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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.
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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.
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Thirty Years Later: We've Only Just BegunThe 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.
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New Drugs Bring New QuestionsThe treatment of metastatic renal cell carcinoma (RCC) has changed dramatically over the past few years. An improved understanding of the biology of RCC has resulted in the development of novel targeted therapeutic agents that have altered the natural history of this disease. In particular, the hypoxia-inducible factor (HIF)/vascular endothelial growth factor (VEGF) pathway and the mammalian target of rapamycin (mTOR) signal transduction pathway have been exploited. Sunitinib malate (Sutent), sorafenib tosylate (Nexavar), bevacizumab (Avastin)/interferon alfa, and temsirolimus (Torisel) have improved clinical outcomes in randomized trials by inhibiting these tumorigenic pathways. Combinations and sequences of these agents are being evaluated. Other novel multitargeted tyrosine kinase inhibitors (pazopanib and axitinib) and mTOR inhibitors (everolimus) are in clinical development. Recently reported and ongoing clinical trials will help further define the role of these agents as therapy for metastatic RCC.
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The Emerging Epidemic of Gastroesophageal Cancers: A Neglected Volcano?Esophageal, gastroesophageal junction, and gastric cancers are underpublicized but are frequently lethal, and gastroesophageal junction adenocarcinomas are increasingly common diseases in the United States and around the world. Although often grouped together in studies of chemotherapy, clear distinctions can be made in the locoregional therapy of these diseases. Esophageal squamous cell carcinomas may be treated with surgery or radiation with concurrent chemotherapy, whereas esophageal adenocarcinomas and gastroesophageal junction adenocarcinomas are often treated with all three treatment modalities. Over the past several years, it has become increasingly evident that gastric cancer is a disease that is potentially sensitive to chemotherapy. In the perioperative setting—at least in the Western world—chemotherapy and sometimes radiation are applied. However, the optimal chemotherapy for advanced gastric or esophageal cancer remains unsettled, and there is no single standard regimen. Several new chemotherapy agents have demonstrated activity in these diseases, but the best chemotherapy remains to be determined. This paper will review the role of chemotherapy in gastroesophageal cancers.
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The Emerging Epidemic of Gastroesophageal Cancers: A Neglected Volcano?Esophageal, gastroesophageal junction, and gastric cancers are underpublicized but are frequently lethal, and gastroesophageal junction adenocarcinomas are increasingly common diseases in the United States and around the world. Although often grouped together in studies of chemotherapy, clear distinctions can be made in the locoregional therapy of these diseases. Esophageal squamous cell carcinomas may be treated with surgery or radiation with concurrent chemotherapy, whereas esophageal adenocarcinomas and gastroesophageal junction adenocarcinomas are often treated with all three treatment modalities. Over the past several years, it has become increasingly evident that gastric cancer is a disease that is potentially sensitive to chemotherapy. In the perioperative setting—at least in the Western world—chemotherapy and sometimes radiation are applied. However, the optimal chemotherapy for advanced gastric or esophageal cancer remains unsettled, and there is no single standard regimen. Several new chemotherapy agents have demonstrated activity in these diseases, but the best chemotherapy remains to be determined. This paper will review the role of chemotherapy in gastroesophageal cancers.
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Searching for Standards of Care in Gastroesophageal CancersEsophageal, gastroesophageal junction, and gastric cancers are underpublicized but are frequently lethal, and gastroesophageal junction adenocarcinomas are increasingly common diseases in the United States and around the world. Although often grouped together in studies of chemotherapy, clear distinctions can be made in the locoregional therapy of these diseases. Esophageal squamous cell carcinomas may be treated with surgery or radiation with concurrent chemotherapy, whereas esophageal adenocarcinomas and gastroesophageal junction adenocarcinomas are often treated with all three treatment modalities. Over the past several years, it has become increasingly evident that gastric cancer is a disease that is potentially sensitive to chemotherapy. In the perioperative setting—at least in the Western world—chemotherapy and sometimes radiation are applied. However, the optimal chemotherapy for advanced gastric or esophageal cancer remains unsettled, and there is no single standard regimen. Several new chemotherapy agents have demonstrated activity in these diseases, but the best chemotherapy remains to be determined. This paper will review the role of chemotherapy in gastroesophageal cancers.
Latest:
Searching for Standards of Care in Gastroesophageal CancersEsophageal, gastroesophageal junction, and gastric cancers are underpublicized but are frequently lethal, and gastroesophageal junction adenocarcinomas are increasingly common diseases in the United States and around the world. Although often grouped together in studies of chemotherapy, clear distinctions can be made in the locoregional therapy of these diseases. Esophageal squamous cell carcinomas may be treated with surgery or radiation with concurrent chemotherapy, whereas esophageal adenocarcinomas and gastroesophageal junction adenocarcinomas are often treated with all three treatment modalities. Over the past several years, it has become increasingly evident that gastric cancer is a disease that is potentially sensitive to chemotherapy. In the perioperative setting—at least in the Western world—chemotherapy and sometimes radiation are applied. However, the optimal chemotherapy for advanced gastric or esophageal cancer remains unsettled, and there is no single standard regimen. Several new chemotherapy agents have demonstrated activity in these diseases, but the best chemotherapy remains to be determined. This paper will review the role of chemotherapy in gastroesophageal cancers.
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Bladder Cancer and Current Evidence for TreatmentOccult 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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AACR: Developmental Signaling Takes the Front StageThe Wnt signaling pathway was demonstrated as a promising target in cancer stem cell therapy through a series of talks highlighting the promise and efficacy of a new generation of inhibitors that are making their way into the clinic.
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Improved Metastatic Uterine Papillary Serous Cancer Outcome With Treatment of Mast Cell Activation SyndromeA 71-year-old woman not on hormone replacement therapy presented with uterine bleeding. Dilation and curettage revealed complex hyperplasia with atypia, focal clear-cell features, and endocervicitis. Endometrial intraepithelial carcinoma was suspected.
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Improved Metastatic Uterine Papillary Serous Cancer Outcome With Treatment of Mast Cell Activation SyndromeA 71-year-old woman not on hormone replacement therapy presented with uterine bleeding. Dilation and curettage revealed complex hyperplasia with atypia, focal clear-cell features, and endocervicitis. Endometrial intraepithelial carcinoma was suspected.
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Improved Metastatic Uterine Papillary Serous Cancer Outcome With Treatment of Mast Cell Activation SyndromeA 71-year-old woman not on hormone replacement therapy presented with uterine bleeding. Dilation and curettage revealed complex hyperplasia with atypia, focal clear-cell features, and endocervicitis. Endometrial intraepithelial carcinoma was suspected.
