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The Future of Metastatic Urothelial Carcinoma ManagementClosing out their review of metastatic urothelial carcinoma management, panelists share what they most look forward to in the evolving treatment landscape.
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Renal-Cell CarcinomaRenal-cell carcinoma (RCC) is curable only in patients presenting with resectable, early-stage disease. Advanced local or metastatic disease carries an approximate 15% 5-year survival rate. However, the natural history of metastatic RCC is heterogeneous, and aggressive palliative treatment is recommended, especially for patients with a solitary metastatic site and good performance status.
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Perioperative Treatment of Gastrointestinal Stromal TumorsGastrointestinal stromal tumors (GISTs) originate from the interstitial cells of Cajal or a precursor and are the most common mesenchymal neoplasms of the gastrointestinal (GI) tract.[1] Although GISTs often present as localized masses, they are typified by a high risk of metastatic relapse, most commonly in the liver and peritoneum.
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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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Vaccine Therapy for Patients With MelanomaInvestigation into the therapeutic use of vaccines in patients with metastatic melanoma is critically important because of the lack of effective conventional modalities. The most extensively studied melanoma vaccines in clinical trials are whole-cell preparations or cell lysates that contain multiple antigens capable of stimulating an immune response. Unfortunately, in the majority of studies, immune responses to these vaccines have not translated into a survival advantage. Advances in tumor cell immunology have led to the identification of candidate tumor cell antigens that can stimulate an immune response; this, in turn, has allowed for refinements in vaccine design. However, the exact tumor antigens that should be targeted with a specific vaccine are unknown. The univalent antigen vaccines, which have greater purity, ease of manufacturing, and reproducibility compared with polyvalent vaccines, may suffer from poorer efficacy due to immunoselection and appearance of antigen-negative clones within the tumor. Novel approaches to vaccine design using gene transfection with cytokines and dendritic cells are all promising. However, the induction of immune responses does not necessarily confer a therapeutic benefit. Therefore, these elegant newer strategies need to be studied in carefully designed clinical trials so that outcomes can be compared objectively with standard therapy. If survival is improved with these vaccine approaches, their ease of administration and lack of toxicity will firmly entrench active specific vaccine immunotherapy as a standard modality in the treatment of the melanoma patient.[ONCOLOGY 13(11):1561-1574, 1999].
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A 40-Year-Old Woman With a New Triple-Negative Breast Mass, Shown on Biopsy to Be Metaplastic CarcinomaA 40-year-old woman noted a large mass in her right breast. A diagnostic mammogram and ultrasound confirmed a 3.4-cm mass with associated microcalcifications.
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Cancer Treatment for LGBTQ PatientsIn this interview we discuss the approach to treating cancer in lesbian, gay, bisexual, transgender, and queer (LGBTQ) patients.
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Nuances in the Changing Epidemiology of Head and Neck CancerHead and neck squamous cell carcinoma (HNSCC) represents a heterogeneous group of malignancies caused by the traditional risk factors of tobacco, alcohol, and poor oral hygiene, as well as more recently identified roles of human papillomavirus (HPV) and Epstein-Barr virus (EBV).[1-3] We commend Kim and colleagues on their comprehensive review of the epidemiology of HNSCC. There has been a clear change in the epidemiology of HNSCC which has further accentuated differences in etiology, survival, and demographics among HNSCC patients. We will discuss several important nuances of this changing epidemiology, including the role of tobacco, race, sexual behavior, and gender, as well as HNSCC in nonsmokers and nondrinkers.
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C-11 choline PET/CT boosts early prostate ca detectionFindings of a study by researchers in Italy suggest C-11 choline PET/CT could diagnose prostate cancer recurrence sooner than transrectal ultrasound, CT, MRI, or bone scintigraphy in patients who have undergone radical prostatectomy.
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PSA Testing in Prostate Cancer: Early Treatment vs ObservationIn this interview we discuss the role of early treatment, active surveillance, and watchful waiting in patients with PSA-detected early-stage prostate cancer.
