Lung Cancer

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

Bronchoscopy, which is routinely used when there is suspicion of lung cancer, has a sensitivity ranging from 30% to 70%. Now, a gene expression microarray added to bronchoscopy has dramatically increased that figure, detecting 95% of lung cancers in initial studies with a high-risk population.

Targeted therapy shows promise in extending survival in non-small-cell lung cancer (NSCLC), but trial results are mixed and much further work needs to be done. One important next step is research on selecting patients according to the target protein, said Paul Bunn, MD, director of the University of Colorado Comprehensive Cancer Center in Aurora.

According to a new multicenter study, the drug sunitinib malate (Sutent) is more effective than the current standard cytokine treatment given as initial therapy for patients with metastatic renal cell carcinoma. The study was presented at the annual American Society of Clinical Oncology meeting in Atlanta.

Abraxis BioScience Inc presented data at the American Society of Clinical Oncology (ASCO) annual meeting from multiple phase II studies with paclitaxel albumin-bound particles for injectable suspension (Abraxane) as first-line treatment for late-stage non-small-cell lung cancer (NSCLC).

Lung cancer is estimated to be the second most commonly diagnosed cancer in both men and women in 2006, and the leading cause of cancer mortality. Non-small-cell lung cancer represents the majority of such cases. Most of these patients have locally advanced disease at presentation and are not eligible for curative resection. For the minority of patients who are technically resectable at presentation, lobectomy or pneumonectomy and pathologic mediastinal nodal staging offer the best overall survival. The high rate of comorbid medical illness and poor baseline pulmonary function in this population, however, make many such early-stage patients medically inoperable. For these patients, conventional single-modality radiotherapy has been the primary definitive treatment option, as discussed in part 1 of this article, which appeared in last month's issue. Numerous retrospective reports demonstrate long-term disease-free and overall survival data that are modestly superior to that expected after observation, but both local and distant failure continue to be significant risks. Investigation of radiotherapy dose escalation is ongoing, in an effort to improve local control while maintaining minimal toxicity. Additionally, emerging evidence suggests that new modalities, such as stereotactic radiosurgery and radiofrequency ablation, may also be potentially curative treatment alternatives. These modalities are addressed in part 2.

Lung cancer is estimated to be the second most commonly diagnosed cancer in both men and women in 2006, and the leading cause of cancer mortality. Non-small-cell lung cancer represents the majority of such cases. Most of these patients have locally advanced disease at presentation and are not eligible for curative resection. For the minority of patients who are technically resectable at presentation, lobectomy or pneumonectomy and pathologic mediastinal nodal staging offer the best overall survival. The high rate of comorbid medical illness and poor baseline pulmonary function in this population, however, make many such early-stage patients medically inoperable. For these patients, conventional single-modality radiotherapy has been the primary definitive treatment option, as discussed in part 1 of this article, which appeared in last month's issue. Numerous retrospective reports demonstrate long-term disease-free and overall survival data that are modestly superior to that expected after observation, but both local and distant failure continue to be significant risks. Investigation of radiotherapy dose escalation is ongoing, in an effort to improve local control while maintaining minimal toxicity. Additionally, emerging evidence suggests that new modalities, such as stereotactic radiosurgery and radiofrequency ablation, may also be potentially curative treatment alternatives. These modalities are addressed in part 2.

Lung cancer is estimated to be the second most commonly diagnosed cancer in both men and women in 2006, and the leading cause of cancer mortality. Non-small-cell lung cancer represents the majority of such cases. Most of these patients have locally advanced disease at presentation and are not eligible for curative resection. For the minority of patients who are technically resectable at presentation, lobectomy or pneumonectomy and pathologic mediastinal nodal staging offer the best overall survival. The high rate of comorbid medical illness and poor baseline pulmonary function in this population, however, make many such early-stage patients medically inoperable. For these patients, conventional single-modality radiotherapy has been the primary definitive treatment option, as discussed in part 1 of this article, which appeared in last month's issue. Numerous retrospective reports demonstrate long-term disease-free and overall survival data that are modestly superior to that expected after observation, but both local and distant failure continue to be significant risks. Investigation of radiotherapy dose escalation is ongoing, in an effort to improve local control while maintaining minimal toxicity. Additionally, emerging evidence suggests that new modalities, such as stereotactic radiosurgery and radiofrequency ablation, may also be potentially curative treatment alternatives. These modalities are addressed in part 2.

Image-guided thermal ablation can provide much needed relief of chronic pain in chest wall tumor patients. According to research presented at the annual meeting of the Society of Interventional Radiology (abstract 168), thermal ablation not only relieves pain but may even contribute to longer survival. In addition, ablation may have synergistic effects with radiation therapy.

Dramatic improvements in high-resolution, or spiral, CT imaging over the past decade have created widespread and increasing demand for both lung and cardiac screening, two procedures that could and probably should be combined, according to David Yankelevitz, MD, professor of radiology at Weill Medical College of Cornell University in New York.

