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Biomedical subjects

J Bonneterre

Publications and source records attributed to J Bonneterre.

At least 73 records · Page 4Linked to original sources
PubMed1996

Does induction chemotherapy with a mitoxantrone/vinorelbine regimen allow a breast-conservative treatment in patients with operable locoregional breast cancer? A French Northern Oncology Group trial in 105 patients. French Northern Oncology Group.

BACKGROUND: In recent years, induction chemotherapy has been tested by several investigators in the management of operable breast cancer. PATIENTS AND METHODS: Our current study was aimed to evaluate, pragmatically, in patients (74 stage II and 30 stage III) whose treatment would have been mastectomy, the percentage of them in whom a conservative treatment can be performed if primarily treated with a mitoxantrone/vinorelbine regimen. RESULTS: 67/104 patients (64%; 95% CI: 55-74%) had a conservative treatment (lumpectomy: 54, radiation therapy: 12, radiation therapy then lumpectomy: 1) Neutropenia was the major dose-limiting side effect, with grade 3 or 4 neutropenia registered in 83% of patients and 53.3% of the 442 cycles. Overall, a grade 3 or 4 non hematologic side effect occurred in 19.8% of patients and in 9.1% of cycles. One toxic death was observed after 2 cycles in a patient with aplasia who developped septicemia. Seventy one per cent of the patients experienced nausea and vomiting but grade 3 were observed in only 12% of the patients. Other side effects, including stomatitis, asthenia, alopecia, and constipation, were generally mild and uncommon. CONCLUSIONS: This mitoxantrone/vinorelbine regimen is an efficient induction treatment with only neutropenia as a noticeable side effect. It allows 64% of conservative treatment in patients whose treatment would have been mastectomy.

Adult↗
PubMed1996

Plasma c-erbB2 concentrations in relation to chemotherapy in breast cancer patients.

Amplification and overexpression of the C-ERBB2 oncogene have been associated with a poor prognosis and a lower response to chemotherapy in human breast cancer. In this study, plasma c-erbB2 concentrations were determined using an enzyme immunoassay in patients with breast cancer. The links between c-erbB2 concentration and tumoral response to chemotherapy were established. The patients with a c-erbB2 concentration higher than the cut-off value (27 U/ml) were considered as c-erbB2+. Ten of the 33 metastatic breast cancers were c-erbB2+. No statistically significant difference in response to chemotherapy was noted between c-erbB2+ and c-erbB2- patients (4/10 objective responses versus 10/23). Variations in c-erbB2 concentrations during treatment were not related to response to treatment.

Antineoplastic Combined Chemotherapy Protocols↗
PubMed1996

A phase II study in advanced breast cancer: ZD1694 ('Tomudex') a novel direct and specific thymidylate synthase inhibitor.

ZD1694 ('Tomudex'), a novel, direct and specific thymidylate synthase (TS) inhibitor, was developed in a collaborative research programme between Zeneca Pharmaceuticals and the Institute of Cancer Research (UK) and entered clinical trials in 1991; phase II studies began in 1992, using 3.0 mg m-2 every 3 weeks as a short 15 min infusion. Forty-six patients entered a phase II study of ZD1694 in advanced breast cancer. A total of 74% of patients had received prior systemic therapy (either as adjuvant cytotoxic or hormonal therapy or hormone therapy for advanced disease); 39% had received prior adjuvant cytotoxic chemotherapy. All patients had measurable disease and 50% had liver metastases. In all 43 patients were evaluable for response. Of these patients 26% achieved complete (CR) or partial response (PR) (95% Cl 14-42%). A response rate of 44% was seen in liver metastases. Two patients achieved CR of 265 and 301 days' duration respectively, one in locoregional disease, and one in liver metastases. The most common grade 3/4 adverse events were nausea and vomiting (11%), diarrhoea (11%) and leucopenia (20%). Grade 3/4, self-limited and reversible increases in transaminases were seen in 22% of patients. ZD1694 has useful single agent activity in patients with hormone-refractory advanced breast cancer, comparable with that reported for other anti-metabolites, with acceptable tolerability.

Adult↗
PubMed1996

Current status of larynx preservation trials.

