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Biomedical subjects

G Vicario

Publications and source records attributed to G Vicario.

At least 19 recordsLinked to original sources
PubMed1997

Intra-arterial chemotherapy followed by chemo-embolisation in unresectable hepatocellular carcinoma.

Unresectable hepatocellular carcinoma is related to a poor prognosis. Encouraging response rates and survival have been reported with intra-arterial (i.a.) chemotherapy and chemo-embolisation, but limited data are available on the association of the two treatment modalities. We therefore started a new programme combining i.a. chemotherapy with chemo-embolisation. The treatment regimen consisted of L-leucovorin (100 mg/m2 i.v.), 5-fluorouracil (800 mg/m2 i.a.), and carboplatin (250 mg/m2 i.a.). Chemo-embolisation with mitoxantrone (10 mg/m2) plus ethiodized oil followed immediately. The same treatment plus gelatin sponge was given after 28 days. 26 patients entered the study and were evaluable for response and side-effects. Main patient characteristics were: males 21, females 5: median age 68 years (range 42-76 years); stage TNM II-III 17, IVA 9; Child's A 12, Child's B 14; elevated baseline alpha-fetoprotein 17; cirrhosis 25. 14 patients had a partial response (54%; 95% confidence interval 33-73%), 3 had stabilisation and 9 had progressive disease. Median survival was 11 months (range 2-20+). 16 patients had grade I-II pain and 15 grade I-II fever. Our results indicate that the regimen is safe, well tolerated and capable of inducing objective remissions in a high percentage of patients with hepatocellular carcinoma.

Adult↗
PubMed1997

Activity of combination chemotherapy in brain metastases from breast and lung adenocarcinoma.

Brain metastases represent a common complication of breast and lung cancer, with an overall incidence exceeding 30-40% of cases. Results achieved with radiotherapy are disappointing, with a median survival of a few months, and no clear activity has been observed with chemotherapy. The aims of this study were to assess the activity and feasibility of a new chemotherapeutic approach according to the following schedule: lomustine, 80 mg/m2 day 1; carboplatin, 80 mg/m2 days 1, 8, 15, 22; vinorelbine, 20 mg/m2 days 1, 8, 15, 22; L-leucovorin 250 mg/m2 days 1, 8, 15, 22; and fluorouracil, 500 mg/m2 days 1, 8, 15, 22. Cycles were repeated every 6 weeks. Since January 1994, 28 patients have been enrolled and 26 are evaluable for response and side effects. Major patient characteristics were median age, 55 years (range 31-72); men/women 15/11; lung primary, 20; breast primary, 6; performance status Eastern Cooperative Oncology Group, 0-2. A total of 64 cycles were administered (median/patient, two cycles). Nine partial remissions have been observed (35%, 95% confidence interval 17-56%), 6 disease stabilizations, and 11 disease progressions. Median duration of response was 3 months, and median time to progression for the whole group was 3.7 months (range 1-7). Treatment was well tolerated. Mild or moderate side effects included neutropenia, thrombocytopenia, mucositis, and nausea/vomiting; grade III-IV toxicity included neutropenia and thrombocytopenia. In conclusion, our results indicate that the schedule proposed is feasible and effective in this subset of patients.

Adenocarcinoma↗
PubMed1997

Phase II study of estramustine, oral etoposide, and vinorelbine in hormone-refractory prostate cancer.

Hormone-refractory prostate cancer is characterized by a low response rate following second-line therapy. Encouraging results have been reported in Phase II studies with estramustine associated with vinblastine or etoposide. Vinorelbine is a new semisynthetic vinca alkaloid that has demonstrated activity in prostate cancer. We therefore evaluated the activity of the following schedule: estramustine, 400 mg/m2 orally days 1-42; etoposide, 50 mg/m2 orally days 1-14; and 28-42; vinorelbine, 20 mg/m2 days 1, 8, 28, and 35; cycles being repeated every 8 weeks. Twenty-five patients have been included and are assessable for response and side effects. Patient characteristics were as follows: median age, 71 years (range 55-81); ECOG performance status 0-2; nonosseous disease, 3 cases; bone metastases, 23 cases. Sixty-two cycles have been delivered. Two patients with measurable disease and six patients with bone disease had a partial remission for an overall response rate of 32% (95% confidence interval 15-53%). Seven patients had stabilization of disease and 10 had progression of disease. Median duration of response was 3 months (range 2-5). Prostate-specific antigen in 14 patients (56%) decreased from baseline by at least 50%. Toxicity was manageable. Neutropenia was mild, with only three cases of grade III-IV toxicity. Two patients had severe anemia. The results of this study indicate that the schedule is active and well tolerated in hormone-refractory prostate cancer patients.

