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T Le Chevalier

Publications and source records attributed to T Le Chevalier.

At least 109 records · Page 6Linked to original sources
PubMed1995

Impact of chemotherapy on survival in locally advanced non-small cell lung cancer: the Gustave-Roussy experience.

The high local and distant recurrence rate after thoracic radiation deserves the development of new strategies to improve the outcome of patients with Stage III non-small cell lung cancer (NSCLC). The addition of chemotherapy (CT) to radiotherapy has seen a decrease in the metastasis rate in some controlled studies with a favorable impact on overall survival. However, the optimal schedule of both modalities remains to be defined. The persistent poor local control in these studies underestimates the real impact of chemotherapy on patients' outcome and calls for new investigational approaches.

Antineoplastic Combined Chemotherapy Protocols↗
PubMed1995

Neoadjuvant chemotherapy of locally advanced non-small cell lung cancer.

Neoadjuvant chemotherapy was tested in non-small cell lung cancer in an attempt to increase the resectability of the tumor and to treat the microscopic metastatic disease known to be responsible for the majority of failures in surgically treated patients. This review deals with published trials. Most of them are feasibility studies in Stage III NSCLC. Obviously, the heterogeneity of eligibility criteria from one study to another prevents general conclusions on the usefulness of neoadjuvant chemotherapy. However, it is possible to conclude that neoadjuvant chemotherapy has an antitumor activity; the majority of the studies report a 60% objective response rate including a significant number of complete responses and a 50% complete resection rate. Neoadjuvant chemotherapy does not increase morbidity after surgery except when it is combined with preoperative radiation therapy. At the time of writing, one Phase III randomized study comparing neoadjuvant chemotherapy followed by surgery with surgery alone has been published. This study concludes that the combined modality treatment improves the survival of patients with locally advanced non-small cell lung cancer. Taken as a whole, the literature deserves further studies to determine the place of neoadjuvant chemotherapy in lung cancer.

Antineoplastic Combined Chemotherapy Protocols↗
PubMed1995

Phase I-II and pharmacokinetic study of a new fotemustine schedule in advanced non-small cell lung cancer.

UNLABELLED: Fotemustine, a new nitrosourea derivative has already demonstrated activity in non-small cell lung cancer (NSCLC). In order to improve its therapeutic index, we designed a protocol in which Fotemustine was delivered with dose escalation on 3 consecutive days as induction therapy followed by a 5-week rest period. Maintenance therapy consisted of 100 mg/m2 once every 3 weeks. Pharmacokinetic data were assessed during this Phase I-II study and reported here. PATIENTS AND METHODS: Nineteen patients with metastatic (17) or locally advanced (2) NSCLC were included in the present study. Ten of those with metastatic disease had brain metastases and 15 had previously received chemotherapy. Fotemustine was given at 50 mg/m2 on day 1-2-3 (group 1: four patients), 75 mg/m2 on day 1-2-3 (group 2: 16 patients including two who had already received 50 mg/m2) and 100 mg/m2 on day 1-2-3 (group 3: one patient). RESULTS: The maximal tolerated dose was 75 mg/m2 on day 1-2-3 (total cumulated dose 225 mg/m2). At this dose level, we observed 25% of Grade 3-4 neutropenia and 31% of Grade 3-4 thrombocytopenia. One patient died of pulmonary infection during aplasia. No other significant toxicity occurred. Of the 17 evaluable patients, one obtained a PR lasting 6 months in group 2 and 1 PR lasting 3 months in group 3. No significant difference was noted in the AUC between days 1, 2 or 3 in any of the seven patients in whom a pharmacokinetic study of Fotemustine was performed. CONCLUSION: Administered on 3 consecutive days, Fotemustine seems to be less effective and more toxic than other schedules tested in NSCLC. Despite the quality of the two responses observed, this protocol has been discontinued and the standard administration on days 1 and 8 remains the schedule of choice in NSCLC.

Adult↗
PubMed1995

Adding a reverser (verapamil) to combined chemotherapy overrides resistance in small cell lung cancer xenografts.

