinical data that provide a rationale for the gene replacement approach, and discusses the clinical trial data available to date. [ ONCOLOGY 13(Suppl 5):148-154, 1999]
