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Special Targets for the Treatment and Prevention of Cancer: Angiogenesis, VEGF, COX-2Identification of targets in tumor cells vs normal cells (or at least a differential in their expression) is certainly a promising method for approaching the treatment and, indeed, the prevention of cancer. Presently, targeting of patient tumor cells has taken on even greater importance and interest with the discovery of the new agent imatinib mesylate (STI571, Gleevec), which is targeted to a kinase present in chronic myeloid leukemia (CML) cells (p210 BCR-ABL abnormal cells), which is required for CML cells to survive, but is not present in normal leucocytes.[1] The results with this agent targeted to the p210 BCR-ABL tyrosine kinase are indeed spectacular. The agent is of even greater interest in that it also works against some gastrointestinal stromal sarcomas with gain of function mutations in c-kit (CD117).[2] This activity of a targeted agent against a solid tumor increases the interest in targeted therapy to an even greater degree.
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Use of Bisphosphonates in Patients With Metastatic Bone DiseaseThe urge to control the manifestations of incurable chronic diseases, such as the anemia, renal failure, and bony disease of myeloma and the bone disease of breast cancer, is understandable. Successful control of these disease manifestations greatly improves a patient’s quality of life. This is especially important since patients with either of these malignancies may live with the disease for 20 years or more. Considerable success has been achieved in the correction of anemia with erythopoietin (Epogen, Procrit), and simple hydration has reversed renal failure and improved the survival of patients with myeloma.[1] Anyone who has witnessed the frightening spasms of back pain in myeloma patients, precipitated by a sneeze or an attempt to turn over in bed, understands the dreadful fear that patients have of uncontrolled bone pain.
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New Targets and New Mechanisms in Lung CancerThis review will describe the well-known use of VEGF antibodies; the current uses of EGFR and ALK tyrosine kinase inhibitors; newer agents being used against MET, FGFR, and other intracellular targets; insights regarding the field of immunotherapy in lung cancer; and finally, newer developments in chemotherapy.
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Novel Prostate Cancer Risk Classifier Highly Prognostic for MetastasesThis video highlights a clinical-genomic risk classification system that is highly prognostic for distant metastasis and more accurate than clinical risk assessments.
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CYP2D6 Testing for Breast Cancer Patients: Is There More to the Story?The promise of pharmacogenetics is personalization of therapy for individuals through refinement of the risk/benefit profile of pharmaceuticals based on inherited gene mutations. Classic examples of the impact of pharmacogenetics in clinical practice include variants in dihydropyrimidine dehydrogenase and treatment with fluorouracil.
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Breast CancerThis is a comprehensive 701-page volume filled with excellent illustrations, photographs, tables, and schematics. The overall structure of the book takes the reader from molecular oncology issues through pathology, diagnosis, staging, treatment, and a
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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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Commentary (Coit): Management of Small Bowel AdenocarcinomaMalignant small bowel tumors are extremely rare, accounting for 0.1% to 0.3% of all malignancies. Fewer than 2,400 new cases of small bowel malignancy are reported in the United States each year.[1] Malignant tumors, which account for about two-thirds of all primary small bowel tumors, consist of four primary subtypes: adenocarcinoma, carcinoid tumor, lymphoma, and sarcoma (or gastrointestinal [GI] stromal tumor). Each malignancy is characterized by unique predisposing factors, anatomy, and biology. The prevalence, pattern, and relevance of both regional lymph node and distant metastases differ. As a result, the study of malignant small bowel tumors, taken as an aggregate, is fraught with difficulty.
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Commentary (Hewitt/Haller): Adjuvant Therapy for Colorectal CancerDuring the 1980s, the only drug routinely used to treat colorectal carcinoma was single-agent fluorouracil (5-FU), a drug that had shown no proven benefit in the adjuvant setting. Since then, significant improvements in the overall management of colorectal cancer have been made. This review will compare today's standard of care for adjuvant colorectal carcinoma to that practiced 20 years ago. The authors examine key questions asked about adjuvant therapy and the answers that ultimately changed clinical practice standards and improved overall survival for patients diagnosed with this disease. In addition, this review explores whether 5-FU should be given as part of a multidrug regimen and which route of administration is best when this drug is given. Further, the authors delve into both the use of locally directed therapies to the liver or peritoneum to improve outcomes and the selection of patients to receive adjuvant chemotherapy. Finally, a look to the future shows monoclonal antibodies to be an avenue of great promise in fighting colorectal cancer.
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A Huge Value Question REGARDless of the RAINBOWThe cost of healthcare is spiraling out of control in the United States, and compared with other countries we don’t even have better health indices to show for it. We currently spend $2.8 trillion annually on healthcare, and this is predicted to increase greatly in the coming years.