Administration, Oral↗
PubMed1995

Biological and clinical evaluation of lanreotide (BIM 23014), a somatostatin analogue, in the treatment of advanced breast cancer. A pilot study by the I.T.M.O. Group. Italian Trials in Medical Oncology.

Biological data support the development of clinical trials designed to evaluate the activity of somatostatin (SMS) analogues in advanced breast cancer (ABC). Although previous clinical trials have failed to show antitumor activity, various factors may have biased their results. In an attempt to improve our understanding of the role of SMS analogues in ABC, 10 patients with favourable prognostic factors and who had not been heavily pretreated for advanced disease were treated with lanreotide 30 mg i.m. fortnightly (depot formulation). Blood samples were periodically taken to evaluate the effect of the drug on growth hormone (GH) and insulin-like growth factor 1 (IGF-1) and to determine drug serum levels. Although the drug was well tolerated, no clinical activity was observed. Serum GH and IGF-1 levels were not properly suppressed over time and drug serum concentrations fluctuated widely. In conclusion, SMS analogues cannot be recommended even as palliative treatment of ABC. Further studies should be undertaken to investigate the effect of higher drug doses, given subcutaneously or by means of continuous infusion, in suppressing GH and IGF-1 serum levels.

Adult↗
PubMed1995

Formestane: an effective first-line endocrine treatment for advanced breast cancer.

Formestane, a new selective aromatase inhibitor devoid of severe side-effects, has been shown to be active in patients with advanced breast cancer. To investigate the clinical activity and endocrinological effects of formestane as a first-line treatment, 52 patients were administered two different doses: 24 received 250 mg formestane and 28 received 500 mg formestane i.m. fortnightly. All of the patients had a performance status of 2 or less (ECOG scale), 34 (65%) had a disease-free interval of at least 2 years and 21 (40%) were both oestrogen-receptor- and progesterone-receptor-positive; 20 patients received hormone and 13, received chemotherapeutical adjuvant treatment. Objective responses were obtained in 8 patients in the 250-mg group (33%; 95% CI: 14%-52%) and in 13 patients in the 500-mg group (46%; 95% CI: 28%-64%). The median response duration in the two groups was respectively 11 and 12 months. E2 serum levels of oestradiol had significantly (P < 0.001) decreased to more than 40% below the baseline value in both groups after 15 days of treatment, and remained unchanged thereafter. Local and systemic tolerability was satisfactory. We conclude that formestane is an effective and well-tolerated agent in previously untreated patients, and that these results should be confirmed by further studies.

17-Hydroxycorticosteroids↗
PubMed1995

A phase I study of recombinant interferon-alpha administered as a seven-day continuous venous infusion at circadian-rhythm modulated rate in patients with cancer.

A Phase I trial of interferon-alpha (IFN-alpha) administered at circadian-rhythm modulated rate was carried out to evaluate maximum tolerated dose (MTD) and toxicity in patients with advanced malignancies. Recombinant IFN-alpha-2b was administered as a 7-day continuous venous infusion with maximum delivery between 6 p.m. and 3 a.m. Entry dose levels were 0.2, 2 and 4 MU/m2/day. The dose was escalated by an amount equal to the starting dose until a maximum of 6 entry dose levels was achieved, with a 1-week rest between each cycle. The maximal daily dose of IFN-alpha administered was 24 MU/m2/day. A programmable-in-time ambulatory pump was used, so that all patients could receive their treatment at home. Eighteen patients were entered in the study and 16 were evaluable for toxicity. Toxicity was mild to moderate except for two patients who developed WHO grade III toxicity. No significant decline in performance status was associated with treatment. Two objective responses were observed in patients with previously treated metastatic renal cell carcinoma. As compared to standard s.c./i.m. administration or continuous nonchronomodulated i.v. infusion of IFN-alpha, this circadian schedule has allowed to deliver high doses of drug with acceptable toxicity.

Aged↗
PubMed1994

Formestane as treatment of advanced breast cancer in elderly women.

