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Biomedical subjects

F Demard

Publications and source records attributed to F Demard.

At least 19 recordsLinked to original sources
PubMed1992

Correlation between dihydropyrimidine dehydrogenase activity in peripheral mononuclear cells and systemic clearance of fluorouracil in cancer patients.

Dihydropyrimidine dehydrogenase (DPD) is the initial key enzyme in the catabolism of 5-fluorouracil (5-FU). We measured DPD activity in lymphocytes from 57 consecutive head and neck cancer patients while simultaneously monitoring 5-FU pharmacokinetics during 5-day, continuous infusion (1000 mg/m2/day) 5-FU therapy (82 cycles in total). The mean value for DPD activity was 0.186 +/- 0.068 (SD) nmol/min/mg of protein (range, 0.058 to 0.357). The mean value for 5-FU clearance was 2522.6 +/- 684.2 ml/min/m2 (range, 1052 to 4029). A significant linear correlation was observed between DPD activity and 5-FU clearance (r = 0.716, P less than 0.0001). DPD activity was poorly correlated to plasma uracil concentrations (r = -0.260, P = 0.0215). Likewise, plasma uracil concentrations were poorly correlated to 5-FU clearance (r = -0.214, P = 0.0595). In patients evaluated for more than one cycle (n = 18), there was large intrapatient variability in both DPD activity and 5-FU clearance. No significant difference was noted between cycles for DPD activity or 5-FU clearance (Kruskal-Wallis test). Monitoring DPD activity in lymphocytes may be useful in identifying patients at risk for altered 5-FU disposition.

Adult↗
PubMed1992

No effect of dose, hepatic function, or nutritional status on 5-FU clearance following continuous (5-day), 5-FU infusion.

One hundred and eighty seven patients (155 males, 32 females) with histologically proven and previously untreated head and neck cancer were entered in the study. A total of 222 cycles of therapy were analyzed (cisplatin 100 mg m-2 on day 1 and 5-day continuous intravenous infusion of 5-FU 550-1069 mg m-2 day-1, mean 875.5 mg m-2 day-1). Significant interpatient variability for various 5-FU pharmacokinetic parameters was observed including an almost ten-fold range in 5-FU clearance (5-FU Cl, ml min-1 m-2 = 791-7769, mean 2820.7). Log 5-FU Cl was not modified by 5-FU dose (r = -0.1034, P = 0.124, n = 222). Poor linear correlations between log 5-FU Cl and hepatic function tests were observed (respective r and P values for 222 cycles, log AST:0.0526, 0.4365; Log ALT: -0.1167, 0.0842; Log A1K. Phos.:0.154, 0.0214; Log GGT: 0.0652, 0.3436; Log LDH: -0.0984, 0.1563; Log bilirubin: 0.1278, 0.0601). The log 5-FU Cl was also poorly correlated with the serum concentration of various nutritional proteins (respective r and P values for 222 cycles, Albumin: 0.0110, 0.8714; prealbumin: -0.1067, 0.1129; transferrin: 0.0439, 0.5226). Laboratory data including indices of hepatic function and nutritional status cannot account for the interpatient variability in 5-FU disposition.

Blood Proteins↗
PubMed1992

Influence of sex and age on fluorouracil clearance.

PURPOSE: Currently, fluorouracil (5-FU) is one of the major drugs used in cancer chemotherapy. Several investigators, including ourselves, have demonstrated a link between abnormalities in 5-FU clearance (Cl) and the risk of developing more or less 5-FU-related toxicities. Age and sex are among the host factors that have been implicated in the pharmacokinetic variability of drugs. Presently, no data are available on the possible influence of sex and age on 5-FU Cl. PATIENTS AND METHODS: Three hundred eighty patients (mean age, 61.7 years; range, 25 to 91; 301 men and 79 women) with squamous cell carcinoma (sre) of the head and neck were treated in our institution between 1987 and 1991. 5-FU Cl was determined for a total of 1,092 chemotherapy cycles. Each cycle consisted of cisplatin and 5-day continuous intravenous infusion 5-FU (daily doses ranging between 365 and 1,224 mg/m2). RESULTS: 5-FU Cl values (L/h/m2) showed a wide dispersion for both men (median, 179; range, 29 to 739) and women (median, 155; range, 56 to 466). 5-FU Cl values were lower significantly for women compared with men (P = .0005). When adjusted for age and dose, the influence of sex on log Cl remained significant (P = .013). There was no evidence that age modified 5-FU Cl when adjusted for sex and dose. Interestingly, for both men and women, the oldest patients (greater than 70 years) maintained their ability to clear 5-FU with daily doses that ranged from 500 to 1,000 mg/m2. CONCLUSIONS: These data indicate that the capacities to clear 5-FU are lower in women compared with men and are not influenced by age. It would be of interest to know whether this sex-related difference in 5-FU Cl may be clinically relevant by considering both toxicity and tumor response to 5-FU treatment.

