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Biomedical subjects

M Marty

Publications and source records attributed to M Marty.

At least 109 records · Page 6Linked to original sources
PubMed1994

[Long-term surgical results of osteochondrosis dissecans of the knee joint in adolescents less than 16 years of age].

The correct therapy of osteochondritis dissecans in patients under 16 years is very important to prevent the knee joint from secondary arthritis. We analysed clinical, radiological and with MRI the long term (10 years) results of a follow-up study on 36 patients under 16 years with 42 operatively treated osteochondritis dissecans of the knee joint. There were excellent and good results in 81% of the patients. After an average of 10 years there were no signs of arthritis which would necessitate any treatment.

Adolescent↗
PubMed1993

Combined chemotherapy-radiotherapy in advanced Hodgkin's disease: results of a prospective clinical trial with 70 stage IIIB-IV patients.

PURPOSE: To evaluate two regimens of chemotherapy followed by high dose total or subtotal nodal irradiation in advanced Stages of Hodgkin's disease. METHODS AND MATERIALS: From October 1980 to September 1985, 70 patients with Hodgkin's disease, with clinical Stages IIIB (35 cases) and IV (35 cases) were treated with combined modality therapy. Patients were randomly assigned to receive four cycles of chemotherapy, mechlorethamine, vincristine, procarbazine and prednisone (MOPP) versus the same regimen alternating with adriamycin, bleomycin, vinblastine and dacarbazine, ABVD-derived regimen, followed by high-dose (40 Gy) total or subtotal nodal irradiation. Because of partial response, 13 patients (18.5%) got additional chemotherapy (1-4 cycles). RESULTS: After chemotherapy, 49 patients (70%) achieved complete remission or good partial response and 15 patients (21.5%) partial response. Five primary failures (7%) and one death (1.5%) occurred. After combined modality therapy, 59 patients (84%) achieved complete remission, one patient partial response (1.5%) and eight patients (11.5%) failed to primary treatment. Two toxic deaths (3%) were observed during initial treatment. There was no significant difference in response rates between MOPP/radiotherapy and MOPP/ABVD/radiotherapy. Nine patients relapsed (15%). A total of 21 patients died, 13 because of Hodgkin's disease and eight from other causes. High dose total or subtotal nodal irradiation following four courses of chemotherapy was feasible, although hematological toxicity grade > or = 2 (World Health Organization) was observed in one-third of the patients, particularly in patients aged over 40. The median duration of follow-up was 75 months. Actuarial survival curves indicate a 8 years disease-free survival and survival of 70% and 65% respectively, without any significant difference between the two regimens. Because of hematological toxicity, the percentage of planned full treatment was lower in MOPP/radiotherapy regimen. CONCLUSION: These results lead to recommend the alternating regimen. Patients restaged as poor responders after initial chemotherapy did not survive for long. More intensive treatment is now proposed for this subgroup of patients.

Adolescent↗
PubMed1993

Phase I and pharmacokinetic study of Taxotere (RP 56976; NSC 628503) given as a short intravenous infusion.

Taxotere (N-debenzoyl-N-tert-butoxycarbonyl-10-deacetyl Taxol; RP 56976; NSC 628503) is a semisynthetic analogue of Taxol. It is twice as active in inhibiting tubuline depolymerization and has a better in vivo activity on B16 melanoma, with responses in advanced colon 38 and PO3 adenocarcinoma. Sixty-five patients (49 women, 16 men), with a median age of 57 years, received 248 courses of Taxotere given as a 1-2-h i.v. infusion every 2 or 3 weeks. Ten distinct dose levels from 5 to 115 mg/m2 were studied. Dose-dependent, reversible neutropenia was the limiting toxicity. Delayed and cumulative skin reactions occurred beyond 70 mg/m2. Alopecia was observed in the majority of patients beyond 70 mg/m2. Four partial responses were achieved in patients with ovarian carcinoma, breast carcinoma, small cell lung cancer, and carcinoma with unknown primary. The pharmacokinetics of Taxotere, determined in 23 patients receiving 20 to 115 mg/m2, was linear. At the highest doses, the Taxotere plasma profile was typically triphasic, with a terminal half-life of 13.5 +/- 7.5 (SD) h, a plasma clearance of 21.1 +/- 5.3 liters/h/m2, and a distribution volume of 72 +/- 40 liters/m2. AUC correlated with the percentage decrease of neutrophils in a sigmoid Emax model. The renal excretion of unchanged Taxotere was very low (< 5% of the dose). The recommended dose for phase II trials with this schedule is 100 mg/m2 every 3 weeks.

