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T Le Chevalier

Publications and source records attributed to T Le Chevalier.

At least 37 records · Page 2Linked to original sources
PubMed2002

Patterns of failure after prophylactic cranial irradiation in small-cell lung cancer: analysis of 505 randomized patients.

BACKGROUND: Prophylactic cranial irradiation (PCI) has a beneficial effect on overall survival in patients with small-cell lung cancer (SCLC) in complete remission as shown in a worldwide meta-analysis. The current analysis aimed to evaluate PCI effects on patterns of failure in this patient category. PATIENTS AND METHODS: The Institut Gustave-Roussy coordinated two parallel randomized studies including a total of 511 patients with SCLC. Patients were randomly assigned to either PCI (24 Gy in eight fractions and 12 days) or no PCI. Patterns of failure were analyzed according to (i) total event rates and (ii) isolated first site of relapse using a competing risk approach. RESULTS: Five hundred and five patients were analyzed. The 5-year cumulative rate of brain metastasis as an isolated first site of relapse was 37% in the control group and 20% in the PCI group (P < 0.001). The overall 5-year rates of brain metastasis were 59% and 43%, respectively [relative risk (RR) 0.50; P < 0.001]. The 5-year overall survival rates were 15% in the control group and 18% in the PCI group (RR 0.84; P = 0.06). CONCLUSIONS: PCI decreased significantly the risk of brain metastasis. Other events were not influenced. The relative death risk reduction was of borderline significance. Results reported as isolated first cause of failure and subsequent competing events may explain why a major treatment effect on brain metastases rate has a rather moderate effect on survival.

Adult↗
PubMed2002

Phase I-II and pharmacokinetic study of gemcitabine combined with oxaliplatin in patients with advanced non-small-cell lung cancer and ovarian carcinoma.

BACKGROUND: The aim of this study was to determine the toxicity profile, the recommended dose (RD) and the pharmacokinetic parameters, and to evaluate the antitumor activity of gemcitabine combined with oxaliplatin in patients with advanced non-small-cell lung cancer (NSCLC) and ovarian carcinoma (OC). METHODS: Gemcitabine was administered as a 30-min infusion followed by a 2-h infusion of oxaliplatin, repeated every 2 weeks. Doses of gemcitabine and oxaliplatin ranged from 800 to 1500 and 70 to 100 mg/m(2), respectively. RESULTS: Forty-four patients (26 males, 18 females; median age 55 years) including 35 NSCLC (five platinum pretreated) and nine OC patients (all platinum pretreated) received a total of 355 cycles. All patients were evaluable for toxicity. No dose-limiting toxicity at any dose level occurred during the first two cycles; therefore, the highest dose-level of gemcitabine (1500 mg/m(2)) and oxaliplatin (85 mg/m(2)) was considered as the RD. Hematological toxicity was moderate amongst the 22 patients treated (167 cycles) at that dose level. Thirteen cycles were associated with grade 3-4 non-febrile neutropenia in six patients, and eight cycles with grade 3-4 thrombocytopenia in two patients. Other toxicities were mild to moderate, consisting of asthenia and peripheral neurotoxicity. Four of the 35 patients treated with oxaliplatin 85 mg/m(2) experienced grade 3 neurotoxicity requiring treatment discontinuation at cycle 10. In the range of the doses used, gemcitabine and its main metabolite 2',2'-difluorodeoxyuridine appeared not to be affected by oxaliplatin 70-100 mg/m(2). Of the 44 patients evaluable for activity, 12 NSCLC patients experienced objective responses (one complete and 11 partial responses) and three OC patients showed tumor stabilization lasting for 6 months with a 50% decrease of CA 125 level. Two partial responses (NSCLC) and one tumor stabilization (OC) occurred in platinum-resistant patients. CONCLUSIONS: The combination of gemcitabine and oxaliplatin could be safely administered on an out-patient schedule in patients with advanced NSCLC and OC. The RD was gemcitabine 1500 mg/m(2) and oxaliplatin 85 mg/m(2) every 2 weeks. Promising antitumor activity was reported in patients with NSCLC and platinum-pretreated OC, and thus, deserves further evaluation.

Adenocarcinoma↗
PubMed2002

Patterns of failure in a randomized trial of adjuvant chemotherapy in postmenopausal patients with early breast cancer treated with tamoxifen.

