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Biomedical subjects

M Namer

Publications and source records attributed to M Namer.

At least 109 records · Page 6Linked to original sources

Prognostic value of total cathepsin D in breast tumors. A possible role in selection of chemoresistant patients.

Evaluation of prognostic factors for breast cancers is important for therapeutic decisions both at the time of surgery and during postoperative surveillance. In 1979, H. Rochefort described an induced protein with a molecular weight of 52,000 Daltons identified as procathepsin D. Total cathepsin D (TCD) (52K + 48K + 34K), expressed in pmol/mg protein, can be measured by an immunoradiometric method commercialized by Cis-Biointernational. Total cathepsin D was assayed in 413 breast cancer tumors from patients who underwent surgery between January 1, 1978, and December 31, 1985. Using a cut-off of 35 pmol/mg protein, patients with an elevated level had a significantly poorer survival than those with a low level (p = 0.03). This difference was not found for node-negative patients but was very significant for node-positive patients (p less than 0.008). The survival of node-positive patients with a low total cathepsin level was not statistically different from that of node-negative patients. Analysis of the N+ subgroup of patients who did not receive adjuvant chemotherapy revealed that TCD no longer had any prognostic value, whereas it was still important for the N+ subgroup who received an adjuvant treatment. Cox multivariate analysis of prognostic value for survival placed total cathepsin D in third position, after nodal invasion and progesterone receptor status, for the entire population, and in first position before progesterone receptor status for the node-positive population. The association of a low cathepsin level and positive progesterone receptors characterized the subgroup of patients with the longest survival. TCD levels played the same role for prediction of the outcome of metastasis.(ABSTRACT TRUNCATED AT 250 WORDS)

Breast Neoplasms↗

Assessment of "squamous cell carcinoma antigen" (SCC) as a marker of epidermoid carcinoma of the anal canal.

We measured squamous cell carcinoma antigen (SCC) in epidermoid carcinoma of the anal canal in 66 patients. Samples were taken at diagnosis, before treatment, and during follow-up; 353 samples were analyzed. The positive threshold was taken as 2 ng/ml. At diagnosis, the sensitivity of the marker was 44 percent and its specificity 92 percent. In our series, the pretherapeutic level of SCC does not correlate with T as in Papillons' Clinical Staging System, but it does correlate with nodal invasion (P less than 0.05). It is of no prognostic value at the time of diagnosis. During follow-up, at relapse the level of SCC is 20.3 +/- 43 ng/ml. This increase is significant (P less than 0.01): the sensitivity of the marker is 77 percent. In patients who have relapsed, development of the illness correlates with the level of SCC, which is of prognostic value (P less than 0.01). In conclusion, the level of SCC should be associated with the clinical follow-up of patients with epidermoid carcinoma of the anal canal.

Adult↗

Phase II study of fotemustine in recurrent supratentorial malignant gliomas.

38 adults with recurrent supratentorial malignant gliomas, including glioblastoma multiforme (21), anaplastic astrocytomas (9), probably transformed low-grade astrocytomas (6), pinealoblastoma (1) and non-metastatic tumour of unknown histology (1), were treated with fotemustine 100 mg/m2 intravenously every week for 3 consecutive weeks followed by a 5-week rest period. Maintenance treatment consisted of one infusion every 3 weeks. Patients were divided into three groups according to treatment effect. 10 objective responses (26%) with a median time without progression of 32.7 weeks, 18 stabilisations (47%) and 10 failures (26%) were observed. Pathological findings of the initial primary tumour and neurological functional status were unequally distributed in these groups. Haematological and liver toxicities were mild, delayed, transient and reversible. Thrombocytopenia and leukopenia were more frequent (30%) in patients treated with prior chemotherapy. Fotemustine is a well tolerated active drug in recurrent malignant gliomas with an original and short treatment schedule.

Adolescent↗

Oestrogen and progesterone receptor status in bone biopsy specimens from patients with breast cancer.

Of 16 breast cancer patients with histologically proven, tumour-infiltrating biopsy specimens most had low ER and PR values; the ER and PR contents varied between 0 and 135 and 0 and 44 fmol/mg protein, respectively. With the conventional clinical threshold of 10 fmol/mg protein, 8 specimens (50%) were ER-PR-, 4 (25%) ER-PR+, 3 (19%) ER+PR+ and 1 (6%) ER+PR-. ER levels were significantly lower in the tumoral bone lesion compared with the primary tumour. For 15 patients with negative biopsies and without endocrine treatment, ER and PR concentrations were quantifiable (2 fmol/mg protein or more) in 9 (60%) and 11 cases (73%), respectively. 8 of 9 patients over 55 (89%) were ER+ (2 fmol/mg protein or more). Conversely, for patients under 55, 1 of 6 (17%) was ER+ (P less than 0.001). Results for PR were similar. These data strongly suggest that steroid receptors are present in healthy bone tissue.

Adult↗

Analysis of tissue platinum distribution in patients with cancer of the oesophagus.

