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Propelling Immunotherapy Combinations Into the ClinicThis review summarizes promising new targets and immunotherapy combination strategies currently under clinical development.
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Node-Positive Prostate Cancer: A Call for Level 1 EvidenceDespite the lack of level 1 evidence, retrospective studies support the need for appropriate local treatment, even in the context of node-positive disease.
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Commentary (Selman/Copeland): Management of Intestinal Obstruction in the Patient With Ovarian CancerAuthors Thomas Randall, MD, and Stephen Rubin, MD, provide a thoughtful, state-of-the-art discussion on current controversies in the management of intestinal obstruction in patients with ovarian cancer.
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Controversies in the Pathology of Thymoma Viewed Through the Prism of Evidence-Based PathologyThymomas are uncommon neoplasms that have generated considerable controversy among pathologists. The following questions can be used to evaluate the evidence supporting current concepts about the pathology of thymomas and the clinical applicability of those concepts.
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Doxorubicin and Paclitaxel (Sequential Combination) in the TreatmentBased on preclinical data, we designed a phase I/II clinical trial to determine the efficacy and toxicity of doxorubicin followed by paclitaxel in the treatment of advanced breast cancer (either untreated or relapsed after
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Multidisciplinary Management of Pediatric Soft-Tissue SarcomaThe management of pediatric soft-tissue sarcomas has improved drastically through the use of multimodal therapy. These tumors include rhabdomyosarcomas and nonrhabdomyosarcomas. Both are staged using
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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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Gemcitabine/Paclitaxel as First-Line Treatment of Advanced Breast CancerGemcitabine (Gemzar) and paclitaxel exhibit good activity and goodsafety profiles when used alone and together in the treatment of advancedbreast cancer. In a phase II trial, 45 patients with metastaticbreast cancer received gemcitabine at 1,200 mg/m2 on days 1 and 8 andpaclitaxel at 175 mg/m2 on day 1 every 21 days. Twenty-seven patients(60.0%) had prior adjuvant therapy. Objective response was observedin 30 patients (objective response rate 66.7%, 95% confidence interval[CI] = 52%–71%), including complete response in 10 (22.2%) and partialresponse in 20 (44.4%). Median duration of response was 18 months(95% CI = 11–26.7 months), median time to tumor progression for theentire population was 11 months (95% CI = 7.1–18.7 months), medianoverall survival was 19 months (95% CI = 17.3–21.7 months), and the1-year survival rate was 69%. Treatment was well tolerated, with grade3/4 toxicities being infrequent. Grade 3/4 leukopenia, neutropenia, andthrombocytopenia were each observed in six patients (13.3%). No patientwas discontinued from the study due to hematologic ornonhematologic toxicity. Thus, the gemcitabine/paclitaxel combinationshows promising activity and tolerability when used as first-line treatmentin advanced disease. The combination recently has been shownto be superior to paclitaxel alone as first-line treatment in anthracyclinepretreatedadvanced disease according to interim results of a phase IIItrial and it should be further evaluated in comparative trials in breastcancer.
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Novel Therapeutic Avenues in Myeloma: Changing the Treatment ParadigmOur better understanding of the complex interaction of multiple myeloma (MM) cells with their bone marrow microenvironment and the signaling pathways that are dysregulated in this process has resulted in a dramatic increase in the therapeutic agents available for this disease. A number of these new agents have demonstrated significant activity in patients with MM. Over the past 5 years, three drugs have received approval from the US Food and Drug Administration for therapy in MM—bortezomib, thalidomide, and lenalidomide. To date, the choice of therapy for MM is not individualized according to the biologic characteristics of the disease, but future studies should enable us to identify patients who may benefit most from certain therapeutic interventions, and thus develop individualized therapy for MM. In this review, we will present some of the treatment algorithms currently developed for patients with MM and focus on established advances in therapy, specifically with thalidomide, bortezomib, and lenalidomide. We will also discuss some of the emerging novel therapeutic agents showing promise in phase I/II clinical trials in MM.
