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Biomedical subjects

Fabrice Barlési

Publications and source records attributed to Fabrice Barlési.

15 recordsLinked to original sources

Unsuccessful rechallenge with pemetrexed after a previous radiation recall dermatitis.

Radiation recall dermatitis is characterized by an inflammatory reaction within a previously irradiated volume after administration of a drug. Antineoplastic drugs have mainly been involved in radiation recall reactions. This phenomenon is well known but poorly understood. Many hypotheses as stem-cell depletion in the radiotherapy field, heritable mutations within surviving stem cells, local vascular changes as well as a drug hypersensitivity reaction have been proposed to explain these reactions. In this report, we describe a non-small cell lung cancer patient treated with a carboplatin plus gemcitabine combination chemotherapy as first line followed by pemetrexed as second line therapy. Twenty-five years ago, she completed radiation therapy for breast cancer. Three days after the first cycle of pemetrexed, she presented with a radiation recall dermatitis. As EGFR-staining was negative, we rechallenged the patient with pemetrexed. Unfortunately, although less intense, we faced a recurrence of the skin reaction and pemetrexed was no longer continued.

Aged↗

Preoperative psychological global well being index (PGWBI) predicts postoperative quality of life for patients with non-small cell lung cancer managed with thoracic surgery.

OBJECTIVE: Non-small cell lung cancer (NSCLC) patients surgically treated often experienced a postoperative disability related to the surgery but did not benefit from a long-term survival advantage (postoperative death and relapse). Therefore, improvement of quality of life (QOL) for all NSCLC patients surgically treated is necessary and the assessment of factors influencing the short-term postoperative QOL is required. Therefore, a prospective study to assess the value of the psychological global well being index (PGWBI) to predict short-term postoperative QOL was conducted. PATIENTS AND METHODS: Prospective study in Academic Hospital's departments of thoracic oncology and surgery. Socio-demographic and clinical characteristics as well as PGWBI scores of 110 NSCLC patients referred for thoracic surgery were prospectively compared to postoperative QOL evaluated by the mean of the EORTC QLQ-C30 and LC13 questionnaires, completed before hospital discharge. RESULTS: Eighty-four patients completed the postoperative QOL questionnaires. In the univariate analysis, most of the PGWBI scores significantly correlated with the postoperative QOL. Also, patients living alone presented with a significantly higher risk of experiencing a poor postoperative QOL. In the multivariate analysis, patients showing a lower preoperative global health status as evaluated through the PGWBI experienced a statistically significant lower postoperative global QOL (hazard ratio (HR) = 1.39, 95% confidence interval (CI) 1.12-1.74, p = 0.003) as well as a reduced physical (HR = 1.32, 95% CI 1.09-1.60, p = 0.004) and emotional (HR = 1.21, 95% CI 1.06-1.39, p = 0.004) functions. CONCLUSIONS: A simple assessment of patients at higher risk of a poor short-term postoperative QOL could be easily performed preoperatively, taking into account certain socio-demographic factors and the results of the QOL assessment using the PGWBI.

Adult↗

Second-line treatment for advanced non-small cell lung cancer: a systematic review.

BACKGROUND: Among advanced non-small cell lung cancer (NSCLC) patients, most will resist or relapse after first-line chemotherapy. As a result, second-line therapy has been a major focus for clinical research. MATERIALS AND METHODS: A systematic review was carried out from 1996 to February 2005. RESULTS: Second-line chemotherapy provides pre-treated NSCLC patients with a clear survival advantage. Docetaxel 75 mg/m(2) every 3 weeks is the present standard second-line chemotherapy. Despite promising results regarding efficacy and toxicity in phase III studies, a docetaxel weekly schedule could not be recommended. Pemetrexed recently emerged as an alternative with similar efficacy and less toxicity. Although the combination of two drugs was not associated with a survival benefit when compared with single-agent chemotherapy, such regimens induced a dramatic increase in toxicities and therefore mono-chemotherapy remains the standard as second-line therapy. Finally, few new agents were reported with better results than those used previously and clinical research on second-line therapy currently focuses on combinations with targeted therapies. CONCLUSION: Second-line chemotherapy offers NSCLC patients a small but significant survival improvement. However, this field of clinical research needs further investigations in order to answer certain remaining questions especially concerning targeted therapies.