The objective of this work has been to analyse the repartition of platinum (Pt) tissular levels within the tumour (T), the peritumoral adjacent non-tumoral area (P) and distant healthy tissue of the same anatomical zone (H) in oesophagus cancer. Forty-two biopsies (congruent to 5 mg) have been performed under endoscopy and after informed consent in 11 patients (mean age 61 yr, range 43-74) with squamous cell carcinoma of the oesophagus treated by the neoadjuvant chemotherapy protocol including cisplatin (100 mg/m2) and 5-FU (1 g/m2 x 5 days). Biopsies were done 34-36 h after cisplatin. Additional biopsies were obtained for histological controls. Pt was measured by flameless atomic absorption spectrometry. Considering Pt concentration in T, P and H there was no significant accumulation during repeated treatment (3 cycles). For all cycles, mean [S.D.] values (micrograms/g dry tissue) were 2.03 [2.39] for H, 2.75 [2.03] for P and 3.73 [2.3] for T (H vs. T, P = 0.006). In addition, Pt concentrations were found comparable between the upper and lower poles of the tumours (5 patients). Pt concentrations in T did not predict antitumour activity. These data complete the rather limited knowledge on tissular Pt levels in treated patients and suggest a decreasing gradient of Pt concentrations from tumour to healthy tissue in oesophagus cancer.

Adult↗

[Evaluation of the "squamous cell carcinoma antigen" as marker of epidermoid cancer of the anal canal].

The authors studied the value of Squamous Cell Carcinoma Antigen (SCC) in squamous carcinoma of the anal canal in 66 patients. Assays were made at the time of diagnosis, before any treatment and during follow-up. A total of 353 assays were made. The positive threshold was selected at 2 ng/ml. At the time of diagnosis, sensitivity of the marker was 44 per cent and its specificity 92 per cent. In our series, pre-treatment SCC levels were not correlated with T by the Papillon classification, but were correlated with lymph node involvement (p less than 0.05). They had no prognostic value at the time of the initial diagnosis. During follow-up, at the time of recurrence, SCC levels were 20.3 +/- 43 ng/ml. This rise was significant (p less than 0.01), the sensitivity of the marker being 77 per cent. In patients who had a recurrence, the outcome was correlated with SCC levels and the latter were of prognostic value (p less than 0.01). In conclusion, SCC levels should form part of the clinical monitoring of patients with a squamous carcinoma of the anal canal.

Adult↗

[Advanced cancer of the exocrine pancreas treated by a long-acting luteinising hormone releasing hormone (LH-RH) analogue, triptorelin: phase II study].

Between 1987 and 1989 we treated 18 patients with advanced pancreatic adenocarcinoma with a long acting LH-RH analogue: triptorelin. Seventeen patients were evaluated. We obtained no objective responses. The median survival time was 4.5 months. The treatment was well tolerated without any major secondary effects. The absence of dosage of hormonal receptors did not allow the selection of hormone sensitive patients. The future study of hormone therapy will analyse the pancreatic hormonal receptors.

Adenocarcinoma↗

A randomized double-blind study evaluating Anandron associated with orchiectomy in stage D prostate cancer.

A randomized double-blind study with a 3-yr follow-up comparing the two arms "orchiectomy + Anandron (300 mg)" vs "orchiectomy + placebo" in 125 patients with stage D prostate cancer has confirmed the beneficial effects of the combined Anandron therapy on subjective parameters and on the best objective response (NPCP criteria), although these effects were not statistically significant, but failed to detect any improvement in time-to-disease progression or survival. Comparison with the results of other trials emphasizes the urgent need to establish suitable prognostic factors by further clinical research before evaluating the benefits of individual drugs.

Aged↗

Final report of the French multicenter phase II study of the nitrosourea fotemustine in 153 evaluable patients with disseminated malignant melanoma including patients with cerebral metastases.

One hundred sixty-nine patients with histologic evidence of disseminated malignant melanoma, including patients with cerebral metastases, were entered into a Phase II study of the nitrosourea fotemustine. The treatment regimen consisted of a 100 mg/m2 1 hour IV infusion every week for 3 consecutive weeks, followed by a 4- to 5-week rest period (induction therapy). In responding or stabilized patients, maintenance therapy consisted of 100 mg/m2 every 3 weeks until the disease progressed. One hundred fifty-three patients were evaluable for response. Three complete responses and 34 partial responses were observed (according to the World Health Organization criteria), leading to an objective response rate of 24.2% (95% confidence interval: 17.4% to 31.0%). Responses were also documented on cerebral (25.0%), visceral (19.2%), or nonvisceral (31.8%) metastatic sites. The median duration of response was 22 weeks (range, 7 to 80 weeks). The objective response rate in previously untreated patients was 30.7% (19 of 62 patients). The main toxicity was hematologic with delayed and reversible leukopenia and/or thrombopenia. The objective response rate observed (especially in untreated patients), the activity on cerebral metastases, and the small amount of extra-hematologic toxicity encountered suggest that fotemustine is an effective drug in disseminated malignant melanoma.

Adult↗

Chemotherapy by fotemustine in cerebral metastases of disseminated malignant melanoma.

