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The current biological agents available have demonstrated significant efficacy and an acceptable toxicity profile in the metastatic setting as well as in the second-line setting. It is unlikely that oral TKI therapy will be instigated as maintenance therapy given the recent results of two cooperative group trials. Preclinical data have indicated that oral TKI therapy also appears to have the potential to act as a radiation sensitizer, and may have a role in the chemoradiotherapy portion of stage III treatment. The use of monoclonal antibodies to target the EGFR is also an area of active interest. The fact that preliminary evidence indicates that these monoclonal antibodies can be combined with chemotherapy without a significant increase in toxicity is promising and these agents may have a role in treatment of systemic disease. The synergy between radiation therapy and monoclonal antibodies directed at EGFR may improve local-regional therapy in stage III disease. The activity of bevacizumab in combination with standard chemotherapy and in the second-line setting in a select group of patients is also quite promising. The integration of these agents into current treatment paradigms for locally advanced disease is currently being explored in many cooperative group and institutional phase II trials, and the results of these trials are eagerly awaited.

Platinum compounds provide the foundation for the treatment of patients with advanced NSCLC. Treatments with such regimens offer patients with an improvement in good performance status, in quality of life and prolonged survival, compared to BSC. Carboplatin very likely offers similar efficacy outcomes compared to cisplatin in this setting, and with less toxicity. Treatment with a platinum-based doublet incorporating a newer, third-generation cytotoxic agent is the recommended therapy for good-performance-status patients with advanced NSCLC, yielding an approximate response rate of 30%, median survival of 8–12 months, 1-year survival of 30%, and 2-year survival of 10%. No single regimen is recommended as superior; selection of the regimen can be flexible, contingent upon the patient’s comorbidities, treatment cost, and administration schedule. Adding a third cytotoxic agent is only likely to exacerbate toxicity, without improving efficacy. Treatment should be limited to four cycles in patients with stable disease, and possibly a maximum of six cycles, as tolerated, in responding patients. Age alone should not preclude consideration for treatment with a platinum doublet, although prospective data using platinum agents in studies restricted to elderly patients are lacking. Finally, research continues into the identification of platinum-sensitive patients based upon pharmacoge-nomic parameters, and the development of newer platinum compounds.

The development of cerebral metastases represents a life-threatening condition in patients with NSCLC. The approach to management should be guided initially by consideration of the relevant prognostic factors. The RTOG RPA classification, which is based on age, the presence or absence of extracranial disease, and the Karnofsky performance status, functions as a useful means of dividing patients into groups with different outcomes. The RPA can be used to select patients for either aggressive management with potentially curative intent (for patients in RPA class 1), more palliative treatment (RPA class 2), or best supportive care (RPA class 3). Surgery, WBRT and radiosurgery may all have a role in treatment. There is a pressing need for appropriately controlled randomized trials to define more accurately the indications for each of these modalities.

Although the selected information from randomized clinical trials for therapeutic management of lung cancer in the elderly seems to need further evaluation, some conclusions can be drawn from the published data. First of all, treatment approaches should be tailored to individual patients and based upon the patient’s biological age and not their chronological age. For early stage lung cancer patients with good performance status and satisfactory cardiopulmonary reserves, the first therapeutic option is represented by surgery. In the presence of contraindications, radiotherapy is the alternative solution. Patients with a locally advanced disease and a good performance status should benefit more from radiochemotherapy, while frail patients should receive radiotherapy alone. Systemic chemotherapy offers the best potential results for metastatic disease. Single-agent chemotherapy with vinorelbine represents the first choice for elderly patients with good performance status, with the alternative of the single agent gemcitabine. In only very selective patients may the use of combination chemotherapeutic agents be given. Physicians should overcome their fears for possible surgical complications or unmanageable chemoradiotherapy toxicities when treating elderly people. Careful selection of individuals and detailed clinical assessment of comorbidities leads to effective management of this disease.

The use of combination chemotherapy for SCLC has contributed to significant improvements in local control and survival in limited-stage disease. The initial enthusiasm generated by these significant therapeutic advances has waned with the realization that a plateau has been reached and no additional survival increments have been gained in the last decade. While a number of chemotherapy regimens may be equivalent to EP or EC, alternating regimens or dose-intense regimens have not gained widespread acceptance. The role for thoracic irradiation and prophylactic cranial irradiation in LDSCLC has been firmly established. What remains to be determined is whether chemotherapy combinations incorporating some of the newer “targeted” agents will move us away from this therapeutic plateau.

The treatment of patients with extensive SCLC still remains palliative. In this setting, it is highly important to include patients in clinical trials that evaluate new drugs. For patients who can not be included in trials, the treatment should be tailored according to performance status and patients’ wishes. Three options can be discussed: a four-drug combination when performance status is unaltered, a standard etoposide/cisplatin regimen when there is a minimal alteration of performance status, and when the patient asks for a good quality of life. The combination of carboplatin and etoposide should be given only to patients who present an important performance status alteration or a contraindication to a standard chemotherapy.