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Biomedical subjects

F Pannuti

Publications and source records attributed to F Pannuti.

At least 73 records · Page 4Linked to original sources
PubMed1988

Treatment of advanced head and neck tumors with PEV-B regimen: a pilot study.

Thirty-seven patients with advanced head and neck tumors were treated with a polychemotherapy regimen (PEV-B: platinum 30 mg/m2 i.v., epirubicin 30 mg/m2 i.v., etoposide 75 mg/m2 i.v. on days 1 and 2 every 28 days, and bleomycin 15 mg i.m. weekly up to the total dose of 300 mg). All but 7 patients were pretreated with surgery and/or radiotherapy. Thirty-six patients were evaluable for response. Partial response (PR) was observed in 19 cases (53%), no change (NC) in 13 cases (36%) and progression (P) in 4 cases (11%). The median duration of PR was 5 months. The most frequent side-effects were leukopenia (78%), vomiting (57%) and alopecia (46%). The median duration of survival was 8 months for the responders and 5 months for the non-responders.

Adult↗
PubMed1988

Mitoxantrone, 5-fluorouracil and cyclophosphamide in advanced breast cancer.

Thirty patients with advanced breast cancer, not pretreated with chemotherapy, received a polychemotherapy regimen containing mitoxantrone, fluorouracil and cyclophosphamide at the dose of 10 mg/m2, 500 mg/m2 and 500 mg/m2 i.v. respectively every 28 days. Out of 25 patients evaluable for response 9 patients achieved a partial remission (36%) for a median duration of 20.5 weeks. The main side effects were leukopenia (grade 3-4 in 70%) and nausea-vomiting (grade 3-4 in 27%). Alopecia was present only in 5 patients (17%). Three patients demonstrated instrumental signs of cardiotoxicity without clinical symptoms.

Adult↗
PubMed1988

Pharmacokinetics of PTT-119 in man.

The pharmacokinetics of PTT-119, a new alkylating agent, was studied in 8 advanced cancer patients. PTT-119 disappeared rapidly from plasma after administration at a dose of 3 mg/kg by i.v. bolus injection. The HPLC method shows plasma levels of m-bis (dichloroethyl)amino-phenyl-L-alanine which is the major metabolite of PPT-119. Elimination of the drug from plasma can be described by a one-compartment model. Mean values of 77.8 min for the half-life, 510.8 ml/min for the total plasma clearance and 0.69 l/kg for the volume of distribution were found.

Aged↗
PubMed1987

Medroxyprogesterone acetate plasma pharmacokinetics after intravenous administration in rabbits.

Medroxyprogesterone acetate (MAP) plasma pharmacokinetics was followed up in a total of 30 New Zealand rabbits after i.v. administration (0.1, 0.5, and 1.0 mg/kg) of either an aqueous suspension or a homogeneous solution of the drug in dimethylsulphoxide (DMSO). A well-defined triphasic decay of MAP plasma levels was noticeable in the animals treated with DMSO solutions. A delayed concentration peak was often present when aqueous suspensions were used, so if is not feasible to fit the experiment with simple polyexponential equations. Model-independent pharmacokinetic analysis (statistical moment theory) revealed a significant dependence of plasma clearance and mean residence time on the dose administered in both conditions.

Animals↗
PubMed1987

Medroxyprogesterone acetate at very high doses in postmenopausal advanced breast cancer patients.

Twenty-six postmenopausal consecutive patients with advanced breast cancer were treated with very high medroxyprogesterone acetate doses (4000 mg/day orally for 30 days and then 3000 mg/day orally until progression or intolerance). The dominant metastatic lesion was bone in 13 patients, soft tissue in 3 patients and viscera in 10 patients (C.I. = V/ST + 0 = 0.62). An objective partial remission was achieved in 16 pts (61%), no change in 8 (31%), progression in 2 (8%). The median duration of objective remission was 7.5+ months with a median survival of 14.5+ months in responders. Toxicity was minor and only two patients discontinued the treatment because of side-effects. These results confirm the utility of medroxyprogesterone acetate at very high doses in these patients and the feasibility of this kind of dose.

Adult↗
PubMed1987

4'-Epidoxorubicin plus cisplatin as first-line therapy in the treatment of small cell bronchogenic carcinoma.

Twenty-seven patients with small cell bronchogenic carcinoma were treated with a combination of 4'-Epidoxorubicin 60 mg/m2 and cisplatin 50 mg/m2 i.v. every 3-4 weeks. Three patients (11%) had a complete remission (CR), and 12 (44%) had a partial remission (PR) with a 55% overall remission rate. The median duration of response was 36 weeks (range 11-256+). No severe bone marrow depression was noted. The other side effects were of mild grade. Because of the "minimal aggressiveness" of this combination for the patients, the results obtained in this preliminary phase can probably be improved by the integration of other drugs in the scheme.

