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Chemotherapy for Brain TumorsTraditionally, cytotoxic drugs have played a limited role in the treatment of brain tumors, but important advances in chemotherapy have occurred during the past decade. Certain central nervous system (CNS) malignancies are
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UFT Plus Leucovorin for Metastatic Colorectal Cancer: Japanese ExperienceIn the United States and Europe, the combination of oral UFT plus leucovorin has been reported to produce objective responses and survival rates similar to those achieved with standard intravenous 5-fluorouracil plus leucovorin in patients with metastatic colorectal cancer, with reduced toxicity.
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Current Clinical Trials of R115777 (Zarnestra)R115777 (Zarnestra) is an orally available methylquinolone derivative from Johnson & Johnson Pharmaceutical Research and Development L.L.C. that is a potent and selective nonpeptidomimetic farnesyltransferase inhibitor (FTI).[1] FTIs represent a new class of agents that were originally developed to inhibit tumors by interfering with posttranslational processing of oncogenic Ras protein. The anticancer activity of FTIs might stem from their ability to effect various proteins other than Ras that can also mediate signal transduction, apoptosis, angiogenesis, and growth.[2]
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New Therapeutic Options for Chronic Lymphocytic LeukemiaFor decades, initial therapy for chronic lymphocytic leukemia (CLL) consisted of alkylators such as chlorambucil (Leukeran). The introduction of nucleoside analogs such as fludarabine and monoclonal antibodies such as rituximab (Rituxan) markedly changed the initial therapy of CLL, particularly in the United States. Fludarabine and combination regimens such as fludarabine/cyclophosphamide (FC) have achieved higher complete response (CR) rates and progression-free survival (PFS) than chlorambucil in previously untreated CLL, but long-term overall survival has not improved, due to concurrent improvement in salvage therapy of relapsed CLL patients. Upfront chemoimmunotherapy regimens such as fludarabine/rituximab (FR) and fludarabine/cyclophosphamide/rituximab (FCR) have similarly improved CR rates and PFS in previously untreated CLL patients, but it is unclear whether overall survival is improved. Advances in cytogenetic analysis and other biologic prognostic factors have greatly enhanced clinicians' ability to risk-stratify newly diagnosed CLL patients, and knowledge of such prognostic factors is necessary to properly interpret results of clinical treatment studies. The choice of initial therapy for an individual patient should depend upon the patient's age and medical condition, cytogenetic and other prognostic factors, and whether the goal of therapy is maximization of CR and PFS or palliation of symptoms with minimal toxicity.
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Gleason 6 Cancer Is Still CancerAs long as there is any risk of progression, G6 cancer cannot be equated to just a precursor lesion, and the emphasis should remain on screening patients with serum PSA measurement, contrary to the recommendation of the US Preventive Services Task Force.
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Choices in the Treatment of Cutaneous T-Cell LymphomaMycosis fungoides is responsive to treatment in the early stages; patients have a long duration of survival but are rarely cured of the disease. Therefore, patients require long-term, sequential therapies with as little toxicity as possible. In the early stages, skin-directed therapies, such as psoralen plus ultraviolet A in combination with retinoids or interferon, generally produce good, long-term responses. Once the disease progresses, systemic agents such as cytokines and retinoids are introduced. The cytokines provide a rational treatment approach for cutaneous T-cell lymphoma (CTCL) and produce good, long-lasting responses with few immunosuppressant effects. Denileukin diftitox (Ontak) has also been shown to produce good treatment effects, and its toxic effects can usually be controlled using prophylactic therapies. The synthetic retinoid bexarotene (Targretin) is taken orally and produces high response rates in CTCL, with a good long-term tolerability profile. Conventional systemic chemotherapies produce rapid responses and high response rates in CTCL, but these are generally of short duration and accompanied by myelosuppression and immunosuppression. Current treatment strategies therefore consist of the use of initial skin-directed therapies, with the addition of low-toxicity systemic biologic agents as the disease progresses; patients who do not respond to biologic agents should then receive conventional chemotherapies, starting with single agents and progressing to combination therapies.
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GM-CSF and Low-Dose Cytosine Arabinoside in High-Risk, Elderly Patients With AML or MDSPriming of leukemic cells with cytokines may enhance the efficacy of cell-cycle chemotherapy. In this study, we utilized these synergistic effects of granulocyte-macrophage colony-stimulating factor (GM-CSF, sargramostim [Leukine]), hydroxyurea, and low-dose cytosine arabinoside to treat elderly patients with acute myelogenous leukemia (AML) or myelodysplastic syndrome (MDS). In a single-institution, retrospective study, we evaluated 94 treatments with concomitant hydroxyurea, cytosine arabinoside, and GM-CSF between the years of 1997 and 2003 in high-risk elderly patients with AML or MDS. A total of 80% of patients received all of the GM-CSF doses; 78% of patients received all of the cytosine arabinoside doses. Adverse events were minimal. No patient developed mucositis or alopecia. The most common adverse event was neutropenic fever, which was noted in 57% of patients. Twenty-one percent of patients remained neutropenic after treatment until death or relapse. Sixty-eight percent of patients reached an absolute neutrophil count of greater than 1,000 μL in a median of 33.5 days. Our data show an overall response rate of 52%, with a complete response rate of 39% and a partial response rate of 13%. Overall, our study showed that low-dose cytosine arabinoside given by continuous infusion together with continuous infusion GM-CSF and hydroxyurea was well-tolerated and effective in treating elderly AML and MDS patients who were not eligible for standard induction therapy.
