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Commentary (Flores/Rusch): Diffuse Malignant Mesothelioma of the Pleural Space and Its ManagementDrs. Zellos and Sugarbaker nicely summarize the current treatment strategies for malignant pleural mesothelioma. The management of this disease remains controversial, and several aspects of the review merit discussion.
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Successful Diagnosis and Treatment of Occult Prostate Cancer Despite Multiple Negative Prostate Biopsies and Negative Prostate MRIsDr. Judd W. Moul, MD, and colleagues present the case of a man, aged 73 years, with a prostate-specific antigen level of 110 ng/mL after 4 negative prostate biopsies and 4 negative prostate MRIs.
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Commentary (Roy/Rai)-Chronic Myeloid Leukemia: Changing the Treatment ParadigmsMolecular discoveries and clinical advances over the past few decades have made the treatment of chronic myeloid leukemia (CML) one of the great success stories of modern medicine. Before the 1980s, the focus was on maintaining normal white blood cell counts with agents such as hydroxyurea and busulfan. With the use of interferon, treatment strategies turned more toward cytogenetic remission. In 1998, targeted therapy was introduced to this setting with the first studies of imatinib mesylate. Since then, treatment objectives have shifted toward the attainment of molecular remission. In this review, we consider the variety of approaches to treating CML, efforts to minimize treatment failures, and possible future directions in therapy.
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Management of Acute Promyelocytic Leukemia: Implications for Treatment of Other CancersThe article by Drs. Stein and Tallman is an excellent summary indicating that several different approaches may lead to the cure of acute promyelocytic leukemia (APL).
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Esophageal CancerThis comprehensive guide for oncologists covers the diagnosis, staging, treatment, and management of esophageal cancer.
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Erlotinib/Gemcitabine for First-Line Treatment of Locally Advanced or Metastatic Adenocarcinoma of the PancreasErlotinib (Tarceva) is a human epidermal growth factor receptor type 1/epidermal growth factor receptor (HER1/EGFR) tyrosine kinase inhibitor initially approved by the US Food and Drug Administration for the treatment of patients with locally advanced or metastatic non–small-cell lung cancer after failure of at least one prior chemotherapy regimen. In this report, we present the pivotal study that led to the approval of erlotinib in combination with gemcitabine (Gemzar) in patients with locally advanced/metastatic chemonaive pancreatic cancer patients. The combination demonstrated a statistically significant increase in overall survival accompanied by an increase in toxicity. Physicians and patients now have a new option for the treatment of locally advanced/metastatic adenocarcinoma of the pancreas.
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Personalized Medicine for Non–Small-Cell Lung CancerIt is estimated that more than 1.5 million individuals in the United States will be diagnosed with cancer this year. Of these, nearly 145,000 will be diagnosed with non–small-cell lung cancer (NSCLC).
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Targeted Therapy in Rectal CancerEpidermal growth factor receptor (EGFR) and vascular endothelial growth factor (VEGF) are often overexpressed in colorectal cancer and are associated with inferior outcomes. Based on successful randomized phase III trials, anti-EGFR and anti-VEGF therapeutics have entered clinical practice. Cetuximab (Erbitux), an EGFR-specific antibody, is currently approved in the United States in combination with irinotecan (Camptosar) for patients with metastatic colorectal cancer refractory to irinotecan or as a single agent for patients unable to tolerate irinotecan-based therapy. In retrospective analyses, patients with EGFR-expressing rectal cancer undergoing neoadjuvant radiation therapy had a significantly inferior disease-free survival and lower rates of achieving pathologic complete response. Based on the positive data in metastatic colorectal cancer and synergy with radiation therapy seen in preclinical models, there is a strong rationale to combine cetuximab with neoadjuvant radiation therapy and chemotherapy in rectal cancer. Bevacizumab (Avastin), a VEGF-specific antibody, was the first antiangiogenic agent to be approved in the United States for use in combination with standard chemotherapy in the first- and second-line of treatment in metastatic colorectal cancer. VEGF-targeted therapy may lead to indirect killing of cancer cells by damaging tumor blood vessels, and may increase the radiosensitivity of tumor-associated endothelial cells. VEGF blockade can also "normalize" tumor vasculature, thereby leading to greater tumor oxygenation and drug penetration. This review will address completed and ongoing trials that have established and continue to clarify the effects of these agents in rectal cancer.
