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P Bougnoux

Publications and source records attributed to P Bougnoux.

At least 19 recordsLinked to original sources
PubMed2006

A phase II study of a paclitaxel and oxaliplatin combination in platinum-sensitive recurrent advanced ovarian cancer patients.

PURPOSE: A multicentric, phase II study to evaluate the efficacy and safety of the combination paclitaxel and oxaliplatin in patients with platinum-sensitive recurrent ovarian cancer. PATIENTS AND METHODS: Patients received 175 mg/m(2) paclitaxel (over 3 h) followed by 130 mg/m(2) oxaliplatin (over 2 h) every 21 days for up to nine cycles without hydration or primary granulocyte colony-stimulating factor prophylaxis. Patients had to have an Eastern Cooperative Oncology Group performance status of 0-2 and to have received no more than one prior cisplatin- and/or carboplatin-containing chemotherapy regimen with a platinum-progression-free interval > or =6 months. RESULTS: Of the 105 patients enrolled and treated, 98 were eligible. An overall response rate of 81% (79 of 98 patients) (95% confidence interval 71% to 88%) was observed according to RECIST criteria (third party reviewed), and 88% (86 of 98) when this was complemented with CA-125 response. With a median follow up of 43.6 months (range 30.2-64.2) the median progression-free survival was 10.2 months (range 0.3-21.4) and the overall survival 32.4 months. Seven hundred and eight cycles were administered (median seven per patient; range one to nine). A total of 67% of patients experienced National Cancer Institute Common Toxicity Criteria grade 3-4 neutropenia, including 8% with concomitant febrile episode, without treatment-related deaths. Ninety-three per cent of patients experienced neuropathy of grade 1 or more, including 25% with cumulative reversible peripheral neuropathy of grade 3-4. Oxaliplatin doses were reduced in 30 patients due to neurotoxicity. CONCLUSIONS: The oxaliplatin/paclitaxel combination can be administered in an outpatient setting every 3 weeks without specific measures. The high level of activity and its duration observed warrants further evaluation of this combination in pretreated platinum-sensitive advanced ovarian cancer patients.

Adult↗
PubMed2005

Tumor parameters, clinical and pathological responses, medical management, and survival through time on 710 operable breast cancers.

The aim of the current study is an analysis of tumor parameters, clinical and pathological responses, medical management, and survival on 710 operable breast cancer patients who received neoadjuvant chemotherapy from 1982 to 2004 and were grouped into four successive periods according to diagnosis date: (1) 1982-1989; (2) 1990-1994; (3) 1995-1999; and (4) 2000-2004. Patients were treated by different neoadjuvant chemotherapies combinations: AVCF/M, TNCF, NEM, NET, TAXOTERE, FEC 50, 75, 100, FAC 50, and TAXOTERE-TNCF, mainly in successive prospective phase II trials. They received a median number of six cycles (range, 1-9). After primary chemotherapy, patients underwent a surgery and a radiotherapy. In case of significant residual disease, some patients received additional courses of chemotherapy. In addition, menopausal patients with hormonal receptor-positive tumors received tamoxifen for 5 yr. Clinical factors had some remarkable variations with time. The median age of the patients was 49.5 yr (range, 26-81). The size of the tumor was significantly greater from 1995; conversely, clinical lymph-node involvement was lower in period 4 than in the first period. The percentage of invasive ductal carcinoma and of SBR III tumors increased about 20% from 1982-1989 to 2000-2004. The number of positive hormonal receptors increased from 38.3% in period 1 to 74% in period 4. The clinical response rate improved recently from before 1990. The pathological response rate was greater in periods 2 and 3 than in periods 1 and 4. An adjuvant hormonotherapy became progressively more frequently given (44.7 for period 1 and 73.3% for period 4). Finally, no significant difference was found when we compared overall and disease-free survival through the four periods. It appears that the progressive increase of tumor burden was compensated by more effective treatments.

Adult↗
PubMed2004

Phase II multicentre randomised study of docetaxel plus epirubicin vs 5-fluorouracil plus epirubicin and cyclophosphamide in metastatic breast cancer.

