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Biomedical subjects

M Namer

Publications and source records attributed to M Namer.

At least 127 records · Page 7Linked to original sources
PubMed1990

Randomized comparison of cyclophosphamide, doxorubicin and cisplatin (CAP) versus cyclophosphamide and doxorubicin (CA) for the treatment of advanced ovarian cancer (ADOVCA). A EORTC Gynecological Cancer Cooperative Group Study.

The possible advantage of adding cisplatin (P) to cyclophosphamide (C) + adriamycin (A) in the management of stages III and IV ovarian cancer of epithelial origin was tested in a trial in which 149 patients were randomized to receive, after initial surgery, either CAP (C = 600 mg/sqm, A = 45 mg/sqm, P = 50 mg/sqm) or CA (C = 600 mg/sqm, A = 45 mg/sqm) every 4 weeks for 6 to 12 cycles, at which time follow-up laparotomoy was to be performed in responding or clinically disease-free patients. Fifteen patients were not included in the final analysis and the remaining 134 patients were considered fully or partially evaluable and are used in analysis of response and survival. The complete and partial response rates were 45.6% in the CAP arm and 45.4% in the CA arm, but the CAP regimen is of special importance in patients with bulky disease. Median survival CAP = 24 m and CA = 24.2 m), time to progression and survival was found not significantly different when CAP and CA were compared. However, more patients in the CA regimen had no macroscopic disease left after surgery than in CAP regimen (11 versus 6) and more patients in the CAP arm dose reductions and schedule delays than in the CA arm (61.1% versus 38.2%).

Antineoplastic Combined Chemotherapy Protocols↗
PubMed1990

[Should systematic bone scintigraphy be carried out on breast cancer patients with small tumors?].

Bone metastases are frequent in the evolution of breast cancer. Bone scan is the best method for early detection. At initial presentation the frequency of bone metastases is low, and it is usefulness to recommend this exam except for old people or patients with risks factors. During the follow-up, the utility of repeated bone scan is discussed. For the majority of authors, it may be reserved for symptomatic patients or when biological modifications appeared. The follow-up of these patients must be essentially clinical. This strategy delay the diagnosis of bone metastases of only a few weeks; and it don't seem to affect the prognosis of these patients.

Age Factors↗
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

Factors affecting relapse in node-negative breast cancer. A multivariate analysis including the labeling index.

Between 1975 and 1982, 167 patients with carcinoma of the breast without axillary lymph node metastases were studied. The thymidine labeling index (LI), representing the percentage of cells in the DNA synthesis phase, was measured in all these patients. High LI values were more frequently encountered in young patients (P = 0.05), in low estrogen receptor (ER) tumor content (P = 0.007) and in high grade tumors (P = 0.0002). The overall 8-year relapse-free survival (RFS) was 68%. Univariate analysis demonstrated that RFS was influenced by histological grading (P = 0.03), ER (P = 0.03), PR (P = 0.02) and LI (P = 0.01). Multivariate analysis using the Cox regression model selected the LI as the single significant prognostic factor with regard to RFS (P = 0.037). These results emphasize the important role of cell proliferation kinetics in defining node-negative breast cancer patients with a high risk of relapse.

Adult↗
PubMed1989

Tamoxifen metabolism: pharmacokinetic and in vitro study.

The qualitative and quantitative importance of tamoxifen (TMX) metabolism in vivo led us to investigate further the metabolic profile of this major anti-oestrogenic drug in a significant group of 81 breast cancer patients and to evaluate the respective in vitro activity of each metabolite. TMX and its four metabolites described until now (NDT, 4-OHT, Y, Z) were measured in blood (HPLC method) at the time of first drug intake and at the steady state. Between these two states, the unchanged drug relative proportion dropped from 65% to 27%. Demethylation was the major metabolic pathway. For 13 clinically evaluable patients, there was no significant difference in the distribution of serum levels of TMX and metabolites as a function of response to treatment. In vitro studies were performed on two human breast cancer cell lines: MCF-7, oestrogen receptor and progesterone receptor positive (ER+, PR+) and CAL-18 B (ER-, PR-). Cytostatic effects were evaluated by the tritiated thymidine incorporation test. TMX and all metabolites were active on these two cell lines, but the 50% inhibitory concentrations (IC50) were 4-250-fold higher in CAL-18 B than in MCF-7, depending on the metabolite considered. For the MCF-7 cells only, the antiproliferating activity was parallel to the relative binding affinity for ER. Moreover, for the MCF-7 cells only, the effects of these drugs were partially reversed by oestradiol (E2), the higher the metabolite affinity for ER, the lower the reversal efficacy. These compounds were tested in mixtures at proportions duplicating those found in patients after initial drug intake (mixture D1), and the steady state (mixture Css). The mixtures were also compared to the equimolar unchanged drug. No differences were seen among these three experimental conditions for either MCF-7 or CAL-18 B. A dose-effect relationship was noted. Overall, TMX and its metabolites exert a dual effect: when concentrations are below a threshold between 2 x 10(-6) and 10(-5) M, the drugs are mainly cytostatic; this effect is related to their affinity for ER. At higher relevant clinical concentrations, a cytotoxic activity is observed and it appears independent of the presence of ER.

