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About 35 years ago, I encountered several children and adolescents with acute lymphoblastic leukemia or widespread non-Hodgkin lymphoma who presented with or who developed, upon initiation of therapy, severe renal and metabolic derangements.

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Over the past 20 years, dramatic improvements have been made in the treatment of childhood malignancies. Today, most children who have cancer are expected to survive their disease and become healthy, productive members of society. Children with acute lymphoblastic leukemia (ALL) are a good example. Although pediatric ALL was an invariably fatal disorder in the past, children with this cancer now have a 5-year event-free survival rate of more than 70%.

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Managed care and proper cancer care need not be mutually exclusive entities. Managed-care organizations (MCOs) that are committed to patients and society should have the following characteristics: accountability for

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In this review, we critically analyze clinical trials that were specifically designed for the very elderly, and we discuss the challenges encountered by investigators who are conducting studies in this patient population. We conclude by proposing an algorithm to help clinicians determine the optimal therapeutic strategy for treatment of DLBCL in very elderly patients.

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Acute lymphoblastic leukemia (ALL) in adults is clearly a "different disease" than ALL in children-a fact that is well documented in the article by Ong and Larson. As they indicate, more than half of adult patients relapse despite modern therapy, most within the first 2 years. It should be pointed out, however, as is mentioned at the beginning of the article, that "modern" induction was defined by Cancer and Leukemia Group B study 7612--a study begun in 1976 [1]. Thus, induction therapy has not changed substantially in 20 years. The addition of consolidation therapy and prolonged maintenance therapy has resulted in modest increases in response duration, but despite many variations on current regimens, there has been little change in outcome during the past decade.

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Early results suggest that the new targeted therapies for CLL may have a profound impact on survival-and thus on the incidence of Richter's transformation. It will therefore become increasingly important to study Richter's transformation more assiduously, to diagnose it sooner, and to develop strategies to treat this extremely challenging entity.

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Clinical results with irinotecan (CPT-11 [Camptosar]) and other camptothecin derivatives in various cancers, although encouraging, have fallen short of the expectations predicted by preclinical models. One proposed

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The combination of irinotecan and fluorouracil (5-FU) is synergistic when applied to human colon cancer cell lines in vitro and appears to be schedule-dependent: maximal activity occurs when irinotecan is administered prior to 5-FU. In this phase I study, irinotecan is administered in combination with UFT and leucovorin in patients with advanced solid tumors.

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This interview examines the role of functional imaging to direct therapy (escalation or de-escalation) for early and advanced Hodgkin lymphoma.

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Granulocyte-macrophage colony-stimulating factor (GM-CSF,sargramostim [Leukine]) is a powerful cytokine that is able to stimulatethe generation of dendritic cells. Adjuvant treatment with continuous lowdoseGM-CSF has been shown to prolong survival of stage III/IV melanomapatients. Data on continuous low-dose GM-CSF therapy in tumorsother than prostate cancer are still lacking.

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A 35-year-old woman noticed a mass in her right breast and underwent a diagnostic workup, including a mammogram that revealed a 2.4-cm mass and ultrasound that showed two adjacent masses, as well as enlarged axillary lymph nodes.

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Paclitaxel (Taxol) and vinorelbine (Navelbine) are both microtubule toxins but with opposite mechanisms of action. Paclitaxel promotes the assembly of microtubules, whereas vinorelbine prevents microtuble assembly.

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The current health-care environment is creating many new challenges for physicians, and addressing these challenges has led to new ideas in office practice management.

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Gallbladder carcinoma and carcinoma of the bile ducts are relativelyrare cancers in the United States. These cancers are often diagnosedin an advanced stage due to their nonspecific symptomatologyand until recently have been associated with a dismal prognosis. Recentadvances in imaging and surgical techniques along with emergingoptions in palliative chemotherapy have improved the outlook inthese cancers. While complete surgical resection remains the only hopeof cure in both these cancers, palliative biliary decompression and chemotherapyresult in substantial improvement in quality of life. Part 1 ofthis review, which appeared in last month’s issue, provided a relevantand comprehensive update of molecular pathology, imaging modalities,and surgical care. In part 2, we examine palliative care and systemictherapy in gallbladder and biliary tract carcinomas, as well asthe use of liver transplantation in the treatment of cholangiocarcinomas.These strategies are of relevance to internists as well as oncologistscaring for these patients.

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Active surveillance is an excellent alternative to surgery or radiation in patients with low-risk cancers. However, the current methods of ascertaining whether a patient harbors a low-risk cancer are flawed.

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Primary systemic therapy (ie, preoperative or neoadjuvant) increasesthe possibility for breast-conserving surgery in patients with primarybreast cancer. Patients with pathologic complete response to primarysystemic therapy have improved survival compared with those with persistenttumors. Several phase II trials have evaluated gemcitabine-containingdoublet or triplet regimens as primary systemic therapy for breastcancer, results of which have shown promising clinical and pathologicresponse rates with manageable toxicity. Results of a phase I/II studyof gemcitabine (Gemzar)/epirubicin (Ellence)/docetaxel (Taxotere), orGEDoc, with prophylactic filgrastim (Neupogen), as primary systemictherapy in 77 evaluable patients with primary breast cancer are reportedherein. Dose-limiting toxicities were grade 3 febrile neutropenia(n = 1) and grade 3 diarrhea (n = 2) at the fourth dose level ofGEDoc tested (gemcitabine at 800 mg/m2 days 1 and 8, epirubicin at90 mg/ m2 day 1, and docetaxel at 75 mg/m2 day 1). As assessed byultrasound, 92% of patients responded overall (22% complete response),and 79% of patients could undergo breast-conserving surgery. Thepathologic complete response rate in resected breast tissue was 26%.

