peplomycin and Skin-Diseases

In interdisciplinary oncotherapy by radiation and chemical substances, the injurious effects of radiation on the normal skin are occasionally modified by combined chemical substances. In the present experiment, the possible modifying effects of Peplomycin (PEP, 30 mg/kg body weight) and Camptothecin-11, an inhibitor of DNA topoisomerase I (CPT-11, 15 and 50 mg/kg body weight), on radiation skin injury were studied. Macroscopic changes on the thigh skin of male ICR hairless mice (at 8 weeks of age) induced by 10 Gy X-ray irradiation alone and the combined treatment with the anticancer substances were estimated by a modified scoring first reported by Lowy and Baker. Intraperitoneal administration of PEP significantly enhanced radiation skin injury; while CPT-11 (15 mg/kg), within the clinical dose range and in the similar molarities to that of PEP, did not show any appreciable modification effect. Treatment with CPT-11 (50 mg/kg) showed a radiation enhancement without significant difference. The chemotherapeutic radioenhancement ratios of the combined treatments of X-ray and PEP or CPT-11 (15 or 50 mg/kg) were 1.49, 1.17 or 1.34, respectively. Treatment with PEP at the accepted dose showed a radiation enhancement, while CPT-11 did not show any radiation enhancement within the clinical dose.

Topics: Animals; Camptothecin; DNA Topoisomerases, Type I; Dose-Response Relationship, Drug; Dose-Response Relationship, Radiation; Irinotecan; Male; Mice; Mice, Hairless; Mice, Inbred ICR; Peplomycin; Radiation Dosage; Radiation Injuries, Experimental; Radiation-Sensitizing Agents; Skin; Skin Diseases; Thigh; Topoisomerase I Inhibitors; X-Rays

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.

Topics: Adult; Aged; Antibiotics, Antineoplastic; Bleomycin; Breast Neoplasms; Dose-Response Relationship, Drug; Drug Evaluation; Female; Humans; Kidney Neoplasms; Lung Diseases; Middle Aged; Ovarian Neoplasms; Peplomycin; Respiratory Function Tests; Skin Diseases; Uterine Cervical Neoplasms