Over the past 15 years, larynx preservation has been extensively assessed but only in the light of induction chemotherapy. From these evaluations, it appeared that the use of induction chemotherapy was safe and adequate for patient selection: irradiation with or without salvage surgery for induction chemotherapy responders and surgery with or without postoperative irradiation for induction chemotherapy nonresponders. Neither the ultimate local control nor survival worsened, and at least, half the patients retained their larynxes. Such results should not lead researchers to forget other larynx-preserving possibilities. Irradiation alone and, moreover, irradiation with modified fractionation or chemotherapy permits cure and preservation of function in many larynx and hypopharynx cases. Conversely, subtotal surgery may, in very selected cases, reach a similar goal. Finally, the new advances in imaging and biology could lead to fine tuning of patient selection. These advances could have the additional advantage of permitting use, thereafter, of chemotherapy as a real treatment and not as simply a selection parameter.

Antineoplastic Combined Chemotherapy Protocols↗
PubMed1996

Multicenter, randomized comparative study of two doses of paclitaxel in patients with metastatic breast cancer.

PURPOSE AND METHODS: The objective of this multicenter study was to compare the therapeutic index of two different doses of paclitaxel given as a 3-hour infusion in patients with metastatic breast cancer (MBC), who had failed to respond to previous chemotherapy. A total of 471 patients with MBC were randomized to receive intravenous paclitaxel at a dose of 175 or 135 mg/m2 every 3 weeks. RESULTS: Better treatment results were achieved with high-dose (HD) versus low-dose (LD) paclitaxel: overall response rate, 29% versus 22% (P = .108); complete response (CR) rate, 5% versus 2% (P = .088); median time to disease progression, 4.2 versus 3.0 months (P = .027); and median survival time, 11.7 versus 10.5 months (P = .321). Patients previously exposed or resistant to anthracyclines were as likely to respond as those without such prior exposure. Treatment was well tolerated, as documented by the number of administered treatment courses (median, six v five; range, one 17 v one to 18), the low frequency of dose reductions (14% v 7%, P = .024), and the small number of patients (n = 9 or 4% vn = 5 or 2%) who required treatment discontinuation for adverse reactions. The incidence and severity of neutropenia and peripheral neuropathy were dose-related. After quality-of-life-adjusted time-to-progression analysis, the HD arm (175 mg/m2) retained its advantage over the LD arm (135 mg/m2). CONCLUSION: The results of this trial substantiate the activity of paclitaxel in the treatment of MBC. The observed superior efficacy with a dose of 175 mg/m2 over 135 mg/m2 suggests a dose-effect relationship. The clinical activity in anthracycline-resistant patients is particularly noteworthy. Paclitaxel in breast cancer needs further evaluation in large trials that use combination chemotherapy and involve earlier disease stages.

Adult↗
PubMed1996

Delay in progression of bone metastases in breast cancer patients treated with intravenous pamidronate: results from a multinational randomized controlled trial. The Aredia Multinational Cooperative Group.

PURPOSE: Bone metastases are a major cause of morbidity in breast cancer, resulting in complications that include pain, loss of mobility, pathologic fracture, and tumor-induced hypercalcemia (TIH). Inhibition of osteoclast-mediated bone destruction using bisphosphonates represents a promising new management approach. PATIENTS AND METHODS: Breast cancer patients with bone metastases were randomly allocated to receive chemotherapy alone (152 patients) or chemotherapy plus pamidronate 45 mg in 250 mL of saline as a 1-hour intravenous infusion every 3 weeks (143 patients). Whenever possible, treatment continued until progression of disease (PD) in bone appeared on radiographs or bone scan. Time to PD in bone and pain reduction according to a self-assessment six-point scale were selected as primary end points. PD in bone was verified during extramural review (EMR) of all imaging studies by blinded observers, and these data were used as the main efficacy criterion. Analgesic intake, World Health Organization (WHO) performance status, and complications of bone metastases (radiotherapy, TIH, fractures, orthopedic surgery) were also compared in the two groups. RESULTS AND CONCLUSION: At EMR, median time to PD in bone was increased by 48% in patients who received pamidronate (249 v 168 days; P = .02, Wilcoxon test). Marked pain relief, defined as a two-point decrease lasting for > or = 6 weeks, was reported by 44% of pamidronate patients and by 30% of controls (P = .025, chi 2 test). The infusions (median, nine per patient; range, 0 to 39) were well tolerated, with no major toxicities reported. Pamidronate by repeated infusion can significantly slow the progression of bone metastases and reduce attendant morbidity.

