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Biomedical subjects

J L Breau

Publications and source records attributed to J L Breau.

At least 19 recordsLinked to original sources
PubMed2004

Randomized phase II study evaluating oxaliplatin alone, oxaliplatin combined with infusional 5-FU, and infusional 5-FU alone in advanced pancreatic carcinoma patients.

BACKGROUND: A randomized phase II, open-label multicenter study evaluating oxaliplatin alone (OXA), infusional 5-fluorouracil alone (5-FU) and an oxaliplatin/infusional 5-FU combination (OXFU) in untreated, advanced pancreatic carcinoma (APC). PATIENTS AND METHODS: Chemotherapy-naïve patients with advanced or metastatic, histologically/cytologically proven pancreatic carcinoma with measurable disease, received OXA [130 mg/m2, 2-h intravenous (i.v.) infusion] alone, OXA combined with 5-FU (1000 mg/m2/day, continuous i.v., days 1-4), or 5-FU alone, every 3 weeks. RESULTS: Sixty-three patients (42 males/21 females) were treated: 17 patients/52 cycles OXA, 31 patients/ 175 cycles OXFU, 15 patients/41 cycles 5-FU, with a median of three, six and two cycles/patient, respectively. Patient characteristics were similar in all arms. Median age was 57 years (range 21-75), and 83% of patients had PS 0-1. Most patients (62%) had moderate to well-differentiated tumors, 90% had metastatic disease, 81% with liver metastases. All responses (three partial responses; WHO) occurred in the OXFU arm (10% response rate). Five of 32 patients evaluable for clinical benefit were responders (OXA, 14%; OXFU, 21%). Median time to progression and overall survival were higher in the combination arm (4.2 and 9.0 months, respectively) than either single-agent arm (OXA, 2.0 and 3.4 months; 5-FU, 1.5 and 2.4 months, respectively). Moderate hematotoxicity without morbidity was seen in all arms. Two OXFU patients had grade 3 oxaliplatin neurosensory toxicity. CONCLUSIONS: With a 10% response rate, median overall survival of 9 months and an encouraging safety profile, the OXFU combination is effective, appears superior to infusional 5-FU and warrants further studies in APC patients.

Adult↗
PubMed2003

Transfer into a mesothelioma cell line of tumor suppressor gene p16 by cholesterol-based cationic lipids.

In this work, the tumor suppressor gene p16 was efficiently transferred into FR cells isolated from a patient with malignant mesothelioma using cationic liposomes prepared from trimethyl aminoethane carbamoyl cholesterol (TMAEC-Chol) and triethyl aminopropane carbamoyl cholesterol (TEAPC-Chol). This transfer was performed after preliminary assays were undertaken to find the optimal transfection conditions. Results showed that an efficient transfer of plasmids containing the reporter gene pCMV-beta galactosidase vectorized by TMAEC-Chol/DOPE and TEAPC-Chol/DOPE liposomes into mesothelioma FR cells was obtained as assessed by luminometric measurements of beta-galactosidase activity. Cytotoxicity studied by MTT test showed that at concentrations used for this study, the cationic liposomes have no effect on cell growth. Transfer into mesothelioma FR cells of a plasmid construct containing the tumor suppressor gene p16 was carried out with these liposomes. Western blotting and immunofluorescence showed the presence of p16 in treated cells. An inhibition of cell growth was observed, indicating that efficient tumor suppressor gene transfer can be performed by using cationic liposomes.

Cell Division↗
PubMed2002

Phase III randomised trial comparing paclitaxel/carboplatin with paclitaxel/cisplatin in patients with advanced non-small-cell lung cancer: a cooperative multinational trial.

