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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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Commentary (Cabanillas)-Follicular Lymphoma: Expanding Therapeutic OptionsIn their manuscript, Ganti et al tackle a very intricate and controversial subject: follicular non-Hodgkin’s lymphoma (NHL). The manuscript attempts to exhaustively cover multiple aspects of the disease, including pathology, prognostic factors, natural history, treatment of early-stage as well as advanced disease, relapsed disease, newer agents, monoclonal antibodies, interferon, radioimmunotherapy, stem cell transplantation, and future directions. To review all these topics thoroughly would almost require a textbook. To meticulously cover all of these aspects in a review article is a nearly impossible task. From my standpoint as a reviewer, to critique this article is an equally complicated task. I will therefore focus on only a few major issues.
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Extended Transbasal Approach to Skull Base TumorsA variety of novel surgical approaches have been developed in recentyears to manage disease of the cranial base. Few offer the widthand depth of exposure achievable with the extended transbasal approach.This approach combines a bifrontal craniotomy with anorbitonasal or orbitonasoethmoidal osteotomy, and potentially asphenoethmoidotomy to provide broad access to malignancies of theanterior, middle, and posterior skull base. The approach enables the enbloc resection of tumors within the frontal lobes, orbits, paranasal sinuses,and sphenoclival corridors without brain retraction and mayobviate the need for transfacial access. This can be combined with additionalapproaches, based on the tumor's epicenter. Reconstruction isaccomplished with the use of pericranium, and in some instances, atemporalis muscle pedicle or a gracilis microvascular free flap. Complicationsinclude cerebral spinal fluid leakage, pneumocephalus, infection,and cranial neuropathies. However, the morbidity and mortalityassociated with this approach is low. The extended transbasal approachis a relatively novel exposure that enables the skilled cranialbase surgeon to safely excise many malignant lesions previously felt tobe unresectable.
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Renal Cancer Management in a Patient With Chronic Kidney DiseaseA 69-year-old man presented in the urology clinic for evaluation of bilateral renal masses, discovered incidentally during routine exams for follow-up of his chronic kidney disease.
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A Phase II Study of Doxorubicin/Paclitaxel Plus G-CSF for Metastatic Breast CancerThis phase II trial was conducted to evaluate the percentage of objective responses and the toxicity profile of combination doxorubicin (Adriamycin) and paclitaxel (Taxol) with granulocyte colony-stimulating factor as first-line
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Pemetrexed in Second-Line Treatment of Non–Small-Cell Lung CancerAccording to the updated 2004 guidelines of the American Societyof Clinical Oncology (ASCO) on the treatment of advanced non–smallcelllung cancer (NSCLC), docetaxel (Taxotere) can be considered thestandard second-line chemotherapy in patients relapsing after frontlinetherapy. This was based on two phase III trials (TAX 317 and TAX320) that demonstrated the superiority of docetaxel at 75 mg/m2 in theparameters of survival, quality of life, and disease/symptom controlwhen compared to best supportive care or alternative single-agent chemotherapy.The response rate was approximately 6%, with a mediansurvival time of 7 months and a 1-year survival rate of 30%. Despitethe activity demonstrated, this schedule showed an important toxicityprofile, with grade 3/4 neutropenia and febrile neutropenia occurringin 70% and 11% of patients, respectively. However, the results obtainedby these studies stimulated research interest in new drugs for this diseasesetting. Pemetrexed (Alimta), a new multitargeted antifolate, hasachieved promising results in NSCLC treatment, as a single agent or incombination with other drugs. In the second-line setting, a large phaseII study demonstrated good activity of pemetrexed, with an acceptabletoxicity profile. This led to a phase III registration trial that comparedpemetrexed at 500 mg/m2 to the standard docetaxel dose of 75 mg/m2.While results from this trial demonstrated a similar efficacy of the tworegimens in response rate and survival, pemetrexed achieved a bettersafety profile. These results support the use of pemetrexed as a newoption in the second-line treatment of NSCLC.