Aged↗
PubMed1989

[Current status of hormonotherapy of metastatic cancer of the breast].

Hormonotherapy of metastatic breast cancer was begun in 1896. The first trials were based on surgery (ovariectomy, adrenalectomy, hypophysectomy). Medical hormone therapy began with the administration of estrogens to postmenopausal women, and was then extended to include androgens. The use of tamoxifen, medroxyprogesterone acetate or aminoglutethimide combined with hydrocortisone progressively enlarged therapeutic applications. Comparison of the results obtained with these various substances reveals that they are all of equal therapeutic value, but that tamoxifen is the best tolerated hormonotherapy. No two-drug association has yet been found better that any one product used alone. By contrast, successive administration of 2 drugs has resulted in longer maintenance of benefits. Clinical and especially biological criteria (hormone receptor assays) allow identification of the population that has the most chance of responding to this type of treatment.

Aminoglutethimide↗
PubMed1989

[Response of bone metastases to medical treatment: definition of evaluation criteria and classification trials].

Bone metastases are very frequent. Some are sensitive to the action of anticancer drugs. However, there is as yet an unsolved methodological problem in the evaluation of response to these drugs. The uniquely radiological UICC criteria are quite insufficient, in as much as they appear with a long delay and sometimes give erroneous results. In this work we give a brief review of biological and clinical knowledge about bone metastases, and we attempt to give an array of the possible evaluation criteria and their respective value. We propose as a working hypothesis a classification of responses taking into account the criteria: the urinary hydroxyproline to urinary creatinine ratio, the serum dosage of bone isoenzyme of alkaline phosphatase and propeptide of type III procollagen (P III NP), and as an essential element, an analysis of all available imaging techniques. A visual study of bone scintillation scans must precede that of radiographs and, when possible, it must be associated to computerized scintillation scanning. When metastasis are located to the pelvis, the vertebral column, or the sternum, a CT scan or better, a nuclear magnetic resonance study (IRM), is indispensable in order to have a direct measure of the tumor extension to soft tissues. Furthermore, in the case of isolated metastases, one of these imaging techniques allows a diagnostic biopsy. Finally an analysis of response at the bone level will always be associated with a measure of their duration and an evaluation of metastases to other sites.

Acid Phosphatase↗
PubMed1988

Interim report of phase II study of new nitrosourea S 10036 in disseminated malignant melanoma.

Thirty-three patients with disseminated malignant melanoma were entered in a phase II study of the new nitrosourea S 10036 using a 100-mg/m2 weekly induction schedule for 3-4 consecutive weeks. Patients who responded to this treatment were followed with a maintenance therapy every 3 weeks. Toxic effects were mainly hematological and consisted of delayed thrombocytopenia and leukopenia. Among 30 patients who could be evaluated, eight partial responses were observed (response rate, 26.67%); among seven patients with cerebral metastasis, two partial responses were observed. This multicentric study is currently being continued to confirm this interim report.

Antineoplastic Agents↗
PubMed1988

Dose versus pharmacokinetics for predicting tolerance to 5-day continuous infusion of 5-FU.

This non-randomized study reports pharmaco-clinical data on 5-FU administered by the widely used 5-day continuous infusion schedule to 42 patients with metastatic colorectal cancer; 5-FU was given by hepatic intra-arterial route (h.i.a.) at doses ranging from 800 to 1,450 mg/m2, and by a systemic intravenous route (i.v.) at doses ranging from 650 to 1,300 mg/m2. 5-FU blood levels were available for a total of 179 cycles. Toxicity was dose-dependent during h.i.a. cycles but not during i.v. cycles. For h.i.a. cycles, 1,000 mg/m2/day represented the threshold dose for tolerance. The individual total cycle drug concentration-time product might predict toxicity for both i.v. and h.i.a. cycle when the threshold is set at 30,000 ng/ml.hr. These data may be of practical value for improving the therapeutic index of 5-day continuous treatment by 5-FU given by i.v. or h.i.a. routes.

Adult↗
PubMed1988

Clinical applications of antiandrogens.

Antiandrogens, substances that prevent androgens from expressing their activity at target cells, play an important role in the treatment of prostate cancer. The most frequently used substances have either a steroidal structure (cyproterone acetate) or a non-steroidal structure (Flutamide or Anandron). Antiandrogens have been tested both alone and in combination with treatments aimed at inhibiting testicular secretion (castration, LH-RH analogs), thereby producing complete blockade of androgen secretion and action. Patients treated by such combination protocols have often shown an improvement in the percentage of remissions and, less often, improvement in survival. Administration of antiandrogens improves the clinical symptoms of patients with benign prostatic hypertrophy, but the exact mechanism of their action requires further investigation. Cutaneous manifestations due to hyperandrogenicity (hirsutism, alopecia, acne) have also been improved by cyproterone acetate, which is often given together with estrogens (reversed sequential regime), by spironolactone or topically applied products. Finally, antiandrogens have been successfully used to treat breast cancer in men, early puberty, hypersexuality and sexual deviations.