Small cell lung carcinomas (SCLC) are characterised by chemosensitivity to diverse antitumoral compounds. However, responses are transitory and relapses are commonly observed. We examined the ability of verapamil, a reverser of P-glycoprotein (Pgp)-related resistance, to improve the efficacy of CyCAV combined chemotherapy (Cy, cyclophosphamide (CPA); C, cisplatin (CDDP); A, doxorubicin (ADM);V, etoposide (VP16)), as currently administered to SCLC patients at Institut Gustave-Roussy, France, and adapted to the treatment of nude mice implanted with these tumours. Although Pgp encoded by the MDR1 (multidrug resistance) gene is not the only mechanism for multidrug resistance (MDR), and not all drugs included in this regimen are recognised by Pgp, we anticipated a therapeutic benefit. Four different SCLC lines, expressing the MDR1 gene and recently grafted into nude mice, were used. SCLC-75, SCLC-6 and SCLC-41 originated from untreated patients, and SCLC-74T was derived from a patient treated with a combination of ADM, CPA and VP16. SCLC-41% and SCLC-6T tumours were used after having undergone, respectively, five and nine cycles of in vivo passage and CyCAV treatment of the tumour-bearing nude mice, to reinforce their chemoresistance. The efficacy of the CyCAV regimen, associated with or without verapamil (given 24 h before CyCAV on days 1-5), was tested on the growth of these SCLC. Verapamil (25 mg/kg) improved the antitumour effect of CyCAV in mice bearing SCLC-6T, SCLC-41T and SCLC-75 tumours, although toxicity was observed. Verapamil modestly delayed the plasma clearance of ADM. Two daily injections of 10 mg/kg of verapamil, administered at a 3 h interval, proved to be effective, whereas the same total dose administered as a bolus was not. These results indicate that the association of some reversers of MDR, including drugs possibly interacting with Pgp, might potentiate SCLC combined chemotherapy.

Animals↗
PubMed1995

Chemotherapy of stage IIIB and IV non-small-cell lung cancer.

Currently, lung cancer is a leading cause of death in men with more than half million new cases diagnosed every year. Eighty percent of these tumors are non-small-cell carcinoma and 70% of these are unresectable or metastatic at the time of presentation, resulting in dramatically poor survival rates. The increasing number of drugs showing a significant activity against non-small-cell lung cancer and the widespread use of modern cisplatin based regimens offer some hope of progress and suggest that chemotherapy may have a role in treating this disease. A recent meta-analysis has confirmed the modest but significant survival benefit for patients treated with combined chemotherapy both in case of metastatic disease and in addition to radiotherapy, in locally advanced disease.

Antineoplastic Agents↗
PubMed1995

Dealing with initial chemotherapy doses: a new basis for treatment optimisation in limited small-cell lung cancer.

Treatment of patients with small-cell lung cancer (SCLC) remains disappointing despite initially high complete response rates. The dramatic initial chemosensitivity of tumor cells is rapidly thwarted by the early emergence of chemoresistant clonogenic cells, regardless of front line treatments. Although a dose-response relationship is well established its effect on survival is inconclusive. From 1980 to 1988, 202 patients with limited SCLC were included in four consecutive trials using an alternating schedule of thoracic radiotherapy and chemotherapy. Despite an increase in chemotherapy and/or the total radiation dose, no significant difference was observed between the four trials in terms of response, disease-free or overall survival. However, a retrospective analysis performed on a total of 131 consecutive patients led us to postulate that a moderate increase in the initial dose, i.e. first course, of cisplatin and cyclophosphamide, could improve overall survival. From 1988 to 1991, 105 consecutive patients were included in a large randomized trial to address this question. The difference in treatment options only concerned the initial doses of cisplatin (80 vs. 100 mg/m2) and cyclophosphamide (900 vs. 1200 mg/m2). According to the triangular test used in this study the trial was closed after inclusion of 105 patients, 32 months after the start of the study because, at that time, overall survival was significantly better in the higher-dose group (p = 0.001). This debatable concept of dose-intensity having an impact on survival offers new possibilities for the management of SCLC. The contribution of hematopoietic support may help to validate this concept.

Antineoplastic Agents↗
PubMed1995

Docetaxel: meeting the challenge of non-small cell lung cancer management.