The purpose of the study was to evaluate the efficacy and safety of docetaxel plus epirubicin (ET) and of 5-fluorouracil plus epirubicin and cyclophosphamide (FEC) as first-line chemotherapy for metastatic breast cancer. A total of 142 patients (intent-to-treat (ITT)) with at least one measurable lesion were randomised to receive docetaxel 75 mg m(-2) plus epirubicin 75 mg m(-2) or 5-fluorouracil 500 mg m(-2) plus epirubicin 75 mg m(-2) and cyclophosphamide 500 mg m(-2) intravenously once every 3 weeks for up to eight cycles. Prophylactic granulocyte-colony-stimulating factor was only permitted after the first cycle, if required. Per-protocol analysis (n=132) gave an overall response rate for ET of 63.1% (95% confidence interval (CI), 50-78%) and for FEC 34.3% (95% CI, 23-47%) after a median seven and six cycles, respectively. Intent-to-treat population (n=142) gave an overall response rate for ET of 59% (95% CI, 47-70%) and for FEC 32% (95% CI, 21-43%) after a median seven and six cycles, respectively. The median response duration for ET was 8.6 months (95% CI, 7.2-9.6 months) and for FEC 7.8 months (95% CI, 6.5-10.4 months). The median time to progression (ITT) for ET was 7.8 months (95% CI, 5.8-9.6 months) and for FEC 5.9 months (95% CI, 4.6-7.8 months). After a median follow-up of 23.8 months, median survival (ITT) for ET and FEC were 34 and 28 months, respectively. Nonhaematologic grade 3-4 toxicities were infrequent in both arms. Haematologic toxicity was more common with ET and febrile neutropenia was reported in 13 patients (18.6%) in the ET group. Two deaths in the ET group were possibly related to study treatment. In conclusion, both ET and FEC were associated with acceptable toxicity. ET is a highly active first-line therapy for metastatic breast cancer.

Adolescent↗
PubMed2003

Phase II multicentre study of docetaxel plus 5-fluorouracil in patients with anthracycline-pretreated metastatic breast cancer.

The purpose of the study was to determine the efficacy and safety of docetaxel plus continuous infusion of 5-fluorouracil (5-FU) in patients with metastatic breast cancer previously treated with anthracyclines. A total of 41 patients with histologically proven metastatic breast cancer and performance status 0-2, who had received at least one anthracycline-containing regimen, received docetaxel 85 mg m(-2) followed by continuous infusion of 5-FU 750 mg m(-2) day(-1) for 5 days every 3 weeks for up to eight cycles. All patients received corticosteroid premedication, but there was no prophylactic colony-stimulating factor support. The most frequent metastatic sites were the liver (61%), bone (29%), and lung (29%). All 41 patients were assessable for toxicity and 30 were eligible and assessable for efficacy. The objective response rate was 70.0% (95% CI: 53.6-86.4%) for the per protocol group and 53.7% (95% CI: 38.4-68.9%) for the intent-to-treat (ITT) population. For the ITT population, median duration of response was 8.4 months (95% CI: 6.7-12.2 months), median time to progression was 6.7 months (95% CI 5.5-8.6 months), and median survival was 17 months (95% CI: 12.3-not recorded months). Grade 3/4 neutropenia occurred in 54% of patients, with febrile neutropenia in 24% of patients and 5% of cycles, but infections were rare. Stomatitis was frequent, grade 3 in 24% of patients and grade 4 in one patient (2%), but manageable. Diarrhoea was rare, grade 3 in 7% of patients and 1% of cycles. Other grade 3/4 nonhaematological toxicities were infrequent. In conclusion, this docetaxel/5-FU regimen is highly active and well tolerated in patients with anthracycline-pretreated metastatic breast cancer. The efficacy is particularly promising, as one-third of patients were either second-line and/or anthracycline-resistant/refractory.

Adenocarcinoma↗
PubMed2003

Neoadjuvant docetaxel for operable breast cancer induces a high pathological response and breast-conservation rate.

