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L Mignot

Publications and source records attributed to L Mignot.

At least 19 recordsLinked to original sources

Antitumour activity of three second-line treatment combinations in patients with metastatic colorectal cancer after optimal 5-FU regimen failure: a randomised, multicentre phase II study.

BACKGROUND: We have investigated the efficacy, safety and quality of life profiles of three therapeutic combinations [irinotecan + leucovorin (LV)/5-fluorouracil (5-FU), oxaliplatin + LV/5-FU and irinotecan +oxaliplatin] in patients with metastatic colorectal cancer after failure of a 5-FU-based regimen, or whose disease had progressed within 6 months of the end of treatment. PATIENTS AND METHODS: One hundred and one patients were randomised to receive either: (i) irinotecan 180 mg/m(2) on day 1 followed by an LV 200 mg/m(2) infusion, before a 5-FU 400 mg/m(2) bolus followed by a 5-FU 600 mg/m(2) infusion (LV5FU2 regimen), on days 1 and 2 every 2 weeks; (ii) oxaliplatin 85 mg/m(2) on day 1 followed by the LV5FU2 regimen on days 1 and 2 every 2 weeks; or (iii) oxaliplatin 85 mg/m(2) followed by irinotecan 200 mg/m(2), both on day 1 every 3 weeks. The primary end point was overall response rate (ORR). RESULTS: The intention-to-treat ORRs were 11.4% [95% confidence interval (CI) 3.2-26.7), 21.2% (95% CI 9.0-38.9) and 15.2% (95% CI 5.1-31.9), respectively, in the three arms. Tumour growth control was >or=60% for all three combinations and overall survivals were 12.2 months (95% CI 9.2-16.0), 11.5 months (95% CI 9.0-14.1) and 11.0 months (95% CI 8.1-12.2), respectively. All patients were evaluable for safety. Main grade 3-4 toxicity was neutropenia (33 to 39% of patients). CONCLUSIONS: Thus, second-line treatment with irinotecan/LV5FU2, oxaliplatin/LV5FU2 or irinotecan/oxaliplatin, provides good tumour growth control and survival coupled with an acceptable safety profile.

Adult↗

Sugar beet Ca-pectate gel as a cost-effective immobilized-cell matrix for metal biosorption.

Whole bacterial (Pseudomonas putida) and yeast (Saccharomyces cerevisiae) cells were immobilized by entrapment in gel beads of Ca-pectate obtained from sugar beet pulp and gel beads of commercial Ca-alginate (of algal origin). These immobilized-cell particles were tested for Cd2+ removal from dilute aqueous solutions and their mechanical properties were evaluated. Only Ca-pectate gel beads loaded with yeast cells displayed enhanced cadmium-binding efficiency (13.8 mg Cd2+ per g dry matter) as compared to sterile beads (10.7 mg/g). Sterile Ca-pectate gel beads were noticeably more brittle than algal alginate counterparts. The presence of cells reduced the mechanical resistance of both types of beads, however. The practical use of cell-loaded sugar beet Ca-pectate gel as a metal biosorbent is discussed in light of these results.

Adsorption↗

Continuous marennin production by agar-entrapped Haslea ostrearia using a tubular photobioreactor with internal illumination.

The marine diatom Haslea ostrearia was immobilized in a tubular agar gel layer introduced into a photobioreactor of original design with internal illumination for the continuous synthesis of marennin, a blue-green pigment of biotechnological interest. Marennin was produced for a long-term period (27-43 days) and the volumetric productivity was maximum (18.7 mg day(-1) l(-1) gel) at the highest dilution rate (0.25 day(-1)) and lowest agar layer thickness (3 mm). Heterogeneous cell distribution in the agar layer revealed diffusional limitation of light and nutrients. However, the 3 mm gel thickness led to a more homogeneous cell distribution during incubation and to an increase of the whole biomass in the agar gel layer.

Agar↗

High-dose epirubicin and cyclophosphamide every two weeks as first-line chemotherapy for relapsing metastatic breast cancer patients.