Adult↗
PubMed1993

[Arthroscopic treatment of subacromial impingement syndrome: possibilities and limitations].

Serious impingement syndromes of the shoulder unresponsive to conservative measures can be relieved by means of the approved open anterior acromioplasty. However, the rise of shoulder arthroscopy allowed the same procedure to be performed arthroscopically. Based on an accurate indication the outcome of arthroscopic subacromial decompression may be considered as equally successful as that obtained by the open procedure. The advantages of the arthroscopic approach are: a significantly less gross destruction of the deltoid and--as a result--a reduced rehabilitation period a smaller incision and the possibility of an arthroscopic inspection of the joint prior to decompression For the repair of complete tears of the rotator cuff the arthroscopic procedure will provide less satisfactory long-term results. For those cases the open reconstruction will remain the treatment of choice.

Acromion↗
PubMed1993

Design and rationale of a randomised comparison of cyclophosphamide, methotrexate and fluorouracil vs fluorouracil, epirubicin and cyclophosphamide in node-positive premenopausal women with operable breast cancer. A trial of the International Collaborative Cancer Group (ICCG).

In 1984, the International Collaborative Cancer Group (ICCG) started a randomised trial comparing adjuvant treatment with cyclophosphamide 100 mg/m2 orally on days 1 to 14, methotrexate 40 mg/m2 intravenously on days 1 and 8 plus fluorouracil 600 mg/m2 intravenously on days 1 and 8 every 4 weeks for 6 cycles (CMF) vs fluorouracil 600 mg/m2, epirubicin 50 mg/m2 and cyclophosphamide 600 mg/m2 (FEC), all given intravenously on day 1 for 8 cycles at 3-week intervals in premenopausal patients with node-positive breast cancer. However, a large French institution that joined the ICCG shortly after the trial was initiated utilised different schedules of both CMF and FEC. Because different dose intensities were also employed, particularly of FEC, both patient groups, the French and non-French, will be analysed separately. A total of 761 patients were randomised as of March 1992. Patients were well balanced for prognostic factors. The median follow-up is now 3.5 years. Preliminary data have previously been reported in abstract form. Final data will be presented pending further follow-up.

Administration, Oral↗
PubMed1993

[Promising results of bimonthly chemotherapy with high dose cyclophosphamide and epirubicin in induction treatment of inflammatory cancer of the breast].

Forty-eight patients with inflammatory breast cancer were treated by an induction regimen with cyclophosphamide (1200 mg/m2), and epirubicin (75 mg/m2). Four to six courses were given every two weeks, whatever the absolute leukocyte counts, before mastectomy, loco-regional radiation, and conventional, or reinforced, for selected patients, chemotherapy. Main toxicity was leukopenia, with grade IV in 25% of cases. However, febrile neutropenia was rare, and relative dose intensity was 102% after four courses, and 97% after six courses. Complete disappearance of inflammatory signs was observed in 90% of patients. Three patients had a pathological complete response, and ten patients had negative axillary lymph nodes. Furthermore, 13 patients had a major pathological response. With a median follow-up of 42 months, progression-free survival and overall survival are 48% and 66%, respectively.

Adolescent↗
PubMed1993

[High dose chemotherapy with autologous bone marrow transplantation in ovarian adenocarcinoma].

The present treatment of advanced ovarian adenocarcinoma patients is unsatisfactory, with 5-year survival rates of less than 15%. To obtain better results, one possibility is the use of therapeutic intensification with autologous bone marrow support. In effect, there is a known dose-response relationship in ovarian carcinoma, especially with alkylating agents. To date, a 69% response rate has been achieved with this kind of treatment in 39 patients refractory to standard therapy. However, responses are of short duration, with a median range of 6-7 months. Therapeutic intensification has been used in over 100 patients, as consolidation therapy, following first-line chemotherapy. For these patients, projected 3-year overall survival and disease-free survival rates are 30-50% and 20-40% respectively. These results compare favorably to those of standard therapy. Early deaths are more frequent in refractory patients (18%). Complete hematological recovery usually occurred within 3-4 weeks. Extra-hematological toxicity is related to previous treatment and to cytotoxic drugs used during intensification. These preliminary results, limited to a small series of patients, are sufficiently promising to continue and extend these trials.

Adenocarcinoma↗
PubMed1993

[Antiemetic effect of ondansetron in recurrent chemotherapy with cisplatin].