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ACR Appropriateness Criteria® Recurrent Hodgkin LymphomaBy combining the most recent medical literature and expert opinion, this revised guideline can aid clinicians in the complex decision-making associated with the management of recurrent Hodgkin lymphoma.
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Changing the ParadigmONCOLOGY recently sat down with Kenneth C. Anderson, MD, to discuss the current trends in multiple myeloma treatment, and the explosion of novel therapies that are paving the way to better and more durable outcomes and allowing patients to live longer and more meaningful lives.
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Plastic Surgery: A Component in the Comprehensive Care of Cancer PatientsThis article underscores what I believe is an important concept in the current state of the art of cancer therapy-namely that reconstructive plastic surgery is a key component in the treatment of many cancer patients. Clearly, the treatment of advanced-stage malignancies is now interdisciplinary, multimodal, and comprehensive. Chemotherapy and radiation therapy are becoming increasingly complementary modalities in the treatment of patients with more advanced disease.
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ACR Appropriateness Criteria® Nonsurgical Treatment for Locally Advanced Non–Small-Cell Lung Cancer: Good Performance Status/Definitive IntentThe treatment of inoperable stage III non–small-cell lung cancer (NSCLC) remains a challenge due to high rates of distant metastasis, local recurrence, and toxicity associated with definitive therapy.
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The Multidisciplinary Management of Paragangliomas of the Head and Neck, Part 2Paragangliomas most commonly occur in the carotid body, jugulotympanicarea, and vagus nerve but have also been reported in otherareas of the head and neck. These tumors are highly vascular andcharacteristically have early blood vessel and neural involvement,making their treatment particularly challenging. Surgery has traditionallybeen the preferred method of treatment, especially in light of recentadvances in technique. However, compared to radiation therapy, it canresult in a higher incidence of cranial nerve dysfunction. Radiationtherapy has the advantage of avoiding the increased morbidity ofsurgery while offering an equal possibility of cure. Part 2 of this articlediscusses radiation therapy as primary treatment of patients who areineligible for surgery and the elderly and infirm. Results with radiotherapyare comparable to those achieved with surgery. The efficacy ofsalvage therapy with either surgery or radiation is discussed, and atreatment algorithm for these tumors is proposed.
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Challenges to the FDA Review Process: Cost Considerations and Long-Term Benefit BenchmarksIn this interview, Christopher-Paul Milne and Kenneth Kaitin, Tufts Center for the Study of Drug Development. discuss the current challenges of the US Food and Drug Administration review process as it relates to oncology therapeutics and upcoming changes to the Prescription Drug User Fee Act.
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Commentary (Cohen/Glod): Current Management of Childhood EpendymomaEpendymoma is a rare central nervous system (CNS) tumor in children, and our progress in treating this disease has been hampered by its rarity as well as by a nonuniform approach to treatment among practitioners. Dr. Merchant’s comprehensive review provides a framework for plotting a course of further progress in treating children with ependymoma.
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Further Thoughts on a Rare EntityPrimary neuroendocrine neoplasms of the lung represent a clinical spectrum of tumors ranging from the relatively benign and slow-growing typical carcinoid to the highly aggressive small-cell lung carcinoma. The rarity of carcinoids has made the role of radiation therapy in their management controversial. This review considers the results of published studies to generate treatment recommendations and identify areas for future research. Surgery remains the standard of care for medically operable disease. Histology plays the most important role in determining the role of adjuvant radiation. Resected typical carcinoids likely do not require adjuvant therapy irrespective of nodal status. Resected atypical carcinoids and large-cell neuroendocrine carcinomas have a significant risk of local failure, for which adjuvant radiation likely improves local control. Definitive radiation is warranted in unresectable disease. Palliative radiation for symptomatic lesions has demonstrated efficacy for all histologies. Collaborative group trials are warranted.
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Use of Bisphosphonates in the Treatment of Prostate CancerRecently, there has been much controversy over whether patients with prostate cancer should be treated with bisphosphonates not only to decrease pain, but to prevent metastasis.
