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Small-Cell Lung Cancer: Therapeutic ChangesAlmost 40% of patients with newly diagnosed small-cell lung cancer (SCLC) have disease confined to the ipsilateral hemithorax and within a single radiation port, ie, limited-stage disease. The median survival for this group of patients after treatment is approximately 15 months, with one in every four patients surviving 2 years. Current optimal treatment consists of chemotherapy with platinum/etoposide, given concurrently with thoracic radiation. Surgery may represent an option for very early-stage disease, but its added value is uncertain. Prophylactic cranial irradiation (PCI) is used for patients with limited-stage SCLC who have achieved a complete response following initial therapy, as it decreases the risk of brain metastases and provides an overall survival benefit. Newer targeted agents are currently being evaluated in this disease and hold the promise of improving current outcomes seen in patients with early-stage disease.
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QOL of Multiple Myeloma Patients Receiving Maintenance TherapyThis interview examines a study that looked at the health-related quality of life of multiple myeloma patients in a real-world setting who underwent maintenance therapy after autologous stem cell transplant.
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Cisplatin, Fluorouracil, Celecoxib, and RT in Resectable Esophageal Cancer: Preliminary ResultsEsophageal cancer frequently expresses cyclooxygenase-2 (COX-2)enzyme. In preclinical studies, COX-2 inhibition results in decreasedcell proliferation and potentiation of chemotherapy and radiation. Wereport preliminary results of a phase II study conducted by the HoosierOncology Group in patients with potentially resectable esophageal cancer.All patients received cisplatin at 75 mg/m2 given on days 1 and 29and fluorouracil (5-FU) at 1,000 mg/m2 on days 1 to 4 and 29 to 32with radiation (50.4 Gy beginning on day 1). Celecoxib (Celebrex) wasadministered at 200 mg orally twice daily beginning on day 1 untilsurgery and then at 400 mg orally twice daily until disease progressionor unexpected toxicities, or for a maximum of 5 years. Esophagectomywas performed 4 to 6 weeks after completion of chemoradiation. Theprimary study end point was pathologic complete response (pCR). Secondaryend points included response rate, toxicity, overall survival, andcorrelation between COX-2 expression and pCR. Thirty-one patientswere enrolled from March 2001 to July 2002. Respective grade 3/4 toxicitieswere experienced by 58%/19% of patients, and consisted of granulocytopenia(16%), nausea/vomiting (16%), esophagitis (10%), dehydration(10%), stomatitis (6%), and diarrhea (3%). Seven patients (24%)required initiation of enteral feedings. There have been seven deathsso far, resulting from postoperative complications (2), pulmonary embolism(1), pneumonia (1), and progressive disease (3). Of the 22 patients(71%) who underwent surgery, 5 had pCR (22%). We concludethat the addition of celecoxib to chemoradiation is well tolerated. ThepCR rate of 22% in this study is similar to that reported with the use ofpreoperative chemoradiation in other trials. Further follow-up is necessaryto assess the impact of maintenance therapy with celecoxib onoverall survival.
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Clinical and Pathological Features Are Still the Best Determinants of Prognosis in MesotheliomaSignificant advances have been made in our understanding of the factors affecting the prognosis of malignant mesothelioma, and a number of biomarkers appear promising. However, at present it may be more fruitful to better define and characterize clinical factors that are well recognized as significantly impacting patient survival.
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New Targets and New Mechanisms in Lung CancerThis review will describe the well-known use of VEGF antibodies; the current uses of EGFR and ALK tyrosine kinase inhibitors; newer agents being used against MET, FGFR, and other intracellular targets; insights regarding the field of immunotherapy in lung cancer; and finally, newer developments in chemotherapy.
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The Limitations and Promise of Immunotherapy With Chimeric Antigen–Modified T CellsIdentification of effective lymphodepletion strategies, optimization of patient selection, and management of novel toxicities remain challenges in the growing field of cellular immunotherapy.
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The Absent-Minded Professor: An Unusual Complication of MelanomaThe University of Colorado Health Sciences Center holds weekly second opinion conferences focusing on cancer cases that represent most major cancer sites. Patients seen for second opinions are evaluated by an oncologist.
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Current and Emerging Treatments for Brain MetastasesConventional methods for treating brain metastasis, such as surgery, WBRT, and SRS, each compete with and complement one another. A plethora of recent studies have helped define and expand the utility of these tools.
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Deadly Aggressive Form of Prostate Cancer Is Surprisingly CommonSmall-cell neuroendocrine disease associated with prostate cancer treatment appears to be more common than previously believed.
