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Biomedical subjects

A Thyss

Publications and source records attributed to A Thyss.

At least 127 records · Page 7Linked to original sources
PubMed1989

Salivary passage of 5-fluorouracil during continuous infusion.

Plasmatic and salivary concentrations of 5-FU were investigated in ten patients given 5-day continuous infusions of 5-fluorouracil (5-FU) (1 g/m2/day). Measurable concentrations of salivary 5-FU were scattered ranging from 6 to 100 ng/ml. Between individual 5-FU concentrations in saliva and plasma the coefficient of correlation was low. The theoretically predicted ratios of 5-FU concentrations in saliva over those in plasma, calculated as a function of salivary pH, did not correlate with the observed ratios, the majority of which ranged between 0.1 and 0.5. Noteworthy, 8 of 10 patients exhibited a more or less pronounced increase in 5-FU salivary excretion during 5-day continuous i.v. infusions.

Aged↗
PubMed1989

Pharmacokinetics of weekly low dose doxorubicin.

Weekly low dose doxorubicin (WLD-dox) is an interesting alternative to the classical 3 week schedule because of its reduced cardiotoxicity, the major dose-related side-effect. This study characterized the pharmacokinetic behaviour of WLD-dox with particular attention to the effect of treatment duration on the variability of individual pharmacokinetic parameters. Twenty-eight patients with advanced breast cancer were treated by WLD-dox (12 mg/m2 week). Individual pharmacokinetic analyses were performed at the first injection and every month thereafter; residual drug levels were measured every week before injection. Dox and its main metabolite doxol were measured by HPLC and fluorescence. Pharmacokinetic data were available for 51 cycles. The mean concentration-time profile for 25 patients with normal liver function tests fitted well with a two-compartment model: COext (nM) = 2905 +/- 1834; t 1/2 alpha = 0.08 +/- 0.03 h; t 1/2 beta = 10.4 +/- 3.6 h; clearance (1/h) = 55.4 +/- 24.8; Vd (1) = 809 +/- 434. The findings concur with those for classical 3-week dox schedule (45 mg/m2) analysed in six patients as controls. Exceptions were the initial extrapolated concentration and area under curves which were reduced for WLD-dox according to the dose. Dox and/or doxol overexposure was patent in all three patients with elevated pre-treatment serum bilirubin. During treatment, up to 48 WLD-dox administrations, no significant trends were noted for 10 patients in the evolution of initial extrapolated concentration, terminal half-life, total body clearance or the proportion of doxol formed. Residual drug levels were controlled up to 40 WLD-dox administrations (135 samples); in half the cases they comprised between 1 and 20 nM without particular sign of increasing along the treatment course. In this case WLD-dox can be assimilated to a continuous exposure to low drug levels with intermittent pulses thus representing an original pharmacological profile for dox.

Adult↗
PubMed1989

Evidence for CSF accumulation of 5-methyltetrahydrofolate during repeated courses of methotrexate plus folinic acid rescue.

In the first part of this study the availability of folinic acid (FA) and its main active circulating metabolite, 5-methyltetrahydrofolate (5-MTHF), were studied in plasma and cerebrospinal fluid (CSF) from normal subjects after i.v. administration of 100 and 250 mg of FA. 5-MTHF rapidly appeared in plasma, the maximum value being reached at the first observation time point (1 h). FA was eliminated in plasma more slowly than 5-MTHF. Between the two doses, there was no evidence of modification in pharmacokinetic parameters (terminal half-life, clearance) for either FA or 5-MTHF in plasma and CSF; 5-MTHF was the only product detectable in CSF. Considering FA plus 5-MTHF together, the AUC (area under the curve) ratios between CSF and plasma were close to 1%. 5-MTHF was cleared very slowly from CSF (t 1/2 = 85 h). This finding suggested possible accumulation of 5-MTHF in CSF during repeated administration of FA combined with medium or high dose MTX. In the second part of the study, dealing with a group of eight children treated by such protocols, an increase in CSF 5-MTHF was detected from cycle to cycle in five (r = 0.91, P less than 0.01) with a maximum at 5 x 10(-8) M. This progressive accumulation of 5-MTHF in CSF may have a negative effect on the local action of MTX and should be taken into account for therapeutic strategies designed for the management of meningeal leukaemia.

