Phase I evaluation of peplomycin with special reference to pulmonary toxicity

In the search for bleomycin analogues with less pulmonary toxicity than bleomycin itself, peplomycin was selected for a phase I clinical trial, based on experimental animal data. Eighteen patients received peplomycin at three exploratory levels. Six patients were treated at a level of 5 mg/m2, 8 patients at 10 mg/m2 and 4 patients at 15 mg/m2 of peplomycin, each dosage being given twice weekly intravenously. Pulmonary function tests were performed prior to treatment and serially thereafter. Pulmonary toxicity was encountered when the administered total dose of peplomycin was in the range 190-350 mg in patients who had received either 10 or 15 mg/m2 twice weekly. Pulmonary toxicity was not observed when the dosage of peplomycin was restricted to 5 mg/m2 twice weekly. During the trial no haematological, hepatic or renal changes induced by the drug were observed. Skin changes, stomatitis and fever were observed with increasing frequency the higher the cumulative dose of peplomycin, and these effects were similar to those seen with bleomycin. Two of fifteen patients with cervical cancer obtained a partial response, lasting 1 and 2 months respectively. Although peplomycin is free from pulmonary toxicity at a dose of 5 mg/m2 twice weekly, the maximum tolerated cumulative dose has still to be defined.