AIMS AND BACKGROUND: The number of elderly people is increasing, and the proportion of breast cancer in female cancer patients older than 65 years is 26%. In elderly patients, hormone therapy is widely accepted as the treatment of choice, because of its efficacy and good tolerability compared to chemotherapy. The aim of this study was to evaluate the endocrinologic and clinical activity of formestane (4-hydroxyandrostenedione), a selective aromatase inhibitor, in elderly patients with advanced breast cancer. METHODS: Thirty-five patients older than 65 years, selected from a larger group, were given formestane (250 mg or 500 mg i.m. fortnightly). Patients were evaluable for tumor response after 4 doses of formestane. Blood samples were collected to evaluate E2, FSH, LH, SHBG and DHEAS serum levels at baseline and after 2, 4, 8, 12 and 24 weeks. RESULTS: Thirty patients had PS < or = 1 (ECOG) and only 5 patients had PS = 2. Twenty-six patients were ER positive. Previous hormonal treatment for metastatic disease had been given to 17 patients; only 1 case had received chemotherapy. The overall response rate was 51% (95% C.I. 35-67%) and the median response duration was 9.5 months. Three complete responses were observed on viscera. The best responses were obtained on soft tissues (59%); on bone and viscera the response was respectively 45% and 47%. Local and systemic tolerability was highly satisfactory. Formestane induced prolonged suppression of E2 levels in all of the patients, and a significant reduction in SHBG levels was also observed from month 2 onward. A statistically significant (P = 0.0001) rise in serum FSH was also observed during the therapy. CONCLUSIONS: The study showed that formestane induced a long-lasting suppression of E2 levels and a satisfactory overall response. In our opinion, the drug is an effective and well-tolerated approach in the management of advanced breast cancer in elderly patients.

Aged↗
PubMed1994

An intensive treatment with mitoxantrone and ifosfamide in second-line therapy of epithelial ovarian cancer.

AIMS AND BACKGROUND: Both mitoxantrone (DHAD) and ifosfamide (IFO) have given promising results when administered as single agents in advanced ovarian cancer pretreated with platinum compounds. The aim of this I.T.M.O. group pilot trial was to evaluate, in a selected population of ovarian cancer patients, the efficacy and tolerability of the following intensive second-line regimen: DHAD, 12 mg/m2 i.v., day 1; IFO, 4,000 mg/m2 i.v., days 1 and 2; Mesna, 800 mg/m2 i.v. t.i.d., days 1 and 2. Filgrastim (5 micrograms/kg/day i.m.) was given from day 6 to day 19 to reduce the expected neutropenia. Cycles were repeated every 21 days. METHODS: Nineteen platinum-pretreated patients were enrolled and 14 were evaluated for tumor response; the disease of 5 patients was not measurable clinically or radiologically. RESULTS: Seven responses were observed (3 CRs), with a median response duration of 5 months. The median time to treatment failure and overall survival for all 19 patients was respectively 8 and 13 months. Anemia was observed in all of the treated patients (grade 3-4 in 9 cases). Only 6 of the 19 patients ended the five planned cycles of chemotherapy without any delay. CONCLUSIONS: Although DHAD plus IFO induced a considerable number of objective responses, the limited response duration time to treatment failure, and overall survival as well as the reported side effects suggest that this is not a recommended regimen for the palliative treatment of ovarian cancer patients undergoing second-line chemotherapy.

Adult↗
PubMed1990

The disposition and urinary metabolism of 14C-labelled FCE 22891, a pro-drug of FCE 22101, in animals.

[2-14C]FCE 22891 was given orally and intravenously to the rat, orally to the dog and monkey. Radioactivity was eliminated by both the renal and faecal route after oral administration, but mainly in the urine after the iv route in the rat. Radioactivity as expired 14CO2 was detected in the rat and accounted for less than 1% of the dose after iv and 3.2% after oral dosage within 72 h. After oral FCE 22891 labelled by 14C in the acetoxymethyl moiety, radioactivity recovered as expired 14CO2 accounted for over 55% of the dose at 72 h in the rat. No FCE 22891 was detected in plasma, whereas consistent amounts of FCE 22101 were detected. The metabolism was studied by radio-HPLC in the urine of the animals treated with [2-14C]FCE 22891. No unchanged drug was detected at any time interval. FCE 22101 was the main urinary metabolite with the exception of the dog and accounted for about one-half of the radioactivity excreted in 0-24 h urine. Significant amounts of metabolite P1, an open beta-lactam ring derivative obtained by action of dehydropeptidase, were found in the urine of rat and monkey but not in the dog. The remaining urinary radioactivity was due to other metabolites, named P, X and LP, which might originate from P1, as stability of P1 is pH-dependent.

Administration, Oral↗
PubMed1989

Disposition of 14C-labelled FCE 22101 in animals.

