Lung Cancer

a brief overview of the dosing and administration guidelines for the various targeted therapy agents discussed in this supplement to the ONCOLOGY Nurse Edition. Please consult the manufacturer's package insert for more information.

Primary 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.

Non-small-cell lung cancer (NSCLC) is the leading cause of cancer death worldwide. Before 1980, radiotherapy was considered the only real recourse in advanced disease. In 1995, a landmark meta-analysis of trials conducted in the 1980s and early 1990s demonstrated a survival benefit with platinum-based chemotherapy. Newer chemotherapy agents and improved supportive care measures have allowed more patients to benefit from chemotherapy with reduced toxicity. Concurrent platinum-based chemotherapy and radiotherapy has improved the survival in stage III disease, and recently chemotherapy has also demonstrated improved survival in resected early-stage disease. The majority of patients still present with advanced unresec disease for whom the prognosis remains poor, but for key subpopulations the outlook has improved markedly since the emergence of targeted therapies directed against the epidermal growth factor receptor and vascular endothelial growth factor receptor pathways. Patient selection and the incorporation of targeted therapies with cytotoxic chemotherapy are the focus of many ongoing studies, and there is an abundance of new agents undergoing clinical trials. Together, these developments have moved us away from the nihilism of 20 years ago into an era of unprecedented optimism in taking on the many remaining challenges of managing NSCLC in the 21st century.

A recombinant fusion protein designed to stimulate immune response against the MAGE-A3 tumor antigen has shown some efficacy in patients with completely resected early-stage non-small-cell lung cancer (NSCLC), decreasing the recurrence rate by about one-third.

Use of adjuvant chemotherapy for stage IB non-small-cell lung cancer (NSCLC) is less certain than it appeared to be at last year's American Society of Clinical Oncology (ASCO) meeting, according to a study reported at the 2006 ASCO Annual Meeting.

A new bioengineered protein that targets two apoptosis receptors produced one dramatic tumor regression and stopped tumor growth in several cases of disease stabilization in 60% of the advanced cancer patients treated in a phase I dose-finding trial

Researchers are using large patient datasets and computer programs to develop an expanded cancer staging system, moving beyond the conventional three markers—tumor size, nodal involvement, and metastasis—used in TNM staging. The new system, presented at the International Union Against Cancer's World Cancer Congress, uses TNM stage and other factors, such as histology and tumor grade, to fine tune and personalize prognosis

A systematic approach to early treatment of skin toxicity in patients on erlotinib (Tarceva)-based therapy can reduce the need for dose modification or delay in patients with head and neck cancer or non-small-cell lung cancer (NSCLC)

A vaccine that blocks production of transforming growth factor-beta 2 (TGF-β2) extended 1-year survival in patients with advanced non-small-cell lung cancer (NSCLC)

Brain, lung, and ovarian cancers have been chosen as the first cancers to be studied in the pilot phase of The Cancer Genome Atlas (TCGA) project

 I read with great interest the paper by Michael Brave and colleagues from the US Food and Drug Administration (FDA). The authors describe the FDA's review supporting this first approval of a chemotherapeutic drug for advanced cervical cancer. This decision was made after a Gynecologic Oncology Group trial (GOG-0179) conducted at 94 American study centers demonstrated a survival benefit in patients with stage IVB, recurrent, or persistent carcinoma of the cervix who received cisplatin plus topotecan (Hycamtin) compared with those who received cisplatin alone.

Topotecan, 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.

Topotecan, 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.

Astudy conducted by researchers from the Medical University of South Carolina (MUSC) and University of South Carolina shows that the cancer rate among blacks living in South Carolina is nearly twice as great as it is for whites in the state.

Topotecan, 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.