Antineoplastic Agents↗

Venobronchial fistula: an unusual complication of long-term central venous access.

A venobronchial fistula developed between the azygous vein and the upper aspect of the right main bronchus 12 months after completion of the treatment of a stage IIIB non-small-cell lung cancer in a 54-year-old man. The fistula contained the tip of the catheter placed for chemotherapy perfusion. The reported case presented risk factors previously identified for such a complication. In addition, some clinical particularities were present, suggesting new potent risk factors and some preventive means for safe long-term central venous catheterization.

Antineoplastic Agents↗

In vitro and in vivo methotrexate disposition in alveolar macrophages: comparison of pharmacokinetic parameters of two formulations.

MTX-liposomes, prepared with a polymerised core (LSP), were administered in anaesthetised rats by pulmonary instillation versus free drug. No toxicological effects were macroscopically observed. After each time point: 15, 30, 60 and 90 min, animals were humanely killed and analyses of radio-signal were done. This approach allowed recovery of MTX or breakdown products within biological samples. Previously, kinetics of MTX cellular uptake was performed to identify the cytotoxic concentration of drug formulation for human macrophage. Flow cytometry was set-up to characterise liposomal uptake by ex vivo pulmonary macrophage. Cells were isolated by bronchioloalveolar washes from animals. Results have shown clear different pharmacokinetic parameters between free MTX and the liposomal form of MTX. Unlike classical liposomes, which are mainly taken up by the reticulo-endothelial system, LSP-MTX was not targeted to spleen or kidney. The route of administration could be an explanation of this phenomenon. In addition, LSP-MTX was more retained by the lung tissue. Moreover, free form of the drug reaches easily lymph node. This latest result should be taken into consideration for neoplasic disease and more specifically when lymph nodes are a way for pulmonary metastasis. Finally, LSP-MTX should be tested in physio-pathological model of lung cancer to evaluate the influence of the variation of liposomal formulation pharmacokinetic parameters on the drug efficacy.

Animals↗

Comparative prognostic features of stage IIIAN2 and IIIB non-small-cell lung cancer patients treated with surgery after induction therapy.

OBJECTIVE: Induction Therapy (IT) before surgery emerged as a widely used strategy for IIIAN2 and selected IIIB NSCLC patients. However, IT is associated with a possible increase in postoperative complications. Consequently, selection of patients with the best chances to benefit from combined treatment is mandatory. METHODS: Study recorded demographics, treatment and outcome of consecutive patients treated with IT plus surgery for IIIAN2 or IIIB NSCLC. Survival was analysed by Kaplan-Meier and prognostic factors were analysed by log-rank and Cox regression. RESULTS: From 1993 to 2003, 155 patients (IIIAN2=95/IIIB=60) were treated. Complete resection was associated with a significant prolonged median survival both for IIIAN2 (20 vs 16 months, P=0.05) and IIIB (20 vs 15 months, P=0.02) patients. A lower risk of death for IIIAN2 patients was independently associated with postoperative mediastinal lymph node clearance (HR=0.45, 95%CI [0.25-0.81], P=0.009) and absence of postoperative complication (HR=0.54, 95%CI [0.31-0.93], P=0.02). Absence of blood vessel invasion only was identified as an independent predictor of a lower risk of death (HR=0.27, 95%CI [0.12-0.59], P=0.01) for stage IIIB patients. CONCLUSIONS: Besides similarities as the role of a complete R0 resection, treatment-related factors influence outcome of IIIAN2 patients while disease-related factors prevail on survival of IIIB patients, in whom the benefit of IT is unclear.

Adenocarcinoma↗

Combination of chemotherapy without platinum compounds in the treatment of advanced non-small cell lung cancer: a systematic review of phase III trials.