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Local Therapy MattersAs breast cancer remains the most commonly diagnosed cancer among women in the United States, there has been a decline in breast cancer–related mortality for the past 2 decades; this is likely related to diagnosis at an earlier stage and the availability of more effective treatment regimens.
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Neoadjuvant Therapy With Gemcitabine in Breast CancerPrimary 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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UFT/Leucovorin Plus Weekly Irinotecan in Advanced or Metastatic Colorectal CancerThis is an open-label, nonrandomized phase I trial to determine the safety and maximum tolerated dose of irinotecan with a fixed dose of UFT plus oral leucovorin in patients with advanced or metastatic colorectal cancer.
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Commentary (Flores/Rusch): Diffuse Malignant Mesothelioma of the Pleural Space and Its ManagementDrs. Zellos and Sugarbaker nicely summarize the current treatment strategies for malignant pleural mesothelioma. The management of this disease remains controversial, and several aspects of the review merit discussion.
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Successful Diagnosis and Treatment of Occult Prostate Cancer Despite Multiple Negative Prostate Biopsies and Negative Prostate MRIsDr. Judd W. Moul, MD, and colleagues present the case of a man, aged 73 years, with a prostate-specific antigen level of 110 ng/mL after 4 negative prostate biopsies and 4 negative prostate MRIs.
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Commentary (Roy/Rai)-Chronic Myeloid Leukemia: Changing the Treatment ParadigmsMolecular discoveries and clinical advances over the past few decades have made the treatment of chronic myeloid leukemia (CML) one of the great success stories of modern medicine. Before the 1980s, the focus was on maintaining normal white blood cell counts with agents such as hydroxyurea and busulfan. With the use of interferon, treatment strategies turned more toward cytogenetic remission. In 1998, targeted therapy was introduced to this setting with the first studies of imatinib mesylate. Since then, treatment objectives have shifted toward the attainment of molecular remission. In this review, we consider the variety of approaches to treating CML, efforts to minimize treatment failures, and possible future directions in therapy.
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Management of Acute Promyelocytic Leukemia: Implications for Treatment of Other CancersThe article by Drs. Stein and Tallman is an excellent summary indicating that several different approaches may lead to the cure of acute promyelocytic leukemia (APL).
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Esophageal CancerThis comprehensive guide for oncologists covers the diagnosis, staging, treatment, and management of esophageal cancer.
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Erlotinib/Gemcitabine for First-Line Treatment of Locally Advanced or Metastatic Adenocarcinoma of the PancreasErlotinib (Tarceva) is a human epidermal growth factor receptor type 1/epidermal growth factor receptor (HER1/EGFR) tyrosine kinase inhibitor initially approved by the US Food and Drug Administration for the treatment of patients with locally advanced or metastatic non–small-cell lung cancer after failure of at least one prior chemotherapy regimen. In this report, we present the pivotal study that led to the approval of erlotinib in combination with gemcitabine (Gemzar) in patients with locally advanced/metastatic chemonaive pancreatic cancer patients. The combination demonstrated a statistically significant increase in overall survival accompanied by an increase in toxicity. Physicians and patients now have a new option for the treatment of locally advanced/metastatic adenocarcinoma of the pancreas.
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Personalized Medicine for Non–Small-Cell Lung CancerIt is estimated that more than 1.5 million individuals in the United States will be diagnosed with cancer this year. Of these, nearly 145,000 will be diagnosed with non–small-cell lung cancer (NSCLC).
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Targeted Therapy in Rectal CancerEpidermal growth factor receptor (EGFR) and vascular endothelial growth factor (VEGF) are often overexpressed in colorectal cancer and are associated with inferior outcomes. Based on successful randomized phase III trials, anti-EGFR and anti-VEGF therapeutics have entered clinical practice. Cetuximab (Erbitux), an EGFR-specific antibody, is currently approved in the United States in combination with irinotecan (Camptosar) for patients with metastatic colorectal cancer refractory to irinotecan or as a single agent for patients unable to tolerate irinotecan-based therapy. In retrospective analyses, patients with EGFR-expressing rectal cancer undergoing neoadjuvant radiation therapy had a significantly inferior disease-free survival and lower rates of achieving pathologic complete response. Based on the positive data in metastatic colorectal cancer and synergy with radiation therapy seen in preclinical models, there is a strong rationale to combine cetuximab with neoadjuvant radiation therapy and chemotherapy in rectal cancer. Bevacizumab (Avastin), a VEGF-specific antibody, was the first antiangiogenic agent to be approved in the United States for use in combination with standard chemotherapy in the first- and second-line of treatment in metastatic colorectal cancer. VEGF-targeted therapy may lead to indirect killing of cancer cells by damaging tumor blood vessels, and may increase the radiosensitivity of tumor-associated endothelial cells. VEGF blockade can also "normalize" tumor vasculature, thereby leading to greater tumor oxygenation and drug penetration. This review will address completed and ongoing trials that have established and continue to clarify the effects of these agents in rectal cancer.