Precise mediastinal staging of non-small-cell lung cancer is extremely important, as mediastinal lymph node metastases generally indicate unresectable disease. Reliance on computed tomography (CT) and positron-emission tomography (PET) alone to stage and determine resectability is limited by false-positive results. Whenever possible, pathologic confirmation of metastases is desirable. Mediastinoscopy and transbronchial fine-needle aspiration are widely established but imperfect modalities. Endoscopic ultrasound fine-needle aspiration (EUS-FNA) has emerged as a diagnostic and staging tool because of its safety, accuracy, and patient convenience. We reviewed 13 prospective studies evaluating the comparative performance of EUS for staging lung cancer. We conclude that EUS is a valuable staging modality. Further studies of the role of EUS compared to other modalities such as integrated PET/CT and endobronchial ultrasound (EBUS) are forthcoming.

Precise mediastinal staging of non-small-cell lung cancer is extremely important, as mediastinal lymph node metastases generally indicate unresectable disease. Reliance on computed tomography (CT) and positron-emission tomography (PET) alone to stage and determine resectability is limited by false-positive results. Whenever possible, pathologic confirmation of metastases is desirable. Mediastinoscopy and transbronchial fine-needle aspiration are widely established but imperfect modalities. Endoscopic ultrasound fine-needle aspiration (EUS-FNA) has emerged as a diagnostic and staging tool because of its safety, accuracy, and patient convenience. We reviewed 13 prospective studies evaluating the comparative performance of EUS for staging lung cancer. We conclude that EUS is a valuable staging modality. Further studies of the role of EUS compared to other modalities such as integrated PET/CT and endobronchial ultrasound (EBUS) are forthcoming.

Precise mediastinal staging of non-small-cell lung cancer is extremely important, as mediastinal lymph node metastases generally indicate unresectable disease. Reliance on computed tomography (CT) and positron-emission tomography (PET) alone to stage and determine resectability is limited by false-positive results. Whenever possible, pathologic confirmation of metastases is desirable. Mediastinoscopy and transbronchial fine-needle aspiration are widely established but imperfect modalities. Endoscopic ultrasound fine-needle aspiration (EUS-FNA) has emerged as a diagnostic and staging tool because of its safety, accuracy, and patient convenience. We reviewed 13 prospective studies evaluating the comparative performance of EUS for staging lung cancer. We conclude that EUS is a valuable staging modality. Further studies of the role of EUS compared to other modalities such as integrated PET/CT and endobronchial ultrasound (EBUS) are forthcoming.

Precise mediastinal staging of non-small-cell lung cancer is extremely important, as mediastinal lymph node metastases generally indicate unresectable disease. Reliance on computed tomography (CT) and positron-emission tomography (PET) alone to stage and determine resectability is limited by false-positive results. Whenever possible, pathologic confirmation of metastases is desirable. Mediastinoscopy and transbronchial fine-needle aspiration are widely established but imperfect modalities. Endoscopic ultrasound fine-needle aspiration (EUS-FNA) has emerged as a diagnostic and staging tool because of its safety, accuracy, and patient convenience. We reviewed 13 prospective studies evaluating the comparative performance of EUS for staging lung cancer. We conclude that EUS is a valuable staging modality. Further studies of the role of EUS compared to other modalities such as integrated PET/CT and endobronchial ultrasound (EBUS) are forthcoming.

Clinical trials may be running out of volunteers, according to a report at the American Society of Clinical Oncology 2006 meeting

Lung and bronchus cancer rates have declined in California at a faster rate than in the United States as a whole, mirroring a decline in tobacco consumption and helping to validate anti-tobacco efforts aimed primarily at changing societal norms regarding smoking.

The US Justice Department's lawsuit against the major tobacco companies ended with more of a whimper than a bang. A federal judge found that the companies engaged in a decades-long conspiracy to deceive Americans about the dangers of smoking cigarettes but said that a 2005 ruling by a federal appeals court severely limited the penalties she could impose.