Docetaxel (Taxotere), alone or in combination with other anticancer agents, has proven efficacy in the first- and second-line treatment of metastatic breast cancer. This phase II study investigated the efficacy and tolerability of docetaxel as neoadjuvant chemotherapy in women with stage II-III primary operable breast cancer. Patients (n=88) were treated with six cycles of docetaxel at 100 mg m(-2) every 21 days, followed by definitive surgery and radiotherapy. After six cycles of docetaxel, the overall clinical response rate was 68.4% (CI 95%: 58.1-78.7%), including 19.0% complete remissions. Breast conservation was achieved in 72.4% of patients. A high pathological complete response (pCR) rate in breast was confirmed in 15 patients (19.8% (CI 95%: 10.8-28.8%)) on Chevallier's classification restricted to breast and in 27 patients (35.5% (CI 95%: 24.7-46.3%)) on Sataloff's classification. After a median follow-up of 30.8 months, 19 recurrences were documented with a median time to first recurrence of 17.3 months. Patients with stage III tumours had more recurrences than patients with stage II tumours (P=0.02). The principal toxicity of docetaxel is myelosuppression and 70.5% of patients developed grade III or IV neutropenia with 13.6% developing neutropenic sepsis. There was no case of severe cardiac toxicity, thrombocytopenia or any other serious adverse events. In conclusion, neoadjuvant docetaxel induces a high pCR and breast-conservation rate. Docetaxel monotherapy is a highly effective regimen that merits formal comparison with currently used combination regimens in a randomised phase III study.

Antineoplastic Agents, Phytogenic↗
PubMed2003

Phase II study of oral vinorelbine in first-line advanced breast cancer chemotherapy.

PURPOSE: A phase II trial was performed to evaluate the efficacy, tolerance, and pharmacokinetic profiles of oral vinorelbine (Navelbine). Oral Navelbine (NVB; Pierre Fabre Médicament, Boulogne, France) was given as first-line chemotherapy for locally advanced or metastatic breast carcinoma (ABC). PATIENTS AND METHODS: Sixty-four patients were entered to receive oral NVB on a weekly basis for a total of 8 weeks unless progression or toxicity occurred. Oral NVB was given at 60 mg/m(2) weekly for the first three administrations and was increased to 80 mg/m(2) for the subsequent administrations if there was no grade 4 neutropenia or no more than one episode of grade 3 neutropenia. Patients with objective response or stable disease continued treatment up to a total of 12 weeks or more. RESULTS: Fifty-eight evaluable patients were included in our study. Four patients (6.9%) had complete responses, and 14 (24.1%) had partial responses, for an overall response rate of 31% (95% CI, 19% to 43%). Median progression-free survival was 17.4 weeks. Median overall survival is not yet reached. There were no treatment-related deaths. The main toxicity was neutropenia: grade 4 in 17.2% of the patients, and 1.8% of administrations and associated clinical serious events in 4 patients (6.2%). Grade 3 and 4 nausea and/or vomiting were noted in 3.1% and 4.6% of the patients, respectively. Only one patient developed grade 3 neuroconstipation. An analysis of Quality of Life Questionnaire C30 forms revealed no significant alteration between baseline and weeks 8 and 16 in global quality of life. CONCLUSION: Oral NVB at this schedule is an effective and well-tolerated agent in the treatment of ABC and offers a promising alternative to the intravenous route. Combination studies are ongoing.

Administration, Oral↗
PubMed2003

Anthracycline-induced cardiac toxicity is not increased by dietary omega-3 fatty acids.