Child↗
PubMed1989

5-FU therapeutic monitoring with dose adjustment leads to an improved therapeutic index in head and neck cancer.

This 4 year study reports on a pharmacokinetic study for the widely used regimen of cis-platin plus continuous 5-day 5-FU as first-line chemotherapy of head and neck cancer, and the benefit of such data for real-time therapy management. Pharmacokinetic analysis of 177 cycles for 77 patients from a group of 89 patients (group 1; 228 cycles) revealed that both the time-concentration product (AUC) for the entire cycle and the half-cycle AUC (AUC0-3 days) were predictive of cycle toxicity. Real-time analysis of individual AUC0-3 days was used to decide whether to reduce the dose during the second half of the cycle for a total of 249 cycles (81 patients; group 2). The dose in the second half of the course was reduced in 40% of the group 2 courses. There was a statistical difference in complete response rates between group 1 (31%) and group 2 (47%), (0.02 less than P less than 0.05) and a statistically significant reduction was observed in the incidence of toxic cycles (greater than grade 2, group 1 = 20% versus group 2 = 12.4%; 0.02 less than P less than 0.05). Pharmacokinetic follow-up of these patients has proved to be an objective means to improve therapeutic index significantly.

Adult↗
PubMed1989

[Mycotic osteitis of the facial bones. A review of the literature apropos of a case].

The authors report a case of mycotic osteitis of the upper maxillary bone due to Candida Albicans occurring in a 56 year old female patient under treatment for chronic myeloid leukemia. The etiologically difficult diagnosis could only be confirmed after deep surgical biopsy with mycological study of a fragment. A review of the literature confirmed the rarity of upper maxillary involvement by Candida Albicans. Particularly when there is isolated involvement and no evidence of a distant primary focus. The differential diagnosis essentially includes centro-facial malignant granuloma.

Amphotericin B↗
PubMed1989

[Systematic study of various tumoral markers in prevalent bone metastasis].

In the presence of prevalent bone metastases, the precise histo-pathological diagnosis of the primary tumor is often difficult. The authors study the diagnostic value of systematic serum assay of a series of tumoral tracers (ACE, AFP, PAP and PSA, SCC, CA 19:9, CA 15:3, CA 125) which until now were used in evolutive and therapeutic monitoring. 34 patients were selected for this preliminary retrospective study (including 20 with a demonstrated histopathological diagnosis). 70 p. cent of prevalent bone metastases express a target tracer corresponding to the initial location. In some cases, an elevated tracer, because of its specificity, may bring about a diagnostic or therapeutic decision (always according to the context). No conclusion may currently be drawn in case of discordance between the anatomo-clinical context and the "profile" of the markers (1 case in our series).

Biomarkers, Tumor↗
PubMed1989

[Induction chemotherapy with Cis DDP-5FU in cancers of the upper respiratory and digestive tract after 70 years of age].

Sixty one aged patients with advanced squamous cell carcinoma of the upper aerodigestive tract were given a chemotherapy Cis DDP-5 FU before any local treatment. The objective response rate was 77% which included 46% of complete response. Toxic manifestations were more severe than those observed in the general population with the same protocol (nine deaths during the course of the treatment). A few appropriate measures may contribute for the improvement of the therapeutic index: consideration of nutritional and cardiac status, reduction of doses according to age, pharmacokinetic monitoring of 5 FU. An acceptable level of toxicity will be necessary in the design of future, intensive induction trials. The possibility of conservative treatment with a high level of reliability would justify the use of induction chemotherapy in the aged subjects.

