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L Mignot

Publications and source records attributed to L Mignot.

At least 37 records · Page 2Linked to original sources
PubMed1994

[Hyperthyroidism and hypersecretion of chorionic gonadotropin in gastric adenocarcinoma].

We report a case of hyperthyroidism complicating and revealing a metastatized adenocarcinoma of the stomach with high circulating levels of human chorionic gonadotropin and its beta component. To our knowledge, this is the first reported case of a non-trophoblastic tumor with hyperthyroidism and secreting quantities of these hormones. High circulating levels of beta component in such patients have been considered to be a sign of malignancy. The mechanisms of thyroid stimulation could be related to the biological activity of certain forms of the human chorionic gonadotropin.

Adenocarcinoma↗
PubMed1994

High-dose interleukin-2 two days a week for metastatic renal cell carcinoma: a FNCLCC multicenter study.

The purpose of this study was to determine the efficacy and safety of a new high-dose interleukin (IL)-2 regimen, given two days a week, for renal cell carcinoma. One hundred and four patients received IL-2 as a continuous i.v. infusion for 48 h at a daily dose of 24 x 10(6) IU/m2/day for 5 consecutive weeks. Patients were assessed for efficacy 4 and 8 weeks after the end of therapy, and patients who stabilized or responded received maintenance therapy with the same regimen. An objective clinical response was observed in 20 patients (complete in four, partial in 16). The dose of infused IL2 was significantly higher in the responders than in the nonresponders (p < 0.05). Clinical responses were significantly associated with a sedimentation rate of < 20 (p = 0.02), but no other prognostic factor was identified. Mean survival was 13 months. Grade 3 and 4 toxicities were rare, except for hypotension (58% of patients), the main dose-limiting toxic effect. Overall, 83% of the planned dose of IL-2 was given. IL-2 given 2 days a week is active in metastatic renal cell carcinoma and well tolerated.

Adult↗
PubMed1994

Long-term renal effect of cisplatin in man.

Although the acute nephrotoxicity of cisplatin has been well documented, long-term follow-up studies are scanty. We have evaluated the renal function in 35 patients who have had completed therapy with cisplatin at least 3 months before the study. All patients had normal serum creatinine levels before chemotherapy. Evaluation of renal function included: serum creatinine, glomerular filtration rate (inulin clearance), effective renal plasma flow (p-aminohippurate clearance), urinary beta 2-microglobulin and N-acetyl-beta-D-glucosaminidase excretion, and renal tomography. The median cumulated dose of cisplatin was 603 +/- 37 mg/m2. The mean serum creatinine level was 78 +/- 21 and 88 +/- 3 mumol/l before and after chemotherapy, respectively (p < 0.05). Mean glomerular filtration rate (92 +/- 4 ml/min) and effective renal plasma flow (362 +/- 21 ml/min) were significantly lower than in controls (110 +/- 3 and 436 +/- 24 ml/min). The mean enzymuria and the renal size remained within the normal range. In 12 patients who were reevaluated 12 and 24 months later, glomerular filtration rate and effective renal plasma flow remained stable. These results suggest that at usual dosages cisplatin is associated with a nonprogressive loss of renal function which is of a moderate degree.

Acetylglucosaminidase↗
PubMed1993

Cell immobilization in composite agar layer microporous membrane structures: growth kinetics of gel-entrapped cultures and cell leakage limitation by a microporous membrane.

Agar discs containing different amounts of viable Escherichia coli cells (from 10 to 10(6) organisms.g-1 agar) were incubated in a nutrient medium and the growth of agar-entrapped bacteria and free (released) cells was monitored. The study was repeated with composite immobilized-cell structures obtained by placing a microporous membrane filter between the gel matrix and the incubation medium. In both cases, immobilized cells grew exponentially and reached a peak concentration an order of magnitude higher than that of free (suspended) cell cultures. The maximum specific growth rates of entrapped bacteria, ranging between 0.0115 min-1 and 0.0145 min-1, i.e., slightly higher than that of control free cultures (0.011 min-1), showed no clear dependence on the initial cell loading (ICL). The microporous filter proved efficient in limiting cell leakage since it noticeably lengthened the leakage time at a given ICL. This efficiency, however, decreased at high ICL and high growth rate of immobilized organisms.