The combined results of four phase II studies of docetaxel in non-small-cell lung cancer (NSCLC) are presented. All patients had either locally advanced (stage IIIb) or metastatic (stage IV) disease. Results are given for the 248 patients included in the trials who received docetaxel at a dose of 100 mg/m2 given by intravenous infusion every 21 days on an outpatient basis. Among 200 patients evaluable for response, the overall response rate was 31.3% in 128 previously untreated patients and 19.4% in 72 previously treated patients. A subgroup of 30 previously treated patients who were platinum-refractory achieved a response rate of 13.5%. In previously untreated and previously treated patients, median duration of response was 24.6 weeks and 28.7 weeks, respectively, with median times to progression of 14.4 weeks and 13.6 weeks and median survival durations of 9.0 months and 8.1 months. Similar response rates were achieved in patients with stage IIIb and stage IV disease (32% and 25%, respectively) and in patients with visceral metastases (28%) although patients with single-organ involvement did better than those with two or more organs involved. Response rates were comparable to or better than those seen with previous single-agent chemotherapeutic regimens for advanced NSCLC and even with some combination treatments, with a tolerable adverse event profile.

Animals↗
PubMed1995

High-dose ifosfamide: circumvention of resistance to standard-dose ifosfamide in advanced soft tissue sarcomas.

PURPOSE: The study was designed to assess the toxicity and activity of high-dose ifosfamide (HDI) administered by continuous infusion at a dose of 4 g/m2/d over 3 days every 4 weeks in adult patients with advanced soft tissue sarcomas (ASTS) pretreated with doxorubicin and/or a standard-dose ifosfamide (SDI)-containing regimen. PATIENTS AND METHODS: Between January 1991 and November 1993, 40 patients with progressive ASTS were entered onto the study. Twenty-eight patients had been pretreated with a multidrug regimen that contained SDI and were classified as follows: SDI-refractory (n = 21), SDI-resistant (n = 2), and indeterminate SDI-sensitive (n = 5). Patients were treated until progression or major toxicity. RESULTS: One hundred forty-seven cycles of HDI were administered. Neutropenia was dose-limiting, with 100% of patients experiencing grade 3 to 4 toxicity and 12 admissions for febrile neutropenia (30% of patients). Neurotoxicity (17% of patients) was significantly associated with acute renal failure (n = 4) (P < .001), grade 4 thrombocytopenia (P < .01) and febrile neutropenia (P = .048). Chronic renal toxicity (n = 4) was significantly associated with retroperitoneal masses and/or prior nephrectomy (P = .008). Partial responses (PRs) were observed in 12 of 36 assessable patients (33%) and eight patients (22%) experienced disease stabilization. All but one response occurred in patients pretreated with SDI, with five PRs among SDI-refractory patients. Leiomyosarcomas appear resistant to HDI. The median response duration was 8 months (range, 6 to 13+) and the median overall survival time was 12 months. CONCLUSION: The activity of HDI in these pretreated ASTS patients and the apparent circumvention of SDI resistance suggest a real dose-response relationship for ifosfamide and deserve further evaluation. Although toxic, this treatment appears feasible and manageable using routine clinical support. Since prophylaxis of ifosfamide-induced renal damage remains unknown, frequent monitoring of renal and tubular functions during therapy is highly recommended.

Adult↗
PubMed1995

Economic evaluation of a randomized clinical trial comparing vinorelbine, vinorelbine plus cisplatin, and vindesine plus cisplatin for non-small-cell lung cancer.

PURPOSE: To estimate the comparative cost-effectiveness of three regimens for metastatic non-small-cell lung cancer (NSCLC). METHODS: Results from a randomized clinical trial of 612 European patients with NSCLC, and cost data from an academic cancer center, the Medical College of Virginia, were analyzed. In this post-hoc economic analysis, we compared vinorelbine alone, vinorelbine plus cisplatin, and a common regimen of vindesine plus cisplatin. RESULTS: Vinorelbine plus cisplatin resulted in the longest mean survival time of the three regimens, 49.6 weeks, followed by vindesine plus cisplatin, 44.3 weeks, and vinorelbine, 41.6 weeks. Compared with vinorelbine alone, vinorelbine plus cisplatin added 56 days at a cost of $2,700, resulting in a cost-effectiveness ratio of $17,700 per year of life gained. Similarly, vindesine plus cisplatin added 19 days at a cost of $1,150, or $22,100 per year of life gained. Compared with vindesine plus cisplatin, vinorelbine plus cisplatin added 37 days at a cost of $1,570, or $15,500 per year of life gained. CONCLUSION: The most effective regimen of vinorelbine plus cisplatin added substantial benefit compared with vinorelbine alone or another common treatment, vindesine plus cisplatin, at a cost-effectiveness within accepted limits for medical interventions. Vindesine plus cisplatin also added benefit at an acceptable cost per year of life gained. If vinorelbine is preferred because of its toxicity profile, the additional effectiveness of cisplatin added substantial benefit at an acceptable cost. Compared with other common medical interventions, chemotherapy for NSCLC has acceptable efficacy and cost-effectiveness and should not be arbitrarily denied based on clinical or economic grounds.