Aged↗
PubMed1988

[Initial treatment of infiltrating tumors of the bladder. Combined transurethral resection and systemic chemotherapy].

From September 1983 to September 1986, 20 patients (mean age 65 years) with a muscle-infiltrating tumour of the bladder would normally have been treated by total cystectomy. Instead, they were staged by intravenous urography, pelvic and abdominal computerized tomography, physical examination under general anaesthesia and deep transurethral resection, then given neoadjuvant chemotherapy consisting of cisplatinum and 5-fluorouracil, six courses at intervals of 28 days. Results were evaluated after the 3rd and 6th courses by computerized tomography, intravenous pyelography and transurethral resection. Nine patients had a clinical complete response (6 pT2, 2 pT3, 1 pT4). The median follow-up in january, 1988 was 30 months (range 17-52 months). This protocol was objectively active and well tolerated, even by elderly subjects. Two problems remain concerning patients with complete response: the respective roles of chemotherapy and transurethral resection in the outcome, and the prevention of recurrence (5/9 complete response patients).

Adult↗
PubMed1988

Circadian rhythm-varying plasma concentration of 5-fluorouracil during a five-day continuous venous infusion at a constant rate in cancer patients.

A circadian rhythm in the plasma concentration of 5-fluorouracil (5-FUra) is demonstrated in seven patients receiving this drug as a continuous venous infusion at a constant rate for 5 days. All patients had stage C bladder carcinoma and received cis-diamminedichloroplatinum(II) (45-91 mg/m2) on day 1 as a 30-min venous infusion at 5 p.m. Continuous venous infusion of 5-FUra (450-966 mg/m2/day) was started on day 2 at 8:30 a.m. via a volumetric pump and lasted for 5 days (until day 6). Blood samples were obtained on EDTA every 3 h on days 2, 4, and 6 on each patient (20 samples/patient). 5-FUra plasma concentration was determined by high performance liquid chromatography. Data were analyzed by both multiple analysis of variance and cosinor. Mean lowest and highest values (+/- SEM) were, respectively, 254 +/- 33 ng/ml at 1 p.m. and 584 +/- 160 ng/ml at 1 a.m. (F = 2.3; P less than 0.03). Because of large intersubject differences in 24-h mean plasma concentration, data were also expressed as percentages of each patient's 24-h mean. Both analysis of variance and cosinor analysis further validated (P less than 0.0001) a circadian rhythm with a double amplitude (total extent of variation) of 50% of the 24-h mean and an acrophase located at approximately 1 a.m. (estimated time of peak). Such findings warrant a thorough scrutiny at the chronopharmacology of anticancer drugs when designing continuous infusion schedule. A circadian modulation of the infusion rate of this drug may further optimize the therapeutic index of such treatment modality.

Aged↗
PubMed1988

Orosomucoid:prealbumin ratio--a marker of the host-tumor relationship in head and neck cancer.

The OPR was studied in 203 patients with squamous cell carcinoma of the head and neck at the time of diagnosis, before any specific treatment. The mean initial OPR value was significantly higher in cancer patients than in 63 healthy controls: 5.29 +/- 3.09 vs. 2.63 +/- 1.07; P less than 0.001. There was no significant difference by anatomic site, but the OPR was significantly lower in stage I-II disease than in stage III-IV: 5.10 +/- 3.85 vs. 3.23 +/- 1.99, P less than 0.001. An initial OPR under or over 6 seems to be an important prognostic factor: at 2 years, 51% of patients with an OPR less than 6 were alive vs. only 24.5% of those with an OPR greater than 6, P less than 0.001. The difference was also noted in patients with stage III-IV disease (mean survival: 16 months vs. 7 months, P less than 0.001) and in 89 of the patients who received chemotherapy (mean survival 16 months vs. 6 months, P less than 0.001) whatever the response to chemotherapy. The OPR index, which explores nutritional and acute phase reactant proteins, seems to reflect the host-tumor relationship. Its initial value is strongly related to prognosis at 2 years.

Adult↗