The Lung Cancer Alliance applauded a recent court decision on the rights of terminally ill cancer patients to take experimental drugs. In 2003, The Abigail Alliance and the Washington Legal Foundation filed suit against the Food and Drug Administration (FDA) in order to give terminally ill cancer patients access to drugs that have passed initial safety tests but not the full regalia of clinical trials normally required for approval.

Smoking history contributes to poor outcomes in the treatment of lung cancer, according to a new study. Non-small-cell lung cancer (NSCLC) patients who have never smoked before have better overall survival rates and respond better to chemotherapy than current or former smokers.

US Food and Drug Administration (FDA) has approved Pfizer's antismoking pill, varenicline (Chantix). The first new prescription medication approved for smoking cessation in nearly a decade, varenicline received priority review designation by the FDA because of its potential to be a significant therapeutic advance over existing therapies.

Lung cancer is estimated to be the second most commonly diagnosed cancer in both men and women in 2006, and the leading cause of cancer mortality. Non-small-cell lung cancer represents the majority of such cases. Most of these patients have locally advanced disease at presentation and are not eligible for curative resection. For the minority of patients who are technically resectable at presentation, lobectomy or pneumonectomy and pathologic mediastinal nodal staging offer the best overall survival. The high rate of comorbid medical illness and poor baseline pulmonary function in this population, however, make many such early-stage patients medically inoperable. For these patients, conventional single-modality radiotherapy has been the primary definitive treatment option, as discussed in part 1 of this two-part article. Numerous retrospective reports demonstrate long-term disease-free and overall survival data that are modestly superior to that expected after observation, but both local and distant failure continue to be significant risks. Investigation of radiotherapy dose escalation is ongoing, in an effort to improve local control while maintaining minimal toxicity. Additionally, emerging evidence suggests that new modalities, such as stereotactic radiosurgery and radiofrequency ablation, may also be potentially curative treatment alternatives. These modalities will be addressed in part 2.

The Lung Cancer Alliance hailed the US Senate's action declaring lung cancer a national public health priority and calling for an interagency coordinated attack on the number one cancer killer. Laurie Fenton, president of the Lung Cancer Alliance, praised Senator Chuck Hagel (R-NE) and Senator Hillary Clinton (D-NY) for their leadership in reaching across party lines to give the resolution their full support and expedite its passage by the Senate.

Genentech Files sBLA for Avastin for First-Line NSCLC Treatment

Changes in the 2006 National Comprehensive Cancer Network (NCCN) guidelines for non-small-cell lung cancer (NSCLC) reflect fast-moving changes in imaging, in the availability of treatment agents, and in data supporting concurrent chemoradiotherapy (CRT) over sequential chemotherapy plus radiation. David S. Ettinger, MD, of Johns Hopkins Kimmel Comprehensive Cancer Center, and Mark G. Kris, MD, of Memorial Sloan-Kettering Cancer Center, discussed the guidelines changes at the NCCN 11th Annual Conference.

During the past 18 months, researchers have developed substantial evidence supporting the notion that stem cells play a critical role in the development of at least some cancers, their progression, and the prognosis of patients, including breast, brain, lung, and prostate cancer, multiple myeloma, and melanoma.

It's been an interesting time for those of us who treat patients with lung cancer. Over the past few years, non-small-cell lung cancer (NSCLC) has been a target for the numerous companies developing agents that inhibit receptors, growth factors, signaling molecules, and genes involved in tumor growth and development. The "biologic-targeted" approach to treatment is still in its infancy, but it has already given us great expectations, some surprises, some disappointments, and, ultimately, satisfaction that we now have a nonchemotherapeutic option.

Although improved survival is the "gold standard" for proving clinical benefit of oncologic therapy, the US Food and Drug Administration (FDA) has accepted significant results in clinical trials using surrogate endpoints as the basis for drug approval. One surrogate is the amount of tumor reduction, or tumor response. Although tumor shrinkage would seem to be a necessary precondition for improved survival, clinical studies of a variety of oncologic agents have not consistently demonstrated a correlation between the two in patients with renal cell carcinoma. Moreover, tumor response may not be an appropriate endpoint for evaluating the effects of the new targeted therapies, whose putative mechanisms are generally cytostatic rather than cytotoxic. Clinical trials suggest that some patients with other solid tumors, such as lung cancer, may derive clinical benefit from treatment that helps stabilize their disease. There is also controversy as to whether the Response Evaluation Criteria in Solid Tumors (RECIST) provides the most appropriate instrument for assessing tumor burden. Ultimately, use of a variety of endpoints as well as different trial designs may provide an adequate basis for investigating the benefits/risks of newer therapies.

I was saddened to learn this morning of the death of Dana Reeve from lung cancer. Today was a reminder of what it was like to be a doctor, unable to provide a cure for a young person afflicted with cancer Each loss was a personal one, and served as a reminder of how much we needed to accomplish to prevent those tragic deaths.