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Commentary (Wang): Endoscopic Ultrasound Fine-Needle Aspiration in the Staging of Non-Small-Cell Lung CancerPrecise mediastinal staging of non-small-cell lung cancer is extremely important, as mediastinal lymph node metastases generally indicate unresectable disease. Reliance on computed tomography (CT) and positron-emission tomography (PET) alone to stage and determine resectability is limited by false-positive results. Whenever possible, pathologic confirmation of metastases is desirable. Mediastinoscopy and transbronchial fine-needle aspiration are widely established but imperfect modalities. Endoscopic ultrasound fine-needle aspiration (EUS-FNA) has emerged as a diagnostic and staging tool because of its safety, accuracy, and patient convenience. We reviewed 13 prospective studies evaluating the comparative performance of EUS for staging lung cancer. We conclude that EUS is a valuable staging modality. Further studies of the role of EUS compared to other modalities such as integrated PET/CT and endobronchial ultrasound (EBUS) are forthcoming.
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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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Whole-Genome Analyses and Circulating Tumor DNA Approaches in CancerIn this interview we discuss advances in whole-genome analyses, as well as novel blood-based assays in development to help diagnose and follow cancer patients through their treatment.
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Genetic Testing in Gastrointestinal Cancers: A Case-Based ApproachIn this article, we use a case-based approach to focus on the hereditary aspects of the most common GI cancers, including pancreatic, gastric, and colon cancer.
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Gemcitabine, Paclitaxel, and Trastuzumab in Metastatic Breast CancerA phase II trial evaluated the effectiveness and toxicity of combination paclitaxel (Taxol), gemcitabine (Gemzar), and trastuzumab (Herceptin) as first-line therapy for patients with newly diagnosed HER2-overexpressing
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ASCO: Pros/Cons of Follow-Up Imaging in LymphomaAs part of our coverage of the 2014 American Society of Clinical Oncology (ASCO) Annual Meeting, we discuss the pros and cons of follow-up imaging in lymphoma.
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Weekly Irinotecan and Concurrent Radiation Therapy for Stage III Unresectable NSCLCIn preclinical studies, the topoisomerase I inhibitor irinotecan (Camptosar, CPT-11) has demonstrated activity as a radiosensitizer, probably due to its ability to inhibit potentially lethal radiation damage repair. We conducted a
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Intravenous Itraconazole in the Management of Fungal Infections in Bone Marrow TransplantationThe frequency of major fungal infections continues to increase, whether in association with increasing numbers of patients at risk due to under lying disease or its treatment, selection pressures related to increased use of broad-spectrum antimicrobials
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Stereotactic Body Radiation Therapy as an Alternative to Surgery in Early-Stage Non–Small-Cell Lung CancerThree randomized trials of SBRT vs surgical resection closed due to poor accrual, but an analysis of patients treated in these trials suggested that SBRT might even be superior to surgery. New trials are underway to further assess the question of whether SBRT can be the definitive treatment for early-stage NSCLC instead of surgery.
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Bone marrow procedures move into the 21st centuryMore than 700,000 biopsies are performed in the U.S. every year, but the technology has not always kept pace with cancer diagnosis and therapy. A new technique allows rapid and easy access to the marrow space.
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Current Treatment of Infection in the Neutropenic PatientNeutropenia was recognized almost 3 decades ago as a major predisposing factor for the development of infection in patients with cancer [1]. The risk begins to increase when the neutrophil count drops below 1,000/mm³ and is greatest at counts of 100/mm³ or lower. At this level, approximately 20% of febrile episodes are caused by a bacteremic process [2].
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Handbook of Gynecologic OncologyHandbook of Gynecologic Oncology, edited by Drs. Barakat, Bevers, Gershenson, and Hoskins, is a first-edition clinical handbook formulated primarily for fellows in gynecologic oncology as well as for interested fellows in medical oncology and radiation oncology. The textbook presents concise summaries of the critical issues in the care of gynecologic cancer patients and would also be of interest to residents preparing for their gynecologic oncology rotations, obstetrician/gynecologists, other physicians who care for gynecologic cancer patients, and practicing gynecologic oncologists.
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Current Management of Adult T-Cell Leukemia/LymphomaAdult T-cell leukemia/lymphoma (ATL) is defined as a histologically or cytologically proven peripheral T-cell malignancy associated with a retrovirus, human T-cell lymphotropic virus type I (HTLV-1).[1] Southwestern Japan is the district with the highest prevalence of HTLV-1 infection and the highest incidence of ATL in the world. A high prevalence of HTLV-1 infection is also found in the Caribbean islands, tropical Africa, South America, and northern Oceania.
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Current Issues in the Treatment of Resistant Bloodstream InfectionsBloodstream infections cause significant morbidity and mortality for patients with hematologic malignancy. Antimicrobial drugs are the most reliable currently available treatment for infection, but several issues must be
