Search PubMed⌕ Search

Biomedical subjects

F Villani

Publications and source records attributed to F Villani.

At least 91 records · Page 5Linked to original sources
PubMed1988

Evaluation of pulmonary toxicity induced by pepleomycin.

Spirometric parameters and transfer lung factor for carbon monoxide (TLCO) were determined in 14 cancer patients treated with pepleomycin at the dose of 10 mg twice weekly up to the cumulative dose of 200 mg. Mean values recorded after completion of therapy did not significantly differ from those recorded before treatment. Three patients pretreated with bleomycin had a fall in TLCO of more than 20% of pretreatment values. Three patients (2 of them pretreated with bleomycin) showed radiologic signs of pulmonary toxicity without instrumental signs of lung toxicity. In patients with no risk factors, no significant modifications in the tested parameters were observed after completion of therapy. These preliminary results suggest that, in the absence of risk factors, pepleomycin, may have no significant pulmonary toxicity at least up to the cumulative dose of 200 mg.

Adult↗
PubMed1988

Evaluation of cardiotoxicity of a new anthracycline derivative: 4'-deoxy-4'-iodo-doxorubicin.

The present study in rats was performed to evaluate the cardiotoxic activity of 4'-deoxy-4'-iodo-doxorubicin (4'-deoxy-4'-I-DXR), a new anthracycline derivative with interesting antineoplastic properties and possible lower cardiotoxicity than doxorubicin (DXR). DXR produced ECG alterations consisting of a progressive and irreversible prolongation of SaT and QaT. In contrast, in 4'-deoxy-4'-I-DXR-treated rats the increase in SaT and QaT duration was significantly lower than that observed in DXR-treated rats and slightly increased over controls. DXR produced significant histologic changes in myocardium consisting of myocyte vacuolization and myofibrillar loss. No significant modifications were observed in mitochondria. In contrast, no significant cardiac lesions were observed in 4'-deoxy-4'-I-DXR-treated rats. These results suggest that this new anthracycline derivative has a significantly lower degree of cardiotoxic activity than DXR.

Animals↗
PubMed1988

Effect of calcium inhibitors and calcium mobilizers on doxorubicin accumulation in rat myocardial tissue.

The effect of four calcium-modulating agents on myocardial doxorubicin (DXR) accumulation was studied: the calcium-inhibitors verapamil (0.1 microM), trifluoperazine (5 microM) and flunarizine (0.05 microM) and the calcium-mobilizer taurine (50 mM). Myocardial cells of isolated Langendorff rat hearts receiving the drugs showed a significantly enhanced 14C-DXR uptake. These observations are in contrast with the hypothesis that DXR accumulation processes may be related to a decrease in calcium influx and suggest that a combined therapy with DXR and calcium-modulating agents might enhance the drug-induced cardiotoxicity.

Animals↗
PubMed1988

Clinical evaluation of the cardiac toxicity of 4'-deoxy-doxorubicin.

4'-deoxy-doxorubicin, a new doxorubicin analog, was tested in 65 phase II patients with advanced malignancies. Cardiac toxicity evaluation was performed by means of electrocardiography (ECG), left ventricular systolic time intervals, echocardiography and radionuclide left ventricular ejection fraction. ECG abnormalities were observed in a lower percentage of patients (23%) compared to that described for doxorubicin and other anthracycline analogs such as 4'-epi-doxorubicin and 4-demethoxy-daunorubicin. Other functional parameters serially measured to evaluate chronic cardiotoxicity in 23 patients, who received more than 200 mg/m2 were not significantly different from mean pretreatment values. No patient developed congestive heart failure but some of them exhibited a fall of left ventricular function parameters more than 15% from pretreatment values. These data suggest that this new analogue is probably less cardiotoxic than the parent compound doxorubicin but not completely devoid of cardiotoxicity.

Adolescent↗
PubMed1987

A phase I study of recombinant interleukin 2 in melanoma patients. Toxicity and clinical effects.