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Commentary (Grossman): Age-Specific Reference Ranges for PSA in the Detection of Prostate CancerDr. DeAntoni has carefully reviewed the literature on age-specific reference ranges for prostate-specific antigen (PSA) in the diagnosis of prostate cancer and the controversy surrounding their use. Key to understanding of this debate are two fundamental concepts: (1) the definition of "clinically significant prostate cancer" and (2) the use of sensitivity and specificity, which is frequently obscured by the surrounding rhetoric. The assumption that all readers uniformly interpret the meaning of clinically significant prostate cancer and wish to achieve the same results by manipulating sensitivity and specificity is probably incorrect.
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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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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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Rituximab as a Single Agent and in Combination With Interferon Alfa-2a as Treatment of Untreated and First-Relapse Follicular or Other Low-Grade Lymphomas: A Randomized Phase II Study (M 39035)Rituximab (Rituxan) is approved for use in patients with relapsed and refractory follicular lymphoma. Considering the immune modulating effect of interferon alfa-2a (IFN [Roferon-A]) and its efficacy as a single agent in follicular lymphoma, a
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A Phase II Randomized Study of Doxorubicin Alternated With Docetaxel vs Sequential Administration of Four Cycles of Docetaxel Followed by Four Cycles of Doxorubicin as First-Line Chemotherapy in Metastatic Breast Cancer PatientsFrom March 1996 to March 1998, 106 patients with untreated metastatic breast cancer (MBC) were treated with docetaxel (Taxotere) (100 mg/m²) and doxorubicin (75 mg/m²) on an alternating cycle-by-cycle (doxorubicin, docetaxel, doxorubicin, etc) or sequential (four cycles of docetaxel, then four cycles of doxorubicin) basis, every 3 weeks, for a maximum of eight cycles.
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Dose-Dense and Sequential Strategies in Adjuvant Breast Cancer TherapySeveral attempts have been made to improve the survival rates of breast cancer patients. The benefit of adjuvant chemotherapy was clearly shown, but the absolute difference of 2% to 11% in overall survival, depending on the
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Rituximab as a Single Agent and in Combination With Interferon Alfa-2a as Treatment of Untreated and First-Relapse Follicular or Other Low-Grade Lymphomas: A Randomized Phase II Study (M 39035)Rituximab (Rituxan) is approved for use in patients with relapsed and refractory follicular lymphoma. Considering the immune modulating effect of interferon alfa-2a (IFN [Roferon-A]) and its efficacy as a single agent in follicular lymphoma, a
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Initial Control of Chemotherapy-Induced Nausea and Vomiting in Patient Quality of LifeThe side effects commonly experienced by patients receiving chemotherapy for the treatment of cancer can challenge many aspects of daily life. Nausea and vomiting, the most common side effects reported by patients, affect the ability to continue with usual life activities and, thus have a pronounced impact on quality of life.
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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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Chronic Myeloid LeukemiaChronic myeloid leukemia (CML) is a clonal myeloproliferative disorder resulting from the neoplastic transformation of the primitive hematopoietic stem cell.
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Toward a Breast Cancer Vaccine:Work in ProgressAs outlined in the review byDrs. Emens and Jaffee entitled“Toward a Breast CancerVaccine: Work in Progress,” the developmentof anticancer vaccines hasclosely paralleled advances in the fieldof immunology. Basic immunologyhas provided and will continue toprovide important insights intohuman immunity that directly relateto the design and study of immunotherapeutics.To date, the mostimportant scientific observations applicableto immunotherapy include thefollowing:
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UFT/Oral Calcium Folinate Plus Weekly Paclitaxel for Metastatic Breast CancerPaclitaxel (Taxol) is one of the most active drugs in the treatment of ovarian and breast cancers. Combination therapy with paclitaxel and 5-fluorouracil (5-FU) exhibits high activity in anthracycline-pretreated breast cancer,
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A Phase II Randomized Study of Doxorubicin Alternated With Docetaxel vs Sequential Administration of Four Cycles of Docetaxel Followed by Four Cycles of Doxorubicin as First-Line Chemotherapy in Metastatic Breast Cancer PatientsFrom March 1996 to March 1998, 106 patients with untreated metastatic breast cancer (MBC) were treated with docetaxel (Taxotere) (100 mg/m²) and doxorubicin (75 mg/m²) on an alternating cycle-by-cycle (doxorubicin, docetaxel, doxorubicin, etc) or sequential (four cycles of docetaxel, then four cycles of doxorubicin) basis, every 3 weeks, for a maximum of eight cycles.