BACKGROUND: The combination of paclitaxel with cisplatin or carboplatin has significant activity in non-small-cell lung cancer (NSCLC). This phase III study of chemotherapy-naïve advanced NSCLC patients was designed to assess whether response rate in patients receiving a paclitaxel/carboplatin combination was similar to that in patients receiving a paclitaxel/cisplatin combination. Paclitaxel was given at a dose of 200 mg/m(2) (3-h intravenous infusion) followed by either carboplatin at an AUC of 6 or cisplatin at a dose of 80 mg/m(2), all repeated every 3 weeks. Survival, toxicity and quality of life were also compared. PATIENTS AND METHODS: Patients were randomised to receive one of the two combinations, stratified according to centre, performance status, disease stage and histology. The primary analyses of response rate and survival were carried out on response-evaluable patients. Survival was also analysed for all randomised patients. Toxicity analyses were carried out on all treated patients. RESULTS: A total of 618 patients were randomised. The two treatment arms were well balanced with regard to gender (83% male), age (median 58 years), performance status (83% ECOG 0-1), stage (68% IV, 32% IIIB) and histology (38% squamous cell carcinoma). In the paclitaxel/carboplatin arm, 306 patients received a total of 1311 courses (median four courses, range 1-10 courses) while in the paclitaxel/cisplatin arm, 302 patients received a total of 1321 courses (median four courses, range 1-10 courses). In only 76% of courses, carboplatin was administered as planned at an AUC of 6, while in 96% of courses, cisplatin was given at the planned dose of 80 mg/m(2). The response rate was 25% (70 of 279) in the paclitaxel/carboplatin arm and 28% (80 of 284) in the paclitaxel/cisplatin arm (P = 0.45). Responses were reviewed by an independent radiological committee. For all randomised patients, median survival was 8.5 months in the paclitaxel/carboplatin arm and 9.8 months in the paclitaxel/cisplatin arm [hazard ratio 1.20, 90% confidence interval (CI) 1.03-1.40]; the 1-year survival rates were 33% and 38%, respectively. On the same dataset, a survival update after 22 months of additional follow-up yielded a median survival of 8.2 months in the paclitaxel/carboplatin arm and 9.8 months in the paclitaxel/cisplatin arm (hazard ratio 1.22, 90% CI 1.06-1.40; P = 0.019); the 2-year survival rates were 9% and 15%, respectively. Excluding neutropenia and thrombocytopenia, which were more frequent in the paclitaxel/carboplatin arm, and nausea/vomiting and nephrotoxicity, which were more frequent in the paclitaxel/cisplatin arm, the rate of severe toxicities was generally low and comparable between the two arms. Overall quality of life (EORTC QLQ-C30 and LC-13) was also similar between the two arms. CONCLUSIONS: This is the first trial comparing carboplatin and cisplatin in the treatment of advanced NSCLC. Although paclitaxel/carboplatin yielded a similar response rate, the significantly longer median survival obtained with paclitaxel/cisplatin indicates that cisplatin-based chemotherapy should be the first treatment option.

Adult↗
PubMed2000

Dose-finding study of paclitaxel and carboplatin in patients with advanced non-small cell lung cancer.

This dose-finding study was designed to determine the maximum tolerated dose (MTD), efficacy and toxicity of combined paclitaxel and carboplatin in 35 previously untreated patients with advanced non-small cell lung cancer (NSCLC). Paclitaxel was given as a 3-h infusion at escalating dose levels (100-250 mg/m2) immediately followed by carboplatin as a 30-min infusion (325 or 350 mg/m2) every 3 weeks. The dose-limiting toxicity, paresthesia, occurred at the highest dose level, therefore the recommended dose was established one level below (paclitaxel 225 mg/m2 with carboplatin 325 mg/m2). Neutropenia was the most common hematotoxicity; dose dependency was not apparent. Two patients, at different dose levels, had febrile neutropenia. Thrombocytopenia was rare. Non-hematological toxicities grade 3 or higher included infection, anorexia, alopecia and paresthesia. One patient had a hypersensitivity reaction (transient hypotension). The overall response rate was 23% and median survival time was 7.5 months. Promising activity and acceptable toxicity supports the development of this combination as a useful chemotherapeutic option in advanced NSCLC.

Adult↗
PubMed2000

Assessment of malignancy in pulmonary lesions: FDG dual-head coincidence gamma camera imaging in association with serum tumor marker measurement.

