Pulmonary toxicity induced by pepleomycin 3-[(S)-1'-phenylethylamino] propylamino-bleomycin

Chemotherapy regimens containing pepleomycin, a derivative of bleomycin, were used for 81 patients with advanced primary lung cancer and 32 patients with metastatic pulmonary tumors. Among the patients with non-small cell carcinoma of the lung, partial responses were observed in three of 27 patients treated with pepleomycin + carbazilquinone and four of 26 patients treated with pepleomycin + mitomycin C (published in Cancer Treatment Reports, 1983). Five partial responses (primary organ: larynx, esophagus, lung, pancreas and uterus; one patient each) in 23 evaluable patients with metastatic pulmonary tumors were observed during treatment, for an overall response rate of 21.7%. In patients with primary lung cancer, no correlation between the incidence of the decrease in partial arterial oxygen tension (PaO2) during treatment and age was observed. Decrease in PaO2 during treatment was found more frequently in patients with abnormal pulmonary function before treatment than in patients with normal pulmonary function, but the mean lowest values of PaO2 in the two groups were the same. Intravenous weekly injection of pepleomycin is less likely to result in a decrease in PaO2 than two daily intramuscular injections. Definite pulmonary toxicity occurred in seven of the 113 patients (6.2%). Each of the seven received a total dose of over 60 mg and their ages were over 60 yr, although no correlation between the incidence of pulmonary fibrosis and total cumulative dose of pepleomycin was observed. Six of the seven patients died of pulmonary fibrosis in spite of prednisone treatment. Clinical, radiologic and histopathologic findings associated with pepleomycin were the same as those of bleomycin pulmonary toxicity. Further studies are needed to determine the appropriate dose schedule and route of administration of pepleomycin with regard to its benefit and toxicity.