BACKGROUND: Metastatic breast cancer remains incurable with conventional chemotherapy. For any specific chemotherapy, higher dose intensity may be achieved with either increased doses per cycle, or shortened intervals between courses, or both. We demonstrate here the feasibility and encouraging results of a high-dose combination regimen administered every two weeks. PATIENTS AND METHODS: Women with metastatic breast cancer were treated every 14 days for 6 courses with 75 mg/m2 epirubicin and 1200 mg/m2 cyclophosphamide, followed by conventionally-delivered (q 3-4 weeks) chemotherapy. The treatment was to be resumed regardless of the neutrophil count, except in instances of febrile neutropenia. Prophylactic oral antibiotherapy was given, while hematopoietic growth factors and stem cell support were not employed. RESULTS: Eighty-six patients were treated between May 1986 and June 1995. Their median age was 43 years (26-69). Grade 3-4 neutrophil toxicity was observed after 86% of the courses, resulting in febrile neutropenia in 5%-18% of the patients, and the rehospitalization of 5%-10%. The median given/planned dose intensity was 97% (79-106). The objective response rate in 84 evaluable patients was 54% (95% confidence interval (95% CI): 43-65), with a complete response rate of 11%, and a 14% rate of outright progression. Median progression-free survival was 16 months and median overall survival 32 months. Multivariate analysis retained previous adjuvant chemotherapy as a negative survival prognostic factor. CONCLUSIONS: This dose-intensive anthracycline-based regimen is feasible with manageable morbidity despite pronounced myelotoxicity, and yields encouraging survival rates.

Adult↗

[Report of 2 cases of pleural recurrences of surgically treated bronchogenic carcinoids. Diagnostic and therapeutic problems].

Recurrence after surgery for bronchial carcinoid tumors is very uncommon in cases of typical tumors and occasionally seen in cases of atypical tumors. We observed two cases of recurrence in an unusual location, the pleura. Somatostatin analog and MIBG scinigrams were useful for diagnosis. Treatment required surgical excision of the relapsing tumor, cytoreductive hepatic surgery or hepatic arterial chemoembolization for liver metastases, chemotherapy, interferon, radionuclide therapy, and somatostatin analogs for carcinoid syndrome.

Bronchial Neoplasms↗

Efficacy and safety of the paclitaxel and carboplatin combination in patients with previously treated advanced ovarian carcinoma. A multicenter GINECO (Group d'Investigateurs Nationaux pour l'Etude des Cancers Ovariens) phase II study.

BACKGROUND: Platinum compounds are the most active drugs in ovarian cancer treatment; cisplatin and carboplatin demonstrated similar efficacies but different toxicity profiles. Paclitaxel combined with cisplatin as first-line treatment improved overall survival when compared to a cisplatin-cyclophosphamide combination, but generated higher rates of neutropenia, febrile neutropenia and neurotoxicity. The paclitaxel-carboplatin combination may be better tolerated than cisplatin-paclitaxel. DESIGN: The objective of the present study was to assess the efficacy and safety of the combination of paclitaxel and carboplatin in previously treated advanced ovarian cancer patients. PATIENTS AND METHODS: During or after platinum-based chemotherapy, 73 patients with progressive advanced epithelial ovarian carcinoma were enrolled to receive every four weeks a three-hour infusion of paclitaxel 175 mg/m2 followed by a 30-minute carboplatin infusion. The carboplatin dose was calculated to obtain the recommended area concentration-versus-time under the curve of 5 mg x ml-1 x min. RESULTS: Toxicity and response could be evaluated for 72 and 62 patients, respectively. Eleven complete and 15 partial responses gave an overall response rate of 42% (95% CI: 30%-54%). Response rates for platinum-refractory patients and those with early (> or = 3 and < 12 months) and late (> 12 months) relapses were 24%, 33% and 70%, respectively. The respective median response duration, the median progression-free survival and median overall survival were 8, 6 and 14 months. Myelosuppression was the most frequent and severe toxicity. Grade 3 and 4 neutropenia occurred, respectively in 30% and 23% of the cycles; 6% of the cycles benefited from medullary growth factors. Only one episode of febrile neutropenia was observed. Grade 3 and 4 thrombocytopenia occurred, respectively during 3% and 1% of the cycles. Alopecia was frequent. Transient peripheral neuropathy developed in 47% of patients but was severe in only one patient. One early death was attributed to progressive disease and possibly to therapy. CONCLUSION: This combined paclitaxel-carboplatin therapy is effective and can be safely administered to ovarian cancer patients who relapse after one or two regimens of platinum-based chemotherapy.