UNLABELLED: The purpose of the study was to evaluate the performance of dual-head coincidence gamma camera imaging using FDG in association with serum marker assays in identifying lung carcinoma in patients with abnormal findings on chest radiography. METHODS: A prospective evaluation of FDG imaging with coincidence detection emission tomography (CDET) using a dual-head gamma camera combined with the assessment of 3 sensitive serum markers of lung cancer (carcinoembryonic antigen, neuron specific enolase, and CYFRA 21-1) was performed on the same day on 58 consecutive patients with known or suspected lung malignancy. RESULTS: Fifty-three patients were proven to have lung cancer, and 5 patients had benign lung disease. Coincidence imaging showed significantly increased FDG uptake in 49 of 53 patients with proven malignancy (sensitivity, 92.5%) and in 3 patients with benign disease. FDG imaging had negative findings in 4 patients with proven malignancy and 2 patients with benign disease. Serum tumor marker levels were elevated in 42 of 53 cancer patients (sensitivity, 79.2%) and normal in 11 patients with proven malignancy. Nine patients with proven malignancy had positive findings on FDG images and negative marker assays. Two patients with proven malignancy had negative findings on FDG images and positive marker assays. The positive predictive value for lung cancer was 94.2% for FDG alone and 97.6% for FDG in association with serum markers. CONCLUSION: In this study, FDG CDET imaging was a powerful tool for evaluating patients with lung lesions suggestive of malignancy. Although the determination of serum marker levels was less accurate than FDG imaging, positive FDG results found in association with positive markers significantly increased the likelihood of lung malignancy.

Adult↗
PubMed1997

Vinorelbine and ifosfamide for unresectable non-small cell lung cancer.

PURPOSE: The study assessed the efficacy of combination therapy with vinorelbine and ifosfamide in patients with unresectable non-small cell lung cancer. PATIENTS AND METHODS: Forty patients with non-small cell lung cancer whose tumour was unresectable by virtue of the extent of disease or severity of impairment of lung function and who were considered unsuitable for treatment with a cisplatin based treatment were entered onto the study. Thirty-four patients received two cycles of treatment and were considered to be evaluable for response. The treatment schedule consisted of vinorelbine (Navelbine, Pierre Fabre Medicament) 25 mg/m2 on days 1 and 8, and ifosfamide 2 g/m2 per day with mesna 0.5 g/m2 three times daily given on days 1 to 3; cycles were repeated every 21 days and treatment continued in responding patients until progression occurred. RESULTS: Objective responses were observed in 12 patients (30%; CI95, 16-44) with one completed response (CR) and 11 partial response (PR). CONCLUSION: This schedule achieves good levels of response without the use of cisplatin so it is suitable for patients whose performance status or concomitant medical condition precludes the use of platinum based chemotherapy.

Aged↗
PubMed1997

[Induction chemotherapy followed by concomitant combined radiotherapy and chemotherapy in stage III non-small cell bronchial carcinoma].