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Acute Myeloid Leukemia in the Elderly: A Unique DiseaseAcute myeloid leukemia (AML) is a disease of the elderly, with the majority of patients diagnosed in their 6th and 7th decade of life. Older patients with AML are less likely to achieve complete remission after induction chemotherapy, and they suffer from higher rates of leukemia relapse compared to younger cohorts. Suboptimal outcomes are the result of adverse biologic characteristics of leukemia in the elderly, as well as the presence of medical comorbidities and patient or physician preferences as to initiating treatment. In addition, there is a distinct lack of randomized, prospective data to guide management decisions for the treatment of AML in the elderly. Patients who are over age 75, with poor performance status, multiple comorbidities, or poor prognostic features, should be considered for a clinical trial or palliative therapy. Elderly patients who are candidates for standard induction chemotherapy and achieve complete remission are unlikely to benefit from intensive postremission therapy and should be referred to a clinical trial when possible. Further prospective trials are needed to identify a tolerable, effective treatment regimen for older patients with AML.
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New Combinations With Epirubicin in Advanced Breast CancerSeveral trials have shown that anthracyclines and taxanes can be combined to achieve response rates ranging from 70% to 90%, with complete responses ranging from 19% to 41%. In an attempt to increase the activity while
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The Diagnosis and Management of Retroperitoneal SarcomaRetroperitoneal sarcoma is a rare tumor whose diagnosis and management can be challenging and for which management requires a multidisciplinary team.
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Gemcitabine and Pemetrexed Disodium in Treating Breast CancerPemetrexed disodium (Alimta, LY231514) is a novel, multitargeted antifolate that inhibits thymidylate synthase, dihydrofolate reductase, and glycinamide ribonucleotide formyl transferase. This agent is broadly active in a wide
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Mutation-Derived Tumor Antigens: Novel Targets in Cancer ImmunotherapyBecause of the abundance of promising preclinical and early-phase clinical data, mutation-derived tumor antigens an exciting new class of targets in cancer immunotherapy.
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Recent Advances With Chemotherapy for NSCLC: The ECOG ExperienceManagement of disseminated non-small-cell lung cancer has changed over the past 10 years. Newer agents, such as vinorelbine (Navelbine) and paclitaxel (Taxol), have been shown to modestly improve survival in patients with
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Synopsis of Angiogenesis Inhibitors in OncologyAngiogenesis is a dynamic process essential for primary tumor growth and metastases. New insights into the basic understanding of the biologic processes responsible for angiogenesis have led to the characterization of potential therapeutic targets. Several strategies for the development of antiangiogenic therapeutic modalities have been employed, including agents that (1) decrease the activity of specific angiogenic factors, (2) decrease the activity of endothelial survival factors, (3) increase the activity of naturally occurring antiangiogenic agents, or (4) indirectly downregulate angiogenic and survival factor activity.
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Pegylated Liposomal Doxorubicin: Antitumor Activity in Epithelial Ovarian Cancer or Cancers of Peritoneal OriginAfter pegylated liposomal doxorubicin (PEG-LD) (Doxil) was shown to be active in ovarian tumors, several trials were developed at the University of Southern California to determine its safety and efficacy in a variety of gynecologic and peritoneal malignancies. Completed phase I and phase II trials have found PEG-LD to be safe and effective in the treatment of platinum- and paclitaxel-refractory epithelial ovarian carcinoma. A new phase II trial is currently underway in similarly refractory patients with ovarian and other related cancers and various degrees of pretreatment. In addition, the efficacy of PEG-LD is being explored in combination with paclitaxel (Taxol), with cisplatin, and with hyperthermia. [ONCOLOGY 11(Suppl 11):38-44, 1997]
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Update on Newer Non–EGFR-Targeted Agents in Non–Small-Cell Lung CancerMSKCC’s Dr. Alexander Drilon highlights other known alterations that are being targeted or being used as biomarkers in non–small-cell lung cancer.