Adolescent↗

Efficacy and safety of the combination paclitaxel/carboplatin in patients with previously treated advanced ovarian carcinoma: a multicenter French Groupe des Investigateurs Nationaux pour l'Etude des Cancers Ovariens phase II study.

The French Groupe des Investigateurs Nationaux pour l'Etude des Cancers Ovariens (GINECO) conducted a multicenter phase II study of carboplatin and paclitaxel (Taxol; Bristol-Myers Squibb Company, Princeton, NJ) to evaluate the efficacy and side effects of this combination in pretreated advanced ovarian cancer. Patients with progressive ovarian carcinoma during or after platinum-based chemotherapy received paclitaxel 175 mg/m2 intravenously over 3 hours followed by intravenous carboplatin over 30 minutes every 4 weeks. The dose of carboplatin was calculated using a projected area under the concentration-time curve of 5 mg/mL x min. Of the 50 patients entered, 50 were evaluable for toxicity and 42 for response. There were eight complete and 10 partial responses, for an overall response rate of 43% (95% confidence interval, 28% to 56%). Overall response rates in platinum refractory patients and in those with early (> or = 3 and < 12 months) and late (> or = 12 months) relapse was 28%, 33%, and 71%, respectively. Median response duration, progression-free survival, and overall survivals were 8, 6, and 14 months, respectively. The most frequent and severe toxicity was myelosuppression. Grades 3 and 4 neutropenia occurred in 30% and 23% of cycles, and granulocyte colony-stimulating factor was administered in 6%. Only one case of neutropenic fever was observed. Grades 3 and 4 thrombocytopenia occurred in 3% and 1% of cycles, respectively. Alopecia and moderate nausea or vomiting were frequent. Transitory peripheral neuropathy was present in 45% of patients but was severe in only one patient. One early death was observed due to progressive disease and possibly to therapy. The combination of paclitaxel 175 mg/m2 as a 3-hour infusion and carboplatin dosed to an area under the concentration-time curve of 5 is an effective therapy in patients previously treated with platinum-based chemotherapy and may be administered safely to outpatients who relapse after one or two lines of chemotherapy.

Adolescent↗

[Merkel cell carcinoma: primary cutaneous neuroendocrine tumor].

Merkel cell carcinoma is a neuroendocrine primitive tumor of the skin. We report a case who develops node and visceral metastasis, and dead. The clinical presentation, diagnosis, histology, immunocytochemistry, treatment and prognosis of this tumor will be discussed.

Carcinoma, Merkel Cell↗

Efficacy and tolerance of vinorelbine and fluorouracil combination as first-line chemotherapy of advanced breast cancer: results of a phase II study using a sequential group method.

PURPOSE: To assess the antitumor efficacy and safety profile of the combination of Fluorouracil (5FU) and vinorelbine given as first-line therapy to patients with advanced breast cancer. PATIENTS AND METHODS: As defined in the seven consecutive steps of a phase II group sequential design, 63 patients received 5FU 750 mg/m2/d for 5 consecutive days as a continuous infusion and vinorelbine 30 mg/ m2 on days 1 and 5 as a short intravenous (I/V) infusion every 3 weeks. RESULTS: Forty-one of 63 patients achieved an objective response, which allowed us to discontinue the study and reject a response rate less than 50% with a statistical power of 90%. The unbiased estimate of the response rate was 61.6%. Response rate did not differ significantly according to the following: (1) type of prior adjuvant therapy (none, n = 23; without anthracycline, n = 6; with anthracyline, n = 34); (2) site of metastatic disease; and (3) number of metastatic sites. The median time to progression was 8.4 months. The median response duration was 12.3 months, and the median duration of complete response (CR), from the first assessment of CR, was 7.3 months. The median overall survival time was 23 months (28.1 months for patients with a CR). The main toxicities (grades 3 and 4) were neutropenia (90% of patients), infection (12.7%), mucositis (37%), and constipation (9.5%). Nevertheless, treatment could be given on an outpatient basis to the majority of patients, and the median relative dose-intensity was 86%. CONCLUSION: This phase II study, which used a group-sequential design, shows that the combination of 5FU and vinorelbine is an active and tolerable regimen for the treatment of first metastatic progression of breast cancer. It provides an alternative regimen for patients who have previously received anthracycline-based adjuvant chemotherapy or in whom anthracyclines cannot be used.