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The Explanation Behind the Observation?The recommended primary treatment approach for women with metastatic breast cancer and an intact primary tumor is the use of systemic therapy. Local therapy of the primary tumor is recommended only for palliation of symptoms. However, a series of retrospective studies examining practice patterns for this problem show that about half the women presenting with de novo metastatic disease undergo resection of the primary tumor, and suggest that women so treated survive longer than those who do not undergo resection of the intact primary. In analyses that adjust for tumor burden (number of metastatic sites), types of metastases (visceral, nonvisceral), and the use of systemic therapy, the hazard ratio for death is reduced by 40% to 50% in women receiving surgical treatment of the primary tumor. The benefit of surgical treatment appears to be confined to women whose tumors were resected with free margins. However, these results may simply reflect a selection bias (ie, younger, healthier women with a smaller tumor burden are more likely to receive surgical treatment). In addition, the role of other locoregional therapy such as axillary dissection and radiotherapy is not addressed in these studies. In view of these data, the role of local therapy in women with stage IV breast cancer needs to be reevaluated, and local therapy plus systemic therapy should be compared to systemic therapy alone in a randomized trial.
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Attacking a Moving Target: Understanding Resistance and Managing Progression in EGFR-Positive Lung Cancer Patients Treated With Tyrosine Kinase InhibitorsIn this article, we review the available literature addressing the competing treatment strategies in EGFR-Positive Lung Cancer and attempt to clarify best treatment practices, including the emerging role of T790M-directed therapies.
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The Current Clinical Value of the DCIS ScoreThe DCIS Score provides clinically relevant information about personal risk that can guide patient discussions and facilitate shared decision making.
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A Contemporary Review of HPV and Penile CancerThis article provides a comprehensive and up-to-date review of the role of HPV infections in men and in the development of penile cancer.
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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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Clinical Radiation OncologyClinical Radiation Oncology, edited by Drs. Gunderson and Tepper, is a first-edition textbook designed primarily for those
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Lung Cancer After 70: Is it a Different Disease?Despite the fact that elderly patients comprise over 50% of the non-small cell lung cancer (NSCLC) population, our knowledge regarding the efficacy and safety of chemotherapy in this group is suboptimal. The “elderly” (defined as individuals ≥70 years of age) experience physiologically normal aging of their bone marrow and kidneys, which inherently increases toxicity to therapy. Standard practice has often been to discourage the use of combination chemotherapy in these patients; however, general consensus guidelines emphasize that performance status should primarily guide the choice of treatment. Elderly patients with advanced NSCLC treated with platinum doublet therapy demonstrate similar efficacy (but increased toxicity) to their younger counterparts. Patients with metastatic disease in which a targeted and/or biological agent(s) was added to chemotherapy experienced benefits similar to those treated with standard platinum doublets, but with increased morbidity and mortality. In the future, effective testing of molecular targeted therapies will have to include elderly patients among research cohorts or risk excluding a large population of eligible patients. Overall, elderly patients with advanced NSCLC, while experiencing greater toxicity, demonstrate the same response rates and survival benefits as their younger peers.
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Health Literacy: Improving Patient UnderstandingThe review of health literacy and its impact on older adults by Amalraj and colleagues in this issue of ONCOLOGY brings much-needed attention to this very critical issue. The impact of limited health literacy is made even more critical given the increasing number of older adults in the United States, estimated to be 20% of the US population by the year 2030, and the fact that limited health literacy disproportionately affects them.
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Langerhans Cell Histiocytosis: Emerging Insights and Clinical ImplicationsLangerhans cell histiocytosis is a disorder characterized by lesions that include CD207+ dendritic cells along with an inflammatory infiltrate. Langerhans cell histiocytosis has a highly variable clinical presentation, ranging from a single lesion to potentially fatal disseminated disease.
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LHRH Antagonists vs LHRH Agonists: Which Is More Beneficial in Prostate Cancer Therapy?Crawford and Hou[1] review the data on luteinizing hormone-releasing hormone (LHRH) antagonists in prostate cancer. They describe the results of a phase III trial comparing monthly degarelix to monthly leuprolide in men with advanced prostate cancer. Degarelix treatment was associated with a more rapid decline of serum testosterone, and was not associated with an initial surge of serum testosterone seen during the first few days of treatment with leuprolide. They discuss the role of this new form of medical gonadal suppression for the treatment of prostate cancer.