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The Benefits of Achieving Stable Disease in Advanced Lung CancerDr. Karen Kelly has written atimely discussion on the clinicalbenefit of achieving stabledisease in advanced non–smallcelllung cancer (NSCLC). The goalsof current therapy are to palliate symptoms,optimize quality of life (QOL),and prolong survival. It is argued thattumor shrinkage may not be mandatoryto achieve these goals, particularlyin the evaluation of moleculartargeted therapies that may be cytostaticrather than cytotoxic in theirmechanism of action. However, stabledisease is not regarded as evidenceof therapeutic efficacy byregulatory authorities. Furthermore, ifbased on radiologic measurements Continued on page 968.alone, this designation encompasses aheterogeneous population that includespatients who demonstrate unequivocaltumor shrinkage as well asmany with tumor growth. Therefore,the case is presented to define stabledisease in terms of clinical benefit byincorporating alternative trial endpoints such as symptom control, QOL,or biologic end points.
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Commentary (Sahebi/Forman): The Role of Hematopoietic Stem Cell Transplantation in Myelodysplastic SyndromeDrs. Thompson and Luger have written a thoughtful and comprehensive review of the therapeutic options and issues facing physicians caring for patients with myelodysplastic syndrome (MDS). In our commentary, we would like to highlight and expand on several areas of their analysis.
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Nuclear Medicine Imaging in Breast Cancer: Current Strategies and Future DirectionsThe article “PET Scan in the Diagnosis and Management of Breast Cancer” by Jame Abraham and coworkers is a complete, updated review of the existing scientific literature about clinical indications for positron-emission tomography (PET) in this malignancy.
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Late Toxicity of Radiotherapy and Chemotherapy in Hodgkin LymphomaThis interview examines treatment-related cardiotoxicity and the risk of second malignancy in patients with Hodgkin lymphoma.
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Management of Infusion Reactions in Clinical Trials and Beyond: The US and EU PerspectivesInfusion reactions (IRs) can be broadly categorized by their immunologic mechanism. Anaphylaxis is a systemic, immediate hypersensitivity reaction mediated by factors released from interactions between immunoglobulin E (IgE) and mast cells that produce an antigen-antibody reaction.[1] Anaphylactoid reactions can be differentiated from anaphlaxis by the fact that they are not IgE-mediated but rather cytokine-mediated.
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Simultaneously Detected Bilateral Testicular Cancer of Different Histopathological OriginA 36-year-old male with a history of cryptorchidism of the right side, treated with orchidopexy at the age of 4, presented with bilateral testicular swelling. Investigations included laboratory workup, ultrasound of both testes, as well as CT-scan of the chest, abdomen, and pelvis. Initial treatment was bilateral orchiectomy.
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Dealing With Ethical Dilemmas in Oncological Communication Involving Issues of Culture and AutonomyBeginning with its provocative opening case vignette, Nathan Cherny's article provides an opportunity for us to reflect on and possibly redirect our own attitudes and habits regarding difficult ethical issues in communication with our patients and their families, especially in the setting of cultural and religious diversity.
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Anti-Angiogenesis Therapy in Gynecologic MalignanciesThe purpose of this paper is to provide a review of site-specific treatment options that involve the targeting of angiogenesis in gynecologic malignancies.
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Next gen EGFR targeting drug promising in NSCLCFinding an effective treatment for all the complex iterations of cancer is akin to chasing an outlaw through a treacherous mountain range, in the estimation of Louis M. Weiner, MD, director of the Georgetown Lombardi Comprehensive Cancer Center in Washington, DC.
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Pregnancy After Breast Cancer: From Psychosocial Issues Through ConceptionWomen face numerous issues if they either contemplate childbearing or become pregnant after the diagnosis of breast cancer. Based on a search of the English medical literature from 1966 to 1997, we make the following
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Current Paradigms in First-Line Treatment of Non–Small-Cell Lung CancerStandard first-line chemotherapy for the majority of patients withadvanced non–small-cell lung cancer (NSCLC) consists of platinumbasedcombination regimens including one of the newer-generationagents, such as gemcitabine (Gemzar), a taxane, vinorelbine(Navelbine), or irinotecan (Camptosar). Several effective regimens areavailable, the choice of which will depend on treatment goals, individualpatient or disease factors, as well as physician preferences. Thispaper surveys randomized trials of many of the newer-generation chemotherapycombinations in patients with advanced NSCLC to examineseveral issues, such as which new-generation regimen to use, whethera platinum agent is needed, the optimal number of drugs in the combination,and treatment duration.