BACKGROUND: We studied the effect of adjuvant anthracycline-based chemotherapy in postmenopausal patients with resected early breast cancer treated with adjuvant tamoxifen. PATIENTS AND METHODS: The trial included 835 patients with either axillary lymph node involvement, or tumors with histological grade II or III. They were randomized after local surgery to receive either tamoxifen (TAM group) or tamoxifen plus chemotherapy (TAM-CT group) consisting of six courses of 5-fluorouracil, doxorubicin and cyclophosphamide (FAC), or 5-fluorouracil, epidoxorubicin and cyclophosphamide (FEC). Radiotherapy was given after completion of adjuvant chemotherapy in the TAM-CT group and after surgery in the TAM group. RESULTS: The 5-year disease-free survival (DFS) rates were 73% in the TAM group and 79% in the TAM-CT group (log-rank test, P = 0.06). The 5-year overall survival rates were 82% and 87%, respectively (P = 0.06). The 5-year distant metastasis rates were 22% and 16% (P = 0.02), and the 5-year local recurrence rates were 6% and 4%, respectively (P = 0.23). There were no significant differences for contralateral breast cancer or other new primary malignancies. Chemotherapy tended to be more effective for patients who had tumors without estrogen receptors (trend test, P = 0.05). CONCLUSIONS: Anthracycline-based chemotherapy administered to postmenopausal patients receiving adjuvant tamoxifen gave a borderline significant benefit on overall and DFS, mainly by a reduction in distant metastases. Delaying radiotherapy after six courses of chemotherapy did not affect local control after up to 10 years of follow-up.

Aged↗
PubMed2001

Patterns of relapse of N2 nonsmall-cell lung carcinoma patients treated with preoperative chemotherapy: should prophylactic cranial irradiation be reconsidered?

BACKGROUND: Although it induces a relevant reduction in the risk of both visceral metastases and locoregional recurrences, the combination of chemotherapy and surgery only marginally improves the survival of patients with Stage IIIA(N2) (International Union Against Cancer staging and classification system) nonsmall-cell lung carcinoma (NSCLC). The purpose of the current study was to analyze the patterns of relapse in these patients. METHODS: In this study, the authors compared the patterns of relapse in 81 patients with clinically detectable N2 NSCLC who had been treated with preoperative chemotherapy with the relapse patterns of 186 comparable patients who had been treated with primary surgery. Clinically detectable N2 (cN2) denotes mediastinal lymph node enlargement on computed tomography scan, which then is confirmed by mediastinoscopy. RESULTS: Overall 20% of patients developed a locoregional recurrence. Chemotherapy decreased the risk of visceral metastasis as 28% of the patients preoperatively treated and 38%of those not treated with preoperative chemotherapy presented a visceral metastasis (P < 0.05). Preoperative chemotherapy and adenocarcinoma subtypes were associated with a higher rate of brain metastasis (P < 0.05). Thirty-two percent of the patients treated preoperatively and 18% of those not treated with preoperative chemotherapy presented a brain metastasis (P < 0.05), which was isolated in 22% and 11% of the patients, respectively (P < 0.05). CONCLUSION: The current study found that preoperative chemotherapy for cN2 decreases the risk of visceral metastasis but is associated with a high rate of isolated brain metastases. Prophylactic cranial irradiation may need to be reinvestigated in clinical trials, especially in patients who present with an adenocarcinoma.

Adenocarcinoma↗
PubMed2001

Etoposide plus cisplatin with or without the combination of 4'-epidoxorubicin plus cyclophosphamide in treatment of extensive small-cell lung cancer: a French Federation of Cancer Institutes multicenter phase III randomized study.