Toxicity and clinical effects of a new brand of recombinant interleukin 2 (rIL2, BioleukinTM, Biogen, Geneva) were evaluated by a phase I study in 12 patients with stage III melanoma. Escalating doses from 100 micrograms/m2 to 800 micrograms/m2 were administered thrice a day with bolus injections given via a peripheral venous catheter for up to a maximum of 7 days. All patients showed malaise, fever and chills and mild gastrointestinal side effects. A modest electrolyte imbalance (hypocalcemia and hypokalemia) was detected in all 12 patients. Renal toxicity as judged by serum creatinine was not observed, and hepatic toxicity was moderate with the possible exception of one patient who had an unclear previous history of liver dysfunction. Mild, transient leukopenia was found in several patients, whereas thrombocytopenia developed in 4 patients; no anemia was observed. Cutaneous rash was seen in half of the patients treated. Fluid retention was minimal, with a weight gain associated to treatment that never exceeded 10% of pretreatment body weight. Electrocardiographic alterations developed in 2 patients in the form of ventricular and supraventricular extrasystoles. In 2 patients given the highest dose of rIL2, a significant reduction in transfer lung factor for carbon monoxide was seen, indicating alterations in pulmonary functions. Other dose-related toxicities were thrombocytopenia and malaise. All side effects disappeared 2-3 days after the end of rIL2 administration. No major responses were seen in association with the 4-8 days of treatment given in this study.

Adult↗
PubMed1987

Long-term results of combined chemotherapy-radiotherapy approach in Hodgkin's disease: superiority of ABVD plus radiotherapy versus MOPP plus radiotherapy.

In an attempt to reduce some of the delayed sequelae associated with combined modality therapy in Hodgkin's disease, we randomly tested stages IIB, IIIA, and IIIB MOPP (mechlorethamine, vincristine, procarbazine, and prednisone) v ABVD (Adriamycin, bleomycin, vinblastine, and dacarbazine). In 232 previously untreated patients, three cycles of either combination preceded and followed extensive irradiation. The complete remission rate was 80.7% following MOPP and 92.4% following ABVD (P less than .02). The 7-year results indicated that ABVD was superior to MOPP in terms of freedom from progression (80.8% v 62.8%; P less than .002), relapse-free survival (87.7% v 77.2%; P = .06), and overall survival (77.4% v 67.9%; P = .03). Moreover, the comparative iatrogenic morbidity showed that irreversible gonadal dysfunction as well as acute leukemia occurred only in patients subjected to MOPP, while cardiopulmonary studies failed to document significant laboratory differences between the two treatment groups. Present findings indicate that ABVD followed by extensive irradiation represents a valid therapeutic alternative to the widely used alkylating agent-containing regimens plus radiotherapy.

Adult↗
PubMed1986

Relationship between doxorubicin-induced ECG changes and myocardial alterations in rats.

The aim of the present study was to evaluate the dose- and time-dependence of the effect displayed by doxorubicin (DXR) on the electrocardiogram (ECG) and to establish the relationship between structural alterations of the myocardium and ECG changes in rats administered DXR, at a dose of 1.5 or 3.0 mg/kg, every 3 days for a total of three administrations. The most interesting findings consisted of a dose-dependent, but reversible prolongation of the QRS complex, and in a dose-dependent and progressive irreversible increase in QaT and, in particular, in SaT duration. Furthermore, animals treated with the higher DXR dose showed a slight increase in serum K+ concentration and a significant decrease in serum Ca2+ levels. A good correlation was found between the morphologic score indicating the degree of observed tissue damage and SaT prolongation. These results therefore support the usefulness of measuring this ECG parameter for monitoring the development of DXR-induced cardiotoxicity in rats.

Animals↗
PubMed1986

Cardiac arrhythmia: possible complication from treatment with cisplatin.

Cardiotoxicity is rarely observed during cisplatin chemotherapy. A possible synergistic toxic effect of cisplatin with etoposide on cardiac electrical activity is discussed. A case of a 60-year-old woman with squamous cell lung carcinoma who developed paroxysmal supraventricular tachycardia during cisplatin chemotherapy is reported. The potential cardiotoxicity should be considered when cisplatin is combined with other cardiotoxic agents or used in patients with cardiac disease.

Arrhythmias, Cardiac↗
PubMed1986

Myocardial contractility and heart pharmacokinetics of adriamycin following a single administration in rat.