Adult↗
PubMed1986

Biliary excretion and pharmacokinetics of 4'epidoxorubicin (epirubicin) in advanced cancer patients.

Plasma pharmacokinetics and biliary and urinary excretion of the new doxorubicin analogue, epirubicin, have been studied in three patients with extrahepatic obstruction and percutaneous biliary drainage. At variance with the reported observations concerning doxorubicin metabolism, conjugation of epirubicin and 13-dihydroepirubicin with glucuronic acid takes place, and corresponding amounts of 4'-o-beta-D-glucuronyl-4'-epidoxorubicin and 4'-o-beta-D-glucuronyl-13-dihydro-4'-epidoxorubicin can be found in the bile and urine. The total amount of unaltered drug and metabolites excreted in the bile in the first 4 days after treatment accounts for the 37%, 27%, and 40% of the administered dose; urinary excretion accounts for 19%, 16%, and 26%. Biliary clearance of epiDX (32.5, 8.1 and 21.6 l/h) is higher than renal clearance (15.2, 3.3 and 9.41 l/h). The relevance of the biliary disposition of epirubicin suggest prudent dose reduction in patients with impaired biliary drainage.

Bile↗
PubMed1986

Low dose oral administration of 4-demethoxydaunorubicin (idarubicin) in advanced cancer patients. A pharmacokinetic study.

Data relating to 4-demethoxydaunorubicin (DMDR) pharmacokinetics after oral administration (10-15 mg/m2 per day for 3 days) were collected in a total of 12 patients with advanced breast cancer and melanoma. Drug absorption took place in the first 2-4 h after administration. Plasma levels of the reduced metabolite DMDRol were higher than those of the parent compound: Peak levels were 4-10 ng/ml for DMDR and 15-40 ng/ml for DMDRol. The dose-corrected area under the time-concentration curve (AUC) was consequently higher for DMDRol (12.3-74.7, mean 32.6 vs 2.4-7.4, mean 4.6 ng/ml.mg for DMDR). Apparent plasma terminal half-lives after the last dose administered were in the range of 13-36 (mean 23.7) h for DMDR and 30-81 (mean 58.9) h for DMDRol. Drug and the reduced metabolite accumulated in the blood cells; the ratio of AUC (blood) to AUC (plasma) was 1.40-3.75 (mean 2.80) for DMDR and 1.29-3.50 (mean 2.16) for DMDRol. The biliary excretion of the drug and of the fluorescent metabolites was studied in two additional patients with extrahepatic obstruction and percutaneous biliary drainage. In the first 7 days of therapy, biliary excretion (DMDR + DMDRol) accounted for 3.7%-4% of the administered dose. In contrast to our observations with doxorubicin and epirubicin, urinary excretion seems very likely to be more important for this drug than biliary excretion. In these patients urinary excretions were 2.2, 2.9 times (for DMDR) and 1.2, 3.4 times (for DMDRol) the biliary excretion.

Administration, Oral↗
PubMed1986

Intrahepatic arterial administration of 4'epidoxorubicin (epirubicin) in advanced cancer patients. A pharmacokinetic study.

Epirubicin (epiDX) pharmacokinetics was followed in 10 advanced cancer patients with hepatic metastases from colorectal carcinoma or primary liver tumor after single bolus administration (20-40 mg) in the hepatic artery, through a surgically implanted catheter and subcutaneous access port. EpiDX plasma and whole blood concentrations follow a triphasic decay qualitatively similar to that observed after IV administration. Blood levels are consistently higher than plasma levels. Plasma clearance (nine patients, mean: 93.4 l/hr; range: 69.3-129.5 l/hr) is higher than the corresponding parameter determined in patients with hepatic metastases after intravenous therapy. The remaining patient is characterised by an abnormally low plasma clearance (13.6 l/hr), due to a hepato-pulmonary shunt. The subjects in this study were exposed to very low drug concentrations, and therefore experienced no relevant adverse side-effects.

Aged↗
PubMed1986

MPA at high doses in advanced breast cancer: a statistical evaluation.

A computerized, retrospective analysis of clinical and pharmacokinetic data relative to 380 cancer patients under medroxyprogesterone acetate (MPA) therapy has been carried out. A bioavailability:objective- response correlation was found only for mammary cancer patients with visceral metastases and a pain-control effect was observed in advanced cancer patients when MPA plasma levels were higher than 150-200 ng/ml. Discriminant analysis of the known prognostic factors for breast cancer indicates that receptorial status, site of predominant metastases, basal alkaline phosphatase and free interval are good predictors for possible clinical response, while the behavior of prolactin and previous treatments are predictors for non-response. There is no improvement in the efficacy of prediction in combining more than one prognostic factor.

Administration, Oral↗
PubMed1986

Medroxyprogesterone acetate plasma levels after a single oral administration of two drug formulations.