BACKGROUND: The combination of etoposide plus cisplatin (EP) is considered to be standard therapy for small-cell lung cancer (SCLC). To determine whether drug intensification improves survival of patients with extensive SCLC, we compared this treatment with a four-drug regimen containing EP plus cyclophosphamide and 4'-epidoxorubicin (PCDE). METHODS: In a phase III clinical trial organized by the French Federation of Cancer Institutes, patients were randomly assigned to receive either EP (n = 109; etoposide at a dose of 100 mg/m(2) on days 1-3 plus cisplatin at 100 mg/m(2) on day 2) or PCDE (n = 117; etoposide and cisplatin given as in EP plus cyclophosphamide at 400 mg/m(2) on days 1-3 and 4'-epidoxorubicin at 40 mg/m(2) on day 1) every 4 weeks. Both groups received a total of six cycles. Survival differences were analyzed by Wilcoxon and log-rank tests. Associations of treatment group and putative prognostic variables with survival were tested in the Cox proportional hazards model. Quality of life was assessed from the responses to the European Organization for Research and Treatment of Cancer quality-of-life questionnaire (C30, health status and lung cancer module 13). All statistical tests were two-sided. RESULTS: Patients in the PCDE arm had a statistically significant higher frequency of combined complete plus partial responses compared with those in the EP arm (21% plus 55% versus 13% plus 48%, respectively; P =.02 for difference in combined objective responses). Patients in the PCDE arm survived longer than those in the EP arm (1-year survival rate: 40% and 29%, respectively; median survival: 10.5 and 9.3 months, respectively; log-rank P =.0067). In the Cox model, the relative risk of death for patients in the PCDE arm compared with those in the EP arm was 0.70 (95% confidence interval = 0.51 to 0.95); the disease also progressed more slowly in patients in the PCDE arm. Hematologic toxicity was higher in the PCDE arm (22% with documented infections compared with 8% in the EP arm; P =.0038), and the toxicity-related death rate was 9% in the PCDE arm versus 5.5% in the EP arm (P =.22). The global health status showed similar improvement in both arms during treatment. CONCLUSION: Compared with the EP regimen, the PCDE regimen yielded higher response rates and better survival rates in patients with extensive SCLC without affecting the quality of life of the patients during chemotherapy.

Adult↗
PubMed2001

European perspectives on paclitaxel/platinum-based therapy for advanced non-small cell lung cancer.

Paclitaxel (Taxol; Bristol-Myers Squibb Company, Princeton, NJ) has shown high clinical antitumor activity in several tumor types, including ovarian, breast, and lung carcinoma. Preclinical studies have shown that paclitaxel has an additive effect when combined with platinum compounds. Early clinical trials confirmed these data and established the dose range for both drugs. In recent years, several studies were developed in Europe using the combination of paclitaxel and platinum in non-small cell lung cancer, and four large randomized trials have been completed in Europe. The first study compared paclitaxel/cisplatin with teniposide/cisplatin, which was the control arm of the European Organization for Research and Treatment of Cancer at that time. The second study evaluated the benefit of the addition of paclitaxel to cisplatin. The third study compared paclitaxel/cisplatin with paclitaxel/carboplatin, and the fourth compared two doses of paclitaxel combined with carboplatin. Another large randomized study is currently being performed by the European Organization for Research and Treatment of Cancer. Combinations using paclitaxel-based regimens in the preoperative setting are under investigation. An ongoing European Organization for Research and Treatment of Cancer trial compares surgery with radiotherapy following various induction chemotherapy combinations, among which paclitaxel/platinum is one of the most frequently used. Another induction regimen is currently being evaluated by the University Medical School of Essen and Institut Gustave Roussy in Villejuif, France. In this trial, paclitaxel/cisplatin is delivered before etoposide/cisplatin and concurrent radiotherapy followed by surgery in locally advanced non-small cell lung cancer. Preclinical studies underline the radiosensitizing effect of paclitaxel, and many clinical studies are being conducted with radiotherapy in association with paclitaxel alone or in combination with platinum compounds. The use of paclitaxel in regimens without platinum and in triplet combinations is also being studied, and the optimal manner in which to administer this active agent clearly is of interest.

Antineoplastic Combined Chemotherapy Protocols↗
PubMed2001

Carcinoma of an unknown primary site: a chemotherapy strategy based on histological differentiation--results of a prospective study.

BACKGROUND: To evaluate the efficacy and toxicity of a chemotherapy strategy based on histological differentiation, for patients with carcinoma of unknown primary site. PATIENTS AND METHODS: Forty-eight patients were prospectively included in the trial. Thirty patients with poorly-differentiated carcinoma or poorly-differentiated adenocarcinoma (group A) received a combination of cisplatin and etoposide. Patients with a responsive or stable disease after two cycles received the same regimen plus bleomycin, ifosfamide and G-CSF. Eighteen patients with well- or moderately-differentiated carcinoma (group B) received cisplatin, continuous infusion 5-fluorouracil (5-FU) and alpha-interferon. Treatment was maintained in case of response or stable disease for up to six cycles. RESULTS: The overall response rate (RR) for the entire group is 43% (95% confidence interval (CI): 35.9%-50.1%): seven CR and five PR in group A (RR = 40%) and six CR and two PR in group B (RR = 44%). Grade 4 leucopenia was observed in 22 (46%) patients and sepsis in 3 (6%). Median survival is 9.4 months (range 5-13.7 months) and 16.1 months (range 11.8 20.3 months), respectively. CONCLUSIONS: This chemotherapy strategy is one way to achieve high response rates, particularly for patients with well- or moderately-differentiated adenocarcinoma usually considered poorly chemosensitive.