Hitherto, platinum-based combinations are world-wide accepted regimens in the treatment of advanced non-small cell lung cancer (NSCLC) due to a clear survival improvement using various platinum-based doublets in comparison with best supportive care only. However, treatment-allocated time and period with high grade toxicity could be considered as wasted from the patient point of view and the high toxicity induced by platinum-based doublets urges the research of alternate treatments. Newest cytotoxic compounds as so-called third generation drugs (i.e. vinorelbine, docetaxel, paclitaxel and gemcitabine) yield a better efficacy/toxicity ratio. Platinum-free doublet regimens based on these new drugs are expected to offer the patients an improved survival without decreasing his quality of life. Recent update of ASCO guidelines recommended that "for stage IV NSCLC, [...] non-platinum-containing chemotherapy regimens may be used as alternatives to platinum-based regimens in the first line." In spite of this recommendation, the case of non-platinum containing regimen is still debatable and this review deals with methodological statements highlighted by the reports of 14 recently reported randomised studies comparing non-platinum with platinum-based doublets (174 words).

Antineoplastic Combined Chemotherapy Protocols↗

Gefitinib (ZD1839, Iressa) in non-small-cell lung cancer: a review of clinical trials from a daily practice perspective.

Gefitinib (ZD1839) is the most widely studied targeting agent in the area of non-small-cell lung cancer (NSCLC). Gefitinib is an orally active epidermal growth factor receptor (EGFR) tyrosine kinase (TK) inhibitor. In order to assess the role of gefitinib in the management of NSCLC patients, we systematically reviewed published clinical trials from a daily practice perspective. A systematic research was made in the international medical literature. Gefitinib demonstrated a good tolerance and an encouraging efficacy in pretreated NSCLC patients in preclinical studies. These results were then confirmed in two phase II trials (IDEAL 1 and 2) involving more than 400 patients mostly pretreated with a platinum-containing regimen and docetaxel. All these results were reinforced by those of retrospective studies on patients enrolled in a compassionate use programme. Thus, two phase III trials in chemo-naive patients were initiated (INTACT 1 and 2). Unfortunately, the use of gefitinib with standard combination chemotherapy provided no survival benefit nor response rate or progression-free survival improvement over placebo. Furthermore, we also reviewed the results of studies interested in the characterization of predictive clinical or biological markers for response to gefitinib and discussed the results obtained with other EGFR inhibitors. The efficacy of gefitinib in the first-line setting of each stage of NSCLC has to be further studied through clinical trials. Furthermore, translational studies characterizing the molecular features involved in the response to anti-EGFR-targeted therapies are needed.

Adult↗

The place of patient satisfaction in quality assessment of lung cancer thoracic surgery.

STUDY OBJECTIVES: To compare the quality of non-small cell lung cancer (NSCLC) surgical care with patient satisfaction. DESIGN: Prospective study. SETTING: Academic hospital departments of thoracic oncology and surgery. PATIENTS AND METHODS: Patients presenting with recently diagnosed NSCLC and eligible for front-line thoracic surgery were eligible. Patient satisfaction was assessed using the Questionnaire of Satisfaction of Hospitalized Patients. Quality of surgical care was evaluated using an original score built accordingly to British Thoracic Society guidelines. Univariate analysis used parametric (Pearson correlation, t test) and nonparametric tests (Mann-Whitney U test) according to test conditions. Probability of survival was estimated using the Kaplan-Meier method. RESULTS: Seventy patients (mean age, 63.7 years) were included. Lobectomy was performed in 62 cases, and pneumonectomy was performed in 8 cases. In all, 28 patients had a postoperative complication. One-year survival rates for patients with stage I-II and stage IIIA NSCLC were 84% and 58%, respectively. Mean patient satisfaction was 78 +/- 13/100 and 69 +/- 13/100 for global staff and structure index, respectively (+/- SD). Mean score for quality of surgical care was 88.7/100 (range, 51 to 100). The absence of postoperative complication was significantly related to a high level of satisfaction regarding the structure (r = 0.30, p < 0.05). Other features of patient satisfaction did not show a significant correlation with the quality of the preoperative selection process or the surgical procedure itself (r < 0.20). CONCLUSIONS: Considering the lack of significant correlation, the present study does not support a shortcut between quality of care and patient satisfaction. Nonetheless, patient satisfaction should be integrated into rather than substituted for the quality of health-care assessment, which also needs further development.

