Esorubicin (4'-deoxydoxorubicin or DxDx) is an analog of doxorubicin with preclinical antitumor activity and no significant cardiotoxicity in model systems. Eleven patients with small cell lung cancer who had previously received chemotherapy were given esorubicin (25 mg/m2 intravenously) every 3 weeks. No major objective responses were observed (95% confidence limits: 0-25%). Nine of the 11 patients had grade 2 or greater toxicity, with 55% of the patients experiencing grade 3 or greater toxicity [myelosuppression (4/11), anemia (2/11) or elevated liver enzymes (3/11)]. Nausea, vomiting, alopecia and intravenous site phlebitis were also seen. Three of the 11 patients received 3 or more course of esorubicin without evidence of significant cardiotoxicity. At this dose and schedule, no significant antitumor response were seen in this population of patients. Esorubicin, with this low response rate and significant toxicity, appears to be of limited utility in this disease.