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Fabrice Kwiatkowski

Publications and source records attributed to Fabrice Kwiatkowski.

15 recordsLinked to original sources
PubMed2007

Does high-dose carmustine increase overall survival in supratentorial high-grade malignant glioma? An EBMT retrospective study.

Radiotherapy plus concomitant and adjuvant temozolomide have demonstrated improved survival for glioblastoma. However, prognosis remains poor. High-doses chemotherapy with carmustine is another way to improve response and survival by increasing the dose delivered. Myelotoxicity imposes autologous stem cell rescue. European Group for Blood and Marrow Transplantation experience of this treatment in patients with high-grade glioma was reported here. A retrospective analysis of 217 patients from European Group for Blood and Marrow Transplantation database was realized. Ninety-six patients underwent complete surgical resection while the 121 others had partial resection or only biopsy and were evaluable for an antitumor effect. Patients received 800 mg/m2 of carmustine intravenously at least 1 month after neurosurgery. Forty-eight to 72 hr after chemotherapy, 108 patients received autologous hematopoietic stem cells from bone marrow harvest and 109 patients autologous hematopoietic stem cells from peripheral blood. Radiotherapy was started approximately 40 days after transplantation. Ten deaths were related to the treatment. Of the 121 patients evaluable for tumor response, 64 (53%) presented an objective response. This protocol appear feasible, but with toxicity-related mortality of 4.5%. Median overall survival was 20 months and median time to treatment failure was 7 months. Overall survival and time to treatment were correlated with age, quality of resection and histological subtypes. In glioblastoma multiforme, age and surgery quality appeared to be prognostic factors. Compared with Stupp et al.'s recent study, this study did not favor high-dose carmustine for patients with glioblastoma multiforme with complete surgical resection.

Adolescent↗
PubMed2006

Docetaxel and gemcitabine combination in 133 advanced soft-tissue sarcomas: a retrospective analysis.

Advanced soft-tissue sarcomas are usually resistant to cytotoxic agents such as doxorubicin and ifosfamide. Antitumor activity has been observed for gemcitabine and docetaxel combination. We conducted a retrospective study on 133 patients (58 males/75 females) with unresectable or metastatic soft-tissue sarcoma. The median age at diagnosis was 51.7 (18-82), with 76 patients with leiomoyosarcoma and 57 patients with other histological subtypes. The initial localizations were limb (44), uterine (32), retroperitoneal (23) and organs or bone (34). Patients received 900 mg/m2 of gemcitabine (days 1 and 8) over 90 min plus 100 mg/m2 of docetaxel (day 8), intravenously every 21 days. Gemcitabine/docetaxel combination was well tolerated with an overall response of 18.4% and with no clear statistical difference between leiomyosarcomas and other histological subtypes (24.2% versus 10.4% (p=0.06)). No difference was found between uterine soft-tissue sarcomas versus others. The median overall survival was 12.1 months (1-28). Better overall survival was correlated with leiomyosarcoma (p=0.01) and with the quality of the response, even for patients with stable disease (p<10(-4)). No statistical difference was found for the initial localization. Response to treatment and overall survival were better for patients in World Health Organization (WHO) performance status classification (PS) 0 at baseline versus patients in WHO PS-1, 2 or 3 (p=0.023 and p<10(-4), respectively). Gemcitabine/docetaxel combination was tolerable and demonstrated better response and survival for leiomyosarcoma, especially for patients in WHO PS-0 at baseline. For the other histological subtypes, the response was not encouraging, but the survival for patients in response or stable suggests further investigation.

Adolescent↗
PubMed2006

Randomized Phase II study comparing paclitaxel and carboplatin versus mitoxantrone in patients with hormone-refractory prostate cancer.