Exogenous n-3 polyunsaturated fatty acids (PUFA) and specially docosahexaenoic acid (DHA) have been previously reported to potentiate the efficacy of anticancer agents that generate an oxidative stress, such as anthracyclines, by enhancing the susceptibility of cell membranes to lipid peroxidation. Since lipid peroxidation has also been suggested to mediate anthracycline-induced heart failure, we designed a study aimed at investigating whether a DHA-enriched diet coupled with controlled oxidative conditions prevents or aggravates this serious side effect in vivo. Female Sprague-Dawley rats were submitted for at least 3 weeks to diet enriched in DHA, which was provided either as natural oil (sardine oil, experiment 1) or in a purified form (DHASCO, experiment 2). At the same time, to constrain the nutritional oxidative status, the anti-oxidant Vitamin E or the pro-oxidant menadione/sodium ascorbate redox mixture was added. Then, epirubicin was administered weekly at two cumulative doses, 9 mg x kg(-1) (experiment 1) or 15 mg x kg(-1) (experiment 2). Cardiotoxicity was assessed by electrocardiographic (ECG) and hemodynamic measurements, completed with histological examination. Epirubicin-induced dose-dependent mortality, alterations of hemodynamic parameters and histological damages, all features characterizing the occurrence of congestive heart failure. Moreover, the addition of anti- or pro-oxidant did not change the hemodynamics either at the lowest (experiment 1) or the highest dose (experiment 2). Similarly, the ECG measurements and histological examinations did not reveal any difference. DHA was actually incorporated, as evaluated through the adipose tissue fatty acid composition. All these observations indicated that the DHA-enriched diet, placed under controlled oxidative conditions, did not appear to prevent but neither to aggravate epirubicin-induced cardiotoxicity. These findings support the idea that DHA improves the anthracycline therapeutic index.

Adipose Tissue↗
PubMed2002

A phase II trial of ZD0473 in platinum-pretreated ovarian cancer.

The primary aim of this phase II trial was to assess the antitumour activity of ZD0473 in ovarian cancer patients who had failed initial platinum-based therapy. Patients (n=94) were classified as either platinum-sensitive (n=35) or platinum-resistant (n=59) depending on whether they had relapsed or progressed within 26 weeks of completing first-line platinum-based chemotherapy. Patients initially received 120 mg/m(2) ZD0473 as a 1-h intravenous (i.v.) infusion on day 1 of a 3-week cycle. If well tolerated, the dose could be escalated to 150 mg/m(2). Few patients (9%) withdrew because of treatment-related adverse events and no clinically significant oto-, nephro- or neurotoxicity was observed. Objective response rates for platinum-resistant and sensitive patients were 8.3 and 32.4%, respectively, and clinical benefit was observed in 76.5% of the sensitive patients. Median time to progression was 57 and 180 days, and median time to death was 242 and 402 days, for resistant and sensitive patients, respectively. In conclusion, ZD0473 has a manageable toxicity profile and encouraging activity in platinum-sensitive ovarian cancer patients.

Adult↗
PubMed2002

Results of ZD0473 in platinum-pretreated ovarian cancer: analysis according to platinum free interval.

Resistance to platinum-containing regimens can develop in many women with ovarian cancer and may lead to relapse in > 80% of patients. ZD0473 is a new-generation platinum agent that, in preclinical studies, shows evidence of antitumour activity and overcomes platinum-resistance mechanisms. This Phase II trial has evaluated the efficacy and tolerability of ZD0473 in second-line ovarian cancer patients. Patients received ZD0473 120 mg/m2 (1-h iv infusion, day 1 q 3-weeks); the starting dose was increased to 150 mg/m2 after a safety review. We report here on results when patients are divided into four cohorts depending upon whether they were considered platinum-resistant or -sensitive. Patients were placed into one of 3 cohorts if they were platinum resistant (relapsed/progressed < or = 26 weeks after completion of prior platinum-based chemotherapy) or cohort 4 if this period was > 26 weeks (sensitive). Ninety-four patients were recruited to the trial (59 resistant, 35 sensitive; median age 58 [range 27-75] years; 86 with performance status [PS] < or = 1). Forty-nine patients received a starting dose of 120 mg/m2, of which 15 escalated to 150 mg/m2, and 45 received a starting dose of 150 mg/m2. Overall, the median number of treatment cycles received was 3 (range 1-8). Grade 3/4 thrombocytopenia was the most common haematological adverse event occurring in 62% of patients overall. Grade 3/4 lethargy, vomiting and nausea were the most common non-haematological toxicities. No clinically significant oto-, nephro- or neurotoxicity was observed. Overall response rates for all platinum-resistant and -sensitive patients were 8.3% and 32.4%, respectively. Stable disease occurred in 17 resistant and 15 sensitive patients.

Adult↗
PubMed2002

Multicentre phase II study of oxaliplatin as a single-agent in cisplatin/carboplatin +/- taxane-pretreated ovarian cancer patients.