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Epidemiology and Pathogenesis of AIDS-Related LymphomasDr. Aboulafia provides an accurate overview of the relationship between immunodeficiency and malignant lymphoma, the lymphoproliferative disorders that occur following solid organ transplantation, and the epidemiology and pathogenetic mechanisms possibly involved in acquired immunodeficiency syndrome (AIDS)-related lymphomagenesis.
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Commentary (Miller): Adjuvant Chemotherapy for Resected Non–Small-Cell Lung CancerLung cancer continues to be themost common cause of cancerdeaths in the United States forboth men and women. Unfortunately,the majority of patients presentwith local or distant disease at thetime of diagnosis. Surgical resectioncontinues to offer the best chance forlong-term survival; however, less than25% of patients have surgically resectabledisease. Even after surgicalresection for early-stage disease a significantnumber of patients will developrecurrent disease, with themajority being distant in nature. Developmentof distant disease usuallyproves to be the terminal event inmost patients. Multiple treatmentmodalities have been investigated asadjuvant therapy to decrease the incidenceof distant disease after completesurgical resection. Untilrecently, no modality has shown asurvival advantage in patients afterresection for non–small-cell lung cancer(NSCLC).
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In Hormone-Naive Metastatic Prostate Cancer, Should All Patients Now Receive Docetaxel? Yes; We Must Beware of Drawing Conclusions From a Subset AnalysisUltimately, while further follow-up will be enlightening, we believe that there is sufficient evidence now from the primary analysis of CHAARTED to justify the combination of docetaxel and androgen deprivation therapy in all men with metastatic hormone-sensitive prostate cancer.
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KS Clearly Not a Conventional NeoplasmSAN FRANCISCO-“Kaposi’s sarcoma (KS) conforms very poorly to conventional notions about cancer,” Donald Ganem, MD, of the University of California, San Francisco, said at a conference on globally emerging viral infections. “It’s properly classified as in the gray zone between proliferative hyperplasia and frank neoplasm.”
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Current Issues in the Diagnosis and Management of Wilms' TumorPaulino has thoughtfully reviewed the etiology, diagnosis, and management of Wilms' tumor. Investigators from the National Wilms' Tumor Study Group (NWTSG) first divided Wilms' tumors into two groups: those with a favorable histology and those with an unfavorable histology.[1]
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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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Cancer Survivors’ Employment and Insurance Rights: A Primer for OncologistsFrom the survivor’s viewpoint, Ms.Hoffman’s paper addresses a critical need, expressed in both its title and its conclusions: Medical professionals who treat cancer patients need to be aware of the anxieties faced by those diagnosed with cancer “so
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Oncology Peer Review On-The-Go: Cancer Pain and Opioid Use DisorderAuthors Daniel C. McFarland, DO, and Kirk Harris, MD, spoke with CancerNetwork® about their manuscript on cancer pain’s relationship with opioid use disorder that was recently published in the journal ONCOLOGY®.
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Clinical Applications of The Cancer Genome Atlas Project (TCGA) for Squamous Cell Lung CarcinomaWe summarize here key findings from the comprehensive analysis of squamous cell lung cancer by The Cancer Genome Atlas group and discuss the clinical implications of these findings.
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The Role of Irinotecan and Oxaliplatin in the Treatment of Advanced Colorectal CancerColorectal carcinoma is one of the most common malignancies in the western world, and although fluorouracil (5-FU) has been used in its treatment for almost 40 years, new agents with significant activity have been introduced recently. Irinotecan (CPT-11, Camptosar), a topoisomerase I inhibitor, administered at 300 to 350 mg/m2 every 3 weeks is significantly more active than continuous-infusion 5-FU in patients who have experienced disease progression after conventional therapy with 5-FU. In comparison to best supportive care, irinotecan improves survival and preserves quality of life despite treatment-related toxicity. Moreover, the combination of irinotecan and 5-FU has been explored in a number of different schedules. In previously untreated patients, overall response rates are high. Irinotecan can also be combined with mitomycin (mitomycin-C [Mutamycin]), oxaliplatin, or raltitrexed (Tomudex). Oxaliplatin is a new-generation platinum compound that has demonstrated activity against colorectal carcinoma in preclinical trials. It has been evaluated as a single agent against advanced colorectal carcinoma in the salvage setting and also in combination with 5-FU as initial therapy for metastatic disease (where it shows significant activity). The toxicity profile of oxaliplatin (chiefly characterized by neurotoxicity) differs from that of irinotecan (primarily producing diarrhea) and the potential, therefore, exists for combining these agents or for exploiting their possible synergy with 5-FU. The introduction of these two new active agents of different pharmacologic classes promises to enable significant improvements in the treatment of patients with colorectal carcinoma. [ONCOLOGY 15(4):415-434, 2001]