Aged↗
PubMed1995

[Importance of the initial chemotherapy dose in the treatment of small cell lung carcinoma: therapeutic perspectives].

Treatment of patients with small-cell lung cancer (SCLC) remains disappointing despite high initial complete response rates. The dramatic initial chemosensitivity of tumor cells is frustrated by the early emergence of chemoresistant clonogenic cells, regardless of front line treatments. Although the dose relationship is fairly well established regarding the response rate, its effect on survival is inconclusive. From 1980 to 1988, 202 patients with limited SCLC were included in four consecutive protocols using an alternating schedule of thoracic radiotherapy and chemotherapy. Despite an increase of chemotherapy and/or total radiation doses, no significant difference was observed between the four protocols in terms of response rate, disease free and overall survival. However, a retrospective analysis performed on a total of 131 consecutive patients led us to propose the hypothesis that a moderate increase in the initial dose, ie first course, of cisplatin and cyclophosphamide could improve overall survival. From 1988 to 1991, 105 patients were subsequently included in a large randomized trial raising this question. The treatment difference only concerned the initial doses of cisplatin (80 vs 100 mg/m2) and cyclophosphamide (900 vs 1200 mg/m2). The trial was closed after inclusion of 105 patients, 32 months after the start of the study because at that time overall survival was significantly better in the higher-dose group (p = 0.001). The emergence of this debatable concept opens new directions in the therapeutic strategy of SCLC and the contribution of hematopoietic growth factors may be of great interest in the management of this disease.

Antineoplastic Combined Chemotherapy Protocols↗
PubMed1994

Surgery for pulmonary metastases. Who are the 10-year survivors?

BACKGROUND: Surgical resection of pulmonary metastases (PMs) has been shown to produce approximately a 35% 5-year survival rate, but specific data about late survival are not available in the literature. METHODS: A retrospective review and survival analysis of 186 adult patients who underwent surgery for PMs at a single center before June 1984 is presented. RESULTS: Of the 186 patients who had surgery, of whom 34 (18%) had an incomplete resection, the 10-year survival rate (Kaplan-Meier) was 23% (95% CI, 16-30%), and 36 patients, with PMs from nine different primary sites, were still at risk at 10 years. Two patients died of their primary disease more than 10 years after the first thoracotomy, and two are alive with uncontrolled disease. Thirty-one patients are currently alive and disease free. Comparison between the 36 10-year survivors and the 150 nonsurvivors revealed that only the percentage of incomplete resections and the mean number of resections per patient were significantly different between the two groups (P < 0.001); the histologic type of the primary tumor, the disease-free interval, and the number of resected PMs at the first thoracotomy were not found to be statistically significant prognostic factors. CONCLUSIONS: The 23% 10-year survival and the high rate of disease free 10-year survivors in this study constitute support for complete resection as an efficient therapeutic approach in patients with isolated PMs. Relevant criteria to select more precisely those patients who will benefit from resection remain to be developed.

Adolescent↗
PubMed1994

HOX gene expression in human small-cell lung cancers xenografted into nude mice.

