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Biomedical subjects

M Namer

Publications and source records attributed to M Namer.

At least 145 records · Page 8Linked to original sources

Value of urinary hydroxyproline and bone isoenzyme of alkaline phosphatase in the early detection and follow-up of bone metastasis in breast cancer patients.

A multiparametric biological study of 178 evaluable breast cancer patients was performed to evaluate the usefulness of individual parameters for the prediction, diagnosis and follow-up of bone metastasis (BM) as compared to physical tests. Serum and urinary calcium and phosphorus were of little discriminative value. The sensitivity and specificity for the urinary hydroxyproline/creatinine ratio (UHP/creat.) were respectively 75% and 81.4% versus 43.2% and 91.4% for the bone isoenzyme of alkaline phosphatase in serum (BIE). During an average follow-up of 14.3 months for 51 patients with bone metastasis, variations in UHP-creat. and BIE correlated with clinical and physical findings; the best correlation was given by UHP/creat. Twenty patients who were initially free of bone metastasis were followed-up for a mean metastasis-free interval of 14 months; UHP/creat. predicted the appearance of bone metastasis in 50% of cases with a lead time of 5.5 months versus 40% and 8.5 months for BIE. Combined use of UHP/creat. and BIE gave a prediction rate of 70% and a mean lead time of 7 months, and this combination of markers thus merits consideration in the management of breast cancer patients.

Alkaline Phosphatase↗

Relationship between systemic 5-FU passage and response in colorectal cancer patients treated with intrahepatic chemotherapy.

The study described herein was conducted to analyze the relationship between tumor exposure to 5-FU and clinical response. Six patients were placed on continuous 5-day intrahepatic 5-FU chemotherapy for colorectal cancer metastasized to the liver. The starting dose was 600-800 mg/m2 per day; cycles were repeated at 4-week intervals. The 5-FU dose was increased by 250 mg/day at each cycle. All six patients received 3 or more cycles, for a total of 37 cycles. Response was evaluated after each cycle by ultrasonography or computed tomography (CT). Pharmacokinetic data revealed a high individual cycle-to-cycle variability for all six patients in the 5-FU area under the curve (AUC day 1 to day 5) corrected for the dose. These variations in drug biodisposition, reflecting hepatic 5-FU uptake, were significantly related to measurable modifications in the tumor mass in 71% of cycles. The correlation between the reduction in local drug exposure and tumor regrowth was better than that between the increase in local drug exposure and tumor reduction. These findings constitute an original illustration in humans of the experimental concept of the drug exposure/tumor response relationship for 5-FU.

Aged↗

The DNA labelling index: a prognostic factor in node-negative breast cancer.

The DNA labelling index (LI), representing the fraction of S-phase cells, was studied in 76 patients operated on for breast cancer from 1975 to 1979. No patient had lymph node involvement following axillary dissection (N-), and no adjuvant medical treatment was given. Patients were classified in one of two groups according to the median LI. Patient distribution by age, tumour size, and receptor status was identical in both groups. A higher frequency of grade 3 tumours was noted in the group with an LI above the median value. The cell proliferation rate was an important discriminative factor for metastatic potential. The probability of survival at 8 years for patients with a high LI was significantly lower than that of patients with low LI (36% versus 100%; p less than 0.001). Relapse-free survival at 8 years was respectively 56% and 83% (p less than 0.02). At 2 years, these values were 75% and 100%, indicating the early occurrence of metastases. By contrast, the LI had no prognostic value concerning loco-regional disease recurrence or survival after the appearance of metastasis. No relationship was found in this study between survival and other prognostic factors, namely tumour size, histological grade, or hormone receptor level. The LI currently appears to be the best prognostic factor for N- breast cancer. High risk patients identified by this method could thus be offered adjuvant medical treatment.

Adult↗

HPLC micromethod for simultaneous measurement of estradiol, progesterone, androgen and glucocorticoid receptor levels. Application to breast cancer biopsies.