Adult↗
PubMed1992

[Dihydropyrimidine dehydrogenase activity in lymphocytes: predictive factor for 5-fluorouracil clearance].

We previously have shown that pharmacokinetic monitoring of 5-fluorouracil (5-FU) could significantly improve the 5-FU therapeutic index when given in continuous venous infusion (Br J Cancer 59, 287-290, 1989). However, the more rational approach would be to find individual biological factors which could predict 5-FU clearance. Dihydropyrimidine dehydrogenase (DPD) is the initial enzyme in the catabolism of 5-FU. DPD activity was measured in 57 head and neck cancer patients receiving CDDP (100 mg/m2, day 1) plus 5-FU (1 g/m2/day x 5, day 2-day 6). DPD activity was measured in lymphocytes using a radioenzymatic assay (2.5 mM MgCl2, 250 microM NADPH, 20 microM 14C-5-FU) with separation of 14C-5-FU from 14C-5-FUH2 by HPLC coupled with a radiodetector. The average DPD activity measured in lymphocytes was 0.186 +/- 0.068 nmol/min/mg protein (range 0.058-0.357) and the average 5-FU clearance (Cl) was 2,523 +/- 684 ml/min/m2 (range 1,052-4,029). A significant linear correlation was demonstrated between DPD activity and 5-FU clearance (Cl = 1,099 + 7,580 DPD, r2 = 0.613, P < 0.0001). In patients evaluated for more than one cycle (n = 18), variations in 5-FU clearance were associated with corresponding variations in DPD activity. The individual determination of DPD activity measured in lymphocytes could be useful for identifying patients at risk for altered 5-FU pharmacokinetics and could be used to adjust the optimal 5-FU dose for each patient before starting the treatment.

Adult↗
PubMed1992

[Laser therapy in the prevention and treatment of mucositis caused by anticancer chemotherapy].

The appearance of mucositis is a frequent and painful secondary effect of anticancer chemotherapy. Patients who develop oral toxicity during the first course of treatment will almost assuredly show identical side effects during each subsequent course unless the drugs are changed or the doses are lowered. In the absence of an efficacious antidote or preventive prophylaxis for such lesions to date, this report presents the results of a preliminary retrospective non-randomized study of the effect of soft-laser treatments on mucositis in cancer patients receiving combination chemotherapy, including 5-fluorouracil. Iatrogenic mucositis was observed during 43% of 53 chemotherapy cycles in the case control population. Curative laser therapy reduced the time to repair lesions and the rate of therapeutic modifications. For patients who received soft-laser therapy as a preventive measure, the incidence of oral complications was reduced to 6% during 101 cycles of chemotherapy. All of these patients, even those who have encountered mucositis before receiving preventive laser therapy, terminated their cancer therapy as originally scheduled. Well designed and carefully controlled trials will be necessary to define the place of helium-neon laser therapy in the repair and prevention of oral complications due to cancer chemotherapy.

Antineoplastic Combined Chemotherapy Protocols↗
PubMed1991

Dose reduction without loss of efficacy for 5-fluorouracil and cisplatin combined with folinic acid. In vitro study on human head and neck carcinoma cell lines.

Folinic acid (FA) and cisplatin (CDDP) both potentiate the cytotoxicity of 5-fluorouracil (5-FU). The activity of various drug combinations including 5-FU, CDDP and FA was tested on two human cell lines derived from squamous cell carcinomas of the head and neck. Cytotoxicity was assessed by the semi-automated colorimetric MTT test. The drugs were tested in clinically achievable conditions (concentrations and duration of exposure). The dose response curves for 5-FU (0-100 ng ml-1) associated with FA (10(-7)-10(-5) M) reflected a progressive increase in 5-FU cytotoxicity with increasing FA concentrations. When CDDP (0-5 micrograms ml-1) was associated with 5-FU, CDDP-mediated enhancement of 5-FU cytotoxicity was apparent only when CDDP was given before 5-FU. The triple association CDDP, 5-FU and FA was also tested. In this case, for an identical final cytotoxicity, the presence of FA (10(-6) M) permitted reduction of the 5-FU concentration between 24.2 and 42% and reduction of the CDDP concentration between 13.8 and 72.7%. These observations may be beneficial for the design of more rational therapeutic trials associating CDDP, 5-FU and FA.

Antineoplastic Combined Chemotherapy Protocols↗
PubMed1991

[Post-radiation mandibular fibrous histiocytoma. Apropos of a case and literature review].

Postirradiation sarcoma of the head and neck has rarely been reported. A case of malignant fibrous histiocytoma (M.F.H.) occurring in the mandible is presented. Head and neck region was previously irradiated for Hodgkin's disease. The interval from initial radiation to diagnosis of sarcoma was 10 years. Aggressive treatment with early radical excision is the treatment of choice. In spite of extensive surgery, the patient died one year after treatment with local recurrence.