Adult↗

Intraperitoneal recombinant interferon gamma in ovarian cancer patients with residual disease at second-look laparotomy.

PURPOSE: The purpose of this study was to evaluate the efficacy and tolerance of recombinant human interferon gamma (rIFN-gamma) as second-line treatment in patients with persistent disease at second-look laparotomy. PATIENTS AND METHODS: One hundred eight patients with residual disease at second-look laparotomy were treated with rIFN-gamma (20 x 10(6) IU/m2) administered intraperitoneally (IP) twice a week for 3 to 4 months. In the absence of clinically assessable disease, response to rIFN-gamma was assessed with a third-look laparotomy. RESULTS: Of 98 assessable patients, 31 (32%) achieved a surgically documented response, including 23 patients (23%) with a complete response (CR). The age and size of residual tumor were significant prognostic factors for the response to rIFN-gamma. A 41% CR rate was observed in 41 patients younger than 60 years and with residual tumor less than 2 cm. The probability of response was independent of previous response to first-line chemotherapy. The median duration of response was 20 months and the 3-year survival rate in responders was 62%. Response to rIFN-gamma was the most significant prognostic factor for survival of patients with residual disease. Adverse events included fever, flu-like syndrome, neutropenia, and liver enzyme disturbances. No significant peritoneal fibrosis was noted. CONCLUSION: These results support the potential interest of IP rIFN-gamma as adjuvant treatment in ovarian cancer. Controlled prospective trials are required to determine its place in the therapeutic strategy of this malignancy.

Adult↗

[Pregnancy after breast cancer].

In what ways can a premenopausal woman be pregnant after a breast carcinoma's treatment? A survey organized in 1985 by the French Gynecologic Association gave us the opinion of 316 gynecologists: 50% of them disagreed with this pregnancy because of an accrued risk of relapse. 68 observations were collected including 41 of full term pregnancies; the survival curves were, in each group, similar to those of the controls at the same stage. The interruption doesn't improve the prognosis. This confirms the whole of the published series: a subsequent pregnancy doesn't seem to affect the prognosis of a breast carcinoma; it is important to take the contraception into account so that this pregnancy shall be really desired.

Adult↗

[Gene therapy in oncology: applications to lung cancer].

Gene therapy defines a new therapeutic avenue whose site of action is at the level of the gene itself; viral vectors (adenovirus, retrovirus, herpes virus) or non-viral (liposomes, plasmids) enable the transfer of a fraction of DNA (transgenic) to the target itself. In this review, we present recently acquired data on the mechanisms of oncogenesis and anti-tumor immunity which have enabled the application of several therapeutic strategies in oncology; the transfer of gene(s), coding for cytokines or for coactivation factors in order to develop active immunotherapy; the transfer of suicides genes; the transfer of multidrug resistance gene (MDR1); the transfer of tumor suppressor genes or of cDNA coding for antisense oligonucleotides in order to correct genomic anomalies which are responsible for the malign phenotype. The development of gene therapy demands the resolution of a number of technical difficulties such as vectorisation, targeting, and the expression of the stability of the trans-gene. Phase 1 trials in man have established the innocuity of certain vectors and have confirmed the expression of trans-genes (marker genes). Compared to monogenic hereditary diseases, the "molecular heterogenetic" of bronchial tumours, the consequence of the instability of the genome and the diversity of amplified oncogenes are a major difficulty. In addition, each one of these approaches prevents limiting factors: for example the exclusive targeting of malign cells is an indispensable pre-requisite for the transfer of suicide genes and in the same way the expression the tumour in antigens is the pre-requisite for the development of active immunotherapy. We report the overall results of applied trials for pulmonary carcinomas on murine models and present their applications which are underway in men.

