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High-Dose Therapy With Stem-Cell Transplantation in the Malignant LymphomasApproximately 35,000 stem (progenitor)-cell transplants are performed annually worldwide, with an estimated yearly growth rate of between 10% and 20%.[1] Non-Hodgkin’s lymphoma remains the second most common indication for stem-cell transplantation, and Hodgkin’s disease ranks approximately seventh overall.[1]
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High-Dose Therapy With Stem-Cell Transplantation in the Malignant LymphomasApproximately 35,000 stem (progenitor)-cell transplants are performed annually worldwide, with an estimated yearly growth rate of between 10% and 20%.[1] Non-Hodgkin’s lymphoma remains the second most common indication for stem-cell transplantation, and Hodgkin’s disease ranks approximately seventh overall.[1]
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Cancer Management Chapter 20: Melanoma and other skin cancersSkin cancer is the single most common form of cancer, accounting for more than 75% of all cancer diagnoses. More than 1 million cases of squamous cell and basal cell carcinomas are diagnosed annually, with a lifetime risk of more than one in five. The vast majority of skin cancers can be cured with surgery alone. Resection is the mainstay of therapy, even for skin cancer involving regional lymph nodes or, in some cases, more distant metastatic sites.
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Treating Bladder Cancer: Neoadjuvant vs Adjuvant TherapyOccult distant micrometastasis at the time of radical cystectomy leads predominantly to distant failures in patients with locally advanced muscle-invasive transitional cell carcinoma of the bladder. Cisplatin-based combination chemotherapy enhances survival in patients with metastatic urothelial cancer. Studies evaluating adjuvant chemotherapy have been limited by inadequate statistical power. However, randomized clinical trials have demonstrated a survival benefit for neoadjvuant cisplatin-based combination chemotherapy, which should be considered a standard of care. In addition, neoadjuvant therapy may assist in the rapid development of novel systemic therapy regimens, since pathologic complete remission appears to be a powerful prognostic factor for long-term outcomes. Patients who are either unfit for or refuse radical cystectomy may benefit from neoadjuvant chemotherapy with or without radiation to enable bladder preservation.
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Role of Adjuvant Therapy in Resected Stage II/IIIA Non-Small-Cell Lung CancerThe search for effective postoperative adjuvant therapy for patients with resected non-small-cell lung cancer (NSCLC) has been spurred by a high rate of failure after definitive surgery. Except for patients with resected T1, N0, M0 lesions, failure rates exceed 30%. Widespread application of adjuvant therapy has been reined in by a disappointing lack of effectiveness in this setting.
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Current Clinical Trials of Molecularly Targeted Agents in Children With CancerA number of molecularly targeted agents directed at critical pathways involved in cell survival and cell proliferation have recently entered clinical evaluation in children with cancer. These agents offer the potential for more effective anticancer therapy while diminishing acute and long-term toxic effects. Systematic evaluations of agents such as these are essential if continuing improvements in outcome are to be achieved in children with cancer. Brief summaries of the rationale for conducting studies of several agents in children are provided below. Following these summaries is a listing of phase I, phase I/II, phase II, and pilot studies of these agents in pediatric populations
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Current Clinical Trials of Molecularly Targeted Agents in Children With CancerA number of molecularly targeted agents directed at critical pathways involved in cell survival and cell proliferation have recently entered clinical evaluation in children with cancer. These agents offer the potential for more effective anticancer therapy while diminishing acute and long-term toxic effects. Systematic evaluations of agents such as these are essential if continuing improvements in outcome are to be achieved in children with cancer. Brief summaries of the rationale for conducting studies of several agents in children are provided below. Following these summaries is a listing of phase I, phase I/II, phase II, and pilot studies of these agents in pediatric populations
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Is There a Role for Dose-Intensive Chemotherapy With Stem Cell Rescue in Breast Cancer?During the 1990s, perhaps no other therapy for women with breast cancer was more controversial than high-dose chemotherapy with autologous bone marrow and/or peripheral stem cell support. With encouraging results from late phase I and early phase II trials in the early to mid-1990s, high-dose chemotherapy was promoted by its many enthusiastic proponents as a potentially great leap forward for women with high-risk, node-positive or metastatic disease.
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High-Dose Chemotherapy in Poor-Risk Germ-Cell TumorsTesticular cancer is a highly curable cancer. However, 30% of patients are refractory to standard therapy and will need additional therapy. This article focuses on the use of high-dose chemotherapy in germ-cell tumors.
