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Biomedical subjects

G Tabaro

Publications and source records attributed to G Tabaro.

14 recordsLinked to original sources

Ifosfamide in advanced/disseminated breast cancer.

Ifosfamide is an alkylating agent active in various tumor types including breast cancer. The availability of mesna (sodium 2-mercaptoethanesulfonate) has increased its safety, avoiding the main dose-limiting side effect, urotoxicity. Interesting activity as a single agent, with response rates ranging from 7 to 30%, is reported in pretreated patients; more attractive data derived from phase II studies on ifosfamide combined with drugs known to be active in advanced breast cancer show response rates always over 35%. This review has taken in consideration papers published after 1995 and available on PubMed medline: the data indicate a potential usefulness of ifosfamide in the clinical management of advanced breast cancer, even if the exact therapeutic role of the drug in this setting should be derived from randomized studies not yet available.

Antineoplastic Agents, Alkylating↗

Oral 5-fluorouracil in squamous cell carcinoma of the skin in the aged.

Multiple or recurrent squamous cell skin carcinoma is a rare tumor in the aged. These patients are currently treated with 5-fluorouracil (5-FU) cream as a local chemotherapy; in cases in which the disease progresses, few treatments are available. Two reports deal with the treatment of progressive squamous cell skin carcinoma with systemic 5-FU, but in only eight patients age less than 70 years. We prospectively investigated oral 5-FU therapy in 14 consecutive patients (average age 76 1/2 years) with histologically proven squamous cell skin carcinoma. The disease was aggressive, multiple, or recurrent and had not been eradicated by surgery, radiation therapy, topical 5-FU cream, and non-5-FU chemotherapy. Oral 5-FU was administered as mannitol-coated 5-FU tablets at the daily dose of 175 mg/m2 for 3 weeks every 5 weeks. Toxicity, effectiveness, quality of life, and compliance to therapy were evaluated. Total cycles amounted to 55 (range: 2-6, mean: 4 for each patient) at an average dose intensity of 740 mg/m2/week for from 12 to 36 weeks. Only gastrointestinal toxicity World Health grade I occurred. Quality of life and compliance to therapy were 90%. Therapy induced measurable improvement in nine patients (64.3%): two partial remissions (14.3%), three minimal remissions (21.4%), and four arrests of disease (28.6%) with a median duration of 30+ months. The study ended because of a lack of patients. We can conclude that, if elderly patients require chemotherapy because of progressive multiple or advanced squamous cell skin carcinoma, appreciable results may be obtained with oral 5-FU as a single agent.

Administration, Oral↗

Cisplatin and gemcitabine in non-small-cell lung cancer.

The nucleoside analogue, gemcitabine, has shown activity as a single agent in the treatment of metastatic non-small-cell lung cancer (NSCLC), producing consistent response rates of 20% and above. Because of its unique mechanism of action and its non-overlapping toxicity with other active agents, gemcitabine is an attractive candidate for trials in combination with other cytotoxic agents. In preclinical models, the cisplatin-gemcitabine combination suggested synergy between the two drugs. In phase I-II studies, response rates are as high as 54% when gemcitabine is combined with cisplatin, both in stage III and IV NSCLC. The gemcitabine-containing regimens showed a favourable safety-efficacy profile and compared well with standard regimens used in NSCLC. These preliminary results must be validated by large randomised trials comparing gemcitabine-containing regimens with NSCLC reference chemotherapy regimens.

Antineoplastic Combined Chemotherapy Protocols↗

Synthetic thymic fraction 5: effects of high dose administration on circulating lymphocytes in patients.

The synthetic pentapeptide (Arg-Lys-Asp-Val-Tyr; TP-5) corresponding to the active site of the hormone thymopoietin, was given at the dose of 300 mg/m2/day (1 day), higher than the usually administered, to a group of 27 immunodepressed patients in order to determine the tolerability and the immunomodulatory activity. The examination of a series of hematological parameters including counts of differential clustering of lymphocytes by cytofluorimetric analysis was performed 24 hr and 48 hr after treatment, and repeated at different intervals up to 14 days after treatment. TP-5 caused a significant increase of circulating lymphocytes and particularly of CD3+CD4+ and CD3+CD8+ subtypes, peaking at 48 hr and maintaining the increased values up to the last examination on day 14 from treatment. A faster increase (zenith at 24 hr) was observed for CD4+ cells, in comparison with CD8+ cells (zenith at 48 hr). The number of patients that increased total lymphocytes or lymphocyte subset after treatment ranged between 52.6 (CD4+ cells) and 69.2% (NK cells), whereas about 7.7% (NK cells) to 36.9% (CD4+ cells) remained unchanged and a smaller amount of 10.5% (CD4+ and CD8+ cells) or 23.1% (NK cells) showed a decrease greater than 10% of their respective basal value. No significant relationship between responders and non-responders can be found on the basis of previous treatments, cancer type, sex or age.

Adjuvants, Immunologic↗

A phase II study of oral fluorouracil for gastrointestinal cancer.