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Changing Concepts in the Management of Endometrial CancerThe authors present the major issues and controversies surrounding the treatment of endometrial cancer. A variety of therapeutic approaches have been used in the past, including surgery alone, preoperative radiation and surgery, surgery and
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Continuous Low-Dose GM-CSF as Salvage Therapy in Refractory Recurrent Breast or Female Genital Tract CarcinomaGranulocyte-macrophage colony-stimulating factor (GM-CSF,sargramostim [Leukine]) is a powerful cytokine that is able to stimulatethe generation of dendritic cells. Adjuvant treatment with continuous lowdoseGM-CSF has been shown to prolong survival of stage III/IV melanomapatients. Data on continuous low-dose GM-CSF therapy in tumorsother than prostate cancer are still lacking.
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Pemetrexed in Advanced NSCLC: A Review of the Clinical DataThe novel multitargeted antimetabolite pemetrexed (Alimta), recentlyapproved by the US Food and Drug Administration for the treatment ofmesothelioma when combined with cisplatin, is also active in first- andsecond-line non–small-cell lung cancer (NSCLC). In a phase III trialcomparing single-agent pemetrexed vs docetaxel (Taxotere) as secondlinetherapy in advanced NSCLC, survival was shown to be comparablebetween these agents, but side effects were significantly less frequentand severe for patients who received pemetrexed. In the frontlinesetting, phase II studies have shown significant activity and a veryfavorable toxicity profile of the combination of pemetrexed with a platinumagent. Pemetrexed has been well tolerated at systemic doses as aradiosensitizer when given as concurrent chest radiation, and a phaseI study is under way to assess its tolerability in combination withcarboplatin (Paraplatin) in this setting. Pemetrexed is an importantaddition to the armamentarium of medicines used to treat thoracicmalignancies, and merits study in combination with other drugs havingnovel mechanisms of action.
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Pancreatic Cancer: Recognizing an Hereditary PredispositionAlthough candidate genes for hereditary pancreatic cancer have been identified (Figure 1), namely p16 and BRCA2, pancreatic cancer patients having an inherited predisposition will not be easy to recognize on clinical grounds.
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Prostate Cancer Immunotherapy: Promising BeginningsThere has been a resurgence of interest in developing noncytotoxic immune therapies for patients with either hormone-naive biochemically relapsed post-primary therapy or castrate metastatic prostate cancer. The rationale for developing an immunotherapeutic approach has been based on the overexpression and underglycosylation of a wide variety of altered "self" molecules including prostate-specific antigen (PSA), acid phosphatase (ACP), prostate stem cell antigen (PSCA), and prostate-specific membrane antigen (PSMA), which can serve as targets for immune recognition and attack. In addition, such a strategy could theoretically make use of the patient's immune system to fight the tumor particularly if their disease is of reasonably low volume. A variety of immunotherapeutic approaches have been explored through phase I, II, and now phase III trials demonstrating that immunologic tolerance could be broken, as evidenced by the development of high-titer antibodies and T-cell responses specific for the tumor. What appears to be revolutionizing the immunotherapy field is the combination of vaccines with cytokines or immune modulators, which not only potentiate immune reactivity in vivo but foster dramatic antitumor responses. This review explores the challenges now faced in establishing a role for immune therapies for prostate cancer treatment.
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Surgical Approach to Organ Preservation in the Treatment of Cancer of the LarynxThe article by Dr. Weinstein is a discussion of the newer surgical options available for the treatment of patients with laryngeal cancer. Several aspects of the article deserve mention.
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Gestational Trophoblastic TumorsGestational trophoblastic tumors (GTTs) encompass a spectrum of neoplastic disorders that arise from placental trophoblastic tissue after abnormal fertilization. GTTs are classified histologically into four distinct groups: hydatidiform mole (complete and partial), chorioadenoma destruens (invasive mole), choriocarcinoma, and placental site tumor [1,2].
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Predicting Prognosis in Patients With Superficial Bladder CancerBladder cancer is the most common urologic malignancy and is expected to affect approximately 54,000 people in 1998. Superficial bladder tumors (Tis, Ta, and T1 lesions) account for approximately 70% to 80% of these
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Next-Generation Sequencing for Lung Cancer in Clinical PracticeThis video highlights some of the latest developments guiding precision medicine for lung cancer in clinical practice.
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Optimizing Radiotherapy With Immunotherapy in Lung Cancer TreatmentThis video examines how the use of radiation therapy in patients on immunotherapy can trigger immunogenic cell death, and reviews some of the challenges related to unwanted immune responses from radiotherapy.
