Search PubMed⌕ Search

Biomedical subjects

F Pannuti

Publications and source records attributed to F Pannuti.

At least 91 records · Page 5Linked to original sources
PubMed1985

Analgesic activity of medroxyprogesterone acetate (MAP) in cancer patients: an antiinflammatory mediated activity?

When we initially used high doses of MAP (greater than 500 mg/day/im or greater than 2000 mg/day p.o.) in advanced cases of breast cancer, we noticed that, even before objective remission became apparent, the treatment induced subjective remission and a strong analgesic effect. Overall, our breast cancer patients treated with MAP at high doses (300 patients) showed a 65% incidence of pain relief. The analgesic effect of MAP does not seem to be closely related to its antitumour effect, because the same effect was also observed in patients with hormone-insensitive tumours. Our pharmacokinetic studies have demonstrated that it is important to use high doses in order to obtain high plasma levels. In order to clarify the mode of action of this MAP analgesy, hot-plate, tail-flick, Randall, writhing and carrageenin-oedema tests were carried out on rats. We found no evidence for central or peripheral analgesic activity, but there was evidence for an antiinflammatory activity of MAP.

Animals↗
PubMed1985

Epirubicin pharmacokinetics after intrahepatic arterial and intraperitoneal administration.

The high hepatic clearance of the new doxorubicin analogue epirubicin (4'-epidoxorubicin, epiDX) suggests a possible use of this drug in local and regional therapy where a first pass through the liver is required before the drug can reach systemic circulation. EpiDX pharmacokinetics was followed in advanced cancer patients with liver metastases or a primary tumour after single bolus administration in the hepatic artery, through a surgically implanted catheter and subcutaneous access port. The first-pass effect through the liver was appreciable and only a relatively low fraction of the drug reached systemic circulation. Mild leucopenia and alopecia were observed only in a patient with a hepatopulmonary shunt; this subject was actually exposed to higher epiDX plasma levels. Low intraperitoneal doses of epiDX were administered in a weekly schedule to advanced cancer patients with peritoneal metastases and ascites. Drug concentrations were monitored in the ascitic effusion and in plasma. A high concentration gradient was present between the peritoneal cavity and peripheral circulation. No relevant local or systemic toxicity was observed.

Adult↗
PubMed1985

Prolactin levels and hormonal profile in postmenopausal patients with advanced breast cancer during endocrine treatments.

Seventy postmenopausal patients with advanced breast cancer, the majority not having been pretreated, underwent a hormonal profile study (LH, FSH, PRL, E2, testosterone, TSH, T3, T4, FT3, FT4 serum levels) by RIA standard methods. The result was that these patients had the same mean hormonal profile of normal controls. The hormonal profile was studied in 66 patients before and after one month of treatment with medroxyprogesterone acetate at high doses (MAP h.d.) (45 patients), tamoxifen (TAM) (10 pts.) and MAP h.d. + TAM + bromocriptine (MTB) (11 pts.). No significant difference in the pre-treatment hormonal profile was observed in either patients who responded to the subsequent treatment or in those who did not. MAP h.d. induced a marked inhibition of gonadotropins, E2, testosterone, T3, T4 while PRL, TSH and FT3 remained unchanged and FT4 increased. TAM induced a decrease of gonadotropins and T4 while all the other hormones remained unchanged. MTB induced the same effects of MAP h.d. as well as a decrease of PRL serum levels. All hormonal variations except PRL occurred independently of the clinical response. A particular behaviour of PRL was evident after one month of treatment with MAP h.d. and TAM: patients who did not respond had a statistically significant increase of PRL serum levels while in responders the PRL serum levels decreased or remained unchanged. Specifically 24 out of 28 (86%) patients with an increase greater than 20% of the PRL levels were non-responders.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1985

Epirubicin plasma and blood pharmacokinetics after single i.v. bolus in advanced cancer patients.