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Prostate Cancer in a Man With Multiple Previous Cancerspatient is a 67-year-old male with mild obstructive symptoms and an American Urology Association symptom score of 8.[1] He was noted to have a prostate-specific antigen (PSA) level of 3.2 ng/mL. Because this represented a significant increase in his PSA velocity (rate of change over time), he proceeded to have a biopsy, which was positive for prostate cancer. He has no other complaints and visits us for an opinion on the treatment of his prostate cancer.
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Anthracycline vs Nonanthracycline Adjuvant Therapy for Breast CancerThe treatment of breast cancer has progressed substantially overthe past 15 years. Data from randomized adjuvant trials have shownthat the risk of disease recurrence and death is significantly reducedwhen adjuvant chemotherapy and/or hormonal therapy is added to treatment.As new strategies are incorporated, one of the continued controversiesin patient management is whether adjuvant anthracyclinesshould be the preferred treatment for all patients. Data from randomizedand translational clinical trials have become available and arehelping to elucidate the proper role of anthracyclines, as well as their acuteand long-term toxicities. In most situations, an anthracycline is currentlypreferred, but other single and combination chemotherapies arecurrently under evaluation and appear promising for use in the adjuvantsetting. Continued breast cancer research using molecular markers(such as topoisomerase II–alpha and gene clusters) as predictors oftreatment response, could help individualize decisions regardingwhether to incorporate anthracyclines into adjuvant therapy regimens.
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Diffusion-weighted MRI looks to add new biomarker for oncologic imagingThe technique provides a new and continuously evolving tool in oncologic imaging for lesion detection, characterization, and therapy assessment.
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Gemcitabine and Cisplatin Combination in Early-Stage Non-Small-Cell Lung CancerA number of randomized clinical trials now support the conclusion that the combined-modality regimen that includes gemcitabine (Gemzar) and cisplatin (Platinol) may improve survival in disseminated non-small-cell lung
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Gemcitabine/Epirubicin/Paclitaxel Trials in Advanced Breast CancerNumerous trials have shown that the pharmacokinetic interferences of epirubicin (Ellence)/paclitaxel (Taxol) combinations produce less pharmacodynamic effect than doxorubicin/paclitaxel regimens. Paclitaxel is more easily
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The Management of Nongastric MALT LymphomasNo definite guidelines exist for the management of nongastric MALT lymphoma. Retrospective series have included patients treated with different modalities, and excellent cause-specific and overall survival have been demonstrated, independent of the type of treatment adopted.
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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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Current Perspectives on Preoperative Integrated Treatments for Locally Advanced Rectal Cancer: A Review of Agreement and ControversiesThe preferred integrated treatment modality for locally advanced rectal cancer is preoperative radio(chemo)therapy followed by total mesorectal excision, though certain aspects of this standard are still debated.
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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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POINT: Is Lymphadenectomy Required in Endometrial Cancer for Adequate Surgical Staging?The diagnostic benefits of SLN evaluation include an ability to identify the extent of tumor dissemination and the utility of SLN mapping in guiding targeted adjuvant treatment in high-risk patients.
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The Importance of Accurately Characterizing Lymphoproliferative DiseaseThe primary cutaneous CD30-positive (CD30+) T-cell lymphoproliferative disorders are a group of largely indolent diseases that manifest as nodules or tumors of the skin. The European Organisation for Research and Treatment of Cancer (EORTC) has developed a modification of the World Health Organization (WHO) lymphoma classification system that specifically categorizes these entities.
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Response of the Normal Eye to High Dose RadiotherapyRadiation therapy of tumors near the eye or optic nerves often requires incidental irradiation of these structures, even when they are not clinically involved by tumor. Depending on the radiation treatment volume and dose required, radiation injury to the lens, lacrimal apparatus, retina, or optic nerve may result. The time to expression and severity of injury are dose-dependent. This paper reviews the results of 157 patients who were followed for a minimum of 3 years after radiotherapy for primary extracranial tumors at the University of Florida, in which the lacrimal gland, lens, retina, and/or optic nerve(s) received irradiation. This review shows that, after treatment at approximately 1.8 to 2.0 Gy per fraction, the incidence of severe dry-eye syndrome, retinopathy, and optic neuropathy appears to increase steeply after doses of 40, 50, and 60 Gy, respectively. [ONCOLOGY 10(6):837-852, 1996]
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Is Personalized Medicine Here?This review describes the achievements in therapeutic and molecular diagnostics, details evolving molecular platforms, and highlights the challenges for the translation of these developments to daily clinical practice.