Adenocarcinoma↗
PubMed2001

Do all patients with advanced non-small-cell lung cancer benefit from cisplatin-based combination therapy?

BACKGROUND: Platinum-based chemotherapy has been shown to be effective in improving survival and quality of life in advanced non-small-cell lung cancer (NSCLC) patients. The objective of this study was to identify patients more likely to benefit from chemotherapy in order to avoid the indiscriminate treatment of all patients. PATIENTS AND METHODS: A multivariate analysis of survival was performed using the database of the European randomized phase III trial that compared vinorelbine (navelbine) (NVB), vinorelbine-cisplatin (NVB-P) and vindesine-cisplatin (VDS-P) in 612 patients with inoperable NSCLC (stage III or IV). Interactions between treatment and the prognostic factors singled out by the Cox procedure were specifically tested. RESULTS: The performance status (PS) was the only significant interaction among the selected prognostic factors and treatment. Subgroup analysis showed that the advantage obtained with NVB-P predominantly concerned PS 0-1 patients, whose median survival lasted 43 weeks (95% confidence interval (95% CI): 39-50 weeks) with a one-year survival rate of 38% (95% CI: 31%-46%) versus 36 weeks (95%, CI: 30-40 weeks) and 34% (95% CI: 27%-42%) for NVB alone, and 33 weeks (95% CI: 30-39 weeks) and 29% (95% CI: 22%-36%) for VDS-P. In sharp contrast, survival in PS 2 patients was similar (median 18 weeks) (NVB-P 95% CI: 11-34 weeks; NVB 95% CI: 11-35 weeks; VDS-P 95% CI: 14-32 weeks) whatever the treatment. CONCLUSION: PS 2 patients with advanced NSCLC might not benefit from cisplatin combination therapy.

Aged↗
PubMed2001

Benefit of surgery after chemoradiotherapy in stage IIIB (T4 and/or N3) non-small cell lung cancer.

OBJECTIVE: The purpose of this study was to evaluate postchemoradiotherapy surgery in stage IIIB non-small cell lung cancer. METHODS: Forty patients with stage IIIB non-small cell lung cancer were included in this phase II study. A preoperative diagnosis of stage IIIB cancer was based on mediastinoscopy or a thoracotomy in all patients. Induction treatment included two cycles of cisplatin (100 mg/m(2), day 1), 5-fluorouracil (1 g/m(2), days 1-3), and vinblastine (4 mg/m(2), day 1) combined with 42 Gy of hyperfractionated radiotherapy delivering 21 Gy in two sessions. Patients with a clinical response were offered surgery. RESULTS: The minimum follow-up for survivors was 48 months. Thirty patients had a T4 lesion and 18 had N3 disease. Twenty-nine patients (73%) had a clinical objective tumor response after induction treatment. These 29 patients underwent thoracotomy, and a complete resection was performed in 23 (58%). Two postoperative deaths occurred (7%). Four patients had a pathologic complete response at the time of surgery (10%). The 5-year survival is 19% for the overall population. When only patients who had persistent viable tumor cells at surgery are considered (n = 25), the 5-year survival is 28%. The 5-year survival is 42% for patients having no mediastinal lymph node involvement at the time of surgery and being treated with complete resection. CONCLUSION: This study shows that surgery, when feasible, is associated with a 28% long-term survival for patients in whom chemoradiotherapy alone fails to control disease.

Adult↗
PubMed2001

Long term analysis of survival in the European randomized trial comparing vinorelbine/cisplatin to vindesine/cisplatin and vinorelbine alone in advanced non-small cell lung cancer.