PURPOSE: To determine the efficacy and safety of induction chemotherapy followed by concomitant chemoradiotherapy in the treatment of stage III non-small cell lung cancer and whether the response to induction chemotherapy can predict the response to subsequent chemoradiotherapy and survival. MATERIALS AND METHODS: Between December 1987 and June 1993, 46 patients with previously untreated stage III non-small cell lung cancer received every 21 days induction chemotherapy (ICT) including three cycles of 5-fluorouracil (600 mg/m2/d in short infusion from d1 to d5), cisplatin (15 mg/m2/d from d1 to d5), etoposide (50 mg/m2/d from d1 to d5) and hydroxyurea (1,500 mg/d from d1 to d5). The first 21 patients also received bleomycin (3 mg/m2/d from d1 to d5). All patients received concomitant chemotherapy and had chest radiotherapy (CCRT). Patients received irradiation (65 Gy/33-6 fractions/7 weeks) on d25 after the third cycle of chemotherapy. Concomitant chemotherapy was composed of cisplatin (20 mg/m2) and 5-fluorouracil (500 mg/m2) that were administered each Monday and Thursday during radiotherapy. Maintenance chemotherapy consisted of thiotepa (10 mg/m2) and methotrexate (10 mg/m2) that were administered every 2 weeks for 6 months. RESULTS: Pulmonary toxicity was observed in four out of 21 patients who had received bleomycin and subsequently developed pulmonary fibrosis, leading to death for two of them. ICT alone produced five complete responses (11%) and 13 partial responses (28%). The combination of chemotherapy and radiotherapy led to 19 complete responses (41%) and 14 partial responses (30%). Eighteen of the 18 responders (100%) to ICT responded to subsequent CCRT, of whom 13 (72%) became complete responders. Fifteen of the 28 non-responders to ICT (53%) responded to CCRT, six of them being complete responders (21%) (P < 0.001). The median overall survival rate was 17 months when considering all patients, 25 months in patients responding to ICT and 13 months in non-responders. The 2-year survival rates were 28, 55 and 11%, respectively (P < 0.05). ICT did not influence the rate of subsequent metastatic events. However, locoregional reprogression was lower in responders to ICT. The number of metastatic events was not significantly related to response to ICT. By contrast, the rate of local failure was higher when there was resistance to ICT (75% versus 39%). Out of the 19 complete responders to CCRT (13 responders to ICT and six non-responders to ICT), four developed secondary locoregional reprogression (21%) and six developed metastatic disease (31%). In complete responders to CCRT, the rate of locoregional failure was 15% in responders to ICT (2/13) and 33% (2/6) in non-responders to ICT. Four out of the 13 responders to CCRT after response to ICT (31%) and two out of the six complete responders to CCRT developed metastatic disease after non-response to ICT. CONCLUSION: There is a statistically significant relationship not only between the response to ICT and the response to CCRT, but also between the response to ICT and the local outcome and survival.

Adenocarcinoma↗
PubMed1996

Somatostatin receptor imaging in small cell lung cancer.

To determine its usefulness, we evaluated 111In-DTPA-Octreotide (octreotide scintigraphy) in the initial staging of 19 patients with histologically proven small cell lung cancer (SCLC) and compared the results to those of conventional imaging. Images performed during initial staging demonstrated 21 known pulmonary lesions and two known supraclavicular nodes. We detected a previously unknown mediastinal lesion. The number of metastases was underestimated, with no liver (5), brain (1) or skin metastases detected. Bone lesions were identified in 4 out of 5 patients. There were fewer lesions detected with octreotide scintigraphy than with bone scintigraphy (except for one case). We therefore conclude that octreotide scintigraphy is a highly effective method for detecting SCLC primary tumour and supraclavicular nodes; the procedure is of limited value for distant metastasis. Further studies are needed to establish its ability for detecting residual intrathoracic disease, and confirm the value of octreotide scintigraphy in differentiating residual disease from other benign lesions.

Adult↗
PubMed1993

[Infectious complications during treatments with interleukin-2].

Between January 1989 and May 1991, 97 patients were treated with interleukin 2 in the Oncology Department of the Avicenne Hospital (Bobigny, France). IL 2 was given over 5 days by continuous infusion through an implantable port. Ten patients (4 males, 6 females), mean age 46 years (36-67) with various cancers (breast 3, kidney 1, melanoma 1, colorectal 5), developed infection: 4 local infections around the port, 1 phlebitis, 4 septicemias, 1 bacteremia were observed. In 9 cases blood cultures were positive: Staphylococcus aureus 5, Staphylococcus epidermidis 3, Streptococcus G 1. In 5 cases the same pathogen was isolated from the port and from the blood. The mean leucocyte count was 10,627/mm3 at the time of infection. The delay between the beginning of interleukin 2 treatment and the infection was 3 months. The mean dose of IL 2 administered before infection was 456 million IU. In all cases infection was controlled without lethal complication by antibiotics and catheter removal. This high incidence (8 percent) of staphylococcal infection is partly due to the skin toxicity of IL 2 and to depressed neutrophil chemotactic response. Prophylactic antibiotics are warranted during IL 2 intravenous therapy.

Adult↗
PubMed1993

[Cancer of the kidney: changes in blood lymphocyte subsets induced by treatment with interferon alpha-2b and interleukin-2r].

