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Jean-Louis Pujol

Publications and source records attributed to Jean-Louis Pujol.

11 recordsLinked to original sources
PubMed2006

Should chemotherapy combinations for advanced non-small cell lung cancer be platinum-based? A meta-analysis of phase III randomized trials.

BACKGROUND: Non-platinum regimens have been proposed as an alternative to the platinum-based combinations for treatment of advanced non-small cell lung cancer. However, conflicting results were reported. METHODS: Meta-analysis of phase III trials randomizing platinum-based versus non-platinum combinations as first-line chemotherapy with 1-year survival rate as a primary endpoint. Fourteen trials have been identified. Experimental arms were gemcitabine/vinorelbine (n=4), gemcitabine/taxane (n=7), gemcitabine/epirubicin (n=1), paclitaxel/vinorelbine (n=1), and gemcitabine/ifosfamide (n=1). The comparator was a doublet of a platinum compound plus a third generation agent for all but two studies (triplets). Updated data were available for 13 studies. The Peto and Yusuf method was used to generate odds ratios (OR). All tests are two-sided. RESULTS: A statistical heterogeneity was detected when the 13 studies were analyzed. Considering that current guidelines recommend platinum-based doublets as standard therapy we therefore limited the meta-analysis to the set of 11 phase III studies which used a platinum-based doublet (2298 and 2304 patients in platinum-based and non-platinum arms, respectively). No significant heterogeneity was detected in this consistent group of studies. Patients treated with a platinum-based regimen benefited from a statically significant reduction in the risk of death at 1 year (OR: 0.88, 95% CI 0.78-0.99; p=0.044) and a lower risk of being refractory to chemotherapy (OR: 0.87, 0.73-0.99; p=0.049). Forty-four (1.9%) and 29 (1.3%) toxic-related deaths were reported for platinum-based and non-platinum regimens, respectively (OR: 1.53; 0.96-2.49, p=0.08). An increased risk of grade 3-4 gastro-intestinal and hematological toxicity for patients receiving platinum-based chemotherapy was statistically demonstrated. There was no statically significant increase in risk of febrile neutropenia, OR=1.23 (0.94-1.60, p=0.063). CONCLUSION: A platinum-based doublet induced a statically significant reduction in the risk of death when compared with non-platinum chemotherapy without inducing an unacceptable increase in toxicity.

Antineoplastic Combined Chemotherapy Protocols↗
PubMed2005

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↗
PubMed2005

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↗
PubMed2003

[Small cell lung carcinoma].

In most of the cases, small cell lung cancer is diagnosed at the extensive disease stage. Regarding the micrometastatic process, it might be considered as a metastatic disease in almost all cases. Therefore, chemotherapy is the cornerstone of small cell lung cancer therapy. Cisplatin and VP-16-based combinations are recommended. Chemotherapy alone remains the only recommended therapy in extensive disease, whereas radiochemotherapy is the treatment of limited disease. Concomitant or alternate modalities are acceptable standards in this latter setting. Prophylactic cranial irradiation is recommended for complete responders with initially limited disease.

Antineoplastic Combined Chemotherapy Protocols↗
PubMed2003

Neuroendocrine and cytokeratin serum markers as prognostic determinants of small cell lung cancer.

This retrospective study aimed at determining the prognostic significance of neuroendocrine markers chromogranin A (CgA), pro-gastrin releasing peptide (ProGRP) and neuron-specific enolase (NSE), together with the cytokeratin 19 marker CYFRA 21-1 in small cell lung cancer (SCLC). A total of 148 histologically proven and previously untreated SCLC patients were included. Among them 118 patients received a cisplatin-etoposide combination or cisplatin-etoposide-cyclophosphamide-4'-epidoxorubicin combination. All tumour markers were tested using immunoradiometric assays except for ProGRP which was tested using an enzyme-linked immunosorbent assay. The thresholds for marker serum titrations were 53 pg/ml, 65, 17, and 3.6 ng/ml for ProGRP, CgA, NSE and CYFRA 21-1 respectively. Univariate analysis showed that patients affected by one of the following characteristics proved to have a significant shorter survival in comparison with the opposite status of each variable: age over 63 years, extensive-stage, serum LDH level higher than 600 U/l, serum NSE level higher than 17 ng/ml, serum CgA level higher than 65 ng/ml and serum CYFRA 21-1 level higher than 3.6 ng/ml. In addition, there was a trend towards a statistical significance for a high serum alkaline phosphatase level and a performance status equal to or worse than two. The following variables were independent determinants of a poor outcome: a poor performance status (hazard ratio [95% confidence interval]: 1.51 [1.02-2.22]), a high CgA level (HR: 1.61 [1.06-2.45]), a high CYFRA 21-1 level (HR: 2.10 [1.40-3.14]) and an age older than 63 years (HR: 1.68 [1.14-2.48]). When the multivariate analysis was restricted to patients receiving a cisplatin-etoposide-based chemotherapy, the same variables were prognostic determinants with nearly similar hazard ratios. In conclusion, aside classical variables such as age and performance status, high serum CYFRA 21-1 and high serum CgA level in SCLC are both prognostic determinants of prognosis, in particular in patients receiving conventional chemotherapy consisting of cisplatin and etoposide-based combinations.

