PULMONARY-FUNCTION CHANGES IN LUNG-CANCER PATIENTS TREATED WITH RADIATION WITH OR WITHOUT CARBOPLATIN

In order to examine changes in pulmonary function in patients with locally advanced non-small-cell lung cancer (NSCLC) before, during, and after standard radiotherapy or combined chemoradiotherapy, we conducted a prospective study involving patients with such cancer, who were treated with radiation alone or with concurrent radiation and carboplatin from October 1992 to February 1994 at the University Hospital in Groningen, the Netherlands. Thirty-five patients were treated. Two patients were excluded because of pulmonary emphysema. Pretreatment values of TLC, VC, the gas-transfer coefficient (Kco), the pulmonary diffusing membrane factor (Dm), and pulmonary capillary blood volume (Vcap) were lower than in normal subjects and patients with chemotherapy-naive germ-cell carcinoma who had a similar pulmonary tumor load as the result of hematogenous metastase. The NSCLC patients' reduced Kco was explained by a decrease in Dm, a measure of alveolar-capillary membrane disturbance, and a similar decrease in Vcap. Pretreatment TLC did not correlate with Vcap or Dm, indicating extra- rather than intrapulmonary vascular and lymphatic obstruction as an explanation for the reduced Vcap and Dm. Locally advanced NSCLC was treated with radiation (n = 16) or combined continuous carboplatin infusion and radiation (n = 17). No changes in TLC, VC, Kco, Dm, or Vcap were observed during and 2 wk after the end of either treatment, nor were any differences in pulmonary function observed with the two treatments, indicating an absence of additional acute pulmonary toxicity caused by continuously infused carboplatin in this patient group. Neither total or free plasma platinum levels measured at weekly intervals during 6 wk of treatment with continuously infused carboplatin nor the area under the total plasma platinum concentration curve correlated with Kco, Dm, or Vcap. After a half year, TLC decreased by 10%, while Kco, Dm, and Vcap remained unchanged. The most characteristic disturbance of pulmonary function in untreated, locally advanced NSCLC is a reduced Kco. An unchanged 30% reduction in Dm and Vcap at 2 to 6 mo after the beginning of radiation therapy with or without continuously administered carboplatin is explained by an unrelieved obstruction of the mediastinal vascular and lymphatic system. The addition of continuously infused carboplatin to radiation did not add any pulmonary toxicity in this patient group.