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T Mazzei

Publications and source records attributed to T Mazzei.

100 records · Page 6Linked to original sources
PubMedDate not supplied

Oxaliplatin plus raltitrexed in the treatment of patients with advanced colorectal cancer: a phase II study.

UNLABELLED: The combination of Oxaliplatin (OXA) and Raltitrexed (RTX) may represent a more convenient regimen as compared with OXA + 5-FU with Folinic acid (FA) modulation regimens. The present trial has been designed to explore the activity and tolerability of this combination in untreated and pretreated patients with advanced colorectal cancer (ACC). OXA and RTX were administered at the dose of 130 mg/m2 as i.v. 3-hour infusion and 3 mg/m2 over a 15-minute i.v. infusion, respectively, repeated every 21 days. Fifty patients were enrolled between February 1999 and March 2001. A total of 293 cycles were administered, with a median number of 6 cycles (range 1-14) per patient. The median dose intensity for OXA and RTX was 100% (50-100) and 86% (21-100), respectively. Reasons for RTX dose reduction were increases in transaminase serum levels and a reduction in creatinine clearance. Myelotoxicity was limited. A transaminase increase was observed in 74% of patients (14% grade 3 and 10% grade 4). Peripheral sensorial neurotoxicity was the most frequent side-effect (88%), although its intensity was mild in most patients (grade I 48%, grade II 24%, grade III 16%). Of 46 evaluable patients, 3 CR, 5 PR, 22 S and 16 P were observed. The CR + PR remission rate, according to the intention to treat analysis, was 16% with a 95% confidence limit of 7.2%-29.1%; in patients not pretreated for advanced disease the CR + PR rate was 26%, while only 2 out of 27 pretreated patients responded to the treatment (7%). The median time to progression was 5 months (2-11). The median survival was not reached after a median follow-up of 14 months. One-year survival is 60%. CONCLUSION: In this trial the OXA + RTX combination is confirmed to be active in ACC, although the level of activity seems to be lower than that of the other combination including OXA and 5-FU with or without FA modulation. The reasons for the low activity observed could at least in part be related to a reduction in the RTX dose intensity.

Adult↗
PubMedDate not supplied

[Plasma and tissue antibiotic concentrations: what is their prognostic value?].

Pharmacokinetic studies of antimicrobial agents usually involve the determination of tissue distribution, since most infections develop outside the vascular compartment. Comparative analyses of the results are often complicated by their extreme variability, depending on the various types of methods used, the type of antimicrobial agent, and the characteristics of the various tissue compartments. In general, concentrations in tissue and body fluids with no barriers to penetration of drugs are fairly predictable from blood levels in relation to simple diffusion through capillary pores. This is valid for hydrosoluble drugs such as the beta-lactams as well as liposoluble drugs like the quinolones and most of the macrolides. Thus we may derive, in a predictive sense for the clinical results, both the hematic and interstitial fluid pharmacokinetic profile of the above molecules, which are useful in relation to the MIC or MBC of extracellular pathogens. For molecules such as azithromycin, in which tropism is mainly intracellular, hematic levels do not reflect those which are therapeutic in the infection site. In tissues and body fluids with barriers to the penetration of drugs, such as the central nervous system, eye and bronchial secretions, it is always useful and especially for any new antimicrobial agent to determine the concentrations which are achieved in relation to both dosage and pathological state of the tissue compartment. The significance of the chemotherapeutic formula which gives substantial predictive value of the therapeutic efficacy at the level of blood concentrations in relation to minimal inhibitory concentration of sensitive bacteria, needs to be critically re-evaluated in light of the pharmacokinetic behavior of newer antimicrobial agents.

Anti-Bacterial Agents↗
PubMedDate not supplied

Intra-arterial hepatic chemotherapy with 5-fluorouracil and 5-methyltetrahydrofolate in the treatment of unresectable liver metastases from colorectal cancer.

Treatment of patients with hepatic metastases from colorectal cancer using hepatic artery fluorodeoxyuridine (FUDR) has been reported to induce high remission rates but also a high incidence of limiting hepatobiliary toxicity. In an attempt to obviate the limiting FUDR toxic effects, a phase I-II study was undertaken to establish the efficacy and tolerability of intra-hepatic 5-fluorouracil (5-FU) when given in combination with 5-methyltetrahydrofolate. Patients with colorectal liver metastases (n = 17) received escalating doses of 5-FU as a 1 h infusion with a fixed dose (100 mg/m2) of intra-hepatic 5-methyltetrahydrofolate (4 h infusion) once a week. Dose limiting toxicity was hepatic and gastrointestinal (diarrhea) and occurred at doses > or = 350 mg/m2 5-FU. Other adverse effects included nausea/vomiting and cutaneous toxicity. One patient achieved a complete response and 2 a partial response (mean duration = 9 months) while 11 had stable disease. Patients with complete or partial responses had a mean survival of 17 months, while patients with stable disease survived 13 months and those with disease progression 5.5 months on average. These results suggest that this is a well tolerated regimen although with efficacy at the lower level of the range observed with fluoropyrimidines.

Adult↗
PubMedDate not supplied

Flow cytometric analysis of DNA ploidy and cell proliferation activity in colorectal carcinoma.

The aim of this study was to evaluate the relationship between DNA ploidy, proliferative activity and other prognostic factors and the survival of patients with colorectal cancer. 45 patients were prospectively investigated for 6 years. Fresh multiple samples for flow cytometric analysis of DNA content were collected during surgical resection of primary tumor. A 42% frequency of aneuploidy was observed with a median DNA index value of 1.54. The proliferative activity (%S+G2M cells) was higher in the aneuploid cell sub-population (28.6%) compared to the diploid counterpart (22.7%)(p = 0.05). No significant relationship between DNA ploidy and tumor site, Dukes' stage, histological type, grading age or sex was observed. No correlation between DNA ploidy and survival was demonstrated, including in the analysis of patient subsets according to stage. No additive prognostic information was obtained from a breakdown analysis as a function of DI values, percentages of aneuploid cells and proliferative activity. This study suggests that flow cytometric content analysis lacks prognostic value in colorectal carcinoma.

Adult↗