Six hundred and twenty-eight courses of cisplatin containing chemotherapy were recorded in patients receiving up to three courses of cytotoxic drugs with ondansetron (OND) given as an antiemetic agent (32 mg as a single iv dose or as a continuous infusion). The sample size of patients decreases from one course to another due to phenomena which may or may not be related to the chemotherapy and the anti-emetic treatment or to the evolution of the cancer disease. For patients with incomplete response to ondansetron, withdrawals could be related to an insufficient antiemetic effect as is known with other antiemetic drugs. Conversely, it is not the case for patients who had a complete response. Therefore, to avoid any bias due to patient selection, the analysis is based on the probability of changes from complete to incomplete response or from complete to complete response between two subsequent courses (i and i + 1). The response to OND treatment for the course i + 1 depends not only on the efficacy during this course (i + 1) but also on the response during the prior course (i). A discrete time-dependent statistical model (Markov chain) was used to test the evolution of the probability of remaining in complete response. This probability was equal to 66% between the first and the second course, and to 88% between the second and the third one. The probability of remaining in complete response significantly increased during repeated courses (P = 0.001). These results show that in patients for whom OND treatment allows a complete antiemetic control during the first course of chemotherapy, the probability of remaining with no emetic episodes at all increases during the two subsequent courses.

Adult↗
PubMed1993

[Treatment of advanced breast cancer in postmenopausal women with droloxifene: results of a double-blind phase II trial for dose determination].

To determine the optimal daily dose of a new antiestrogen, droloxifene, for the treatment of advanced breast cancer, we have conducted a multicenter, randomized, double blind trial. Postmenopausal women with advanced breast cancer, who could not benefit from loco regional therapy, with positive or unknown estrogen or progesterone receptors were entered in this study. Droloxifene was administered in a double blind randomized design, with daily dose of either 20 (group I), 40 (group II) or 100 mg (group III). None of the patients had received previous systemic antitumor therapy, with the exception of adjuvant chemotherapy terminated at least one year before the patient's recruitment. Patients with at least one measurable tumoral lesion were entered into the trial. Three hundred and sixty nine patients have been enrolled, 234 are fully evaluable for efficacy. Objective response rate (CR + PR) is 31.1, 44.6 and 41.9% for the groups I, II and III respectively (P = NS). Time to response has been short: in the three groups, 50% of the responses have been observed within the 2 first months of treatment. Time to disease progression is 6, 8.3 and 6 months respectively for the 20, 40 and 100 mg/day treatment group. Side effects have been moderate and not dose related. Hot flushes and gastro intestinal disorders have been observed most often. This promising new drug deserves further study and randomized comparison versus tamoxifen.

Aged↗
PubMed1992

The immune response to p53 in breast cancer patients is directed against immunodominant epitopes unrelated to the mutational hot spot.

Alteration of the p53 gene is the most frequent genetic feature of human cancer and leads to overexpression of the altered protein in the tumor cell nucleus. Two diagnostic procedures are currently available to assess p53 mutations: (a) molecular analysis of the gene sequence; and (b) immunohistochemical analysis of p53 protein accumulation. We now report a third approach, serological analysis. Fifteen % of primary breast cancer patients were found to have circulating antibodies to p53 protein by immunoprecipitation or immunoblotting. We have found a close correlation between the presence of such antibodies and bad prognosis such as high histological grade and the absence of hormone receptors. Furthermore, we found that the B-cell response to p53 protein is induced by two immunodominant regions located at the carboxy and amino termini of the protein, outside the central mutational hot spot region. These findings suggest that serological analysis, combined with molecular and histochemical methods, may be suitable for assessing the state of the p53 gene in cancer patients.

Antibodies, Neoplasm↗
PubMed1992

[Cancer of the breast at the time of diagnosis. A national CANAM study: analysis of 3007 cases].

Between April 1988 and February 1990, 3,007 cases of female breast cancer were recorded among people insured by CANAM*; 118 cancers were bilateral from the start and 2,889 were unilateral. At the time of diagnosis the patients' age ranged from 24 to 101 years (median: 60 years), and 35.6 percent of the tumours were virtually subclinical. Lymph node involvement was clinically absent in 75 percent of the cases and histologically absent in 57 percent. In women under 50 the proportion of small TO-T1 tumours was greater than 40 percent, which pleaded for detection before the age of 50 years. Conversely, in economically weak populations and in women who were followed up for cancerous disease, breast cancer was diagnosed at a later stage. In older (retired) women (median age: 74), who accounted for 44 percent of the whole population, the proportion of advanced tumours was practically doubled (T4: 11 percent versus 6 percent), and the probability of metastases at the time of diagnosis had risen from 4.2 to 6.1 percent. In these patients, clinical examination once a year should contribute to an earlier diagnosis.

