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Management of Heavy Chain Diseases: The Challenges of Biologic HeterogeneityIn the absence of a clear understanding of the underlying biologic heterogeneity, the etiology of the different heavy chain diseases (HCDs) should be taken into consideration when treatment decisions are made. Extrapolation from related conditions, such as aggressive lymphomas (in γ-HCD) and CLL (in μ-HCD), suggests that novel and targeted therapies may be effective in the management of these rare diseases.
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Appropriate Management of Molecular Subtypes of Diffuse Large B-Cell LymphomaThe classification of diffuse large B-cell lymphoma into three distinct molecular diseases--germinal center B-cell–like subtype, an activated B-cell–like subtype, and a primary mediastinal B-cell lymphoma subtype--has laid the foundation for the development of new agents and novel strategies that target individual subtypes.
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Cryoglobulinemic DiseaseIn spite of the complicated etiologic, clinical, and pathologic scenario of cryoglobulinemia, physicians can play a key role in its successful management by early recognition of the most common clinical presentations.
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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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Topotecan in Combination With Cisplatin for the Treatment of Stage IVB, Recurrent, or Persistent Cervical CancerTopotecan, a camptothecin analog previously approved for the treatment of ovarian cancer and small-cell lung cancer, was granted regular approval by the US Food and Drug Administration (FDA) on June 14, 2006, for use in combination with cisplatin to treat women with stage IVB, recurrent, or persistent carcinoma of the cervix not amenable to curative treatment with surgery and/or radiation therapy. The purpose of this summary is to review the database supporting this approval.
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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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Efficiency of In Vivo Purging With Rituximab Followed by High-Dose Therapy With Autologous Peripheral Blood Stem Cell Transplantation in B-Cell Non-Hodgkin’s Lymphomas: A Single-Institution StudyHigh-dose therapy (HDT) with peripheral blood stem cell transplantation is a treatment option for patients with advanced follicular, marginal, and mantle cell lymphoma. In this setting, frequent contamination of peripheral blood stem cell harvests by
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In Patients With Colorectal Liver Metastases, Can We Still Rely on Number to Define Treatment and Outcome?The surgical strategies of “classic, reversed, or combined” resection of colorectal cancer and colorectal liver metastases have to be tailored to a specific patient, and all three strategies have a role in the treatment of stage IV colorectal cancer today.
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Panobinostat Regimen Yields Benefit for R/R Myeloma After Frontline ASCTEvidence from a matched pair comparison with a concurrent control cohort suggests that panobinostat plus gemcitabine, busulfan, and melphalan improves progression-free survival in those with relapsed or refractory multiple myeloma, especially after first transplant.
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Surgical Management of Hepatic Breast Cancer MetastasesTremendous gains have been made regarding the treatment of breastcancer. The combination of chemotherapy, radiation therapy, and surgeryhave vastly improved patient course. Hepatic manifestations ofmetastatic breast cancer are extremely difficult to treat. Traditionally,chemotherapy and hormonal treatment of hepatic metastases of breastcarcinoma have not significantly improved survival. For patients withbreast cancer metastases isolated to the liver, operative treatment isincreasingly being used to prolong life and disease-free intervals. Thisarticle reviews the use of surgery for treatment of isolated breast cancermetastases to the liver.
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Targeting Metastatic Colorectal Cancer in 2008: A Long Way From 5-FUColorectal cancer is one of the leading causes of cancer-related death worldwide, with almost 20% of all patients presenting with metastatic disease at the time of their diagnosis. The treatment regimens and options of metastatic colorectal cancer have significantly changed in the last 10 years, leading to an improvement of response rates to about 50%, progression-free survival of about 10 months, and overall survival reaching over 2 years.
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Preclinical Studies Using the Intratumoral Aromatase Model for Postmenopausal Breast CancerTo determine the most effective strategies for the treatment of postmenopausal hormone dependent breast cancer, we recently developed a model system in nude mice. In this model, estrogen receptor-positive human breast cancer cells (MCF-7) stably transfected with the aromatase gene are inoculated into ovariectomized, immunosuppressed (nude) mice.
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Liposomal Doxorubicin in Combination With Bortezomib for Relapsed or Refractory Multiple MyelomaLiposomal doxorubicin received FDA approval for use in combination with bortezomib in patients with multiple myeloma who have not previously received bortezomib and have received at least one prior therapy.
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Epigenetics in Cancer: What's the Future?The understanding that epigenetic changes are prevalent in cancer and play a causative role in its biology has led to the development of new therapeutic approaches that target the epigenetic machinery.
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Further Considerations About Lymphoblastic LymphomaLymphoblastic lymphoma (LBL) is a rare disease, most commonly of T-cell origin, that shares biologic features with acute lymphoblastic leukemia (ALL). Indeed, LBL and ALL are considered a single entity (lymphoblastic leukemia/lymphoma, T and B types) in the World Health Organization (WHO) classification of precursor lymphoid neoplasms.
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Association Between the Rates of Synchronous and Metachronous Metastases: Analysis of SEER DataPatients with cancer are usually staged based on the presence of detectable regional and/or distant disease. However, staging is inexact and cM0 patients may have microscopic metastases (cM0pM1) that later cause relapse and death. Since the clinical tools used to stage patients are fairly similar for different tumors, the ratio of the rates of metachronous to synchronous metastases should be similar for different tumors (hypothesis #1). Improvements in diagnostic tools should have caused the ratio of metachronous-to-synchronous metastases to have decreased over time (hypothesis #2). Finally, the fraction of patients with either metachronous or synchronous metastases should have declined over time due to increased screening and earlier diagnoses (hypothesis #3). To test these hypotheses, Surveillance, Epidemiology, and End Results (SEER) data from 1973-1998 were analyzed for 19 solid tumors. A linear relationship was seen between the rates of metachronous and synchronous metastases, with modestly strong correlation coefficients, consistent with hypothesis #1. Over time, changes in staging methods have not significantly altered the ratio of metachronous/synchronous metastases, contrary to hypothesis #2. Also over time, a decrease in the number of patients with metastases was found, consistent with hypothesis #3. Therefore, the rate of anticipated metachronous metastases can be estimated from the rate of clinically evident metastases at presentation. Changes in screening/staging of disease over time may have reduced the overall fraction of patients with metastases.