Estradiol (ER), progesterone (PR), androgen (AR) and glucocorticoid receptor (GR) levels were assayed in 25 breast cancer tumors. The tissue was pulverized and homogenized in buffer, then divided into two parts: one was assayed by the standard dextran-coated charcoal method (DCC), with Scatchard plot analysis, the other was assayed by a micromethod developed in our laboratory, as described below: --incubation of the cytosol with several ligands (labelled and unlabelled) selected to avoid unwanted cross-reactions --DCC separation, followed by extraction of all receptor-bound steroids by precipitation of proteins with methanol/TCA --separation of these steroids on a high pressure liquid chromatography (HPLC) column using a methanol/water solvent --collection of the fractions of the column outlet and counting. Use of three labelled ligands and appropriate unlabelled ligands allowed assays of the four receptors. This micromethod was highly correlated with the standard method: ER = 0.985 (P less than 0.001); PR = 0.999 (P greater than 0.001); AR = 0.989 (P less than 0.001); GR = 0.867 (P less than 0.001). Thresholds of positivity were not modified. This micromethod allowed simultaneous measurement of several receptors in 40 mg biopsy specimens and can be applied to other hormone-dependent tissues.

Breast Neoplasms↗

Pulmonary toxicity of a combination of low-dose doxorubicin and irradiation for inoperable lung cancer.

In 1980, 27 patients with inoperable lung cancer (26 non-oat cell, one oat cell) were treated by split-course irradiation (40 Gy/10 fractions) plus concomitant low-dose chemotherapy (doxorubicin 10 mg/m2). Twenty-four of the 27 patients received the entire treatment course. Fifteen of the 27 patients were administered various chemotherapy protocols after a period of one month. Median survival was 16 weeks despite a 60% response rate. The lungs were the main site of complications (13 cases of radiation pneumonitis for the 24 patients), which occurred primarily when an objective response was obtained. These complications partially explain the poor results. Injection of doxorubicin during irradiation appears to have been a determining factor.

Adult↗

Optimised analysis of tamoxifen and its main metabolites in the plasma and cytosol of mammary tumours.

Recent biochemical and pharmacological findings concerning tamoxifen (TMX) have proven that both the unchanged drug and the main metabolites, N-desmethyltamoxifen (NDT) and 4-hydroxytamoxifen (4OHT) are biologically active. An HPLC method based on on-line post-column UV irradiation with fluorescence detection is described. Optimized conditions allowed complete and rapid separation of TMX 4OHT, NDT and two other recently reported metabolites, Y and Z. This method was applied to plasma and cytosol drug and metabolite analyses. In plasma, from the moment of initial drug administration until the steady state (after 1 month or more of continuous oral TMX treatment), the values of NDT to TMX ratios were completely reversed: 22 to 215 in mean %, P less than 0.01. The presence of metabolites Y and Z is significant. 4OHT, hardly detectable at the first dose, was measured at the steady state with high interpatient variability. It is hypothesized that metabolite evolution with time may be due to auto-induction of drug metabolism. In cytosols, which were all obtained during continuous TMX treatment, the ratios between TMX and metabolites were comparable to those observed in plasma, but with greater interpatient variability. Metabolite Y was not detectable in cytosols. This variability was not linked to the levels of cytosolic oestradiol receptors before initiation of treatment.

Breast Neoplasms↗

Value of CA 15:3 in the follow-up of breast cancer patients.

CA 15:3, a new tumour marker detectable by two monoclonal antibodies (115 D 8 and DF 3), was measured by an immunoradiometric technique on the ELSA solid phase. Sixteen percent of patients with localized breast cancer had CA 15:3 levels greater than 25 U ml-1, and levels increased with tumour size. CA 15:3 levels greater than 25 U ml-1 were found in 54% of patients with nodal involvement and in 91% of patients with metastatic breast disease. Measurement of CA 15:3 in 70 women with metastatic breast cancer and a normal CEA revealed positive CA 15:3 levels at diagnosis of the first metastasis in 66% of cases; 63% of these patients could be monitored with CA 15:3.

Antigens, Neoplasm↗

[Adriamycin in low weekly doses. Latest therapy of advanced cancer of the breast].