Agar↗
PubMed1993

[Intraperitoneal administration of interferon gamma. An efficient adjuvant to the chemotherapy of ovarian cancers. Apropos of an European study of 108 patients].

One hundred and eight patients with residual epithelial ovarian cancer at second laparotomy, after first line plastine-based chemotherapy were treated with intraperitoneal rHU-interferon-gamma at a dose of 20 x 10(6) U/m2, twice a week for 3-4 months. 86% of the patients had residual macroscopic tumors and 33% bulky tumors (> 2 cm). From the 99 evaluable patients, 62 had an evaluative third laparotomy and nine additional patients a laparotomy. Complete pathologic and global response rates to interferon-gamma were 23 and 32% respectively. Age and tumor size were independently correlated with treatment response. Patients (n = 41) under the age of 60 with a tumor size less than 2 cm had a complete and global response rate of 42 and 54% respectively. Interferon-gamma was equally effective in chemo-resistant and chemosensitive tumors. Median duration of response was 21 months and median survival of responder patients was 86% at 2 years. In multivariate analysis, response to interferon-gamma was the most prominent prognostic factor of this population of patients with residual ovarian cancer.

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

Phase II study of tetrahydropyranyl adriamycin (pirarubicin) in elderly patients with advanced breast cancer.

Thirty elderly (over 70 years) women with measurable advanced breast cancer entered into this Phase II study. An initial dose of 30 mg/m2 of pirarubicin (THP) every 3 weeks was given intravenously. THP was escalated by levels of 10 mg/m2 according to the blood cell count done at day 14 and day 21 until a maximum dose per cycle of 70 mg/m2 was reached. The mean total cumulative dose of THP received was 204 mg/m2 (range 30-710 mg/m2). The mean number of cycles given was 5.5 (range 1-24). Of 28 evaluable patients, 1 achieved a complete response (CR), 6 had a partial response (PR) (CR + PR = 25%; 95% confidence interval 9-41%), 13 showed no change, and 5 had a progressive disease. The median time to progression was 3 months (range 0.5-18+ months). Of 28 patients evaluable for toxicity, the hematologic toxicity at day 15 was neutropenia grade 3 and 4 in 61% of the patients and thrombopenia grade 3 and 4, 0% of cycles. No cumulative hematologic toxicity was detected. Nonhematologic toxicities consisted of nausea and vomiting in 50% of patients (WHO grade 3 = 5%) and alopecia in 64% (WHO grade 2-3 = 36%). No stomatitis occurred. No cardiac toxicity was observed. The results of this study show that THP is an active drug in elderly patients with advanced breast cancer. Because of its safety, THP deserves further investigation in this application.

Adenocarcinoma↗
PubMed1991

[Study of vinorelbine (V) combined with hexamethylmelamine (H) (combination V-H) in adenocarcinoma of the ovary: results a phase I-IIA trial, NHO-88, of ARTAC "ovarian" group].

The lack of decisive progress in ovarian cancer chemotherapy in recent years led the ARTAC "Ovary" group to initiate a study based on the hypothesis of collateral sensitivities. In this phase I-II trial, NHO-88, the V-H combination (associating vinorelbine (VNB) and hexamethylmelamine (HMM) was studied in patients with advanced ovarian adenocarcinomas, most of which had become resistant to previous chemotherapy. The aim of the study was to find an active combination without complete cross resistance with first-line platinum salt based combinations, such as CAP, FAP or CACb-300. A pilot feasibility study was first carried out to determine the maximum tolerated weekly dose (MTWD) of VNB (20 mg/m2/week), HMM being administered per os on days 1-14 of every 28-day cycle at a standard dose of 250 mg/m2/day. An open phase II-A study was further carried out according to a 2-step sequential analysis method for phase II clinical trials. We observed: 1), a good tolerance of the V-H combination apart from frequent neutropenia; 2), a response rate of 35% (95% confidence interval: 23-47%); 3), a median response duration of 4 months (range: 1-7 months); 4), in some cases, the absence of a complete cross-resistance between the V-H regimen and the previously administered platinum-based combinations. These results, which are currently being validated (phase II-B ongoing), constitute the first step in the search for active systems of sequential or alternate chemotherapeutic regimens for the treatment of advanced carcinomas.