Aged↗

[Impact of a brochure on pain destined for thoracic oncology patients].

OBJECTIVE: To assess the impact of a brochure supplied on pain and analgesic treatment on the knowledge, attitude, belief and perception of patients consulting oncology departments. METHOD: A prospective, comparative, study on patients consulting a thoracic oncology and a general oncology department, suffering from pain and motivating a treatment level > or = to 2 (WHO scale). A group of patients having been given a brochure (case) was compared with a group who had not been given the brochure (controls). The assessment questionnaire, developed according to the KABP (Knowledge, Attitudes, Belief, Practice) method, was distributed to the 2 groups. A second assessment was made 4 weeks after the patients having received the brochure. Visual analog scales (VAS) followed the intensity of the pain. RESULTS: Twenty-one cases and 33 controls were assessed. There was no modification in their belief (risk of addiction) but an improvement in their knowledge (duration of action of morphine agents, management of treatment, multi-disciplinary management). This improvement in knowledge was accompanied by improved control of pain: 2/3 of the patients exhibited a VAS < 1 at the time of the second assessment versus 1/3 during the initial assessment. CONCLUSION: Improvement, if only partial, in the patients' knowledge of pain and its treatment using a brochure, is one of the routes for optimising the management of pain.

Female↗

Video-assisted thoracoscopic management of recurrent primary spontaneous pneumothorax after prior talc pleurodesis: a feasible, safe and efficient treatment option.

OBJECTIVE: To assess the role of video-assisted thoracoscopic surgery (VATS) in the management of a recurrent primary spontaneous pneumothorax after a prior talc pleurodesis. METHODS: From 1996 to 2002, we retrospectively reviewed all patients who were treated for a recurrent primary spontaneous pneumothorax after a previous talc pleurodesis. Data on the talc procedure and the recurrent pneumothorax, delay between both, and operative features were studied. Conversion rate to a thoracotomy and postoperative complications as well as long-term outcome were reported. RESULTS: We collected 39 patients (28 male) with a median age of 25 years (15-41 years). The initial procedure consisted of thoracoscopic talc poudrage in all cases. The median delay between the talc procedure and the recurrence was 23 months [10 days-13 years]. Size of recurrence involved 10-80% of the hemithorax. The VATS procedure was successfully achieved in 27 patients (69%) while 12 required conversion to a thoracotomy. The main cause for conversion was the presence of dense pleural adhesion at the mediastinal part of the pleural cavity. Postoperative morbidity was limited to pleural complications in the VATS group (n=6, 22%). Median follow-up was 26 months [10-38 months]. One patient treated by VATS developed a partial recurrent pneumothorax at 12 months with a favorable outcome without further surgery. CONCLUSIONS: Feasibility, safety and efficacy of VATS for management of recurrent primary spontaneous pneumothorax following thoracoscopic talc poudrage are strongly suggested.

Adolescent↗

Prognostic value of combination of Cyfra 21-1, CEA and NSE in patients with advanced non-small cell lung cancer.

OBJECTIVE: To assess the value of Cyfra 21-1, carcino-embryonic antigen (CEA) and neuron-specific enolase (NSE) combined, all three together as prognostic factors in advanced stage non-small cell lung cancer (NSCLC) patients. PATIENTS AND METHODS: Serum samples from untreated NSCLC patients were prospectively collected. All assays were performed using commercial kits blind to clinical information. Serum levels of CEA, NSE and Cyfra 21-1 higher than 10, 13 and 3.5 ng/ml, respectively, were considered as elevated. RESULTS: 264 patients (men, 87%), with Performans Status (PS) of 0/1 in 80% and stage IV disease in 65% were studied. Cyfra 21-1, CEA and NSE were elevated in 52.5%, 41.8% and 33.2% of patients, respectively. Median survival was 9 months (range, 1-77). Cyfra 21-1, age, PS, stage as well as the combination of the three markers together correlated with prognosis in univariate analysis. Multivariate analysis demonstrated that age > or = 65 years (HR = 1.3 [1.02-1.70], p = 0.03), PS 2 (HR = 4.3 [3.13-6.11], p < 0.0001), Cyfra 21-1 > or = 3.5 ng/ml (HR = 1.3 [1.06-1.78], p = 0.01) and the combination of the three markers (HR = 1.06 [1.009-1.13], p = 0.02) remained prognostic determinants. CONCLUSION: Combining Cyfra 21-1, NSE and CEA correlated with prognosis in a significant and independent manner.

