Small cell lung cancer (SCLC) : high dose chemotherapy and autologous bone marrow transplantation

In the United States, it is estimated that the yearly incidence of lung cancer is about 150.000 with approximately 110.000 deaths from this disease. Lung cancer remains the number one cancer killer among males, accounting for 35% of cancer death. Among female, the incidence of lung cancer has recently surpassed that of all other cancers, included breast cancer and deaths of lung cancer in the female population accounts for 19% of the all cancer deaths. This evolution is clearly related to smoking habits (Spiro S.G., 1988).
There are four major histological subtypes of lung cancer namely squamous cell carcinoma, adenocarcinoma, and large cell carcinoma (collectively referred to as non-small cell lung cancer), and small cell lung carcinoma (SCLC). SCLC accounts fro 25% of all new cases of lung cancer. Among the various histological types of lung cancer, SCLC is the most chemo- and radiosensitive. While the majority of patients will obtain an initial response to cytotoxic therapy, overall survival is poor and less than 5% of all patients will be cured. With the most effective treatment, the median survival time for SCLC patients ranges from 9 to 13 months.
As in many other areas on oncology, our basic understanding of small cell lung cancer has increased over the past years and many data suggest that biological properties inherent within the tumor cells themselves may be of prognostic importance, including expression of genes or oncogenes. In the first chapter, we will discuss recently discovered biological properties of SCLC, including their first applications to the management of patients with the disease.
This management will be the subject of the second chapter. Because it is well recognized that prognostic factors and stratification are crucial to compare the results of different studies, we will focus on these points before describing the up-to-date therapy of SCLC.
As was pointed hereabove, patient’s survival is short and new studies are needed to improve therapy. SCLC is chemosensitive and a clear dose-response relationship was demonstrated in the 1980s leading to the present therapeutic results. With the use of autologous bone marrow transplantation, higher doses of cytotoxic therapy can be delivered, overcoming the limiting toxic effect of most cytotoxic drugs i.e. the bone marrow aplasia. We initiated a randomized trial to compare the effect of a late high-dose intensification therapy followed by autologous bone marrow transplantation with the results of conventional dose chemotherapy. This trial and its impact on SCLC therapy either at the present time or in the future form the third chapter of this work.
The technique of autologous bone marrow transplantation raises some questions among which the risk of the bone marrow contamination with neoplastic cells and the need of purging such graft. Newly developed techniques to solve such problems as well as our contribution in this field are treated in the fourth chapter