Adult↗
PubMed1996

Quality of life as an outcome in breast cancer. Clinical application.

In clinical trials of anticancer agents, the assessment of objective effects has historically been the primary end-point. However, because of the limited impact of these agents on survival, the study of quality of life (QOL) has become increasingly important. QOL evaluation is difficult and the approaches of physicians and reimbursors of healthcare are quite different. In addition, QOL is not a simple concept and several different methods have been used to evaluate it. These methods can be divided into the following 2 groups: experimental methods [the best known is the quality-adjusted life-year (QALY), which utilise some kind of experimentation; and observational methods, which use questionnaires and are often multifactorial. Some of these questionnaires are used for patients with all types of pathologies, while others are cancer-specific; all questionnaires must be validated. We conducted 3 QOL studies in patients with breast cancer using the Functional Living Index-Cancer (FLIC) questionnaire. In the first, a French translation of the FLIC questionnaire was validated. The FLIC and Functional Living Index-Emesis (FLIE) questionnaires were used to assess QOL in a second study comparing 2 different antiemetics for the control of nausea and vomiting. Finally, QOL was evaluated in patients with breast cancer during adjuvant chemotherapy. Several other studies employing different questionnaires in patients with breast cancer have been published. Clinical applications for QOL evaluation in oncology may be the prognostic implications of QOL, evaluation of toxicity and duration of treatment, and evaluation of utility and QOL. However, although assessment of QOL is important for both physicians and funders, there is no gold standard method available, and the results of QOL studies have to be interpreted cautiously.

Breast Neoplasms↗
PubMed1996

A cost-utility analysis of second-line chemotherapy in metastatic breast cancer. Docetaxel versus paclitaxel versus vinorelbine.

The aim of this study was to determine the incremental effectiveness, the incremental health-related quality of life (differences in quality-adjusted progression-free survival between treatments), the incremental cost and the incremental cost-effectiveness and cost-utility ratios, for docetaxel, paclitaxel and vinorelbine, when these drugs were used as second-line treatment in patients with metastatic breast cancer. In the absence of comparative direct evidence of the relative efficacy of docetaxel, paclitaxel and vinorelbine in this setting, a model was designed to determine the effects of the 3 interventions on health outcome and cost. A Markov process model, based on 53 disease states, was thus constructed to evaluate the socioeconomics of the 3 treatment regimens. The model allows assessments from the start of second-line chemotherapy until death. Costs were evaluated from the combined view of the healthcare system and the patient. Direct nonmedical and indirect costs were excluded. Consumption per episode of care was estimated by retrospective analysis of 153 medical reports from 5 different hospitals. Hospital costs were allocated values from the national accounting costs by diagnosis-related group (DRG). The content of the health states was based on the multiattribute health states classification system (MASH). Preference values were assigned by application of a standard reference lottery using 20 oncological nurses as proxies for the patients. The health-related quality-of-life score was used as a quality adjustment weighting factor to calculate quality-adjusted progression-free survival associated with the 3 different regimens. Docetaxel reduces the time spent in progression, decreases the number of complications due to progressive disease and thereby provides better quality of life. It provides a benefit of 57 disease- and discomfort-free days compared with vinorelbine and 22 days compared with paclitaxel. Docetaxel may be thought of as self-financing as a result of savings in hospital admissions, providing net savings of 6800 French francs (FF; 1993 values) compared with expenditure associated with vinorelbine treatment and FF700 compared with the equivalent figures for paclitaxel.

Antineoplastic Agents↗
PubMed1996

[P53 antibodies: a new method for the analysis of alterations of the p53 gene: application to breast cancer].

Alterations in the p53 gene are found in 20% to 40% of breast cancers and are generally associated with factors of adverse prognostic significance. In most instances, point mutations modify the confirmation of p53, causing the gene to accumulate in the nuclei of tumor cells. These alterations can be detected via molecular analysis or immunohistochemical methods. More recent studies have demonstrated that accumulation of the p53 protein in tumor cells may induce an immune response with presence of anti-p53 antibodies in the serum of cancer patients. Assaying serum anti-p53 antibody is a new approach to investigation of the status of the p53 gene in a tumor.