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Docetaxel/Doxorubicin/Cyclophosphamide in the Treatment of Metastatic Breast CancerPreliminary results from phase I trials suggest that the use of docetaxel (Taxotere) and doxorubicin (Adriamycin) is a well tolerated and highly active combination regimen for
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Role of Stereotactic Ablative Radiotherapy in Early-Stage Lung CancerThis video examines the role of radiation therapy in early-stage lung cancer and some of the data comparing stereotactic ablative radiotherapy vs surgery in these patients.
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A Woman With Primary Breast Cancer and a Solitary Sternal MetastasisThe patient presented to her primary care physician 3 months prior with an inverted left nipple and a palpable lump that was highly suggestive of neoplasm on mammogram. An ultrasound-guided core biopsy revealed an infiltrating solid-type ductal carcinoma in situ. The estimated size of the mass was approximately 1 cm. She had no symptoms suggestive of metastatic disease.
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Docetaxel/Doxorubicin/Cyclophosphamide in the Treatment of Metastic Breast CancerA pilot phase II study examined the feasibility of 75 mg/m² of docetaxel (Taxotere) in combination with 50 mg/m²of doxorubicin and 500 mg/m² of cyclophosphamide (Cytoxan, Neosar) in the first-line treatment of metastatic breast cancer. This study was designed to evaluate the efficacy and toxicity of the docetaxel/doxorubicin/cyclophosphamide combination both alone and as induction before high-dose chemotherapy, supplemented by autologous peripheral blood stem-cell transplantation.
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ACR Appropriateness Criteria® Postradical Prostatectomy Irradiation in Prostate CancerThe purpose of this article is to present an updated set of American College of Radiology consensus guidelines formed from an expert panel on the appropriate use of radiation therapy in postprostatectomy prostate cancer.
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Locoregional Recurrence of an HPV-Positive Squamous Cell Carcinoma of the Head and NeckLocoregional recurrences are a major source of morbidity and mortality for patients with squamous cell carcinomas of the head and neck (HNSCC).
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Docetaxel/Doxorubicin/Cyclophosphamide in the Treatment of Metastic Breast CancerA pilot phase II study examined the feasibility of 75 mg/m² of docetaxel (Taxotere) in combination with 50 mg/m²of doxorubicin and 500 mg/m² of cyclophosphamide (Cytoxan, Neosar) in the first-line treatment of metastatic breast cancer. This study was designed to evaluate the efficacy and toxicity of the docetaxel/doxorubicin/cyclophosphamide combination both alone and as induction before high-dose chemotherapy, supplemented by autologous peripheral blood stem-cell transplantation.
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Influence of Aerobic Exercise on QOL During Prostate Cancer TreatmentIn this interview we discuss a study that looked at the effect of an 8-week exercise intervention on treatment side effects for patients with prostate cancer.
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Commentary (Sedlis)-Human Papillomaviruses: Their Clinical Significance in the Management of Cervical CarcinomaCervical cancer, which has claimed over 4,500 deaths annually in the United States and hundreds of thousands of lives in other parts of the world, is a preventable disease. Most cervical cancers are preceded by a prolonged phase of cervical
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A Young Woman With a Small ER-Positive Breast Cancer, a Micrometastatic Axillary Lymph Node, and an Intermediate Oncotype DX Recurrence Scorepatient is a 39-year-old premenopausal woman who presents with a new diagnosis of breast cancer to our multidisciplinary second opinion clinic.
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Modulation of Dose Intensity in Aerodigestive Tract Cancers: Strategies to Reduce ToxicityAdvances in diagnostic and therapeutic radiology and a better understanding of cell biology are being applied in practical ways to modulate treatment morbidity. Conformal radiotherapy targets the cancer precisely and can be combined with new systemically administered radiosensitizers.
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Promoting Smoking Cessation Among Cancer Patients: A Behavioral ModelThe smoking cessation clinical practice guideline recently published by the Agency for Health Care Policy and Research (AHCPR) summarizes current knowledge on smoking cessation treatments. Among its