Thirty-four patients with heavily pretreated advanced breast cancer received adriamycin in weekly doses of 12 mg/m2. Twenty-two patients (18 assessable) had a performance status greater than or equal to 3 (WHO scale). There were 5 (28%) partial responses, 7 (39%) minimal responses, 3 cases (17%) with no change and 3 (17%) with progressive disease; the mean duration of response was superior to 9 months (range: 3-12 months). In the remaining 12 patients, who had resisted a previous multidrug regimen containing adriamycin, there were 3 (25%) partial responses, 2 (17%) minimal responses, 4 cases (33%) with no change and 3 (25%) with progressive disease; the mean duration of response was superior to 5 months (range: 3-11 months). More than 600 weekly injections were administered with only minor blood and digestive tract toxicities. No alopecia was recorded. The total cumulative dose of adriamycin was superior to 900 mg/m2 in 8 patients; none had clinically evident cardiac toxicity. Adriamycin extravasation with subsequent tissue necrosis occurred on 10 occasions due to the frequency of administration; this problem was solved by the systematic installation of central venous catheters.

Adult↗

Conservative treatment (chemotherapy/radiotherapy) of locally advanced breast cancer.

Once treated almost exclusively by radical surgery, locally advanced breast cancers (Stages III, IV; MO) were later treated solely by irradiation, but local results (cosmesis and recurrences) remained poor. Since 1977, we have used induction chemotherapy in an attempt to treat subclinical metastatic disease while allowing better quality mammary conservation in a greater number of patients. From 1977 to 1980, 25 patients (Stages III, IV; MO) were treated by a sequential association of chemotherapy (Adriamycin [doxorubicin], vincristine, cyclophosphamide, 5-fluorouracil; 3 cycles) followed by irradiation (45 Gy to the breast and nodal areas; 15-30 Gy mammary boost dose). Responses of 50% or more were observed in 86% of the breast lesions and in 80% of nodal lesions. This sequential treatment was always well tolerated. Local recurrences occurred in six patients (24%) who underwent mastectomy without any complications. The survival rate at 4 years is 55%.

Adult↗

Clinical and pharmacokinetic evidence of a life-threatening interaction between methotrexate and ketoprofen.

Co-administration of ketoprofen was found in 4 of 118 cycles of high-dose methotrexate (MTX) analysed retrospectively in thirty-six patients. All 4 cycles were characterised by severe MTX toxicity, which was fatal in three cases. Simultaneous administration of ketoprofen was associated with prolonged and striking enhancement of serum MTX levels. There were no abnormalities in MTX kinetics or evidence of MTX toxicity when ketoprofen was given at least 12 h after completion of high-dose MTX infusion. The kidney may be the site of drug interaction. This high-risk association between MTX toxicity and ketoprofen may also apply to other non-steroidal anti-inflammatory drugs.

Adolescent↗

[Comparative study of 3 markers in ovarian cancer: CA 125, CA 19,9 and CEA].

CA 125 is today the best tumour marker to follow up the evolution of epithelial cancers of the ovary where it is elevated in about 80% of cases (as compared with a positive finding in only 20% for CEA and CA 19,9): it is no use as a screening test, it does reflect the quality of the first debulking operation, it makes it possible to follow the clinical evolution of the disease and thus to modify the adjuvant treatment, it helps to indicate whether a second look operation should be carried out; but it does not dispense altogether with the second look operation because even when CA 125 returns to normal the disease is sometimes still not eradicated, finally, it gives an opportunity to look early for any recurrences.

Antigens, Neoplasm↗

[Cancer of the prostate: new hormone therapies].

Beside orchiectomy and estrogens, other endocrine manipulations are proposed for metastatic prostatic cancer patients. Antiandrogens, Cyproterone acetate and Flutamide, are often less efficient but less toxic than DES. Progestational agents medroxyprogesterone acetate, megoestrol acetate, chlormadinone acetate have also a limited activity. Inversely, tamoxifen is very little active. Preliminary results of ketoconazole need more controls. The present aims are to obtain, particularly by hormonal association, a more efficient and less toxic treatment, when DES can be given initially or becomes inefficient.

Androgen Antagonists↗