Modern Management of Small-Cell Lung Cancer

Abstract

In this article, we review best standard practice for the management of small-cell lung cancer (SCLC) and indicate the likely areas of development over the next 5-10 years. A number of prognostic scores have been developed and these allow more rational decisions on treatment. Treatment with cisplatin plus etoposide with early, concurrent radiotherapy is the standard of care for patients with limited-stage disease (LD) suitable for this approach. A 5-year survival rate of 25% has been reported for concurrent hyperfractionated radiotherapy; however, the applicability of this in most busy hospitals is uncertain and this treatment is currently being compared with a high-dose, once-daily regimen. Patients unsuitable for concurrent chemo-radiotherapy are treated with a sequential approach. Patients with LD responding to treatment should be offered prophylactic cranial irradiation (PCI). A variety of strategies for improving survival have been investigated. Intensification of chemotherapy has not shown any clear survival advantage, but maintenance of dose intensity in patients with good prognosis is important. The evidence around maintenance therapy is conflicting and this is not routinely used. Patients with extensive-stage disease but few other adverse prognostic factors should be treated with a platinum compound plus etoposide, and carboplatin is a reasonable choice. Responding patients should be offered PCI as this is associated with a survival benefit. The initial positive results for irinotecan have not been repeated in a larger study. Age is not a prognostic factor, but caution needs to be exercised as prognostic scores do not reflect co-morbidity. Patients with relapsed disease have a poor prognosis, but there is evidence of a survival benefit for salvage chemotherapy in those fit for treatment. The choice of treatment will depend on a number of factors, including the disease-free interval. Topotecan is the only drug licensed in this indication, but myelosuppression is considerable. A number of new drugs are under evaluation and showing promise in SCLC. One of the most promising of these is amrubicin. A large randomised study has failed to show any benefit from the addition of thalidomide to chemotherapy with carboplatin and etoposide in extensive-stage disease patients responding to chemotherapy. Studies of a number of targeted treatments are also ongoing. The challenge for the future is to identify new targets, overcome drug-resistance mechanisms and redundancy in biological systems, and incorporate these new treatments into concurrent chemo-radiotherapy schedules.

Methylation Induced Gene Silencing of HtrA3 in Smoking-Related Lung Cancer

“…A more detailed analysis identified CpG sites 4,6,7,8,11,17,20, and 21 as sites demethylated in both A540 and H157 within 48 hours of 5-aza-dC treatment. Sites that become methylated with NNK treatment seem to differ with dose and the duration of treatment.…”

“…Standard first line treatment for small-cell lung cancer (SCLC) includes platinum-based chemotherapy, generally with the DNA and protein cross-linking agent cis-platinum-(II)-diamine dichloride (cisplatin) or carboplatin plus etoposide, a topoisomerase II inhibitor, with or without radiation (3)(4)(5)(6). Treatment of non-small cell lung carcinoma may include surgical resection, radiotherapy, and/or platinum-based chemotherapy (7)(8)(9)(10).…”

Specific organ metastases and survival in small cell lung cancer

“…It is generally accepted that the life expectancy of SCLC patients depends on the extent of disease and the response to chemotherapy. Performance status (PS), gender, disease extent and response to chemotherapy have been evaluated as prognostic factors (1). Foster et al revealed that the number of metastatic sites was also a prognostic factor in ED-SCLC patients, regardless of the location of the metastatic site (2).…”

Inhibition of proliferation and apoptosis induced by a Na+/H+ exchanger-1 (NHE-1) antisense gene on drug-resistant human small cell lung cancer cells

“…During and after chemotherapy, cancer cells often become resistant to multiple drugs, which affects the effectiveness of chemotherapy and leads to increased mortality (11,36). The H446/DDP cell line was derived from H446 cells that were made resistant to cisplatin, which is in a category of drugs commonly used in clinical chemotherapy (37).…”

“…However, an effective way to treat SCLC multi-drug resistance has been reported (11). NHE-1 can directly interact with other regulatory cellular signaling pathways and is a multifaceted regulator of cell migration, proliferation, and cell death (12)(13)(14).…”