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UFT/Leucovorin vs 5-FU/Leucovorin in Colon CancerAdjuvant chemotherapy has been shown to alter the natural history of resected colon cancer. Two regimens (fluorouracil [5-FU] plus leucovorin and 5-FU plus levamisole) have been found to prolong disease-free survival and overall survival in affected patients.
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Phase II Study of Rituximab in Combination With Fludarabine in Patients With Chronic Lymphocytic LeukemiaThis phase II trial investigated the safety and efficacy of a combined-modality treatment with rituximab (Rituxan) and fludarabine (Fludara) in patients with fludarabine- and anthracycline-naive chronic lymphocytic lymphoma (CLL).
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2 Cycles of ABVD Plus Radiotherapy Is More Effective Than Radiotherapy Alone in Early Stage HD-Interim Ahan Radiotherapy Alone in Early Stage HD-Interim Analysis of the HD7 Trial of the GHSG Clinic of Internal Medicine I University of Cologne/GermanyBACKGROUND: Extended-field radiotherapy is effective in patients with early-stage Hodgkin’s disease, and more than
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Therapeutic Activity of Humanized Anti-CD20 Monoclonal Antibody and Polymorphism in IgG FcReceptor FcgRIIIa GeneRituximab (Rituxan) is a chimeric IgG1 anti-CD20 monoclonal antibody increasingly used in the treatment of non-Hodgkin’s lymphoma (NHL). Previous in vitro studies have suggested the role of antibody-dependent cellular cytotoxicity (ADCC) and FcgR-positive effector cells (natural killer and macrophage) in the antitumor effects of anti-CD20 antibodies, but the actual mechanism of rituximab action in vivo remains largely unknown. The FCGR3A gene coding for the FcgRIIIa receptor displays a functional dimorphism with either a phenylalanine (FCGR3A-158F) or a valine (FCGR3A-158V) at amino acid 158, with a higher affinity of human IgG1 and increased ADCC for the latter. The aim of this study was thus to determine the influence of this FCGR3A polymorphism on clinical and molecular responses to rituximab.
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Acute Myelogenous LeukemiaAcute myelogenous leukemia (AML) is a disorder marked by infiltration of the bone marrow by abnormal hematopoietic progenitors. These cells are unable to differentiate in a normal fashion into myeloid, erythroid, and/or megakaryocytic cell lines and, unlike normal progenitors, are capable of infiltrating vital organs.
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Ponatinib Dose-Ranging Study in Chronic-Phase CML: SummaryJorge E. Cortes, MD and Hagop Kantarjian, MD share a summary on ponatinib in CML and ALL and exploration of potential future studies.
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Chemoradiation in NSCLC: Focus on the Role of GemcitabineResearch to identify the optimal drugs for use in chemoradiotherapyhas led to the development of the potent radiosensitizing agentgemcitabine (Gemzar), which has exhibited excellent activity in non-small-cell cancer. When used in sequential chemoradiotherapy regimens,gemcitabine has been associated with response rates of 57% to68%. A full dose of gemcitabine (1,000 mg/m2) can be safely used asinduction therapy, and there is no definitive indication of enhancementof radiotoxicity. In addition, results from phase I/II trials supportthe efficacy of concurrent gemcitabine/radiation therapy in improvingoverall response rates and overall survival. Rates of 68%, 37%, and28%, respectively, for 1-, 2-, and 3-year survival have been reported forgemcitabine/cisplatin chemotherapy administered concurrently withradiotherapy. Although the optimal dose has yet to be determined, aweekly dose of 300 mg/m2 appears to be effective with an acceptabletoxicity level. Additional clinical trials are warranted to assess the longtermefficacy and safety of gemcitabine in combination with other chemotherapeuticagents and radiation therapy for treatment of non-smallcelllung cancer.