A single administration of adriamycin (DXR) 6.0 mg/kg i.v. to rats brings about a biphasic impairment of the maximal myocardial contractile performance, measured as dF/dt of ex vivo isolated atria incubated in the presence of calcium concentrations varying up to 12 mM. The initial impairment of the contractile performance peaks 1 week after DXR administration and recovers within 3 weeks (acute phase of cardiotoxicity). After this time and up to the end of the observation period (8 weeks after treatment), delayed cardiotoxicity occurs, showing a progressive and irreversible impairment of the contractile performance of the atria. This behaviour parallels the previously shown ECG and morphological abnormalities. Tissue determinations of DXR showed that the drug is present in myocardium during the acute phase of cardiotoxicity, while the metabolite adriamycinol is not detectable 1 week after DXR administration. These data show that the presence of DXR and/or metabolites in heart muscle is not necessary for the delayed form of cardiotoxicity to become apparent and suggest that this form of cardiotoxicity is related to a mechanism different from that involved in acute cardiotoxicity.

Animals↗
PubMed1986

New anthracycline analogs in advanced breast cancer.

To test the activity and toxicity of new anthracycline analogs, a series of Phase II disease-oriented studies were performed in women with advanced breast cancer previously untreated with doxorubicin. All drugs were administered every 3 weeks, and the doses in mg/m2 were as follows: doxorubicin and epirubicin 75 i.v., esorubicin 35 i.v., idarubicin 13 i.v. and 45 p.o. When epirubicin was tested vs doxorubicin, both response rate (13 of 21 or 62% vs 11 of 21 or 52%) and median response duration (11 months vs 13 months) were comparable. In 24 patients, esorubicin yielded complete plus partial response in 21% with a median duration of 15 months. In 27 patients given idarubicin intravenously the response rate was 11% for 4 months and the corresponding findings when the drug was administered orally to 25 women were 24% for 8 months. Acute toxic manifestations were lower following treatment with all three analogs compared to doxorubicin. Cardiac toxicity, as documented by echocardiography, systolic time interval and left ventricular ejection fraction was virtually absent following therapy with epirubicin and idarubicin. After a median cumulative dose of 600 mg/m2 for doxorubicin-treated women there was a significant fall in LVEF compared to basal values. Similar findings were observed after a median cumulative dose of 210 mg/m2 for esorubicin. We conclude that epirubicin is as effective as doxorubicin but comparatively less toxic when administered at the same dose schedule. At the doses and schedules utilized in this study, esorubicin and idarubicin resulted less active in breast cancer.

Adult↗
PubMed1986

Paroxysmal supraventricular tachycardia during treatment with cisplatin and etoposide combination.

We report a case of a 60-year-old woman affected by squamous lung carcinoma, who developed paroxysmal supraventricular tachycardia during cisplatin and etoposide combination chemotherapy. Cisplatin toxicity on cardiac electrical activity is discussed. This observation might suggest caution when cisplatin is used in patients with cardiac disease or pretreated with other potential cardiotoxic antineoplastic agents.

Antineoplastic Combined Chemotherapy Protocols↗
PubMed1986

Ambroxol and pulmonary toxicity induced by antineoplastic drugs.

The authors describe the potential effects of ambroxol on the pulmonary disorders induced by antineoplastic agents (in particular, bleomycin and the nitrosureas). An experimental stage focussed attention on the early modifications occurring in the alveolar surfactant and in the afflux of inflammatory and immune-effector cells following bleomycin-induced lung fibrosis in the rat (by intratracheal instillation). The ambroxol-protected rats showed a slower drop of alveolar lecithins in the first few hours after bleomycin administration and a lower afflux of neutrophils, macrophages and lymphocytes. In the clinical stage, respiratory function was studied in two groups of cancer patients treated with nitrosureas or bleomycin. Preliminary findings indicate a rapid worsening of some functional parameters--maximal expiratory flow at 25% vital capacity, diffusing capacity for carbon monoxide and diffusing capacity/ventilation--in controls, while no such changes occurred in the ambroxol-protected subjects. The possible pathogenetic implications of these results and perspective for future investigations are discussed.

Ambroxol↗