Animals↗

[Cerebral germ cell tumors in adults. A retrospective study of 19 cases].

The authors report on the retrospective analysis of 19 patients with primary cerebral germ cell tumors which were treated between 1965 and 1993. Median age is 18 years (extremes: 16-55 years). There were 16 men and three women. The location of the primary tumor was the pineal area in six patients, suprasellar and hypothalamic area in five patients and other areas in eight patients. The histological pattern was non seminoma in six patients, dysgerminoma in eight; however no histological sample was obtained in five patients who did not have any particular characteristics (either cytological abnormalities or elevated tumor marker level). Three patients were treated by surgery only, eight patients received exclusive radiotherapy and eight patients had first line chemotherapy and further cranial irradiation. One was lost to follow-up. Six of eight assessable patients with dysgerminoma are alive with non evolutive disease (NED) after 15 to 176 month of follow-up. One out of five assessable patients with non seminomatous tumor in NED (163 month of follow-up). Finally all five patients who have no histological subtyping are alive with NED at 24 to 138 months. The standard treatment of dysgerminoma is currently first line chemotherapy followed by relatively low-dose and limited irradiation; the standard treatment of non-seminomatous cerebral germ cell tumor is chemotherapy, the study of which is warranted with the aim to decrease the toxicity and to increase the efficacy.

Adolescent↗

Phase II randomized study of paclitaxel versus mitomycin in advanced breast cancer.

Paclitaxel (Taxol; Bristol-Myers Squibb Company, Princeton, NJ) has been shown to be an effective agent in the treatment of metastatic breast carcinoma. This multicenter randomized study compared paclitaxel 175 mg/m2 given as a 3-hour infusion every 3 weeks with mitomycin 12 mg/m2 given as an intravenous infusion every 6 weeks. Eighty-one patients have been randomized, and preliminary results of a planned analysis of the first 36 evaluable patients per arm are reported. Pretreatment characteristics were well balanced between the two groups. All patients previously have received chemotherapy for metastatic disease, and half had both adjuvant therapy and chemotherapy for metastatic disease. All but one patient previously had received anthracyclines. Of the first 81 randomized patients, 72 were evaluable for response and toxicity (four never treated, five concomitant hormonotherapy). Partial responses were seen in 17% of patients in the paclitaxel arm and 6% in the mitomycin arm (P = .14). Crossover to paclitaxel therapy following progression on mitomycin achieved an objective response rate of 24% (five of 21 patients). Responses to paclitaxel therapy lasted for a median duration of 9.1 months (range, 6.2 to 12+ months). Median time to progression was significantly longer in the paclitaxel arm (3.5 months v 1.6 months; P = .026). The quality-of-life-adjusted analysis confirmed the advantage of paclitaxel therapy, even when the delay of disease progression was adjusted for important adverse events. Adverse events, most importantly neutropenia and neuropathy, were more frequently observed in the paclitaxel arm. However, patients remained on paclitaxel therapy for many more courses than did those treated in the mitomycin arm. In conclusion, paclitaxel 175 mg/m2 given as a 3-hour intravenous infusion has been demonstrated to be an active agent in the treatment of chemotherapy-refractory advanced breast cancer, even after therapy with mitomycin has failed.

Adult↗

High dose chemotherapy with stem-cell transplantation in a metastatic medulloblastoma in an adult: a case report and review of the literature.

Medulloblastoma is a rare tumor in adult. High doses of megavoltage irradiation of the posterior fossa have been resulted in a better survival (48 to 78% at 5 years) of the patient. It is sensitive to a wide variety of chemotherapy drugs, but adjuvant chemotherapy has not been proved effective in adults although data are limited. We report the case of a cerebellar medulloblastoma with bony and medullar metastases. High-dose chemotherapy with peripheral stem-cell transplantation was performed while the patient was in remission following conventional chemotherapy. Complete remission lasted for 8 months. This therapeutic approach of metastatic medulloblastoma might be of value as this tumor is chemosensitive and not cured by conventional treatment. Internal radiotherapy by Samarium-153 was also carried out and proved to be an effective palliative treatment of pain.

Adolescent↗