Adult↗
PubMed2003

[Standards, Options and Recommendations for the management of non-small cell lung carcinoma patients].

CONTEXT: The "Standards, Options and Recommendations" (SOR) project, started in 1993, is a collaboration between the Federation of French Cancer Centers (FNCLCC), the 20 French cancer centers and specialists from French public university and general hospitals and private clinics. Its main objective is the development of clinical practice guidelines to improve the quality of health care and outcome for cancer patients. The methodology is based on literature review and critical appraisal by a multidisciplinary group of experts, with feedback from specialists in cancer care delivery. OBJECTIVES: To develop, according to the definitions of the Standards, Options and Recommendations, clinical practice guidelines for the management of non small cell lung carcinoma patients. METHODS: Data were identified by searching Medline and the personal reference lists of members of the expert groups, then submitted for review to independent reviewers. This is a short version of the SOR guideline covering diagnosis, treatment and follow-up and includes the algorithms for the management of patients with non-small cell lung cancer.

Algorithms↗
PubMed2002

Combination chemotherapy without cisplatin in the treatment of advanced non-small cell lung cancer.

Cisplatin-based combinations are standard regimens in the treatment of advanced non-small cell lung cancer. Survival improvement has been achieved using this therapy. However, the high toxicity induced by cisplatin-based doublets urges the research of alternate treatments. Newest cytotoxic compounds yield a better efficacy-toxicity ratio. Platinum-free doublet regimens based on new drugs are expected to offer the patient an improved survival without decreasing his quality of life. Treatment-allocated time and period with high grade toxicity could be considered as wasted from the patient point of view. QUALY methods based on time without symptoms and toxicity allow the accurate evaluation of this end-point. This brief state-of-the-art deals with methodological statements highlighted by the first publications of randomized studies comparing non-platinum-based doublets with either single-drug chemotherapy or standard cisplatin-based doublets.

Antineoplastic Combined Chemotherapy Protocols↗
PubMed2002

[2000 Standards, Options and Recommendations for prognostic value of oncogenes and tumor suppressor genes in non small cell lung cancer].

CONTEXT: The "Standards, Options and Recommendations" (SOR) project, started in 1993, is a collaboration between the Federation of French cancer centers (FNCLCC), the 20 French cancer centers, and specialists from French public universities, general hospitals and private clinics. The main objective is the development of clinical practice guidelines to improve the quality of health care and the outcome of cancer patients. The methodology is based on a literature review and critical appraisal by a multidisciplinary group of experts, with feedback from specialists in cancer care delivery. OBJECTIVES: To develop clinical practice guidelines for non small cell lung cancer patients according to the definitions of the Standards, Options and Recommendations project. METHODS: Data were identified by searching Medline , web sites, and using the personal reference lists of members of the expert groups. Once the guidelines were defined, the document was submitted for review to independent reviewers. RESULTS: This article presents the chapter "Prognosis significance of oncogenes and tumor suppressor genes" from the full report "Standards, Options and Recommendation for non small cell lung cancer" validated in August 2000. The main recommendations are: 1) No clear clinical prognostic value of oncogenes and tumor suppressor genes (p53, bcl-2, Ki-ras, c-erbB-2, Rb, p16) in non small cell lung cancer, can be established from the available evidences (standard, level of evidence C). 2) Prospective multicenter studies should be performed to assess prognostic significance of oncogenes and tumor suppressor genes in non small cell lung cancer.

Carcinoma, Non-Small-Cell Lung↗
PubMed2002

[Platinum-free gemcitabine-based combinations: an alternative to conventional chemotherapy of non-small-cell lung cancers?].

Cisplatin-based combinations are standard regimens in the treatment of advanced non-small cell lung cancer. Survival improvement has been achieved using this therapy. However, the high toxicity induced by cisplatin-based doublets urges the research of alternate treatments. Newest cytotoxic compounds yield a better efficacy/toxicity ratio. Platinum-free doublet regimens based on new drugs are expected to offer the patient an improved survival without decreasing his quality of life. Treatment-allocated time and period with high grade toxicity could be considered as wasted from the patient point of view. Qualy methods based on time without symptoms and toxicity (TWiST) allow the accurate evaluation of this end-point. This brief state-of-the-art deals with methodological statements highlighted by the first publications of randomized studies comparing gemcitabine--navelbine or gemcitabine--taxane combinations with either single-drug chemotherapy or standard chemotherapy based on cisplatin. The choice of end-points is discussed.

Antimetabolites, Antineoplastic↗