BACKGROUND: This multicentre phase II open-label study evaluated safety and antitumour activity of oxaliplatin in cisplatin or carboplatin (cis/carboplatin) +/- taxane-pretreated advanced ovarian cancer (AOC) patients. PATIENTS AND METHODS: Forty-eight patients received oxaliplatin 130 mg/M2 intravenously every 3 weeks, 94% having a performance status (PS) 0-1. All were pretreated with cis/carboplatin and 21 (44%) with paclitaxel. The median number of involved organs was two, 18 (38%) had liver metastasis, 23 (48%) were platinum-resistant and 14 (29%) were taxane-resistant. Forty-two patients were evaluable for a response, 18 (43%) were platinum-resistant and 11 (26%) were taxane-resistant. RESULTS: A total of 253 cycles was administered (median: 5.5/patient). Median cumulative oxaliplatin dose was 666 mg/m2. National Cancer Institute-Common Toxicity Criteria toxicity analysis showed that seven patients (15%) had grade 3/4 thrombocytopenia, two patients (4%) had grade 3 neutropenia, and one patient had grade 3 anaemia. Eleven patients (23%) experienced grade 3 neurosensory toxicity. Of the 29 patients with peripheral neuropathy at the end of treatment, 55% had recovered or improved 1 month later. Eleven objective responses (two complete) were obtained in the 42 evaluable patients [ORR 26%, 95% confidence interval (CI) 14% to 42%], with 10/24 (42%, 95% CI 22% to 63%) in platinum-sensitive, and 1 of 18 (5.6%, 95% CI 0% to 27%) in platinum-resistant patients. Median response duration was 9.2 months (95% CI 6.6% to 11.8%), and median progression-free and overall survival in all treated patients were 4.3 months (95% CI 3.0% to 5.7%) and 15.0 months (95% CI 11.1% to 18.8%), respectively. CONCLUSION: Oxaliplatin has a good safety profile and is active in cis/carboplatin +/- paclitaxel-pretreated AOC patients.

Adult↗
PubMed2001

Low body mass index is an independent predictive factor of local recurrence after conservative treatment for breast cancer.

BACKGROUND: Obesity or increased body mass index (BMI) has been shown to have two important adverse effects related to breast cancer. First, several studies have identified an association between increased BMI and advanced stage breast cancer. Second, increased BMI has been shown to be associated with poorer prognosis. In a previous report, we had identified low BMI as a risk factor for local reccurence at five years. The objectives of this study were to evaluate the relationship between BMI and local control and to confirm this prognostic factor in a larger population with an important follow-up. MATERIALS AND METHODS: Between 1976 and 1988, 605 women with invasive breast carcinoma less than 4 cm in diameter underwent conservative surgery with axillary dissection and radiation therapy. The median follow-up time was 82 months. The risk of local recurrence and distant metastasis was evaluated by univariate retrospective analysis using Kaplan-Meier method for the main clinical and histologic factors. Those found to be significant were entered in a Cox model for multivariate analysis. RESULTS: Since the beginning of the study, 80 patients had developed local recurrence. The 5 years and 10 years local control rates were 91% and 83%, respectively. Four parameters were independent predictive factors of local recurrence: Age lower than 40 years (HR = 2.42 95% CI = [1.35-4.34]), BMI: elevation of one unit reducing the local recurrence of 0.92 95%CI = [0.85-0.99], multifocality of the tumor on pathological examination (HR = 2.12 95% CI = [1.16-3.88]) and positive axillary nodes HR = 0.54 95% CI = [0.31-0.95]. Size of the breast was not a predictive factor for local cancer recurrence. Low BMI did not increase risk of distant. CONCLUSION: Our study offers new data concerning the possibility that thinness may be related to local recurrence of breast cancer.

Adult↗
PubMed2001

Histologic multifocality is predictive of skin recurrences after conserving treatment of stage I and II breast cancers.