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Regional Strategies for Managing Hepatocellular CarcinomaIn his review, Dr. Venook correctly argues that, in the majority of pa;tients, hepatocellular carcinoma results from underlying liver disease; the most common culprit is cirrhosis, which, in turn, is frequently related to hepatitis B and/or hepatitis C exposure and alcohol abuse. Given that patient outcomes are determined by the “interplay between tumor growth and adequate hepatic reserve,” and that most patients with hepatocellular carcinoma eventually die of liver failure, Dr. Venook argues that there is a good rationale for locoregional tumor control of hepatocellular carcinoma. Locoregional therapies may include hepatic intraarterial (HIA) chemotherapy, transarterial chemoembolization, Lipiodol chemo-embolization, radiation therapy (conformal external radiation therapy or intraarterially delivered radiation), or ablative procedures. These therapies are less aggressive than conventional resectional therapies, such as cryosurg-ery, percutaneous ethanol injection, radiofrequency ablation, and other intratumoral therapies.
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Molecular Profiling Assays in Breast Cancer: Are We Ready for Prime Time?In this review, we will present the current data on commercially available molecular profiling assays in breast cancer and discuss the challenges surrounding their incorporation into routine clinical practice as prognostic and predictive tools.
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Decisional Capacity Determination in Patients With CancerExperts discuss the process of assessing decision-making capacity in patients with cancer.
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Epirubicin, Cisplatin, Oral UFT, and Calcium Folinate in Advanced Gastric CarcinomaUFT (uracil and tegafur in a 4:1 molar ratio) plus calcium folinate treatment has favorable activity and tolerable toxicity in patients with advanced gastric carcinoma. High response rates have been reported in patients with
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The Evolution of Liver-Directed Treatments for Hepatic Colorectal MetastasesThis article will review the current practice of hepatic resection for colorectal liver metastases, including the possibility of combined resection of hepatic metastases at the time of resection of the primary cancer.
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Certification offered to rad oncs for care of dying patientsThe American Board of Radiology (ABR) has introduced a certificate in hospice and palliative care.
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Clinical Status of Laparoscopic Bowel Surgery for GI MalignancyLaparoscopic colorectal surgery is being utilized increasingly for benign diseases. Recent published series have proven that morbidity and mortality from laparoscopic procedures are superior to those seen after traditional open
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The Allegheny General Modification of the Harvard Breast Cosmesis Scale for the Retreated BreastRepeat lumpectomy and retreatment radiotherapy following ipsilateral breast tumor recurrence (IBTR) by either external-beam irradiation or brachytherapy in lieu of salvage mastectomy is an area of significant recent clinical interest. Multiple authors have reported their results, with encouraging numbers of patients avoiding mastectomy.[1‑4]
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Refractory Pancreatic Cancer: Searching for Treatment OptionsThe paper by Almhanna and Kim addresses a clinical dilemma in the treatment of pancreatic cancer, for which no standard currently exists. The review article concisely summarizes studies in the second-line setting that have been conducted to date, many of which have been published only in abstract form. The authors organize the studies into tables according to the number of agents in the trials and highlight the response rates and toxicities. The inclusion of study endpoints (both primary and secondary) would have made the tables more informative. In the article, the studies are organized according to the specific agent studied. Several of the studies continue to use gemcitabine (Gemzar) in combination with other agents in the second-line setting, but we have insufficient data to determine that continuing gemcitabine in this setting is worthwhile.
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UFT Plus Carboplatin for Head and Neck CancerCisplatin plus fluorouracil (5-FU) is widely accepted as neoadjuvant and adjuvant chemotherapy in the treatment of head and neck squamous cell carcinoma; UFT is also an active agent against this disease. In the first retrospective study, we examined the efficacy of UFT as adjuvant chemotherapy in patients with maxillary cancer.
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Combination Therapy for Advanced Breast Cancer: Cyclophosphamide, Doxorubicin, UFT, and TamoxifenWe evaluated combination therapy for advanced and recurrent breast cancer with cyclophosphamide (Cytoxan), doxorubicin (Adriamycin), uracil and tegafur (UFT), and tamoxifen (Nolvadex) (CAUT), designed as
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UFT and Mitomycin Plus Tamoxifen for Stage II, ER-Positive Breast CancerA trial was designed to examine the combination of UFT and mitomycin (Mutamycin) plus tamoxifen (Nolvadex) as postoperative adjuvant therapy in the treatment of patients with stage II, estrogen receptor (ER)-positive
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UFT Plus Carboplatin for Head and Neck CancerCisplatin plus fluorouracil (5-FU) is widely accepted as neoadjuvant and adjuvant chemotherapy in the treatment of head and neck squamous cell carcinoma; UFT is also an active agent against this disease. In the first retrospective study, we examined the efficacy of UFT as adjuvant chemotherapy in patients with maxillary cancer.
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Endocrine Plus Uracil/Tegafur Therapy for Prostate CancerA prospective, randomized clinical trial was conducted to evaluate the efficacy of endocrine chemotherapy with uracil and tegafur (in a molar ratio of 4:1 [UFT]) in patients with prostate cancer. The study included two