Adult↗
PubMed1990

[Extemporaneous anatomopathologic test of the thyroid body. Value, limitations and practical implications. Report of 1,680 thyroidectomies].

The analysis of the results of 1,680 immediate histopathological studies of thyroidectomy specimens allows assessing the value, limitations and pitfalls of this method. Although its specificity for the diagnosis of cancer is 100%, its sensitivity is 70.5% only. Misinterpretation is accounted for by the difficulty to identify the criteria of malignancy in an immediate study. The experience of a pathologist is essential and it ensures the reliability of the method, which is aimed at allowing an optimum one-stage surgical treatment.

Adenocarcinoma↗
PubMed1990

[Autograft procedures in reparative cancer surgery of the loss of substance of the nose. Critical study].

Using several examples, the authors analyse the choice of reconstructive methods available after excision of cutaneous tumours of the nose. Although a variety of procedures exist, one or two specific flap procedures may be preferred in terms of their safety and cosmetic result. Before describing these procedures, the authors briefly review the basis of surgical treatment in the particular case of the nasal region.

Adult↗
PubMed1990

[Malignant maxillofacial non-Hodgkin's lymphoma. Apropos of 15 cases involving the naso-sinus cavities].

Non-Hodgkin's lymphomas include malignant conditions developing within lymphoid tissue, both lymph nodes and extranodal lymphoid tissue. Due to its rich lymphatic supply, the cervico-facial region is frequently involved: 10 to 15% of all NHL (1, 2, 8, 15), i.e. a similar incidence to primary GI involvement (4). The cervical glands and lymphatic structures of the Waldeyer ring are most often and most classically involved. The nasosinusal cavities may be involved, producing diagnostic problems which have to be resolved by the specialist (6). Between 1972 and 1989, 20 cases of NHL involving the bony cavities of the face were seen at the Centre Antoine-Lacassagne. These include the 15 cases reported below involving the naso-sinusal cavities.

Adolescent↗
PubMed1990

[Fractures of the mandible. A critical study of repair procedures].

Based on their personal experience of 110 patients operated on for mandibular trauma, the authors analyse the results of the various techniques used. Screwed micro-plates may be very useful but only complete the therapeutic arsenal of the surgeon. In fact classical methods continue to provide satisfactory results. Poorer results may occur with fractures which combine involvement of the articular surfaces with a lesion of the body of the mandible.

Adolescent↗
PubMed1990

[Use of the conjunctival approach in orbital-palpebral plastic surgery].

The conjunctival route has several indications in palpebral surgery and traumatology. After a brief anatomical summary, the authors review the principles of the technique and differentiate between the preseptal and retroseptal dissection planes. This technique has two indications: in subcutaneous lipectomy for isolated palpebral lipoptosis and in surgery involving the orbital bones, for example in osteotomies or relatively undisplaced fractures of the orbital floor. The conjunctival route has numerous advantages and enlarges the surgical arsenal of the specialist by providing another approach to the orbito-palpebral structures.

Conjunctiva↗
PubMed1990

[Gardner's syndrome. Review of the literature. Report of a familial form].

Through a family form study and a literature review, the authors define the symptoms of the Gardner's disease and the checkup to be carried out. Sometimes, the surgical treatment, proposed in an aesthetical purpose, is difficult to carry out due to the tumor location and consistency. Incomplete forms are likely to be more frequent but the risk of colic degeneration remains the same as for the usual form. Examination and multi-departmental care are required.

Adolescent↗
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

The labelling index: a prognostic factor in head and neck carcinoma.

The thymidine labelling index (LI), representing the percentage of cells in the DNA-synthesis phase, was measured in vitro prior to therapy in 87 patients with squamous cell carcinoma of the head and neck, who were treated between 1977 and 1982. The LI was not related to patient age, site of the tumour, clinical stage or histological grade. Overall survival was 44.5%. Univariate analysis demonstrated that survival was affected by the following factors: (1) age: patients older than 55 had a better outcome (p = 0.03); (2) site of the tumour (p = 0.005): laryngeal tumours had the best survival; (3) clinical stage (p = 0.05). Histological grade did not influence the survival (p = 0.41). Patients having a tumour LI higher than 15.5% (mean + 1 S.D.) had a significantly lower survival than patients with lower tumour LI (p = 0.008). A multivariate analysis using the Cox model showed that clinical stage and LI kept their prognostic impact with regard to survival. Finally, survival after relapse was lower in patients with a high tumour LI. These results demonstrate that a high tumour proliferation rate is an additional factor influencing the disease outcome in head and neck carcinoma. Patients with bad prognosis defined by this parameter could be offered a more energetic treatment.

Adult↗
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↗