OBJECTIVES: Mitoxantrone/prednisone was the 2002 palliative reference treatment for hormone-refractory prostate cancer (HRPC). Paclitaxel and carboplatin has demonstrated antitumor activity in HRPC. The therapeutic benefit of such treatment was compared with that of mitoxantrone. METHODS: A randomized Phase II study was conducted that included 40 patients with HRPC who had not undergone chemotherapy. Patients in arm A received paclitaxel (175 mg/m2 every 3-week cycle) and carboplatin (area under the curve of 5 every 3-week cycle). Patients in arm B received mitoxantrone (12 mg/m2 every 3-week cycle). All the patients treated were receiving low-dose prednisone. The primary endpoint was the prostate-specific antigen response. RESULTS: The prostate-specific antigen response to paclitaxel and carboplatin was significantly greater (40% [95% confidence interval 18.5% to 61.5%] versus 10% [95% confidence interval 1% to 32%], P = 0.031) and more durable (8.6 versus 2 months, P = 0.015) than the response to mitoxantrone. A tendency was noted for patients with measurable disease who were receiving paclitaxel and carboplatin to have a somewhat greater objective response rate than those who received mitoxantrone (23% [95% confidence interval 5.3% to 55%] versus no objective response, P = 0.060). The median overall survival was 14.5 months for the paclitaxel and carboplatin arm compared with 11.1 months for the mitoxantrone arm. The group given paclitaxel and carboplatin had significantly greater rates of sensitive neuropathy (50% versus 0%, P = 0.00026). CONCLUSIONS: The 3-week regimen of paclitaxel and carboplatin induced a greater and more durable prostate-specific antigen response than did mitoxantrone for HRPC treatment. The major additive toxicity induced was peripheral neuropathy due to paclitaxel. Investigations with paclitaxel and carboplatin regimens merit large Phase III studies.

Aged↗
PubMed2006

Predicting postoperative mortality in patients undergoing colorectal surgery.

Well-known and suitable instruments for surgical audit are the POSSUM and P-POSSUM scoring systems. But these scores have not been well validated across the countries. The objective of the present study was to assess the predictive value of scores for colorectal surgery in France. Patients operated on for colorectal malignant or diverticular diseases, whether electively or on emergency basis, within a 4-month period were included in a prospective multicenter study conducted by the French Association for Surgery (Association Française de Chirurgie, AFC). The main outcome measure was postoperative in-hospital mortality. Independent factors leading to death were assessed by multivariate logistic regression analysis (AFC-index). The ratio of expected versus observed deaths was calculated, and the predictive value of the POSSUM and P-POSSUM scores were analyzed by the receiver operating characteristic (ROC) curve. A total of 1426 patients were included. The in-hospital death rate was 3.4%. Four independent preoperative factors (AFC-index) have been found: emergency surgery, loss of more than 10% of weight, neurological disease history, and age > 70 years. POSSUM had a poor predictive value; it overestimated postoperative death in all cases. P-POSSUM had a good predictive value, except for elective surgery, where it overestimated postoperative death twofold. The predictive value of the AFC-index was also good. It had the same sensitivity and specificity as the P-POSSUM. POSSUM has not been validated in France in the field of colorectal surgery. P-POSSUM was as predictive as the AFC-index which is a simpler instrument based on four clinical parameters (without any mathematical formulas).

Aged↗
PubMed2006

Tobacco smoking: a factor of early onset of colorectal cancer.

PURPOSE: Tobacco smoking is associated with a higher risk of developing colorectal cancer. This study was designed to assess the role of smoking in early onset of colorectal pathology. METHODS: This was a prospective cross-sectional study of 997 patients with colorectal cancer. Age of colorectal cancer diagnosis was studied in two groups of patients, i.e., smokers (>10 pack-years) and nonsmokers. Confounding factors, such as alcohol drinking, obesity, and gender, also were studied using a correlation analysis and multivariate logistic regression analysis. RESULTS: Of the 997 patients, 852 had sufficient data for analysis and were included. Baseline analysis showed that excluded patients had similar demographic characteristics. Smokers (n=108) reported symptoms related to colorectal cancer at an earlier mean age (64.1 (standard deviation, 11.7) years) than nonsmokers (69.6 (standard deviation, 12.6) years; mean difference, 5.5 (standard deviation, 1.2 years); P<0.001). Impact of smoking according to the bowel segment involved was significant for slow-transit segments (transverse and sigmoid colon and rectum). Multivariate analysis revealed that tobacco smoking was the only independent risk factor of early onset of colorectal cancers. CONCLUSIONS: Tobacco smoking could be a factor of early onset of colorectal cancers especially for slow-transit bowel segments. If these findings are confirmed in larger studies, screening for colorectal cancer should not involve a simple sigmoidoscopy but also an exploration of transverse colon in smokers.