Antibodies, Neoplasm↗
PubMed1995

Prognostic significance of circulating P53 antibodies in patients undergoing surgery for locoregional breast cancer.

P53 mutations can lead to the production of P53 antibodies in serum of cancer patients. Here we studied the prognostic value of P53 antibodies in 353 primary breast cancer patients. P53 antibodies were detected in 42 cases (12%) and were negatively related to oestradiol and progesterone receptors. The median duration of follow-up for live patients was 5.3 years. In actuarial analyses, overall survival was worse in patients with P53 antibody (p < 0.0005); in Cox's multivariate analysis, P53 antibody was an independent prognostic variable. Thus plasma assay of P53 antibody would be useful to select rapidly and easily a population of patients with poor prognosis.

Adenocarcinoma↗
PubMed1995

Phase II study of a new vinca alkaloid derivative, S12363, in advanced breast cancer.

Vinca alkaloids are widely used in the medical treatment of breast cancer. Our study aimed to evaluate the therapeutic activity of a new vinca alkaloid derivative, S12363 (vinfosiltine), which is 36 and 72 times more cytotoxic in vitro than vincristine and vinblastine, respectively. Because phase I studies did not allow a choice of the best treatment schedule, a randomization was performed between two schedules with the same dose intensity, that is, 0.3 mg/m2 given weekly or 0.6 mg/m2 given every 2 weeks. A total of 16 patients with advanced breast cancer who had failed a first-line treatment without any vinca alkaloid were entered in the study. Additionally, 6 women received the bimonthly regimen as first-line treatment of advanced breast cancer. Altogether, 17 patients received, prior to vinfosiltine, an anthracycline-based regimen given either as adjuvant (n = 4) or as first-line palliative treatment (n = 13). All 22 patients were evaluable for both toxicity and response. Neutropenia was the main toxic event (maximal toxicity per patient) with grade 3 (WHO) toxicity developing in 7/22 patients and grade 4, in 8/22. Other severe toxicities included leukopenia (n = 9), anemia (n = 1), diarrhea (n = 1), constipation (n = 1), and fatigue (n = 1). No patient achieved a complete or partial response. Vinfosiltine does not appear to have significant single-agent activity in advanced breast cancer at the doses and the schedules used in our study.

Adult↗
PubMed1995

[Immunotherapy of malignant melanoma. New prospects].

Malignant melanoma is an immunogenic tumor which can induce host humoral and cellular responses, and is a good model for development of anti-cancer immunotherapy. During the last decade systemically-administrated interferon and interleukin-2 have been used. Advances in immunology and molecular biology could allow a more specific and active immunotherapy. Perspectives include chemo-immunotherapy, monoclonal antibodies alone or in combination with cytotoxic agents, adoptive immunotherapy with tumor-infiltrating lymphocytes (TIL), gene therapy designed to increase tumor immunogenicity, and active immunotherapy with vaccines.

Animals↗
PubMed1995

Type I insulin-like growth factor receptors in human colorectal cancer.

Type I insulin-like growth factor (IGF) receptors have been recently characterised in human colorectal cancers. The aim of this study was to determine whether type I IGF receptor concentration may be related to prognostic variables in colorectal cancers. Saturation experiments with [125I]IGF-I were performed on membrane preparations of 46 frozen specimens (20 tumours, 26 controls) and analysed according to the Scatchard method. In all the studied cases, we found a single class of high affinity binding sites in both normal and malignant colorectal tissues (median 0.17 and 0.15 nmol/l, respectively). Using paired analysis, we found no significant difference in terms of type I IGF receptor concentration between malignant and normal colorectal tissues. There was also no relationship between type I IGF receptors and any of the tumour characteristics studied. This study does not support a critical role of the type I IGF receptors in the clinical management of colorectal cancers.

Adult↗
PubMed1995

Oral ondansetron in the prevention of chemotherapy-induced emesis in breast cancer patients. French Ondansetron Study Group.