Plasma and whole blood pharmacokinetics of epirubicin (4'-epidoxorubicin, epiDX), a new doxorubicin (DX) analogue with an improved spectrum of activity and lower toxicity, were investigated in advanced cancer patients after i.v. bolus administration. Drug decay is triphasic, with a long terminal half-life. Plasma and blood levels of the C-13 reduced epiDX metabolite, epirubicinol (epiDXol), are lower than those of the parent compound. Glucuronides of epiDX and epiDXol are also present in plasma, bile and urine; similar compounds are not described in the literature among the metabolites of DX. EpiDX plasma clearance is consistently higher and mean residence time lower than the corresponding DX parameters, thus indicating a more efficient disposition of the new drug. This behaviour is also reflected in a faster elimination of epiDXol with respect to the corresponding Dx metabolite, doxorubicinol. After an initial induction period, epiDX concentration is higher in whole blood than in plasma. Blood clearance is lower than plasma clearance; volume of distribution at steady state Vss is lower if blood concentration data are used in the pharmacokinetic analysis. Mean Residence Time is similar in plasma and blood. A statistically significant reduction of clearance parameters is observed in patients with liver metastases, even in the absence of altered bilirubin levels. Drug clearance problems induced by renal dysfunction become relevant only in severe renal failure.

Bile↗
PubMed1985

The new anthracycline 4-demethoxydaunorubicin by oral route in advanced pretreated breast cancer and melanoma. A pilot study.

4-Demethoxydaunorubicin (4-DMDR) was administered orally at the dose of 15 mg/m2 daily for 3 consecutive days at three-weekly intervals to 28 patients with advanced pretreated breast cancer and 9 patients with disseminated pretreated melanoma. A partial remission was observed in 6 out of 20 evaluable breast cancer patients (30%) for a median duration of 6 months and in one out of 7 evaluable patients with melanoma (14%) for a duration of 3 months. Side-effects included leucopenia in 78% of patients (less than 1000 wbc/cmm in 8%), nausea in 32% and mild vomiting in 16%. The preliminary results of this ongoing study on 4-DMDR administered orally show that the regimen is well tolerated in the majority of patients and that it has antitumour activity in advanced breast cancer.

Administration, Oral↗
PubMed1984

[Medical therapy of pain in oncology].

The authors report data concerning their study on the incidence of pain in advanced neoplastic patients and on the natural history of this symptom. They also report their experience in the treatment of solid tumours with non steroidal antiinflammatory drugs (Zomepirac, acetylsalicylic acid, Diflunisal, Ketoprofen) with a synthetic progestin (Medroxyprogesterone Acetate employed by authors at high or at very high doses for the first time) and with morphine hydrochloride used by oral, rectal, sublingual and nasal route. The authors also indicate the correct strategy of employing these drugs and criteria of evaluating their effectiveness.

Anti-Inflammatory Agents↗
PubMed1984

A phase-II clinical trial of 4'-epi-doxorubicin in advanced solid tumors.

Sixty-six patients with advanced solid tumors were treated with 4'-epi-doxorubicin at a dose of 90 mg/m2 by rapid IV injection every 21 days until the disease had progressed or to a maximum cumulative dose of 540 mg/m2. Myelosuppression, nausea and vomiting, and alopecia were the almost frequent side effects, but their incidence seemed lower than that after a comparable dosage of doxorubicin. After a cumulative dose of 540 mg/m2 a significant decrease of QRS complex deflection on the electrocardiogram was detected, but no case of congestive heart failure was observed. Partial remission and minor remission were achieved, respectively, in nine (15%) and five (9%) out of 59 evaluable patients for a median duration of 6 months. Partial remission occurred in anthracycline-sensitive tumors like breast cancer (4 of 13), lung cancer (1 of 17), head and neck cancer (1 of 8), gastric cancer (2 of 4), and ovarian cancer (1 of 1).

Adult↗
PubMed1984

A phase II study of 4'-epi-doxorubicin plus cis-platinum in advanced solid tumors.