Age of Onset↗
PubMed2006

[Sentinel lymph node biopsy for breast cancer after neoadjuvant chemotherapy: influence of nodal status before treatment].

OBJECTIVES: To determine feasibility and accuracy of SLN biopsy in locally advanced breast cancer treated by neoadjuvant chemotherapy. MATERIALS AND METHODS: From April 2001 to December 2004, a prospective series was constituted of 74 women with invasive breast carcinoma T1T2T3N0N1 receiving neoadjuvant chemotherapy. The SLN located was removed using subdermal periareolar injection of radiolabelled nanocolloid and axillary lymph node dissection was systematically performed. RESULTS: A SLN was identified in 68/74 (92%) patients. It was metastatic in 30/68 cases (44%). The false negative (FN) rate was 14% (5/35). In the subgroup of 42 patients clinically N(0) before chemotherapy, accuracy was 100 %, and FN rate 0%, in the 32 N1, accuracy was 83%, and FN rate 25%. CONCLUSIONS: SLN biopsy using a single subdermal injection of radiolabelled nanocolloid in patients with a breast cancer treated by neoadjuvant chemotherapy is technically feasible and appears to be highly accurate in the subgroup of patients with a clinically negative axilla breast cancer before treatment.

Adult↗
PubMed2005

Postoperative mortality and morbidity in French patients undergoing colorectal surgery: results of a prospective multicenter study.

HYPOTHESIS: Better knowledge of independent risk factors might decrease mortality and morbidity rates following colorectal surgery. DESIGN: Prospective multicenter study. INTERVENTIONS: From June to September 2002, consecutive patients undergoing open or laparoscopic surgery (electively or on an emergent basis) for colorectal cancers or diverticular disease were prospectively included. Exclusion criteria were colectomy for other causes (eg, inflammatory bowel diseases, benign polyps). The structured sheet of data collection included more than 200 items on all perioperative data concerning the patient, the disease, and the operating surgeons. Postoperative mortality and morbidity were defined as in-hospital death and complications. RESULTS: Among 1421 patients, the in-hospital death rate was 3.4% and the overall morbidity rate was 35%. Four independent preoperative risk factors of mortality were found: emergency surgery, loss of more than 10% of weight, neurological comorbidity, and age older than 70 years. Six independent risk factors of morbidity were found: age older than 70 years, neurologic comorbidity, hypoalbuminemia, cardiorespiratory comorbidity, long duration of operation, and peritoneal contamination. CONCLUSION: Colorectal resection in France is associated with a 3.4% mortality rate and a 35% morbidity rate. Knowledge of the risk factors could help surgeons manage cases.

Age Factors↗
PubMed2005

Mortality and morbidity after surgery of mid and low rectal cancer. Results of a French prospective multicentric study.

BACKGROUND: The aim of the study was to assess both mortality and morbidity following resection of mid and low rectal cancers in a French prospective multicentric study. PATIENTS: From June to September 2002, consecutive patients undergoing resection for cancer of the mid- or lower rectum were prospectively included in a multicentric study. Both postoperative mortality and morbidity were recorded. Multivariate statistical analysis was performed in order to assess risk factors predictive of postoperative morbidity. RESULTS: 238 patients with a mean age of 66 +/- 13 years (range: 26-88) were included. Neoadjuvant radiotherapy was performed in 68% of the patients. Total mesorectal excision was performed in 218 patients (92%), of whom 151 (63%) had a sphincter saving procedure. Six patients died (2.5%). Overall postoperative morbidity rate was 43%, including anastomotic leakage (11%) and reoperation (5%). Mean hospital-in-stay was 20 +/- 16 days (range: 3191). Four independent risk factors of morbidity were found: perioperative fecal contamination (OR = 3.9 [1.1; 13.5]), mean operating time longer than 6 hours (OR = 4.5 [1.7; 12.1]), ASA score > 2 (OR = 3.2 [1.6; 7.9]), and smocking (OR = 3.3 [1.2; 8.9]). CONCLUSIONS: Resection of cancer involving the middle or lower rectum with sphincter saving procedures was possible in two-thirds of the patients and was associated with 2.5% mortality and 43% morbidity.