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The Role of Mitoxantrone in Non-Hodgkin’s LymphomaDr. Armitage presents a succinct and thorough review of the role of mitoxantrone (Novantrone) in patients with non-Hodgkin’s lymphoma (NHL). He begins by emphasizing the importance of accurate diagnosis as described in the World Health Organization classification which evolved from the Revised European American Lymphoma classification. Both of these present day classifications are based on the immunologic principles separating lymphomas into B- and T-cell disorders developed in the 1970s by Lennert, Lukes, and Collins.[1,2] His review addresses multiple issues in mitoxantrone therapy, including dose intensity, cardiotoxicity, combination therapy with nucleoside analogs in low-grade lymphomas, the impact of rituximab (Rituxan), therapy for acquired immunodeficiency syndrome (AIDS)-related lymphoma, and the role of high-dose mitoxantrone as part of a preparative regimen for autologous transplants.
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Romidepsin, an HDAC Inhibitor for Cutaneous T-cell LymphomaDrug is indicated for the treatment of patients with cutaneous T-cell lymphoma (CTCL) who have received at least one prior systemic therapy.
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EPOCH-Rituximab Therapy Obviates Need for Radiotherapy in B-Cell LymphomaA dose-adjusted regimen of etoposide, doxorubicin, and cyclophosphamide with vincristine, prednisone, and rituximab (DA-EPOCH-R) obviated the need for radiotherapy in patients with primary mediastinal B-cell lymphoma in a single-group, phase II, prospective study.
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Erlotinib maintenance therapy in lung cancer sows survival benefitSAN FRANCISCO–Maintenance therapy with erlotinib (Tarceva) in patients with non-small-cell lung cancer following chemotherapy provided a statistically significant improvement in survival, according to results from the SATURN trial.
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The Role of Neck Dissection Following Definitive ChemoradiationThe presence of regional nodal metastases represents a significantadverse prognostic factor for patients with squamous cell carcinoma ofthe head and neck. Early-stage head and neck cancers, localized to theprimary site without regional lymph node metastases have excellentcure rates with either surgery or radiation therapy. The presence ofregional metastases results in cure rates that are approximately half ofthose obtainable in early-stage disease. Therefore, due to the significantadverse impact of neck metastases on prognosis, the treatment ofthe neck remains a vital part of the decision-making process in determiningtherapy for head and neck cancer.
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The Role of Neck Dissection Following Definitive ChemoradiationThe presence of regional nodal metastases represents a significantadverse prognostic factor for patients with squamous cell carcinoma ofthe head and neck. Early-stage head and neck cancers, localized to theprimary site without regional lymph node metastases have excellentcure rates with either surgery or radiation therapy. The presence ofregional metastases results in cure rates that are approximately half ofthose obtainable in early-stage disease. Therefore, due to the significantadverse impact of neck metastases on prognosis, the treatment ofthe neck remains a vital part of the decision-making process in determiningtherapy for head and neck cancer.
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The Role of Neck Dissection Following Definitive ChemoradiationThe presence of regional nodal metastases represents a significantadverse prognostic factor for patients with squamous cell carcinoma ofthe head and neck. Early-stage head and neck cancers, localized to theprimary site without regional lymph node metastases have excellentcure rates with either surgery or radiation therapy. The presence ofregional metastases results in cure rates that are approximately half ofthose obtainable in early-stage disease. Therefore, due to the significantadverse impact of neck metastases on prognosis, the treatment ofthe neck remains a vital part of the decision-making process in determiningtherapy for head and neck cancer.
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Hematopoietic Stem Cell Transplantation for Non-Hodgkin’s LymphomaHigh-dose myeloablative therapy with autologous or allogeneicstem cell rescue is an effective treatment strategy for non-Hodgkin’slymphoma (NHL), but NHL is much less likely to stay in remission afteran autologous transplant than after an allogeneic transplant. Thebenefit of undergoing an autologous transplant earlier in the course ofthe disease, especially for patients who present with intermediate orhigh scores on the International Prognostic Index of risk factors, is stillunclear. The addition of immunotherapy, biologic modifiers, andantibody therapy such as rituximab (Rituxan) or radiolabeled antibodyto the autologous transplant are approaches undergoing evaluation.Historically, there has been a high regimen-related mortality rateassociated with myeloablative allogeneic transplant that has made thisapproach a less appealing option for therapy. The use of nonmyeloablativeallogeneic transplants as treatment for NHL is less well studiedand remains to be defined.