4'-Epi-doxorubicin (4'-epi-DX) is a new doxorubicin derivative that in phase II human studies has been demonstrated to be less toxic than doxorubicin. Sixty-four patients with advanced solid tumors were treated with the drug combination of 4'-epi-DX and cis-dichlorodiammineplatinum (CDDP) at the doses of 40-60 and 50 mg/m2, respectively, every 21-28 days. Out of 52 evaluable patients, complete remission (CR) was recorded in 5, partial remission (PR) in 12, minor remission (MR) in 7, no change (NC) in 16 and progression (P) in 12. The median duration of remission in patients who achieved a CR and PR was 9+ months. In particular, out of 19 patients with ovarian cancer, 2 CR (second look) and 7 PR have been documented. One CR and 3 PR also have been observed in 21 patients with lung carcinoma. Complete and partial responses also have been documented in breast cancer (1 CR/1), in bladder carcinoma (1 CR/2), in renal cancer (1 PR/5) and in testicular cancer (1 PR/1). Hematologic toxicity was generally mild to moderate (leukopenia less than or equal to 1500 cells/mm3 in 3% of the patients; thrombocytopenia less than or equal to 120,000 cells/mm3 in 2% of the patients). Vomiting was present in almost all patients while alopecia has been recorded in 63% of the patients. No case of cardiac toxicity had been observed up to now (median cumulative dose of 4'-epi-DX:240 mg/m2, range 40-650 mg/m2). The combination of 4'-epi-DX with CDDP appears to be an active and well-tolerated regimen in ovarian cancer and lung cancer.

Adult↗
PubMed1984

Injectable ketoprofen vs. acetylsalicylic acid for the relief of severe cancer pain: a double-blind, crossover trial.

Thirty-six patients suffering from severe pain due to bone involvement from cancer participated in an analgesic study that compared single doses of ketoprofen 100 or 400 mg iv or injectable acetylsalicylic acid 1 g. A double-blind, balanced incomplete block design was adopted, in which each patient received two of the three test treatments, with an interval of 24 hours. Ketoprofen 400 mg proved significantly superior to 100 mg of the same drug, and was superior to 1 g of the acetylsalicylic acid derivative in the patients' assessment of the overall response. This was expressed by a visual analog scale and preferences. No adverse reaction was observed with any treatment.

Adult↗
PubMed1984

Clinical trial of combined hormone therapy (MAP + TAM) for metastatic breast cancer.

High dose MAP (medroxyprogesterone acetate) and TAM (tamoxifen) were administered orally to 31 postmenopausal patients with advanced breast cancer. CR (complete remission) was achieved in 1 (3%) and PR (partial remission) in 11 (32%) patients for a median duration of 12 months. The treatment was well tolerated and in no instance was interrupted because of toxicity. This study does not support the hypothesis that the combination of MAP and TAM gives better results than the single agents.

Aged↗
PubMed1984

The effect of high dose medroxyprogesterone acetate on water and salt metabolism in advanced cancer patients.

Ten advanced cancer patients (both with hormone-sensitive and non-hormone sensitive tumors) were treated with high dose medroxyprogesterone acetate (MAP, greater than 500 mg/day). We determined body weight, lean body mass, blood pressure, sodium blood level, urinary excretion, and exchangeable sodium pool by the 22Na method before and after treatment. These data seem to exclude a fluid retentive effect for high-dose MAP.

Antineoplastic Agents↗
PubMed1984

A new six-drug antiblastic regimen (R 14) at low doses (micropolychemotherapy) compared to CMF in the treatment of metastatic breast cancer: phase III study.

Two groups of 23 patients each, having advanced breast cancer, entered this prospective and randomized study. One group was treated with the conventional schedule of CMF (cyclophosphamide 100 mg/m2/po from the first to the 14th day, methotrexate 40 mg/m2/iv the first and the 8th day, 5-fluorouracil 600 mg/m2/iv the first and the 8th day), and the other was treated with a new six-drug regimen, administered at low doses (R 14: cyclophosphamide 2 mg/kg/iv, vincristine 0.01 mg/kg/iv, vinblastine 0.1 mg/kg/iv, the first day and 5-fluorouracil 5 mg/kg/iv, methotrexate 0.7 mg/kg/iv, adriamycin 0.5 mg/kg/iv the 2nd day every 21 days). The remission rate was 35% (8/23) and 39% (9/23) for CMF and R 14 respectively. The median duration of objective remission was 6 months for CMF and 5 months for R 14 regimen. The median survival time of responding patients was 18 months for CMF and 14 months for R 14. This study shows that the new six-drug regimen at low doses is effective (regarding subjective, objective response and survival rate), and its toxicity is no higher than that of CMF (the incidence of leukopenia was significantly lower during the first course). Therefore, R 14 should be considered an alternative regimen to CMF in the treatment of advanced and, possibly, early breast cancer. The advantages for using R 14 are: 1) it is less toxic (a single dose is a very small amount of medicine compared to what is usually administered), 2) an iv administration always follows a therapeutic program (while in a CMF schedule cyclophosphamide is self-administered by the patient).

