peplomycin and Lung-Diseases

A review of hard-copy computed tomography (CT) images of patients who had undergone chemotherapy for testicular teratoma revealed that the incidence of lung toxicity appeared to be lower in those who had received bleomycin by slow infusion [EBCi (3) regimen, etoposide/bleomycin/cisplatin] rather than by intravenous bolus [PVB regimen, cisplatin/vinblastine/bleomycin; BEP (5) regimen, bleomycin/etoposide/cisplatin]. This difference reached statistical significance only for PVB vs EBCi (3) (t = 2.63, P less than 0.01). Nevertheless, in view of continuing reports of mortality resulting from bleomycin-induced pulmonary fibrosis in patients receiving the drug by i.v. bolus, further exploration of these results is clearly justified.

Topics: Antineoplastic Combined Chemotherapy Protocols; Bleomycin; Cisplatin; Etoposide; Humans; Lung Diseases; Peplomycin; Tomography, X-Ray Computed; Vinblastine

In order to find a method to ameliorate pulmonary toxicity of peplomycin (PEP), microscopic changes of the lung following PEP administration and effect of anti-platelet aggregating agents on the toxicity was investigated in mice. When PEP was administered intravenously once a day for 7 days, microthrombi mainly composed of aggregated platelets and fibrin appeared in the capillaries of the lung in an early phase before severe pulmonary edematous lesions and fibrosis occurred. Combination therapy of anti-platelet aggregating agents such as phthalazinol, dipyridamole, ticlopidine and indomethacin suppressed these toxic changes. Especially, ticlopidine was the most effective and superior to prednisolone used clinically for amelioration of the toxicity. Microthrombi, preceding edematous lesions, were considered to be attributed to damages of endothelium by PEP, because PEP itself did not develop platelet aggregation in vitro and ex vivo. Therefore, the microthrombi are likely to produce congestion of pulmonary microcirculation leading to edematous lesions by increase of permeability, and to play significant roles in the development of pulmonary fibrosis in a late phase. Anti-platelet aggregating agents such as ticlopidine are concluded to ameliorate the lung toxicity by preventing microcirculation impairment with the microthrombus.

Topics: Animals; Bleomycin; Lung Diseases; Male; Mice; Mice, Inbred ICR; Peplomycin; Platelet Aggregation Inhibitors; Pulmonary Edema; Pulmonary Embolism; Pulmonary Fibrosis; Ticlopidine

We studied the long term cardiopulmonary function, at rest and during exercise, of 57 patients who were at least 1 year (mean 5 years) post-treatment for Hodgkin's disease. To establish the maximum degree of dysfunction we studied 40 patients who had extensive intrathoracic disease treated with radiotherapy alone (Exten-X; n = 20) or combined modality therapy (Exten-XC; n = 20). Patients without intrathoracic disease given either prophylactic mantle therapy (Proph-X, n = 10) or no chest irradiation (. n = 7) were used as controls. An abnormal electrocardiogram, by virtue of a conduction defect, was observed in seven patients, six in the Exten-X or Exten-XC groups. Borderline abnormalities including ST-T changes, prolonged QT interval, or axis deviation occurred in 14 patients distributed evenly throughout the groups. Resting mean pulmonary function test values were normal in all treatment groups. Exercise tolerance, as indicated by peak oxygen consumption (VO2), was significantly lower for the Exten-XC group compared to Proph-X (p less than 0.01). However, the mean value of VO2 for group Exten-XC was only 15% below that predicted. Of the 12 patients with abnormally low VO2 (greater than 20% below their predicted value), 11 were in the Exten-X or Exten-XC group with no difference between the two groups. Patients who received radiotherapy to at least one lung field, using either the thin lung block technique or open field irradiation, had significantly lower exercise tolerance than those treated with full thickness blocks (p less than 0.05). Despite these abnormalities only a single patient complained of marked dyspnea. We conclude that extensive treatment to the mantle field, especially when followed by chemotherapy in patients with extensive intrathoracic Hodgkin's disease, can result in minimal cardiopulmonary dysfunction in approximately one-third of patients.

Topics: Adolescent; Adult; Antineoplastic Combined Chemotherapy Protocols; Bleomycin; Body Composition; Electrocardiography; Female; Heart Diseases; Hodgkin Disease; Humans; Lung Diseases; Male; Mechlorethamine; Middle Aged; Nimustine; Nitrosourea Compounds; Peplomycin; Procarbazine; Radiotherapy; Respiratory Function Tests; Vincristine

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