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Hypersensitivity Reactions to Oxaliplatin: Incidence and ManagementOxaliplatin (Eloxatin) is a novel platinum compound that has activityin a wide variety of tumors. Several hypersensitivity reactions distinctfrom laryngopharyngeal dysesthesia have been described. We retrospectivelyanalyzed 169 consecutive patients who received oxaliplatinfor esophageal or colorectal cancer between 1/1/00 and 7/31/02 andreviewed any significant adverse reactions labeled as hypersensitivityreactions. Thirty-two patients (19%) reportedly experienced hypersensitivity.Skin rash was the most common event (22 patients), occurringafter a median of three infusions. Fever was seen in five patients aftera median of two infusions. Five patients experienced respiratory symptomsat median infusion number 6. Ocular symptoms of lacrimationand blurring of vision were seen in two patients. Five patients experiencedmore than one type of reaction. Treatments prescribed forhypersensitivity were antihistamines, steroids, and topical emollients.One patient developed grade 4 hypersensitivity during cycle 6, characterizedby laryngeal edema, tongue swelling, and labored breathing.This patient underwent a desensitization procedure, adapted from guidelinesfor carboplatin (Paraplatin) allergy. Subsequently, three cycleswere administered over 6 hours and were well tolerated. However,during the fourth infusion postdesensitization, the patient developedrecurrent signs of hypersensitivity. In conclusion, hypersensitivity isfrequently seen with oxaliplatin, but most reactions are mild.
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Gynecologic Malignancies in Older WomenThe aging of the population is a social phenomenon that will present a challenge to clinical practice in the 21st century. Women constitute a majority of the elderly population as they outlive males by 5 to 7 years. Ovarian,
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How Can We Effectively Address the Medical and Psychological Concerns of Survivors of Pelvic Malignancies?Sexual and urinary morbidities resulting from treatment of pelvic malignancies are common. Awareness of these complications is critical in order to properly counsel patients regarding potential side effects and to facilitate prompt diagnosis and management.
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Gemcitabine and Paclitaxel in Metastatic Breast Cancer: A ReviewGemcitabine (Gemzar) and paclitaxel are active drugs in the treatmentof metastatic breast cancer. Phase I clinical trials data have suggestedthat the gemcitabine plus paclitaxel combination is safe in breastcancer patients. Two doses/administration schedules have been preferredin subsequent phase II and III trials: gemcitabine on days 1 and8 plus a taxane on day 1, every 3 weeks; or gemcitabine plus a taxaneon days 1 and 14, every 4 weeks. In phase II trials, 114 of 221 patients(52%) responded to gemcitabine/paclitaxel therapy. Response rates werelower among patients who received previous chemotherapy for metastaticdisease (response rates: 45%, second line and 70%, first line).Toxicity of gemcitabine/paclitaxel regimens has generally been low, withfew cases of neutropenia or nonhematologic toxicity. Results of therandomized phase III registration trial show a clear advantage forgemcitabine plus paclitaxel over paclitaxel alone in time to disease progression,objective response, and overall survival. Triplet combinations,in which an anthracycline is added to gemcitabine/paclitaxel, are beingexplored in the metastatic and neoadjuvant settings.
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Genomic Testing in Colorectal Cancer: How Much Is Enough?The identification and characterization of gene signatures, driver events, and pharmacogenomics in molecularly homogeneous subsets of patients is likely to advance effective drug development strategies in colorectal cancer.
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Biphasic Tumors of the Female Genital TractIn this installment of Second Opinion, we are presenting two cases of tumors of the female genital tract, specifically, the ovary and uterus, which contain both epithelial and mesenchymal components and therefore have unique diagnostic and therapeutic implications. The first has an unusually poor prognosis and the second is notoriously difficult to diagnose.
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Dendreon vs CMS: Why the Provenge Coverage Controversy Is Bigger Than Just One ProductIt appeared that the controversy surrounding the prostate cancer immunotherapy Provenge ended with FDA approval in April. But now Medicare is questioning whether the government should pay for the new therapy. The CMS decision is just as important to the biopharmaceutical industry as it is to Dendreon.
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The Surgical Management of Peritoneal Carcinomatosis of Colorectal OriginIn the United States, approximately 20% of patients with colorectal cancer present with distant metastasis at diagnosis. In 25% of cases, the peritoneal cavity is the only site of metastatic disease, which is not indicative of a generalized systemic disease, as is the case with lung or liver metastases.
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Treatment of Metastatic Pancreatic Adenocarcinoma: A ReviewGemcitabine monotherapy has been the standard of care for patients with metastatic pancreatic cancer for several decades. Despite recent advances in various chemotherapeutic regimens and in the development of targeted therapies, metastatic pancreatic cancer remains highly resistant to chemotherapy.
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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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Patient-Centered Care in Prostate CancerFocusing on patient-centered care, Rana R. McKay, MD, and the Oncology Brothers discuss the role of PSA and PSMA PET scans in guiding treatment for patients with prostate cancer.
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Proton Therapy for Prostate CancerThis review discusses the rationale, history, and current status of proton therapy for prostate cancer-and controversies regarding it.