A comparison has been made between the absorption of oral medroxyprogesterone acetate (MPA) in an aqueous suspension preparation and in syrup form. Plasma drug profiles were measured after a single administration of the two formulations in 17 advanced cancer patients. On average the standard form (aqueous suspension) gave peak levels which were lower than the syrup mixture. However, the wide intersubject spread in MPA plasma levels observed in both groups did not allow any statistical significance to be assigned to this difference.

Administration, Oral↗
PubMed1986

Phase II studies on weekly cisplatinum plus epirubicin or etoposide in the treatment of advanced non-small cell bronchogenic carcinoma.

Thirty-six patients with advanced non-small cell bronchogenic carcinoma were divided in 2 groups for treatment with two different platinum-based combination therapy regimens. All 16 patients who received the weekly administered combination of 10 mg/m2 cisplatin (CDDP) plus 10 mg/m2 epirubicin (4EPIDX) experienced no clinical response. Among the 20 patients who received the combination CDDP (10 mg/m2) plus etoposide (VP16, 60 mg/m2) weekly, 4 of them (20%) showed partial remission (PR). The side effects of both combinations were of mild grade. Further study is needed to verify the effectiveness of the weekly combination of CDDP and VP16 by comparing the above regimen with the "standard" intermittent doses.

Aged↗
PubMed1986

A pilot study of oral idarubicin in metastatic melanoma.

Seventeen patients with disseminated melanoma were treated with Idarubicin (IDA) at the dose of 15 mg/m2 daily for 3 consecutive days every 4 weeks by oral route. One complete remission and one partial remission were achieved (remission rate: 12%). The treatment was well tolerated. We conclude that oral IDA may be considered for a pilot trial in a regimen of combination therapy in patients with metastatic melanoma.

Administration, Oral↗
PubMed1985

First-line combination chemotherapy with mitoxantrone and cyclophosphamide in advanced breast cancer.

In this study, 30 evaluable patients with advanced carcinoma of the breast were treated with cyclophosphamide 600 mg/m2 i.v. followed one day later with mitoxantrone (Novantrone; dihydroxyanthracenedione) 16 mg/m2 i.v. Drug treatment was repeated every 3-4 weeks, for a maximum of 12 cycles. The overall response rate was 43%; five of 30 patients (16%) attained a complete remission, and eight of 30 (27%) had a partial remission. Median response duration was 12+ months. The greater number of responses was seen in skin and soft tissues. Hematologic toxicity was limiting with 75% of patients experiencing substantial-severe leukopenia. Clinically evident heart failure developed in one patient; in three other patients there was minor-moderate alteration of cardiac function during mitoxantrone-cyclophosphamide therapy. Based on these data, it is believed that this regimen may provide significant long-lasting palliation in patients with advanced breast cancer.

Adult↗
PubMed1985

Medroxyprogesterone acetate (MAP) and tamoxifen (TMX) plasma levels after simultaneous treatment with 'low' TMX and 'high' MAP doses.

Plasma levels of medroxyprogesterone acetate (MAP), tamoxifen (TMX) and its major metabolites, 4-hydroxy TMX and desmethyl TMX, were determined in five patients with advanced breast cancer following simultaneous MAP (2,000 mg/day) and TMX (20 mg/day) oral therapy. The interindividual variance in MAP plasma levels was wide; the mean plasma levels of both drugs were nearly identical, despite the large difference in the administered doses.

Antineoplastic Combined Chemotherapy Protocols↗
PubMed1985

Medroxyprogesterone acetate bioavailability after high-dose intraperitoneal administration in advanced cancer.

Administration of medroxyprogesterone acetate IP in advanced cancer with peritoneal metastases and ascitic effusion generates considerably higher drug plasma levels than those observed after PO or IM treatment. Comparison of areas under the time-concentration curves (AUC) with reference to the three administration routes indicates that after oral administration only 0.2%-17.4% (mean 5.7%; SD 3.77; 40 patients) of the administered dose is absorbed; after IM treatment a daily absorption of 0.7%-7.7% (mean 2.5%; SD 1.66; 30 patients) of the administered dose per injection site was computed.

Antineoplastic Agents↗
PubMed1985

Activity of 4-demethoxydaunorubicin by the oral route in advanced breast cancer.

The new anthracycline-analogue 4-demethoxydaunorubicin (4-DMDR) was administered orally at the dose of 15 mg/m2 daily for three consecutive days and repeated every 21-28 days on 29 patients with advanced pretreated breast cancer. A partial remission was observed in 7/25 evaluable patients (28%) for a median duration of 7 months. Side-effects include leukopenia in 93% of the patients (less than 1000 WBC/mm3 in 7%), nausea in 41%, mild vomiting in 17%, diarrhea in 10% and alopecia in 10% of the patients. No definitive conclusion is possible regarding cardiotoxicity. Only mild changes in ECG were observed in two patients. This study shows that 4-DMDR administered orally is well tolerated in the majority of patients and has antitumor activity in advanced breast cancer.

Administration, Oral↗