In the period 1989-1991, 612 patients with inoperable stage IIIA/B and IV non-small cell lung cancer (NSCLC) were randomized in a phase III trial comparing three chemotherapy regimens. Survival data at five and six years of follow-up confirm the overall benefit of treatment with a combination of vinorelbine and cisplatin compared to vindesine plus cisplatin or vinorelbine alone. Of the 612 patients randomized at the start of the study, 17 have survived beyond five years. Of these patients, eight had entered the trial with metastatic disease. Multivariate analysis to detect prognostic factors suggested a possible interaction between the effect of having cisplatin in the chemotherapy received and baseline performance status. Subgroup analysis subsequently confirmed that the survival benefit of the vinorelbine plus chemotherapy regimen is evident only in patients with initial World Health Organization performance status (PS) of 0-1. Among these patients, the one-year survival rate is 38% for the vinorelbine/cisplatin arm, 29% for vindesine/cisplatin and 34% for vinorelbine alone. The corresponding figures for median survival are 43, 33 and 36 weeks. Among inoperable NSCLC patients with a PS of 2, who appear from this trial not to have benefited from the presence of cisplatin in their chemotherapy, use of single agent vinorelbine is an appropriate treatment option.

Antineoplastic Agents, Phytogenic↗
PubMed2001

[Standards, options and recommendations for the management of locally advanced non small cell lung carcinoma].

CONTEXT: The "Standards, Options and Recommendations" (SOR) project, started in 1993, is a collaboration between the Federation of the French Cancer Centres (FNCLCC), the 20 French Cancer Centres 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 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 clinical practice guidelines according to the definitions of the Standards, Options and Recommendations project for the management of locally advanced non small cell lung carcinoma. METHODS: Data were identified by searching Medline and the personal reference lists of members of the expert groups. Once the guidelines were defined, the document was submitted for review to independent reviewers and to the medical committees of the 20 French Cancer Centres. RESULTS: The main recommendations are: 1) The management of the locally advanced non small cell lung carcinoma has two main goals: firstly to obtain local control of the disease (or to at least delay local progression in order to improve the survival or relapse free survival), and secondly to prevent the development of metastases. 2) There is a consensus that locally advanced non small cell lung carcinoma should be irradiated. External beam radiotherapy should be of optimal quality and delivered at a minimal dose of 60 Gy by standard fractionation. For patients with a poor life expectancy, this can be delivered as a split-course or hypofractionated scheme. 3) Treatment for patients with a performance status of 0-1 should consist of short duration induction chemotherapy (with a least two drugs one of which must be cisplatin), combined sequentially with conventional radiotherapy. 4) Surgery is contraindicated in extensive N3 disease. Combined radio-chemotherapy (adjuvant or neoadjuvant) is not indicated outside clinical trials. Surgery is justified in stage N2 disease as good local control can be achieved. T4-N0 disease should be treated surgically with curative intent.

Adult↗
PubMed2001

[Standards, Options and Recommendations for the management of stage I or II primary bronchial cancers treated exclusively with radiotherapy].

CONTEXT: The 'Standards, Options and Recommendations' (SOR) project, started in 1993, is a collaboration between the Federation of the French Cancer Centres (FNCLCC), the 20 French cancer centres 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 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 clinical practice guidelines according to the definitions of the Standards, Options and Recommendations project for the management of stage I and II non small cell lung carcinoma treated by radiotherapy alone. METHODS: Data were identified by searching Medline and personal reference lists of members of the expert groups. Once the guidelines were defined, the document was submitted for review to independent reviewers, and to the medical committees of the 20 French cancer centres. RESULTS: The main recommendations for the management of stage I and II non small cell lung carcinoma treated by radiotherapy alone are: 1) The curative external irradiation with a continual course is an alternative to surgery only in the case of medically inoperable tumors or because the patient refuses surgery; 2) The external irradiation of the primary tumor only without the mediastinum could be proposed in peripheral stage IA. In proximal stage IA and IB, external irradiation should be carried out only as part of prospective randomised controlled trials comparing a localised irradiation of the primary tumor with a large irradiation of the mediastinum and the primary tumor. The treated volume must include the macroscopic tumoral volume with or without the microscopic tumoral volume and with a security margin from 1.5 to 2 cm; 3) There is a benefit to delivering a total dose in the primary tumor higher than 60 Gy in so far as the proposed irradiation, taking into account the respiratory function, does not increase the likelihood of severe adverse events due to radiation; and 4) The change in fractionation, the radiochemotherapy combination, the endobronchial brachytherapy with high dose rate alone or with external irradiation could be proposed only as part of prospective controlled trials for tumors classified as stage IB or II.

Aged↗