Transcription factors are crucial to an understanding of the molecular basis of neoplasia. Homeobox-containing genes are a family of transcriptional regulators encoding DNA-binding homeodomains, involved in the control of normal development. Class-I human homeobox-containing genes (HOX genes) display a peculiar chromosomal organization, perhaps directly related to their function. Aberrant expression of homeobox-genes has been associated with both morphological abnormalities and oncogenesis. We have recently observed that alterations in HOX gene expression are detectable in kidney and colon cancer when compared to the corresponding normal organs. Here we have analyzed the expression of HOX genes in primary and metastatic human small-cell lung cancer (SCLC) xenografted in nude mice, in order to investigate whether HOX gene expression correlates with the histology and stage of SCLC progression. The results show that different SCLCs display differential patterns of HOX gene expression. Furthermore, in SCLC, the number of actively expressed HOX genes might be substantially lower in metastatic cancers than in primary tumors. The alteration in HOX gene expression in SCLCs mainly concerns the HOX B and C loci. This finding suggests that downregulation of HOX genes may play a role in small-cell lung cancer progression, possibly through their implication in tumor suppression.

Animals↗
PubMed1994

Radiotherapy alone versus combined chemotherapy and radiotherapy in unresectable non-small cell lung carcinoma.

We report the results observed in a large randomized study comparing radiotherapy alone to combined radiotherapy and chemotherapy in unresectable squamous cell and large cell lung carcinoma. Radiation dose was 65 Gy in both groups and chemotherapy included vindesine, cyclophosphamide, cisplatin and lomustine. One hundred seventy-seven patients received radiotherapy alone, and 176 received the combined treatment. The 2-year survival rate was 14% for patients receiving radiotherapy vs. 21% for patients receiving the combined treatment (P = 0.02). The distant metastasis rate was significantly lower in the group receiving the combined treatment (P < 0.001). Local control at 1 year was poor in both groups (17% and 15%, respectively) and remains a major problem in locally advanced non-small cell lung cancer.

Antineoplastic Combined Chemotherapy Protocols↗
PubMed1994

Alternating radiotherapy and chemotherapy in limited small cell lung cancer: the IGR protocols. French FNCLCC Lung Cancer Study Group.

Two-hundred two patients with limited small cell lung cancer were tested by four consecutive alternating radiotherapy and chemotherapy protocols. The alternating schedule consisted of six cycles of chemotherapy (doxorubicin, etoposide, and cyclophosphamide, plus methotrexate in the first protocol; cisplatin replaced methotrexate in the other three protocols) and three courses of thoracic radiotherapy at a total dose of 45, 55, 65 and 61 Gy in the four consecutive protocols, respectively. A 1-week rest followed each chemotherapy cycle and each course of radiotherapy. Seventy-six percent of patients were in complete remission at the end of the induction treatment. Overall results showed a 2-year cumulative incidence rate of failure of 75%. The first cause of failure was local recurrence only, 33%; distant only, 25%; distant and local simultaneously, 9%; and intercurrent death, 8%. Overall survival rate at 5 years was 16%. No significant differences were observed between the four treatment groups. Alternating radio-chemotherapy approaches are feasible and currently included in Phase III trials.

Antineoplastic Combined Chemotherapy Protocols↗
PubMed1994

Cisplatin-fotemustine combination in inoperable non-small cell lung cancer: preliminary report of a French multicentre phase II trial.

Fotemustine is a new nitrosourea derivative whose activity has been demonstrated on metastatic melanoma with specific activity on brain metastases and also on poor prognosis lung cancers. Results of in vitro studies of a cisplatin-fotemustine combination seem promising. In order to evaluate the efficacy and safety of this combination, we performed two trials. 6 patients entered a preliminary study whose schedule was cisplatin 120 mg/m2 on day 1 and fotemustine 100 mg/m2 on days 1 and 8. 22 patients were enrolled in a second study which added 120 mg/m2 cisplatin on day 22 followed by a 4-week rest period. In both trials, maintenance therapy consisted of cisplatin 100 mg/m2 and fotemustine 100 mg/m2 every 3 weeks until progression. Despite the poor prognostic factors which characterised our population (metastatic disease 86%, brain metastases 59%, < or = 80% performance status 45%), the results remain attractive with a 23% partial response rate (29% in non-pretreated patients). Moreover, 3 out of 8 patients with evaluable cerebral metastases achieved a partial response (37.5%). Toxicity was mild and related to the cumulative dose of cisplatin (peripheral neuropathy and renal toxicity). We concluded that these results need to be confirmed in a randomised trial.

Adult↗