Adult↗
PubMed1992

Early assessment of a new anticancer drug analogue--are the historical comparisons obsolete? The French experience with pirarubicin.

Data of all phase II studies of pirarubicin (THP-doxorubicin) have been analysed for toxicity or activity in breast cancer and compared with published reports on doxorubicin, epirubicin or mitoxantrone used as single drugs. A graph of the 95% confidence intervals for each event was used. The results suggest that pirarubicin is as effective as other intercalating drugs in breast cancer and grossly better tolerated than doxorubicin, especially alopecia and cumulative cardiotoxicity. The equimyelotoxic doses of each drug were also estimated. The methodology and the validity of such historical comparisons is discussed: they cannot replace prospective randomised phase III studies, and do not allow definitive conclusions. However, most comparative trials of anticancer drug analogues cannot answer the right questions because their objectives are not adequate (especially for equiefficacy). But early evaluation by historical comparisons can help the conception of phase III studies.

Breast Neoplasms↗
PubMed1992

A comparison of granisetron as a single agent with conventional combination antiemetic therapies in the treatment of cytostatic-induced emesis. The Granisetron Study Group.

The safety and efficacy of intravenous granisetron were compared with combinations of conventional antiemetics in two single-blind, parallel-group studies which have been reported previously. In this review updated data from both studies is presented. In both studies granisetron (40 micrograms/kg) was given as a single 5-min infusion before chemotherapy with two additional doses allowed to control subsequent nausea and vomiting. All patients were naive to chemotherapy. Patients due to receive cisplatin (greater than 49 mg/m2) were randomly assigned to receive either granisetron alone or metoclopramide (3 mg/kg) plus dexamethasone (12 mg) given prophylactically followed by an 8-h infusion of metoclopramide (4 mg/kg). In the 24 h after the start of chemotherapy 70% of granisetron-treated patients and 67% of comparator group were complete responders. In patients due to receive moderately emetogenic chemotherapy, granisetron was compared with chlorpromazine (up to 200 mg/24 h) plus dexamethasone (12 mg). Twenty-four hour efficacy was significantly higher in the granisetron group with complete response in 68% of patients compared to 47% in the comparator group (P less than 0.001). A subset of 40 patients in this study were crossed over to receive the alternative antiemetic on their next cycle of chemotherapy. A significant majority of patients (32/34; 94%) preferred granisetron (P less than 0.001). Around 80% of the granisetron-treated patients in both groups required only a single prophylactic dose of granisetron. Following the first additional dose of granisetron, around 87% of patients reported symptoms to be improved or resolved. Adverse experience reporting was higher in the comparator groups with somnolence and extrapyramidal reactions representing the most common events. Headache was the most commonly reported adverse experience in granisetron-treated patients. Granisetron has proved safe and effective in controlling chemotherapy-induced emesis and is more convenient to administer than conventional antiemetics.

Adolescent↗
PubMed1992

Human pharmacokinetics of N-L-leucyl-doxorubicin, a new anthracycline derivative, and its correlation with clinical toxicities.

A pharmacokinetic study of N-L-leucyl-doxorubicin, a new derivative of doxorubicin, has been undertaken during a phase I trial in 19 patients with advanced cancer after intravenous bolus administration at doses ranging from 30 to 240 mg/m2. The pharmacokinetics of N-L-leucyl-doxorubicin was linear with a total body clearance of 41.3 +/- 25.7 L/hr/m2. N-L-leucyl-doxorubicin was extensively metabolized into doxorubicin, which appeared in plasma immediately after N-L-leucyl-doxorubicin infusion. The mean molar doxorubicin/N-L-leucyl-doxorubicin area under the curve (AUC) ratio was 0.49 +/- 0.22 and was independent of the administered dose. A relationship has been established between the doxorubicin AUC (r = 0.74; p less than 0.001) and the surviving factor in white blood cell counts. Other toxic side effects (thrombocytopenia or stomatitis) did not correlate with any pharmacokinetic parameter. These findings suggest that the degree of metabolization of N-L-leucyl-doxorubicin into doxorubicin may be responsible for the toxicity, that is, N-L-leucyl-doxorubicin may simply represent a pro-drug for doxorubicin.

Dose-Response Relationship, Drug↗