Lung cancer is the leading cause of cancer mortality in the United States. A significant number of patients present with disease involving mediastinal lymph nodes. As survival after surgery alone for stage III disease is poor, radiation therapy and chemotherapy have been evaluated in the neoadjuvant and adjuvant settings to improve outcomes. The benefit of adjuvant chemotherapy in the subgroup of patients with N2 disease is uncertain. Small randomized trials enrolling patients with stage III disease have shown a benefit of neoadjuvant chemotherapy over surgery alone. Whether neoadjuvant chemotherapy is superior to adjuvant chemotherapy is under investigation. Furthermore, whether neoadjuvant chemoradiotherapy is superior to neoadjuvant chemotherapy is controversial, and few randomized studies comparing these approaches have been reported. Nevertheless, neoadjuvant chemoradiotherapy appears to be associated with higher rates of resection, higher rates of clearance of mediastinal nodal disease, and better local/regional control. The use of postoperative radiation therapy (PORT) has declined since the publication of the 1998 meta-analysis suggested a detriment in survival with this strategy. However, radiation techniques are improving and emerging data support the use of carefully delivered PORT. Finally, it remains unclear whether surgical resection offers an advantage over definitive chemoradiotherapy alone for stage III disease. In summary, locally advanced NSCLC remains a formidable challenge with few cures, and optimal treatment requires the careful use of surgery, chemotherapy, and radiation therapy.

The Maryland-based 20/20 GeneSystems, Inc ("20/20") announced study results showing that its multibiomarker blood test may be able to detect non-small-cell lung cancer (NSCLC) significantly earlier and with better accuracy than computed tomography (CT) scans, the most advanced technique in current use for detecting the disease.

Sanofi-Aventis announced that a meta-analysis performed on seven clinical trials in patients with advanced non-small-cell lung cancer (NSCLC) showed that patients receiving docetaxel (Taxotere) had demonstrated overall survival and less febrile neutropenia than those treated with vinca alkaloid (vinorelbine or vindesine) regimens.

Lung cancer is the leading cause of cancer mortality in the United States. A significant number of patients present with disease involving mediastinal lymph nodes. As survival after surgery alone for stage III disease is poor, radiation therapy and chemotherapy have been evaluated in the neoadjuvant and adjuvant settings to improve outcomes. The benefit of adjuvant chemotherapy in the subgroup of patients with N2 disease is uncertain. Small randomized trials enrolling patients with stage III disease have shown a benefit of neoadjuvant chemotherapy over surgery alone. Whether neoadjuvant chemotherapy is superior to adjuvant chemotherapy is under investigation. Furthermore, whether neoadjuvant chemoradiotherapy is superior to neoadjuvant chemotherapy is controversial, and few randomized studies comparing these approaches have been reported. Nevertheless, neoadjuvant chemoradiotherapy appears to be associated with higher rates of resection, higher rates of clearance of mediastinal nodal disease, and better local/regional control. The use of postoperative radiation therapy (PORT) has declined since the publication of the 1998 meta-analysis suggested a detriment in survival with this strategy. However, radiation techniques are improving and emerging data support the use of carefully delivered PORT. Finally, it remains unclear whether surgical resection offers an advantage over definitive chemoradiotherapy alone for stage III disease. In summary, locally advanced NSCLC remains a formidable challenge with few cures, and optimal treatment requires the careful use of surgery, chemotherapy, and radiation therapy.

In small-cell lung cancer (SCLC), a new anthracycline amrubicin demonstrated significant activity, both in patients sensitive to and refractory to previous chemotherapy

Sunitinib (Sutent), which blocks several tumor tyrosine kinase targets, and sorafenib (Nexavar), which targets the tumor Raf/MEK/ERK pathway, are both active in advanced non-small-cell lung cancer (NSCLC), according to phase II studies

In the treatment of recurrent or refractory non-small-cell lung cancer (NSCLC), the addition of bevacizumab (Avastin) to either chemotherapy or erlotinib (Tarceva) was associated with a trend toward improved progression-free and overall survival in a phase II study

Talabostat (PT-100, Point Therapeutics), an oral, small-molecule inhibitor of dipeptidyl peptidase (DPP) fast-tracked by the FDA for stage IIIB/IV non-small-cell lung cancer, also looks promising in salvage regimens for patients with advanced melanoma or chronic lymphocytic leukemia (CLL