Chemotherapy and Radiation Therapy

Clinical Biology of Small Cell Lung Cancer

Small cell lung cancer established itself as an entity distinct from other types of lung cancer, based on several clinical observations made in the 1960s. The prognosis after surgical treatment was dismal, as demonstrated by the British Medical Research Council randomized trial of surgery versus radiation therapy. This study showed a 5-year survival rate of 1% and no cures by surgery, only a

50% resection rate in patients randomized to surgery, and a better (though still poor) outcome for the patients assigned to the radiation therapy arm.

An autopsy study done at the U.S. National Cancer Institute demonstrated

the reason for the poor outcome after local treatment of small cell lung cancer. In patients dying within 30 days of apparent complete resection, 70% had demonstrable metastases and regional persistence of small cell cancer at postmortem examination. The VA Lung Group found that the survival of small cell lung cancer patients could be prolonged by chemotherapy in a prospective randomized placebo control study.(4) This was not true for the other lung cancer cell types. Finally, analysis of the data base, upon which the original American Joint Commission on Cancer Staging TNM staging system was based, showed a 2-year survival rate of 5% for small cell lung cancer patients regardless of stage.(5)

As a consequence of these types of observations, small cell lung cancer was considered a nonsurgical disease. It was regarded to be metastatic by definition and was placed within the purview of the medical oncologist by virtue of its responsiveness to chemotherapy.(6)

Chemotherapy and Radiation Therapy

During the late 1970s and early 1980s, the effectiveness of chemotherapy increased when new agents such as Adriamycin, cisplatin, and etoposide became available and were incorporated into combination regimens. The strategies of adjuvant chemotherapy and multimodality therapy were developed and found to be useful for treatment of some types of cancers in certain clinical situations.

Since small cell cancer is responsive to chemotherapy, it became the object of aggressive treatment programs. Response rates rose to the 60 to 70% range, including complete remissions, especially in limited stage disease (confined to the lung of origin and mediastinum). Sites of relapse became an issue, and the role of chest irradiation was established to try to minimize “recurrence” (actually persistence) at the primary site. (7) However, there is local recurrence (treatment failure) at the primary site in about one-third of cases despite the combining of chest irradiation with chemotherapy. Over the past 15 years or so, little progress has been made in improving the chemotherapy for small cell lung cancer so that the median survival for limited-stage patients remains slightly over 1 year and the search for additional effective systemic agents continues. (8, 9)