Adenocarcinoma↗
PubMed1990

Diffusion in immobilized-cell agar layers: influence of bacterial growth on the diffusivity of potassium chloride.

The diffusivity of potassium chloride in composite agar slab/microporous membrane structures loaded with various amounts of Escherichia coli whole cells was determined using both time-lag and steady-state methods. The diffusion coefficient of KCl decreased linearly with the logarithm of the immobilized-cell content. The effect exerted by bacterial growth inside the immobilization matrices on KCl diffusivity was then investigated. The diffusion coefficient of KCl obtained by time-lag analysis decreased during incubation of the immobilized-cell structures, whereas less consistent results arose from the steady-state method. An apparent doubling time for immobilized E. coli, increasing with the initial cell content of the gel, was obtained from the calibration relationship between KCl diffusivity and the number of organisms in agar.

Culture Media↗
PubMed1990

Phase I study of oxaliplatin in patients with advanced cancer.

Oxaliplatin, or trans-1-diaminocyclohexane-platinum, was tested in a phase I study. A total of 44 patients received 116 courses with dose escalation from 45 to 200 mg/m2. Neither renal nor hematologic toxicities were observed at doses up to 200 mg/m2. Gastrointestinal toxicity was practically constant and often of grade 3-4 on the WHO scale (53% of patients). The dose-limiting toxicity was a peculiar sensory neuropathy; the first neurologic phenomena appeared at a dose of 135 mg/m2 and continued thereafter, occurring after 75% of the courses with mild to moderate intensity (WHO grade 1-2 after 67% of the courses). Neurotoxicity was cumulative and six patients developed grade 3 disabling neuropathy after a cumulative dose of 500 mg/m2, with walking and handwriting difficulties being slowly regressive in three cases. A peculiar symptom was the influence of temperature, with exacerbation of parethesias when patients touched cold surfaces. Nerve-conduction studies carried out in six cases showed a predominantly sensory neuropathy with axonal degeneration. No other toxicities were observed, although audiograms were not systematically done. We observed four partial responses that lasted 6-13 months in patients with oesophageal (2 cases), lung (1), and urothelial cancer (1); two of these patients had been pretreated with cisplatin. Since neurologic side effects occur very frequently and may produce a long-lasting sensory neuropathy, for phase II studies we recommend a starting dose of 135 mg/m2, with a careful neurologic survey.

Adult↗
PubMed1989

[Value of medical treatment of cancer of the kidney].

Renal carcinomas have a very variable natural history and are generally not very sensitive to medical treatment particularly chemotherapy. The response rates obtained in metastatic cancer with various drugs and combinations do not exceed 15% for a duration of response of several months. The most effective drugs are vinca alkaloids such as vinblastine. Over recent years, interferon has been tested in this type of tumour with discordant results reported in the literature. However, it seems that by using high doses of the order of 15 to 20 million units per m2, three times a week, the response rates are of the order of 20% for a duration which may be as long as one year in responding patients. In combination with vinblastine, some authors have obtained response rates of the order of 40%. Treatment is especially effective in the case of lymph node recurrence or small lung metastases. It is of no value in cases of visceral, bone or hepatic dissemination. It is frequently poorly tolerated systemically because of the high doses administered and it is expensive. It should therefore be reserved to young patients and to patients with an reasonable life expectancy. In cases of operated renal cancer at risk of recurrence because of local or lymph node spread, no adjuvant medical treatment has yet been proven to be effective.

Antineoplastic Agents↗