Aged↗
PubMed2004

Pre- and postoperative aminoacidemia in breast cancer: a study vs. matched healthy subjects.

Various alterations of aminoacidemia have been described during breast cancer. The aim of this study was first to establish the specific modifications of plasma-free amino acid concentrations by a comparative study of 19 patients with mammary tumors and 18 healthy volunteers, and, second, to determine the evolution of aminoacidemia after surgical tumor removal. Aminoacidemia was determined the day before (D0), and then five days, one month (M1), and six months after surgical removal of the tumor, and a single determination was performed in control subjects. Plasma levels (mumol/L) of serine and glutamate were higher in cancer-bearing women at D0 (respectively, 124 +/- 3 and 68 +/- 7) than in healthy volunteers (respectively, 110 +/- 6 and 48 +/- 5). Surgical tumor removal induced a normalization of aminoacidemia (in mumol/L at D5: serine: 114 +/- 4; at M1: glutamate: 55 +/- 6 Non Significant (NS) from values of healthy subjects). Among the various patterns reported for breast cancer, we confirm one of those described by Cascino in 1995, and we show that these levels revert to normal after tumor surgical removal.

Adult↗
PubMed2003

[Toward the development of medical applications of chronobiology].

The medical applications of chronobiology have been developed since the properties of biological rhythms were characterized and their parameters were quantified. In particular, the "Association de Chronobiologie Médicale" has played a major role in the creation of the Chronotherapy Group of the European Organisation for Research and Treatment of Cancer, the first cooperative group which investigates the clinical relevance of rhythms for cancer processes and treatments worldwide. In parallel, the molecular mechanisms which generate the cellular rhythms and the hypothalamic clock which coordinate them have been unravelled. We expect that the integration of these new basic findings into clinical chronobiology research will greatly improve the understanding of many physiopathology processes and result in more active treatment schedules for many diseases.

Chronobiology Phenomena↗
PubMed2003

Methodological index for non-randomized studies (minors): development and validation of a new instrument.

BACKGROUND: Because of specific methodological difficulties in conducting randomized trials, surgical research remains dependent predominantly on observational or non-randomized studies. Few validated instruments are available to determine the methodological quality of such studies either from the reader's perspective or for the purpose of meta-analysis. The aim of the present study was to develop and validate such an instrument. METHODS: After an initial conceptualization phase of a methodological index for non-randomized studies (MINORS), a list of 12 potential items was sent to 100 experts from different surgical specialties for evaluation and was also assessed by 10 clinical methodologists. Subsequent testing involved the assessment of inter-reviewer agreement, test-retest reliability at 2 months, internal consistency reliability and external validity. RESULTS: The final version of MINORS contained 12 items, the first eight being specifically for non-comparative studies. Reliability was established on the basis of good inter-reviewer agreement, high test-retest reliability by the kappa-coefficient and good internal consistency by a high Cronbach's alpha-coefficient. External validity was established in terms of the ability of MINORS to identify excellent trials. CONCLUSIONS: MINORS is a valid instrument designed to assess the methodological quality of non-randomized surgical studies, whether comparative or non-comparative. The next step will be to determine its external validity when used in a large number of studies and to compare it with other existing instruments.

Clinical Trials as Topic↗
PubMed2002

Prognostic value of residual node involvement in operable breast cancer after induction chemotherapy.