Adult↗

Gemcitabine-induced severe pulmonary toxicity.

Gemcitabine is a relatively new deoxycytidine analog (2',2'-difluorodeoxycytidine) with structural similarities to cytosine arabinoside (Ara-C). Activity of gemcitabine is demonstrated in the treatment of many solid tumors, like pancreas, ovarian and nonsmall cell lung cancer (NSCLC). Although gemcitabine is considered as a drug with a good safety profile, cases of gemcitabine-induced severe pulmonary toxicity (GISPT) were reported as for Ara-C. We performed a systematic review of reported cases on the GISPT. Twenty-nine clinical trials especially interesting NSCLC patients (21) and 21 reported cases recording 40 patients were analyzed. The incidence of the GISPT varies from 0 to 5%. The clinical presentation is a subacute clinical syndrome and is frequently nonspecific. The predominant radiographic pattern on chest X-ray are reticulo-nodular interstitial infiltrates. It was postulated that the physio-pathological mechanism of the GISPT was an inflammatory reaction of the alveolar capillary wall cytokine-mediated, which created an abnormal permeability of its membrane. After the differential diagnosis were ruled out, the discontinuation of the drug and the early initiation of steroids and diuretics are the most frequently performed treatments. Under these conditions, the outcome was favorable in a delay of few days generally for a majority of patients but 20% of patients died. Some risk factors, as a previous pulmonary disease or a previous thoracic irradiation, for the occurrence of the GISPT were proposed. GISPT is rare but sometimes fatal. Its a necessity to increase awareness about it to enhanced an early and suitable management of patients developing such a toxicity after gemcitabine administration.

Antimetabolites, Antineoplastic↗

Vascular stenting for palliation of superior vena cava obstruction in non-small-cell lung cancer patients: a future 'standard' procedure?

BACKGROUND: Stenting is a relatively new option in the management of superior vena cava obstruction (SVCO), but available data often concern non-malignant and/or various malignant diseases. OBJECTIVE: The aim of this study was to assess the efficacy of vascular stenting as a first-choice treatment in SVCO in the exclusive setting of NSCLC. PATIENTS AND METHODS: Retrospective study of NSCLC patients with SVCO treated in the past year. Demographic data, disease characteristics, etiologic and palliative treatment (use of vascular stenting) were recorded as well as treatment outcome and survival. RESULTS: 17 patients were recruited. Eight had vascular stenting while 9 did not. Except for stenting, there was no difference between the two groups (median age 54 years; 80% men; 53% stage IIIB and 47% stage IV). Stenting (median length 60 mm) achieved complete resolution of SVCO more frequently (75 vs. 25%, p = 0.05) and faster (2 vs. 21 days, p = 0.002) without immediate or delayed complication. All patients with stents received anticoagulation therapy. Relapse rate after complete response (33 g, 50%, p = 0.6) was lower and time to relapse (6.5 g, 2 months) was longer for patients undergoing stenting, without reaching statistical significance. Median overall survival was not statistically different (8 and 5 months, p = 0.06). CONCLUSIONS: This study demonstrated the effectiveness of vascular stenting for SVCO in NSCLC patients. The high response rate, quick effect and safety of vascular stenting make this palliative treatment a candidate as a potential standard procedure. The results, however, must be confirmed in a prospective randomized trial including quality of life assessment.

Adult↗