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Changing Concepts in the Management of Endometrial CancerThe authors present the major issues and controversies surrounding the treatment of endometrial cancer. A variety of therapeutic approaches have been used in the past, including surgery alone, preoperative radiation and surgery, surgery and
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Continuous Low-Dose GM-CSF as Salvage Therapy in Refractory Recurrent Breast or Female Genital Tract CarcinomaGranulocyte-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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Pemetrexed in Advanced NSCLC: A Review of the Clinical DataThe novel multitargeted antimetabolite pemetrexed (Alimta), recentlyapproved by the US Food and Drug Administration for the treatment ofmesothelioma when combined with cisplatin, is also active in first- andsecond-line non–small-cell lung cancer (NSCLC). In a phase III trialcomparing single-agent pemetrexed vs docetaxel (Taxotere) as secondlinetherapy in advanced NSCLC, survival was shown to be comparablebetween these agents, but side effects were significantly less frequentand severe for patients who received pemetrexed. In the frontlinesetting, phase II studies have shown significant activity and a veryfavorable toxicity profile of the combination of pemetrexed with a platinumagent. Pemetrexed has been well tolerated at systemic doses as aradiosensitizer when given as concurrent chest radiation, and a phaseI study is under way to assess its tolerability in combination withcarboplatin (Paraplatin) in this setting. Pemetrexed is an importantaddition to the armamentarium of medicines used to treat thoracicmalignancies, and merits study in combination with other drugs havingnovel mechanisms of action.
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Pancreatic Cancer: Recognizing an Hereditary PredispositionAlthough candidate genes for hereditary pancreatic cancer have been identified (Figure 1), namely p16 and BRCA2, pancreatic cancer patients having an inherited predisposition will not be easy to recognize on clinical grounds.
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Prostate Cancer Immunotherapy: Promising BeginningsThere has been a resurgence of interest in developing noncytotoxic immune therapies for patients with either hormone-naive biochemically relapsed post-primary therapy or castrate metastatic prostate cancer. The rationale for developing an immunotherapeutic approach has been based on the overexpression and underglycosylation of a wide variety of altered "self" molecules including prostate-specific antigen (PSA), acid phosphatase (ACP), prostate stem cell antigen (PSCA), and prostate-specific membrane antigen (PSMA), which can serve as targets for immune recognition and attack. In addition, such a strategy could theoretically make use of the patient's immune system to fight the tumor particularly if their disease is of reasonably low volume. A variety of immunotherapeutic approaches have been explored through phase I, II, and now phase III trials demonstrating that immunologic tolerance could be broken, as evidenced by the development of high-titer antibodies and T-cell responses specific for the tumor. What appears to be revolutionizing the immunotherapy field is the combination of vaccines with cytokines or immune modulators, which not only potentiate immune reactivity in vivo but foster dramatic antitumor responses. This review explores the challenges now faced in establishing a role for immune therapies for prostate cancer treatment.
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Surgical Approach to Organ Preservation in the Treatment of Cancer of the LarynxThe article by Dr. Weinstein is a discussion of the newer surgical options available for the treatment of patients with laryngeal cancer. Several aspects of the article deserve mention.
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Gestational Trophoblastic TumorsGestational trophoblastic tumors (GTTs) encompass a spectrum of neoplastic disorders that arise from placental trophoblastic tissue after abnormal fertilization. GTTs are classified histologically into four distinct groups: hydatidiform mole (complete and partial), chorioadenoma destruens (invasive mole), choriocarcinoma, and placental site tumor [1,2].
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Predicting Prognosis in Patients With Superficial Bladder CancerBladder cancer is the most common urologic malignancy and is expected to affect approximately 54,000 people in 1998. Superficial bladder tumors (Tis, Ta, and T1 lesions) account for approximately 70% to 80% of these
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Next-Generation Sequencing for Lung Cancer in Clinical PracticeThis video highlights some of the latest developments guiding precision medicine for lung cancer in clinical practice.
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Optimizing Radiotherapy With Immunotherapy in Lung Cancer TreatmentThis video examines how the use of radiation therapy in patients on immunotherapy can trigger immunogenic cell death, and reviews some of the challenges related to unwanted immune responses from radiotherapy.