Adult↗
PubMed1984

4'-epi-doxorubicin in combination with cisplatin in advanced ovarian cancer.

Thirty-two patients with advanced ovarian cancer were treated with a combination of 4'-epi-doxorubicin, a new analog of doxorubicin, and cisplatin at a dose of 60 and 50 mg/m2, respectively, every 28 days. Twelve patients had previously received chemotherapy and/or radiotherapy. Of 29 evaluable patients, six (21%) achieved complete remission for a median duration of 19+ months, and 13 (45%) achieved partial remission for a median duration of 8 months. All complete remissions were confirmed by a "second-look" procedure. Main side effects included vomiting in all patients, moderate myelosuppression (67%), and alopecia (65%). No case of congestive heart failure was observed. 4'-Epi-doxorubicin plus cisplatin is an effective and relatively well-tolerated regimen in the treatment of advanced ovarian cancer.

Adenocarcinoma↗
PubMed1983

Medroxyprogesterone acetate (MAP) plasma levels after multiple high-dose administration in advanced cancer patients.

Medroxyprogesterone acetate plasma levels were measured in advanced cancer patients after multiple PO or IM administration (500, 1000, 2000, 3000, 4000, and 5000 mg/day PO and 500, 1000, 2000 mg/day IM for 30 days). After PO administration, the plasma concentration rises quickly and plateau level is reached in 4-10 days. Discontinuation of the treatment produces a fast decay (t1/2 = 62.4 h) of the drug levels. When medroxyprogesterone acetate is given IM plasma levels, steadily increase and after drug discontinuation no noticeable decay is observed for at least 6 months; plateau plasma levels are about three times higher than after the corresponding PO treatment. Extremely high interpatient variation in bioavailability is present with both administration routes. These data may well rationalize the results of previous clinical trials and will help in planning treatment schedules.

Administration, Oral↗
PubMed1983

The anabolic effect of high dose medroxyprogesterone acetate in oncology.

Ten advanced cancer patients not amendable to conventional therapy were treated with high dose (greater than 500 mg/day, for 30 days) Medroxyprogesterone Acetate (MAP) both orally and intramuscularly, in order to evaluate a possible anabolic effect of this hormone. During the treatment, mean protein intake increased from 37.2 gr/day to 58.8 gr/day (p less than 0.01), nitrogen intake from 5.8 to 9.4 gr/day (p less than 0.01) and caloric intake from 1407.9 to 2075 Kcal/day (p less than 0.01). Nitrogen balance also showed a significant increase (p less than 0.05), as well as elementary strength (p less than 0.02). Lean body mass and body weight did not show significant variations. The above data confirms what was already been documented by us in animals and proposed in man-that MAP has an anabolic effect.

Anabolic Agents↗
PubMed1982

Medroxyprogesterone acetate (MAP) plasma levels after simultaneous oral and intramuscular administration in cancer patients.

After simultaneous administration of medroxyprogesterone acetate (MAP) 1,000 mg PO and 1,000 mg IM to ten cancer patients, we observed mean plasma MAP profiles that could be exactly superimposed on the two absorption/decay curves obtained after administration of single doses IM or PO. Treatment with MAP given simultaneously by the IM and PO routes may be effective in overcoming the drawbacks of both routes, and can also more reliably guarantee plasma levels in the therapeutic range.

Administration, Oral↗