A total of 42 patients with cerebral metastases of malignant melanoma were included in this study of the nitrosourea fotemustine. The treatment plan consisted of a l-h i.v. infusion of 100 mg/m2 fotemustine every week for 3-4 weeks, followed by a 4- to 5-week rest period. Responding or stabilised patients then received 100 mg/m2 fotemustine every 3 weeks. Among the 39 evaluable patients, 2 complete responses and 9 partial responses were documented, leading to an overall response rate of 28.2%. Most of the responses were obtained in previously untreated patients and/or those presenting with a single cerebral metastasis. Toxicity was mild and mainly hematological, especially in patients previously treated by polychemotherapeutic regimen. Our study confirms the activity of fotemustine in cerebral metastases of disseminated malignant melanoma.

Adult↗

Combination chemotherapy of dacarbazine and fotemustine in disseminated malignant melanoma. Experience of the French Study Group.

A total of 70 patients presenting with a disseminated malignant melanoma were entered into a multicentric study of combination chemotherapy using dacarbazine and fotemustine. In all, 63 patients were evaluable, 31.8% of whom had previously received cytotoxic chemotherapy. The protocol consisted of induction treatment with a weekly infusion of 100 mg/m2 fotemustine on days 1 and 8 and a daily infusion of 250 mg/m2 dacarbazine on days 15/18 followed by a 4- to 5-week rest period. Responding and stabilized patients were given maintenance treatment comprising fotemustine (100 mg/m2, day 1) and dacarbazine (250 mg/m2, days 2/5) every 3 weeks. The response rate was 33.3% (9 complete responses (CRs) and 12 partial responses (PRs)) and was outstanding among pretreated patients (34.9%). Responses were also documented in cerebral (28.6%), visceral (23.1%) and nonvisceral (43.3%) metastatic sites. Toxicity was mainly hematologic (22.2%, grade III/IV leukopenia; 20.3%, grade III/IV thrombocytopenia) and was acceptable. These results are encouraging in terms of the antitumor activity against nonvisceral metastases (43.3%) and the percentage of CRs obtained (23.3%), and they confirm the activity of fotemustine in cerebral metastatic sites.

Adult↗

Steroid receptors in human osteoblast-like cells.

The presence and functions of steroid receptors were evaluated in three human osteosarcoma cell lines (OS1 = SA OS; OS2 = HOS TE 85, and OS3 = MNNG HOS TE 85). The human breast cancer cell line MCF-7 was used as internal control for oestrogen receptors (E2R). High and low affinity sites were characterised. The high affinity sites had a similar dissociation constant in all four cell lines. In contrast, the number of sites per cell was higher in MCF-7 cells. E2 did not significantly modify the number of progesterone receptors (PgR) per cell in any of the osteosarcoma lines. As expected, E2 increased the number of PgR sites per MCF-7 cell. 4-hydroxytamoxifen decreased the growth of MCF-7 cells only. OS1 and OS2 were sensitive only to the highest concentration tested, which produces only non-specific cytotoxic effects. Thus E2R and PgR were found in osteoblast-like cells, but the function of E2R in such cells remains unknown.

Breast Neoplasms↗

Pirarubicin in advanced breast cancer: a French cooperative phase II study.

79 patients with advanced breast cancer were given Pirarubicin 20-25 mg/m2 during 3 consecutive days every 3 or 4 weeks. 78 were evaluable for response (41 without previous chemotherapy and 37 with only one previous regimen). The overall response rate was 35% (95% CI 24-45) and the complete response rate was 8%. In previously untreated patients, the response rate reached 41.5%. The limiting toxicity was a non-cumulative granulocystopenia, sometimes severe at these high doses, with a prompt recovery. The non-haematological toxicities were mild, and included 13% with grade 3 alopecia.

Adult↗

Phase II study of oral idarubicin in elderly patients with advanced breast cancer.

Thirty-one elderly patients with measurable advanced breast cancer entered this phase II study. A dose of 15 mg/m2/day of Idarubicin (IDA) for 3 consecutive days every 3 weeks was given orally. Mean total cumulative dose of IDA received was 175 mg/m2 (range: 45-475 mg/m2). Mean number of cycles given was four (range: 1-15). Out of 27 evaluable patients, three achieved a complete response (CR), four had a partial response (PR) (CR + PR = 26 +/- 17%), nine showed no change, and 11 had a progressive disease. Median time to progression was 83 days (range: 19-728 days). Out of 26 patients evaluable for toxicity, hematologic toxicity at day 21 was moderate: neutropenia grades 3 and 4 = 16% of cycles: two patients had grade 1 thrombopenia; and three patients, grade 3. No cumulative hematologic toxicity was detected. Nonhematologic toxicities consisted of nausea and vomiting in 72% of patients [World Health Organization (WHO) grades 3 and 4 = 8%)] and alopecia in 76% (WHO grades 2-3 = 38%). Grade 1 stomatitis occurred in 4% of cycles. Chemotherapy was discontinued in one patient because of drop of left ventricular ejection fraction (LVEF) from 0.62 to 0.44 at a cumulative IDA dosage of 322 mg/m2. The results of this study show that IDA is an active drug in elderly patients with advanced breast cancer. Due to its simplicity of administration IDA deserves further investigations in combination with other drugs.

Administration, Oral↗