Non–Small Cell Lung Cancer

Lung cancer is the leading cause of cancer-related death in both men and women in the United States. An estimated 213,380 new cases (114,760 men and 98,620 women) of lung and bronchus cancer will be diagnosed in 2007, and 160,390 deaths (89,510 in men, 70,880 in women) are estimated to occur because of the disease. Non-small cell lung cancer (NSCLC) accounts for 80% to 85% of all lung cancer cases and includes 3 major types: 1) adenocarcinoma; 2) squamous cell (epidermoid) carcinoma; and 3) large-cell carcinoma. Adenocarcinoma is the most common type of lung cancer seen in the United States and is also the most frequently occurring cell type in nonsmokers. Important updates to the 2008 guidelines on NSCLC include the addition of tables on drugs and dosing information on chemotherapy regimens for adjuvant therapy and a new section on the management of thymic malignancies.

Small Cell Lung Cancer

Small cell lung cancer (SCLC) accounts for 15% of all lung cancers. In 2007, approximately 32,000 new cases of SCLC will be diagnosed in the United States. Nearly all cases of SCLC are attributable to cigarette smoking, whereas the remaining cases are presumably caused by environmental or genetic factors. Compared with non‑small cell lung cancer, SCLC generally has a more rapid doubling time, a higher growth fraction, and earlier development of widespread metastases. SCLC is highly sensitive to initial chemotherapy and radiotherapy, but most patients eventually die from recurrent disease. These guidelines detail the management of SCLC from initial diagnosis and staging through treatment, and include information on supportive and palliative care. Important updates to the 2008 version include refined categories for performance status and the addition of topotecan as an option for patients who experience relapse.

Commentary

Should Cost of Care be Considered in a Clinical Practice Guideline?
William K. Evans, MD, FRCPC; Melissa C. Brouwers, PhD; and Chaim M. Bell, MD, PhD, FRCPC

The global increase in the burden of cancer has fueled a large investment in research into more effective treatment strategies. The payoff from this investment has been a knowledge explosion overwhelming to the average oncologist. In response, a knowledge-synthesis industry has developed; this industry uses the tools of systematic searches and standardized analytic processes to make sense of the large volume of frequently contradictory literature.  Experts review and interpret evidence in the context of professional values to guide their colleagues in clinical practice.  However, rarely if ever do these guidelines include the budgetary impacts of implementation. Is this an important omission or an irrelevancy?

Featured Articles

Lung Cancer Screening
Peter B. Bach, MD

Because lung cancer frequently presents at an advanced and incurable stage, interest has risen in developing approaches to detect lung cancer when curable. Decades of research have evaluated various approaches to lung screening, including routine chest radiograph, sputum cytology, and, most recently, CT scanning. No study has suggested that any of these approaches will identify life-threatening lung cancers at an earlier disease stage and allow alteration of their natural history. Therefore, no recommending body or professional society recommends using any of these approaches to screen for lung cancer. However, this general recommendation could change in coming years, if randomized trials examining CT screening suggest that its benefits outweigh its harms.

Adjuvant Chemotherapy for Lung Cancer: Cisplatin Doublets Only?
Daniel Morgensztern, MD, and Ramaswamy Govindan, MD

Lung cancer is the leading cause of cancer-related mortality worldwide. Despite adequate resection, more than half of patients die from recurrent disease, usually at distant sites. The main rationale for the use of adjuvant systemic chemotherapy is to eradicate micrometastatic disease. Since a seminal 1995 meta-analysis showed a trend toward improved survival with cisplatin-based adjuvant  chemotherapy, several randomized prospective adjuvant trials have been conducted and the role for platinum-based adjuvant chemotherapy in patients with completely resected stage II or IIIA non-small cell lung cancer was eventually established. Although no reliable clinical or molecular predictors of recurrent disease after surgical resection are available, preliminary data on gene expression studies are encouraging. In the near future, identifying and perhaps treating only the patients at high risk for relapse may be possible. Furthermore, molecular predictors of resistance may guide the selection of chemotherapy in this setting.

Neoadjuvant Chemotherapy in Stage III Non-Small Cell Lung Cancer
Jeffrey Allen, MD, and Mohammad Jahanzeb, MD

Non-small cell lung cancer (NSCLC) continues to be the leading cause of cancer-related mortality in the United States. Current standard care for treating NSCLC is surgical resection, when feasible, followed by adjuvant chemotherapy in stages II and III, because it has shown a survival advantage in randomized clinical trials. Neoadjuvant or induction chemotherapy may have several potential advantages compared with adjuvant chemotherapy and has been evaluated in randomized and nonrandomized clinical trials in NSCLC. This article reviews the data for neoadjuvant chemotherapy in NSCLC with a particular focus on regionally advanced disease (stage III) that is still amenable to surgical resection.

Novel Systemic Therapies for Small Cell Lung Cancer
Charles M. Rudin, MD, PhD; Christine L. Hann, MD; Craig D. Peacock; and D. Neil Watkins, MBBS, PhD

A diagnosis of small cell lung cancer (SCLC) today confers essentially the same terrible prognosis that it did 25 years ago, when common use of cisplatin-based chemotherapy began for this disease. In contrast to research on many other solid tumors, studies of combination chemotherapy using later-generation cytotoxics and targeted kinase inhibitors have not significantly impacted standard care for SCLC. The past few years have  suggested incrementally improved outcomes with the use of standard cytotoxics, including combination studies of irinotecan and amrubicin, and confirmatory phase III studies are ongoing. Antiangiogenic strategies are also of interest and in late-phase testing. Several novel therapeutics, including high-potency small-molecule inhibitors of Bcl-2 and the Hedgehog signaling pathway and a recently discovered replication-competent picornavirus, have shown remarkable activity preclinical models and are currently in simultaneous phase I clinical development. Novel therapeutic approaches based on advances in understanding of the biology of SCLC have the potential to radically change the outlook for patients with this disease.

Management of Recurrent Small Cell Lung Cancer
Bryan J. Schneider, MD

Small cell lung cancer remains one of the more frustrating malignancies oncologists treat. Although initial responses to platinum-based chemotherapy are high, most are not durable. Therapeutic options for the many patients who are candidates for further palliative chemotherapy include re-induction or single-agent chemotherapy, depending on the response duration to front-line treatment. Topotecan is the only approved agent for patients with relapsed disease. Several phase II studies showed a modest benefit with other agents, although combination chemotherapy should be avoided because of increased toxicity. Palliative care should always be the focus, especially in patients with recurrent or chemo-refractory small cell lung cancer and poor performance status.

Small Cell Lung Cancer in Elderly Patients: A Review
Taofeek K. Owonikoko, MD, PhD, and Suresh Ramalingam, MD

Approximately 40% of small cell lung cancer (SCLC) cases are diagnosed in patients over age 70, and this proportion continues to rise in contrast to a continued decline in SCLC incidence in the general population. The optimal strategy for managing limited-stage SCLC involves a combined-modality approach with platinum-based chemotherapy and external beam thoracic radiation therapy. For extensive disease, platinum-based combination chemotherapy is the mainstay. Elderly patients present unique challenges in terms of drug metabolism and organ reserve, which impact on outcomes. However, limited data are available to guide disease management in elderly patients. This article discusses treatment recommendations for elderly patients with SCLC.