OBJECTIVE: To distinguish various types of local recurrence after conserving treatment of breast cancer and to evaluate their predictive value. MATERIALS AND METHODS: We first researched the pronostic factors after local recurrence and second evaluated the predictive factors of skin and inflammatory recurrences out of a series of 605 cases of stage I and stage II breast cancer of less than 4 cm in diameter that occurred after conserving treatment. RESULTS: Multivariate analysis revealed two major predictors of poor prognosis associated with recurrence: early appearance Hazard ratio 3.0 (1.28-7.00) (p = 0.011) and inflammatory or skin involvement Hazard ratio 3.38 (1.36-8.45) (p = 0.009). A local recurrence multiplied the relative risk for metastasis by 2.6. This result depended on the type of recurrence: when those with inflammatory and cutaneous types were excluded, local recurrence was no longer a poor prognostic factor. Patients who experienced primary invasive tumor with histologic multifocality have a 4.08 (1.44-11.59) (p < 0.004) times greater risk of developing cutaneous or inflammatory recurrences compared with patients who experienced breast cancer unique localization. CONCLUSION: As histologic multifocality is the only factor predictive of dark prognosis local breast cancer recurrences, aggressive therapy at the time of the primary treatment could be the therapeutic implications of such finding on the original tumor.

Adult↗
PubMed2000

Prognostic of DNA-synthesizing enzyme activities (thymidine kinase and thymidylate synthase) in 908 T1-T2, N0-N1, M0 breast cancers: a retrospective multicenter study.

Among the methodological approaches of tumor proliferation, thymidine kinase (TK) and thymidylate synthase (TS) assays take into account the specific pathways of pyrimidine synthesis. Studies pointing to a prognostic value of TK and TS in breast cancer involved small numbers of patients. We investigated the prognostic value of these enzymes and their combination in a large retrospective multicenter study. Nine hundred eight T1T2, N0N1, M0 primary breast cancer samples (median follow-up 68 months) were tested. TK and TS were measured in cytosols by using standardized radioenzymatic methods. Although a positive correlation was obtained between TK and TS (p<10(-5)), major discrepancies were observed in some tumors. High levels of both enzymes were associated with large tumor size, histological grade III and steroid receptor-negative tumors. Univariate analysis showed that TK, TS and their combination were predictive of poor metastasis-free (MFS) (p < 10(-4); p=0.004; p < 10(-4)) and disease-free survival (DFS) (p < 10(-4); p=0.007; p=0.0001). TK was selected as an independent factor for MFS in Cox analysis. It was the only variable selected in node-negative patients. Subgroups with specific outcomes, with possible therapeutic implications, were identified: a) in node-negative patients not receiving adjuvant treatment, TK values in the 4th quartile were associated with poor MFS (p=0.0002) and DFS (p=0.0005) as compared to the other quartiles; b) in node-positive patients receiving adjuvant chemotherapy, low levels of both TK and TS were associated with the highest survival rates (MFS: p=0.04; DFS: p=0. 03).

Adult↗
PubMed2000

Low alpha-linolenic acid content of adipose breast tissue is associated with an increased risk of breast cancer.

Data derived from experimental studies suggest that alpha-linolenic acid may have a protective effect in breast cancer. Observations obtained from epidemiological studies have not allowed conclusions to be drawn about a potential protective effect of dietary alpha-linolenic acid on breast cancer, possibly because of methodological issues. This case-control study conducted in an homogeneous population from a central area in France was designed to explore the hypothesis that alpha-linolenic acid inhibits breast cancer, using fatty acid levels in adipose breast tissue as a biomarker of past qualitative dietary intake of fatty acids. Biopsies of adipose breast tissue at the time of diagnosis were obtained from 123 women with invasive non-metastatic breast carcinoma. 59 women with benign breast disease served as controls. Individual fatty acids were analysed by capillary gas chromatography. An unconditional logistic regression model was used to obtain odds ratio estimates whilst adjusting for age, menopausal status and body mass index (BMI). No association was found between fatty acids (saturates, monounsaturates, long-chain polyunsaturates n-6 or n-3) and the disease, except for alpha-linolenic acid which showed an inverse association with the risk of breast cancer. The relative risk of breast cancer for women in the highest quartile of adipose breast tissue alpha-linolenic acid level was 0.36 (95% confidence interval=0.12-1.02) compared with those in the lowest quartile (P trend=0.026), suggesting a protective effect of alpha-linolenic acid in the risk of breast cancer. The effects of dietary alpha-linolenic on the risk of breast cancer warrant further study.

Adipose Tissue↗