The purpose of this retrospective study was to evaluate the influence of axillary disease on patients' survival after neoadjuvant chemotherapy and to assess patient and tumor characteristics associated with post-chemotherapy axillary involvement. After six induction cycles, 277 patients with operable breast cancer (stage II-III) underwent surgery with axillary dissection, followed by radiotherapy (n = 267) or additional chemotherapy (n = 63) and adjuvant tamoxifen therapy (n = 138). At a median follow-up of 8.5 years, overall survival (OS) and disease-free survival (DFS) were analyzed as a function of node involvement. The differences in OS and DFS according to the number of positive nodes were highly statistically significant with a decreased survival associated with the increasing number of nodes (p = 5 x 10(-6) and 9 x 10(-7), respectively). Upon multivariate analysis, the node number after chemotherapy appeared as the most significant prognostic factor (p = 7 x 10(-4) for OS and p = 3 x 10(-5) for DFS). All the other classical prognostic factors were insignificant, except post-chemotherapy Scarff-Bloom-Richardson (SBR) grading for OS (p = 8 x 10(-4)) and adjuvant hormonotherapy for DFS (p = 1 x 10(-2)). Although constituting a different parameter from primary surgery data, the number of positive nodes after chemotherapy could still remain a valuable prognostic factor at secondary surgery, raising the question for high risk patients of a second non-cross-resistant adjuvant regimen, or high dose chemotherapy with peripheral blood stem cells support.

Adult↗
PubMed2002

O(6)-methylguanine-DNA methyl transferase gene expression and prognosis in breast carcinoma.

O(6)-methylguanine-DNA methyl transferase (MGMT) in human carcinomas has been associated with tumor resistance to alkylating agents. The aims of this study were: i) to correlate tumor MGMT expression and patient and tumor characteristics in malignant breast carcinomas treated with induction chemotherapy including cyclophosphamide (CPM) and ii) to study the predictive and prognostic values of tumor MGMT gene expression. We used RT-PCR to measure the levels of tumor MGMT expression in 107 patients with breast carcinomas prior to neoadjuvant chemotherapy. Sixty patients (56%) received anthracyclines and CPM and 47 (44%) received only anthracyclines. Low levels of MGMT expression correlated with Scarff-Bloom-Richardson grade III (p<0.005), elevated S-phase (p<0.05), negative estrogen receptors (p<0.05), metastatic status (p<0.05) and occurrence of death (p=0.01). MGMT expression was not predictive of treatment response. Unexpectedly, survival was longer when tumor MGMT expression was high (p<0.005). The 4-year survival rate was 76% for high level MGMT patients and only 55% for others. This difference is also significant using the COX model (p<0.05). In breast cancer, tumor MGMT expression was not predictive of response to CPM. A low MGMT expression was significantly related to poor survival.

Breast Neoplasms↗
PubMedDate not supplied

In vitro thermochemotherapy of colon cancer cell lines with irinotecan alone and combined with mitomycin C.

BACKGROUND/AIMS: Irinotecan (CPT-11) is a new drug of the camptothecin family which has shown significant activity in the treatment of metastatic colorectal cancer. Hyperthermia has been shown to enhance the cytotoxic effect of some anticancer drugs and has been combined with intraperitoneal chemotherapy for the treatment of colorectal peritoneal carcinomatosis. The purpose of this study was to evaluate the cytotoxic effect of CPT-11 alone and in combination with mitomycin C (MMC) and hyperthermia on three colorectal cancer cell lines: CACO-2, HT-29, and DHD/K12/TRb (PROb). METHODOLOGY: The cytotoxic effect of CPT-11 was tested at seven different concentrations (from 2.5 to 160microg/mL) for each type of cell line at 37, 39, 42.5 and 44 degrees C. Combined cytotoxic effect of MMC with CPT-11 was tested at 37 and 42.5 degrees C. RESULTS: The cytotoxic effect of CPT-11 alone increased with concentration (p<0.001) and with increasing temperature (p<0.001) at concentration above 5microg/mL in all three cell lines. CPT-11 (20microg/mL) significantly increased the cytotoxicity of MMC (8microg/mL) at 42.5 degrees C on the CACO-2 line. The combination of CPT-11 and MMC had at least 92% cytotoxicity on the three cell lines. CONCLUSIONS: The combination of CPT-11 and MMC at 42.5 degrees C had a large spectrum of cytotoxicity in these in vitro models. Our findings support the clinical use of this combination and provide a rationale for the design of a clinical trial using intraperitoneal chemohyperthermia with MMC and CPT-11 to treat colorectal peritoneal carcinomatosis of colorectal origin.

Animals↗