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Early-stage Hodgkin’s disease accounts for approximately 60% of all cases of the illness. Because of its excellent cure rate (80% to 90%) and high salvage rate, it is difficult to demonstrate survival advantages for

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Estrogen is known to play an important role in skeletal health. Femalebreast cancer patients who receive treatments that reduce estrogenlevels, such as aromatase inhibitors, may increase their risk of developingosteoporosis and their risk of fracture. Clinical guidelinesenable the physician to assess the risk of osteoporosis by patient historyand physical examination. For patients identified as being at risk, it isnecessary to test bone mineral density (BMD), using the result to determinewhich patients require treatment. Two groups can be identified asrequiring BMD assessment according to general guidelines: patients< 45 years old who become menopausal due to treatment, and breastcancer patients receiving aromatase inhibitors. Bisphosphonates appearto be the logical treatment of choice for breast cancer patients, asthey do not interact with the estrogen receptor. Although not all womenreceiving aromatase inhibitors will require additional treatment for bonehealth, postmenopausal women with a history of breast cancer at riskof osteoporosis should be identified, monitored, and managed accordingto practice guidelines.

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This video reviews the treatment of mantle cell lymphoma cases that do not fit the typical mold.

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The indolent non-Hodgkin's lymphomas constitute a heterogeneous group of lymphoproliferative disorders usually associated with relatively prolonged survival. They are categorized based on pathologic and cytologic features, and, with few exceptions [1], they are almost exclusively of B-cell origin.

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Although resection currently remains the standard of care for renalcarcinoma, the search for less invasive treatments has led to alternativesurgical approaches. Even less invasive, and appropriate for manygroups of patients, is percutaneous radiofrequency ablation, which inducestumor necrosis via lethal hyperthermia. Multiple series of renaltumors treated with percutaneous ablation in vivo and left in situ havebeen published; these series reveal that for small renal tumors,radiofrequency ablation results in complete necrosis at imaging in 79%to 100% of cases. Because current results come from tumors left in situwith short postablation follow-up, long-term results are necessary tocompare outcomes to surgical standards. Complication rates are lowerthan those following partial nephrectomy. Future reports will shed lighton the long-term outcomes of percutaneous ablation and the relativeadvantages and disadvantages of various technologies for thermal ablation.

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Conservation of blood is apriority during surgery, owingto shortages of donor bloodand risks associated with transfusionof blood products.[9,10] However,blood transfusions have been linkedto a number of negative postoperativesequelae, including poorer prognosisafter cardiac and cancer surgery.[11-21] In this context, recognition thatallogeneic transfusion-associatedimmunomodulation can increasemorbidity in allogeneically transfusedpatients has become a major concernin transfusion medicine.[9,22,23]

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From the results of recent studies, it is likely that multimodality therapy with chemotherapy and radiation treatment may improve the overall outcome of locally advanced upper gastrointestinal (GI) malignancies, including esophageal, gastric, pancreatic, and biliary tract carcinomas. However, more effective, more optimal, and less toxic chemotherapy regimen(s) with concomitant radiotherapy are needed beyond the concurrent continuous-infusion fluorouracil (5-FU) with radiation that is commonly applied in general practice. Epirubicin (Ellence), cisplatin, and irinotecan (Camptosar) are all active cytotoxic chemotherapy agents in upper GI cancers. Two phase I studies were designed to test the tolerability of the combination of radiotherapy with infusional 5-FU, epirubicin, and cisplatin (ECF) or 5-FU, irinotecan, and epirubicin (EIF) in the treatment of locally advanced upper GI malignancies.

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Focal therapy is an appealing addition to our current AS strategies. As a “lesser evil,” focal therapy is showing promise as a therapy that can provide cancer control, while also avoiding many of the radical treatment–associated morbidities.

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Breast cancer is second only to lung cancer as a leading cause of cancer mortality in women. In women with metastatic, hence, essentially incurable disease, we strive to find effective chemotherapeutic regimens that offer a

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The relatively recent introduction of a new class of chemotherapeutic agents--the taxoids--has raised hope of improved survival for patients with advanced or metastatic cancer. Following encouraging preclinical results of taxoid combinations, this phase I, nonrandomized trial was designed to evaluate a 1-hour intravenous infusion of docetaxel (Taxotere) on day 1 combined with fluorouracil (5-FU) as a daily intravenous bolus for 5 consecutive days.

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A number of randomized clinical trials and meta-analyses now support the conclusion that combined modality regimens that include cisplatin (Platinol)-based chemotherapy improve survival in stage III non–small-cell lung

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Vascular endothelial growth factor (VEGF) plays a crucial role inthe growth and metastatic spread of cancer. Bevacizumab (Avastin) isthe first commercially available VEGF inhibitor, earning US Food andDrug Administration (FDA) approval in February 2004. In combinationwith fluorouracil (5-FU)-based chemotherapy, this agent significantlyprolongs overall and progression-free survival of patients withmetastatic colorectal cancer. This review details the emerging role ofthe drug, its unique side effects, and other practical considerations relatedto bevacizumab therapy. Ongoing trials attempting to define additionalindications for bevacizumab as well as the development ofother promising angiogenesis inhibitors are also reviewed.

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Michael H. Levy, MD: This 38-year-old white male first came to his physician in January of 1993 complaining of epigastric and low back pain. In March of 1993, he was diagnosed with pancreatic cancer that was metastatic to his

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