A multicentre randomised, double-blind parallel group study has been carried out in order to confirm the antiemetic efficacy of orally administered ondansetron. A total of 259 chemotherapy-naive breast cancer patients treated with a 5-fluorouracil, doxorubicin, cyclophosphamide (FAC) or 5-fluorouracil, epirubicin, cyclophosphamide (FEC) regimen were randomly assigned to ondansetron (OND) 8 mg tablet or alizapride (ALI) 150 mg intravenous (i.v.) injection, prior to chemotherapy. These treatments were then followed by OND 8 mg tablet or ALI 50 mg tablet, respectively, 8 to 12 h later. Oral treatment was then continued twice a day over 3-5 days. The number of emetic episodes (EE = vomits+retches) and the grade of nausea were recorded; quality of life was assessed using a specific questionnaire. Of the 254 patients analysed for efficacy, complete or major control (success: 0-2 EE) over the 24 h following start of chemotherapy was obtained in 81% of the OND group compared with 47% of the ALI group (P < 0.001). A significant difference in favour of OND was also observed for nausea (P < 0.0001). For on days 2 to 4 emesis, the arm containing OND was superior to that with ALI (worst day analysis): 77% success versus 63% (P < 0.002). The overall control of emesis (from day 1 to day 4) was better with OND (64% patients success in the OND group versus 41% in the ALI group; P < 0.0001). At the end of the study the number of patients wishing to receive the same anti-emetic treatment for their next course was 83% for OND compared with 54% for ALI (P < 0.0001). In terms of quality of life in relation to emesis phenomena, OND was significantly superior to ALI (P = 0.04). Both treatments were well tolerated. In the prevention of the prolonged emesis induced by FAC/FEC-type emetogenic chemotherapy, orally administered OND was superior to ALI, given as an i.v. injection and followed by tablets.

Administration, Oral↗
PubMed1995

Analysis of p16 gene deletion and point mutation in breast carcinoma.

We looked for p16 gene deletion by Southern analysis and p16 gene point mutation by single-stranded conformation polymorphism (SSCP) analysis and direct sequencing of DNA from fresh tumour samples of 35 and 33 breast carcinomas respectively. No homozygous p16 gene deletion was found in any case. A missense point mutation of the p16 gene was found in only one patient. This point mutation was absent from the patient's lymphocytes, ruling out a polymorphism or a germline mutation. These findings suggest that p16 gene alterations are rarely observed in breast carcinoma.

Base Sequence↗
PubMed1995

Cytarabine and cisplatin as salvage therapy in patients with metastatic colorectal cancer who failed 5-fluorouracil + folinic acid regimen. French Northern Oncology Group.

The combination of CDDP and ARA-C has shown some clinical efficiency as first-line therapy in advanced colorectal cancer. Our study was aimed to evaluate the therapeutic activity of this combination in advanced colorectal cancer who failed 5-fluorouracil (FU) and folinic acid (LV) regimen. Seventeen patients with measureable metastatic colorectal cancer who failed 5FU-LV therapy as first line (n = 14) or second line treatment (n = 3), entered the study. Three patients who recurred during adjuvant treatment with 5FU and levamisol, were also included. Median age was 59.5 (40-69). Performance status was as follows: 0 (n = 5), 1 (n = 11), 2 (n = 3), 3 (n = 1). Site of metastases included liver (n = 16), lung (n = 7), abdomen (n = 2), pelvic recurrences (n = 2), cutaneous (n = 1). Seven patients had 2 metastatic sites and two 3. The treatment was given as follows: ARA-C 75 mg/m2/day, days 1-3, followed 1 hour later by CDDP 30 mg/m2/day, days 1-3, every 28 days. The median number of cycles was 3 (range: 1-6 cycles). All patients but one were evaluable for both response and toxicity. Of these patients, 50% experienced severe hematologic toxicity and nonhematologic toxicity mainly consisted of fatigue and/or vomiting. No objective response was observed, but there were 3 stabilizations and 16 progressive diseases. Median time to progression was 10 weeks. Thus, the CDDP/ARA-C regimen is not of clinical value as salvage therapy in advanced colorectal cancer because of its toxicity and its lack of efficiency.

Adult↗