14C-FCE 22101 was given intravenously to rats (4, 16 and 38 mg/kg), dogs (69 mg/kg), rabbits (99 mg/kg) and monkeys (41 and 99 mg/kg). Radioactivity was eliminated mainly in urine, with faecal excretion being less than 10% in all animal species. Radioactivity as expired 14CO2 was detected in the rat and accounted for less than 0.5% of the dose in 24 h. Tissue distribution was also investigated in the rat (38 mg/kg). After combustion and radioactivity counts the highest concentration of radioactivity was observed in the kidneys, followed by the lung, the skin and hair, and lastly by the liver and adrenals. Brain levels of radioactivity, corrected for blood contamination, were 40 to 60 times lower than the corresponding blood levels. The results of whole body autoradiography confirmed those above. Whole body autoradiography of pregnant rats did not show any transfer of radioactivity into fetuses and only low radioactivity was present in the placenta.

Animals↗
PubMed1989

Urinary metabolites of 14C-labelled FCE 22101 in animals.

The metabolism of 14C-FCE 22101 has been studied by radio-HPLC in the urine of various animal species. Five main chromatographic peaks were detected and named, in order of decreasing polarity, P, P1, X, UD (unchanged drug) and LP. P1 is the open beta-lactam ring metabolite obtained by the action of dehydropeptidase. The stability of FCE 22101 and P1 is pH-dependent, and differences between species in urinary metabolic patterns might therefore be partially explained by different urinary pH values.

Animals↗
PubMedDate not supplied

A dose-escalating study of carboplatin combined with vinorelbine in non-small-cell lung cancer.

Platinum compounds and vinorelbine have been demonstrated to be active in non-small-cell lung cancer (NSCLC). The aims of the study were to assess tolerability and feasibility of increasing doses of carboplatin (level 1: 300 mg/ m2 on day 1, level 2: 350 mg/m2 on day 1, level 3: 400 mg/m2 on day 1) in combination with a fixed dose of vinorelbine (25 mg/m2 on days 1 and 8) in advanced NSCLC. Forty-two patients entered the study and were evaluable for toxicity and response. The patients were not treated using systemic chemotherapy, had TNM stage IIIB-IV, performance status ECOG 0-2, and their median age was 62 (range 41-70) years. The number of patients evaluable for each dose level was 14. A total of 138 (median 3) courses was administered. Nonhematologic side effects included grade I-II mucositis (9%), neurotoxicity (6%), and infections (4%). Myelotoxicity was manageable and generally of short duration, with 19% of the patients having grade III-IV neutropenia. No significant difference was observed for the three treatment groups. No drug-related death was observed. An objective remission was observed in 10 patients (24% response rate; 95% confidence interval 12-39%), with 5 responses in 14 patients treated with the 400-mg/m2 dose. In conclusion, the combination of carboplatin at a dose of 400 mg/m2 on day 1 and vinorelbine at a dose of 25 mg/m2 on days 1 and 8 can be safely administered as first-line cytotoxic therapy in advanced NSCLC and warrants further evaluation.

Adult↗
PubMedDate not supplied

Pain at tumor site after vinorelbine injection: description of an unexpected side effect.

AIMS AND BACKGROUND: Vinorelbine is a new semisynthetic vinka alkaloid that has demonstrated good tolerability and interesting activity in a large spectrum of solid tumors. It was the aim of this paper to report the presence of a rarely documented side effect. METHODS: In our experience, 135 patients were treated with vinorelbine during the period 10/92 to 11/94 for a total of 1080 cycles. In 26% of the cycles, vinorelbine was administered in monochemotherapy and in 74% in polychemotherapy regimens. The dose of vinorelbine, administered in a weekly schedule, was 25 mg/m2 in 109 patients and 30 mg/m2 in 26 patients. In general, no analgesic premedication was used. Sixty-five patients had lung cancer, 45 had breast cancer, and 25 miscellaneous cancer. Only 4 patients had a previous history of neurotoxicity. RESULTS: Ten patients (7%) had pain in the tumor site within a few minutes of the vinorelbine injection. According to WHO grade, 5 cases had moderate and 5 severe pain. Pain was always reversible. In 5 cases ketorolac was administered after pain detection with resolution of the symptoms; in 4 cases it was necessary to deliver buprenorphine. One patient was admitted to the coronary unit because a myocardial infarction was suspected after retrosternal pain and required i.v. morphine. Seven cases refused to continue the treatment, and 3 cases had no further problem after ketorolac premedication. CONCLUSIONS: Although rare, the presence of severe pain after vinorelbine injection may adversely affect the treatment course. Such data are helpful in the recognition and management of this reversible side effect.

Adult↗