Androgen Antagonists↗
PubMed1988

Evaluation of prostate-specific antigen in prostate cancer.

Prostate-specific antigen (PSA) was assayed retrospectively in 131 prostate cancer patients. Pretreatment levels at primary tumor diagnosis were above 5 ng/ml in 13/16 (81%) of stage B and C patients and in 28/28 (100%) of stage D (D1 and D2) patients. At the discovery of metastasis in treated patients, they were above this value in 12/17 (71%) of patients. To determine the value of PSA assays when physical exams were negative, 52 patients were reevaluated at a maximum interval of 12 months as a function of their initial PSA concentration. When the initial PSA was negative, there was no clinical evolution during the next 6 months; when PSA was positive, patients had a 55% risk of progression in the next 4 months. All PSA assays were coupled with prostatic acid phosphatase (PAP) measurements. No PAP values were positive when PSA was negative.

Acid Phosphatase↗
PubMed1988

Zoladex as primary therapy in advanced prostatic cancer. A French cooperative trial.

From April 1984 to May 1986, 129 patients with prostate cancer entered a prospective trial with a new LH-RH agonist, Zoladex. Mean age was 72 years (range of 45-94 years) and, in most cases, patients had metastatic disease, not previously treated by chemotherapy or hormone therapy. Patients received a monthly injection of 3.6 mg. Serum testosterone was lowered into the range of castrate levels after 4 weeks of treatment. In 105 evaluable patients at 3 months, a 65% partial response (PR) rate was observed, with 11% stable and 24% progressive disease. Median time to progression was 37 weeks. Analysis of objective criteria revealed 30% PR for prostate volume and 51% CR-PR for prostatic acid phosphatases. Seventeen percent of lytic metastases had recalcified. One hundred twenty-nine patients were evaluable for toxicity. Endocrinological side effects were common: decrease in libido, 92%; impotence, 86%; hot flushes, 48%; and breast swelling or tenderness, 9%. Nonendocrinologic side effects were rare. The treatment is generally well accepted by patients owing to the convenient depot formulation and to the minor side effects.

Acid Phosphatase↗
PubMed1988

Anandron (RU 23908) associated with orchiectomy in stage D prostate cancer. Preliminary results of a randomized, double-blind study.

A randomized, double-blind, multicenter trial was performed comparing the association of orchiectomy plus the nonsteroid antiandrogen Anandron (300 mg daily) to orchiectomy plus placebo in the treatment of patients with stage C or D prostate cancer. The results for 98 evaluable stage D patients with a median follow-up of 23.4 +/- 8.9 months are given. Although there was no statistically significant difference between the two treatments with regard to any parameter (subjective response, best objective response according to NPCP criteria, and progression-free interval and survival), the results were invariably in favor of the combined treatment, as already reported in other trials on Anandron.

Aged↗
PubMed1988

[Breast cancer: the role of scintigraphy in the initial evaluation and follow-up of patients with small tumors (T less than or equal to 3 cm)].

To evaluate the utility of bone scans for the follow-up of patients with small breast cancers (T less than or equal to 3 cm), the files for 133 patients whose disease was diagnosed between Jan. 1, 1979 and Dec. 31, 1980 were reviewed. At initial presentation, two of these patients already had bone metastases. During their disease course, 30 patients developed metastases and 16 of them had at least one bone metastasis. In 7 of these 16 cases, the bone metastasis was solitary; in 4 cases bone lesions were symptomatic. A total of 178 bone scans were performed during the follow-up of these 133 patients; 16 of these scans were positive, but only 4 examinations allowed the diagnosis of bone metastasis. Despite the slight prognostic value of initial bone scanning in this series, the technique is of little value unless it is combined with clinical examinations aimed at early detection of disease recurrence or metastasis. Except as part of clinical trial protocols, systematic bone scans appear unnecessary for the staging and follow-up of patients with small breast cancers.

Adult↗
PubMed1988

In vitro clonogenicity in relation to kinetic and clinicopathological features of breast cancer.

The clonogenicity in soft agar and the labeling index (LI) which represents the percentage of cells in the DNA synthesis phase, were studied in 59 breast cancer patients and these parameters were related to other known clinicopathological features, namely age, histological grading, estrogen and progesterone receptors and the status of axillary lymph nodes. Out of 59 tumors, 49 could be successfully cloned in soft agar and the mean plating efficiency (PE) was 0.1%. Low grade tumors were more frequently encountered in tumors which did not form colonies (P = 0.025). Cloned tumors had a higher mean LI (P = 0.05). A high PE was associated with low estrogen receptors (ER) (P = 0.03). Clonogenicity was not related to patient age, progesterone receptors (PR) or the status of axillary lymph nodes. These results suggest that a successful in vitro cloning and a high PE are associated with unfavorable prognostic factors in breast cancer.

Agar↗