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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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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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Topotecan in Combination With Cisplatin for the Treatment of Stage IVB, Recurrent, or Persistent Cervical Cancer: Review 2Topotecan, 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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Topotecan in Combination With Cisplatin for the Treatment of Stage IVB, Recurrent, or Persistent Cervical Cancer: Review 2Topotecan, 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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In Search of Rigorous Data on How to Palliate the EGFR Inhibitor–Induced RashEpidermal growth factor receptor (EGFR) inhibitors have emerged as important drugs in cancer therapy, providing a proven survival advantage for some patients with non–small-cell lung cancer, colorectal cancer, head and neck cancer, and pancreas cancer.
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Metastatic Kidney Cancer: An 'Embarrassment of Riches' For Clear Cell HistologyWhile seven drugs have been approved for clear cell renal cell carcinoma (ccRCC) since 2005, the most appropriate systemic therapy for non-clear cell renal cell carcinoma (nccRCC) is unknown.
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Response to Antiangiogenesis Therapy in a Patient With Advanced Adult-Type Testicular Granulosa Cell TumorWe have presented the first case of a patient with metastatic ATGCT with peritoneal carcinomatosis, who responded to treatment with a VEGFR tyrosine kinase inhibitor. Because of the relative paucity of such cases in the literature, no clear treatment strategy exists. For patients with metastatic ATGCT, enrollment in clinical trials testing novel therapies, including angiogenesis inhibitors, is a reasonable option.
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Response to Antiangiogenesis Therapy in a Patient With Advanced Adult-Type Testicular Granulosa Cell TumorWe have presented the first case of a patient with metastatic ATGCT with peritoneal carcinomatosis, who responded to treatment with a VEGFR tyrosine kinase inhibitor. Because of the relative paucity of such cases in the literature, no clear treatment strategy exists. For patients with metastatic ATGCT, enrollment in clinical trials testing novel therapies, including angiogenesis inhibitors, is a reasonable option.
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Response to Antiangiogenesis Therapy in a Patient With Advanced Adult-Type Testicular Granulosa Cell TumorWe have presented the first case of a patient with metastatic ATGCT with peritoneal carcinomatosis, who responded to treatment with a VEGFR tyrosine kinase inhibitor. Because of the relative paucity of such cases in the literature, no clear treatment strategy exists. For patients with metastatic ATGCT, enrollment in clinical trials testing novel therapies, including angiogenesis inhibitors, is a reasonable option.
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The Future of NSCLC: Molecular Profiles Guiding Treatment DecisionsThe authors of "ALK-Targeted Therapy for Lung Cancer: Ready for Prime Time," in this issue of ONCOLOGY, address the newest developments in the field of targeted therapies for advanced non–small-cell lung cancer (NSCLC).
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Treating Small-Cell Lung Cancer: More Consensus Than ControversyAlmost 40% of patients with newly diagnosed small-cell lung cancer (SCLC) have disease confined to the ipsilateral hemithorax and within a single radiation port, ie, limited-stage disease. The median survival for this group of patients after treatment is approximately 15 months, with one in every four patients surviving 2 years. Current optimal treatment consists of chemotherapy with platinum/etoposide, given concurrently with thoracic radiation. Surgery may represent an option for very early-stage disease, but its added value is uncertain. Prophylactic cranial irradiation (PCI) is used for patients with limited-stage SCLC who have achieved a complete response following initial therapy, as it decreases the risk of brain metastases and provides an overall survival benefit. Newer targeted agents are currently being evaluated in this disease and hold the promise of improving current outcomes seen in patients with early-stage disease.
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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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Adjuvant Therapy for Early Lung Cancer: Reflections and PerspectivesThe standard of care with regard to adjuvant chemotherapy of lung cancer has changed remarkably over the past 3 years. Until the initial report of the International Adjuvant Lung Trial in 2003, there was no real evidence from any individual randomized clinical trial (RCT) that adjuvant chemotherapy improves survival in resectable non-small-cell lung cancer. However, five RCTs that have now been reported indicate that adjuvant chemotherapy is effective, at least in certain subgroups of resectable patients. Moreover, numerous meta-analyses have also reported a positive effect from adjuvant treatment. Nonetheless, because of methodologic issues and conflicting results, the question of who should be treated and what constitutes optimal adjuvant therapy remains controversial. This article reviews the recent randomized trials that have contributed to a change in the state of the art, as well as some of the methodologic problems that may have confounded their proper interpretation. It also considers newer approaches to adjuvant therapy, with a particular focus on strategies that incorporate our growing knowledge of molecular medicine and predictive factors to the field of adjuvant chemotherapy of lung cancer.
