Experience of the National Cancer Institute (USA) in the treatment and biology of small cell lung cancer.

This retrospective study deals with 168 patients with small cell lung cancer (SCLC) who were treated at the NCI March 1973 and July 1977 with intensive chemotherapy. Results showed that 12 per cent of all the patients were disease-free for more than 40 months (25% of the limited disease and 3% of the extended stage disease patients which were treated. Complete remission was essential to prolonged survival. The development of a complete remission was favored by a satisfactory initial general condition, localised disease or presence of only one site of metastatic disease. Initial treatment included the following combinations: cyclophosphamide, methotrexate and CCNU. High doses are necessary. However, above a certain level, the toxicity increased without a corresponding increment in activity. Addition of another association without cross-resistance (vincristine-adriamycine-natulan or VP-16 and isophosphamide) may induce a complete remission in cases where only a partial remission was obtained initially. In limited disease, radiotherapy seemed to prolong disease-free survival. This lead the authors to study the use of initial radiotherapy, at the rate of 40 grays in 3 weeks in 15 fractions, at the same time as chemotherapy. The radiotherapist must take certain precautions in the use of this double treatment: reshaped fields and insertion of a spinal cord block above 2 000 rads. In extended disease, thoracic irradiation seemed to be of no benefit. Pilot studies are not underway using intensive chemotherapy with multiple tumor site irradiation and autologous marrow implants 48 per cent of all patients with SCLC will develop cerebral metastatic disease (44% intracranial, 13% leptomeningeal, 9% epidural). At 30 months, 75 percent of those who did not receive prophylactic irradiation developed cerebral disease whereas only 40 per cent of the patients who received a prophylactic dose of 30 grays developed cerebral disease. Inspite of the indisputable but incomplete local benefit of prophylactic brain irradiation, it did not prolong survival. Important biological studies are underway at the NCI. - Cell clone cultures have been established. These were enhanced by the addition of arginine vasopressive (AVP) and bombesine. These two substances may be considered as markers of APUD system and are secreted by the SCLC. Bombesine has been isolated in all the cultures tested. This possible marker was perhaps responsible for the anorexia and cachexia in these patients. - These cultures have allowed for identification of deletion 3p (14-23) chromosome anomalies in all the samples examined. - In vitro chemotherapy studies of these cultures have been carried out. Their correlation with clinical results were encouraging (100% negative p/n; 75% positive p/n). - Lastly, monoclonal AC have been prepared. Inspite of their imperfect specificity and heterogeneity with regard to tumor cells, their potential advantages were considerable.