Twenty patients (6 females and 14 males), age range 36-70 years-old, with metastatic renal cell carcinoma (MRCC), received interferon alpha-2b (IFN-A) 10 x 10(6) units/day IM for 5 days followed by continuous i.v. infusion of interleukin-2 (IL-2) 18 x 10(6) units/day for 5 days. The median follow-up was 10 months. We observed four partial responses (20%), 13 stable (65%) and three progressive diseases (15%). The mean CD4/CD8 ratio, obtained before therapy in patients with MRCC, was compared with CD4/CD8 ratio in 51 patients with different advanced malignancy and in patients with no cancer. The CD4/CD8 ratio was higher in patients with MRCC (2.55) than in other cancers (1.474) and than in populations with no cancer (1.66 x chi 2 = 17,378). The surface phenotypes of peripheral lymphocytes were analysed by cytofluorometry in patients with MRCC during and after treatment with IFN-A and IL-2. Immune modulatory effects of therapy immediately induced a decrease of different sub-populations of lymphocytes except CD25+. Far from the first course, a rise in lymphocyte count was observed. The proliferation effect was as follows: CD4+, CD8+, CD4+ CD45RA- and CD16+ CD8- cells. Far from the second and 3rd course, the sub-populations of lymphocytes decreased, except the CD4+ and CD4- CD45RA+ cells. The CD4/CD8 ratio increased progressively during treatment. Before each course, the CD4/CD8 ratio of patients with response to treatment was higher than the CD4/CD8 ratio of patients with no response. Results were non-significant due to the small number of subjects with responses in this study.

Adult↗
PubMed1993

[Malignant melanoma of the uvea].

Intraocular melanoma is the most common primary ocular malignancy in Whites. Epidemiologic studies demonstrated the role of sun exposure as a risk for uveal melanoma. Conservative treatment techniques are indicated for localised tumors when feasible. External radiation therapy and radioactive eye plaque brachytherapy seem as effective as surgery in term of survival. High tumor doses can be safely administered with either helium or proton beams. A partial preservation of the vision is possible in most of patients. However, even for locally controlled patients, distant metastases can occur. Liver is the most frequent metastatic site, and also the first involved. Liver metastases are associated with a low response rate, to dacarbazine and nitrosourea. Recent studies using a new nitrosourea, fotemustine, administered locally through an intra-arterial catheter, show that it produces encouraging results with a good hepatic and hematologic tolerance.

Antineoplastic Agents↗
PubMed1991

Fibrocystic disease of the breast in premenopausal women: histohormonal correlation and response to luteinizing hormone releasing hormone analog treatment.

Sixty-six patients with fibrocystic mastopathy were enrolled in the trial after being selected according to clinical, radioultrasonographic, and histologic criteria. No characteristic hormonal profile was noted in most patients (52%). Estrogen receptors or progesterone receptors, or both, were found in 57% of patients. Hormone receptor levels were correlated with atypical proliferative mastopathy (87.5%). Mastopathy was associated with a uterine fibroma or a fibromatous uterus in 73% of cases. All patients received intramuscular injections of a sustained delivery system (microcapsules) of luteinizing hormone releasing hormone agonist [D-Trp6]-LHRH, Ipsen-Biotech, Paris) for 3 to 6 months. In case of partial response at 3 months, an antiestrogen (tamoxifen, 40 mg/day, for estrogen receptor-predominant lesions) or a progestin (cyproterone acetate, 50 mg/day, for progesterone receptor-predominant lesions) was added to the luteinizing hormone releasing hormone agonist. A complete response was observed in more than half of the patients (n = 35, 53%) treated by [D-Trp6]-LHRH alone (n = 29) or associated with tamoxifen (n = 4) or cyproterone acetate (n = 2). A significant partial response was observed in 30 other patients (45%). Additionally, half of them received inhibitory drugs. The best responses were seen with cyst reformation (complete response, 100%) and fibrous block. Clinical responses to treatment with [D-Trp6]-LHRH alone were independent of hormone receptor status, but synergistic effects occurred with concomitant use of the corresponding inhibitory drugs. We conclude that chronic mastopathy, particularly when associated with uterine fibroma, can be successfully treated by luteinizing hormone releasing hormone analogs in premenopausal women.

Adult↗