Prolonged exposure to 5-fluorouracil (5-FU) is effective for gastrointestinal malignancy (GIM) and it is considered synergistic or additive to concurrent radiotherapy. Oral 5-FU (OF) could represent an easy therapy. The present study prospectively tested the toxicity and effectiveness of OF in GIM by means of 5-FU mannitol-coated tablets (MCT) at 275 or 225 mg/m2/day according to the patients age (65 years cut-off) for a period of 4 weeks every 7 weeks. Also the drug given over 5 days a week for 4 weeks was studied to assess OF toxicity over a time corresponding to that used in standard radiotherapy. Quality of life (LQ) was analyzed. Patients were 27 individuals (20 males), aged 43-70 years, pretreated with radiotherapy (four patients) or i.v. 5-FU-based chemotherapy (five patients), and with progressive malignancy of colorectum (six patients), stomach (five patients), pancreas (four patients) and liver (two patients). The total number of cycles was 91 and 16 patients had more than two cycles. Myelotoxicity was consistently absent; other toxicities greater than WHO grade 1 were: nausea (grade 2 in four patients), diarrhea (grade 2 in six and grade 3 in 11), palmar erithema (grade 2 in one), brown-turning skin (grade 2 in one) and CNS (grade 2 in one). Diarrhea was less frequent (p = 0.007) in gastric and in colorectal than in pancreas and liver cancer patients. In the 10 patients given the drug of 5 days a week, diarrhea was practically absent. LQ was above 90%. Fourteen patients (51%) had total arrest of disease, and 2 among 16 colorectal cancer patients had PR (12.5%). In conclusion, the MCT-OF was tolerated and as effective as the classic i.v. 5-FU at nonmyelosuppressive dose. The MCT-OF dose recommended for further studies is 275 mg/m2/day (or 225 above 65 years) for 4 weeks followed by a 2 week rest period.

Adult↗

Liver function tests and lidocaine metabolism (MEGX test) during i.v. CMF therapy in breast cancer.

The measurement of monoethylglycinexylidide (MEGX test) is considered a sensitive method for the evaluation of hepatic metabolic capacity. The multidrug chemotherapy CMF (cyclophosphamide 600 mg/m2, methotrexate 40 mg/ m2, 5-fluorouracil 600 mg/m2) is widely used in breast cancer patients but very few clinical studies have investigated its possible liver toxicity. We have prospectively evaluated the possible acute liver toxicity after a cycle (i.e. two courses) of CMF by means of the measurement of standard liver function tests and of MEGX, i.e. the main lidocaine (Lid) metabolite after the i.v. injection of Lid. Consecutive patients (n = 15), aged 43-68 years, were radically operated on because of M0 primary breast cancer and candidates for adjuvant CMF because of nodal axillary involvement (pN1) were studied. Tests were performed before the first (given at day 1) and 48 h after the second course (given at day 8) of an i.v. CMF regimen to be repeated every 28 days. Full blood count, serum ALT, AST, gamma-GT, alkaline phosphatase and albumin were measured with standard methods. To investigate the appearance of MEGX, blood samples were taken before, and 5, 10, 15, 20, 25, 30 and 60 min after i.v. Lid injection. MEGX serum concentration was measured by means of a fluorescent polarization immunoassay. We found no significant variation between pre- and post-CMF standard liver function tests with the exception of ALT levels, which, however, decreased (mean 48%, p < 0.05). The MEGX serum concentration was significantly increased over the sampling time period and the 42% mean rise was statistically significant (p < 0.001). Moreover, the post-CMF increase of circulating MEGX was steeper than the basal pre-CMF values. The slopes relating to the curves of MEGX formation over the first 20 min were 3.30 and 2.24, respectively (p < 0.001). In conclusion, no hepatic acute toxicity was observed during the CMF chemotherapy. Further studies are required to understand the meaning of the unexpected MEGX rise.

Adult↗

Topographic classification, clinical characteristics, and diagnostic delay of cancer of the larynx/hypopharynx in Torino, Italy.

The case series of a population-based case-control study of laryngeal and hypopharyngeal cancers in Torino, Italy, included 281 men with clinical and anamnestic data. Two hundred fifteen, 28, and 38 cancers originated from the endolarynx, epilarynx, and hypopharynx, respectively. Regions invaded by the tumor were divided into 26 subsites. A classification based on the number of invaded subsites was proposed, which agreed well with the T classification of the TNM system. Cancers originating from the hypopharynx invaded more subsites than cancers from the endolarynx, and among the latter, supraglottic were more invasive than glottic lesions. The number of invaded subsites was strongly associated with nodal involvement. Among symptoms at onset of disease and at diagnosis, patients with endolaryngeal lesions reported dysphonia and dyspnea more frequently, and patients with lesions from other regions had a higher prevalence of dysphagia, odynophagia, otalgia, and adenopathia. Clinical and epidemiologic results of this study suggest considering the endolarynx, epilarynx, and hypopharynx as separate anatomic entities. Diagnostic delay was not associated with tumor size and showed a negative trend with involvement of cervical lymph nodes, suggesting that stage at diagnosis is due to intrinsic differences in tumor aggressiveness.

Carcinoma, Squamous Cell↗

Relationships between cervical node histological patterns and rosette test scores: possible prognostic value in laryngeal cancer.

In previous research the authors have remarked that some hystological patterns--macrophagic hyperplasia and thymus-dependent areas hyperplasia--when prevailing in cervical nodes of laryngeal cancer patients, possess a positive prognostic value. In this study the possible relationship between the results of E and EAC-rosettes and prevailing hystologic patterns in cervical nodes is investigated. A positive correlation was not found. Conclusively, the inconsistency of aspecific tests for prognostic purposes and the need for a specific immunological monitoring system are outlined.

Humans↗