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T Le Chevalier

Publications and source records attributed to T Le Chevalier.

At least 73 records · Page 4Linked to original sources
PubMed1998

Primary mediastinal nonseminomatous germ cell tumors: results of modern therapy including cisplatin-based chemotherapy.

PURPOSE: Primary mediastinal nonseminomatous germ cell tumors (NSGCT) are uncommon neoplasms and clinically and biologically distinct from other germ cell tumors (GCT). We describe the clinical and biologic features of these patients and evaluate the results of treatment during the cisplatin era. PATIENTS AND METHODS: Between 1976 and 1993, 38 patients with mediastinal NSGCT received cisplatin-based chemotherapy as part of their primary treatment. Twenty-nine of them were initially treated at the Institut Gustave-Roussy (IGR), VillejuiF, France, and nine were referred for salvage treatment. RESULTS: Of the 29 patients initially treated at IGR, 11 (39%) had metastasis. A complete response (CR) to therapy was obtained in 19 of 29 patients (66%) after chemotherapy and surgery. Ten patients (34.5%) have remained free of disease with a median follow-up of 89 months. All patients who did not achieve a CR died of disease. The 2-year overall survival rate for the IGR patients is 45% and the 2-year disease-free survival is 37%. Only the presence of extrapulmonary metastasis was of prognostic significance in the univariate analysis (P = .0095). None of the 20 patients who required salvage therapy is currently disease-free. Five patients developed and subsequently died of a hematologic malignancy at an interval range of 1 to 47 months from treatment of mediastinal NSGCT. Cytogenetic analysis of leukemic cells found an isochromosome of the short arm of chromosome 12 (12p) in two cases. The incidence of leukemia was 21% in patients who attained a CR. CONCLUSION: Primary mediastinal NSGCT is a clinical and biologic entity that should be distinguished from other GCT. About 40% of these patients can envisage long-term survival with modern therapy that includes cisplatin-based chemotherapy followed by surgical resection of residual masses. New strategies are required for patients who do not attain a CR. Predictive factors and improvement in therapy are required for mediastinal NSGCT-associated leukemia.

Adolescent↗
PubMed1998

Adjuvant chemotherapy in non-small cell lung cancer.

Surgery is the main curative treatment of patients with non-small cell lung cancer (NSCLC), but half of all patients will experience local or distant failure after complete resection. An individual data-based meta-analysis has suggested a 13% reduction in the risk of death and an absolute benefit of 5% at 5 years with adjuvant cisplatin-containing chemotherapy in patients with resected NSCLC. These data led several national and international groups to initiate a new generation of adjuvant trials in resected NSCLC, and more than 2,500 patients have already been included in these randomized studies. Chemotherapy can also be proposed preoperatively. Two randomized studies, which included 60 patients each, strongly suggested a benefit from neoadjuvant chemotherapy in patients with stage III NSCLC. A large French randomized study that included 375 patients with early stage NSCLC who did or did not receive preoperative chemotherapy has recently been completed. This study should help clarify the role of neoadjuvant chemotherapy in operable NSCLC.

Antineoplastic Combined Chemotherapy Protocols↗
PubMed1997

Phase I trial of recombinant adenovirus gene transfer in lung cancer. Longitudinal study of the immune responses to transgene and viral products.

Animal studies indicate that the use of replication-deficient adenovirus for human gene therapy is limited by host antivector immune responses that result in transient recombinant protein expression and blocking of gene transfer when rechallenged. Therefore, we have examined immune responses to an adenoviral vector and to the beta-galactosidase protein in four patients with lung cancer given a single intratumor injection of 10(9) plaque-forming units of recombinant adenovirus. The beta-galactosidase protein was expressed in day-8 tumor biopsies from all patients at variable levels. Recombinant virus DNA was detected by PCR in day-30 and day-60 tumor biopsies from all patients except patient 1. A high level of neutralizing antiadenovirus antibodies was detected in patient 1 before Ad-beta-gal injection whereas it was low (patient 3) or undetectable in the other two patients. All patients developed potent CD4 type 1 helper T cell (Th1) responses to adenoviral particles which increased gradually over time after injection. Antiadenovirus cytotoxic T lymphocyte responses were consistently boosted in the two patients examined (patients 3 and 4). Sustained production of anti-beta-galactosidase IgG was observed in all patients except patient 1. Consistent with anti-beta-gal antibody production, all patients except patient 1 developed intense, dose-dependent Th1 responses to soluble beta-galactosidase which increased over time. Strong beta-galactosidase-specific cytotoxic T lymphocyte responses were detected in patients 2, 3, and 4. Our results clearly show that despite the intensity of antiadenovirus responses, transgene protein expression was sufficient to induce strong and prolonged immunity in three patients. Recombinant adenovirus injected directly into the tumor is a highly efficient vector for immunizing patients against the transgene protein.

Adenoviridae↗
PubMed1997

Non-small cell lung cancer: an overview of current management.

Non-small cell lung cancer (NSCLC) will remain a worldwide health problem for the foreseeable future. Unfortunately, local treatment of this disease is disappointing as most patients develop uncontrollable locally advanced or distant metastatic disease. The recent meta-analysis using updated patient data has suggested a potential role for adjuvant cisplatin-based chemotherapy (CT) in early stage disease, and has shown a significant, albeit modest, improvement in survival when combined with radiotherapy in locally advanced disease and as a single modality in metastatic disease. Although quality and cost of extra life with this more aggressive treatment need to be defined in prospective studies, CT should be considered standard treatment for patients with locally advanced and metastatic NSCLC able to receive cisplatin-based CT. Its role in stage I and II disease is under current investigation. Ongoing clinical studies with more active agents, novel combined modality treatment strategies and laboratory discoveries continue to emerge which may lead to valuable new treatment options to extend this survival advantage.

Antineoplastic Combined Chemotherapy Protocols↗
PubMed1997

Should the number of pulmonary metastases influence the surgical decision?

OBJECTIVE: To assess, using a large homogeneous retrospective series, the prognostic value of the number of resected pulmonary metastases, and thus, to determine to what extent the number of resectable metastases should influence the surgical decision. METHODS: The survival analysis of all patients operated on for pulmonary metastases at a single center, the comparisons of 2 'histologic' groups (sarcoma and carcinoma) and, within each histologic group, of three subgroups with different numbers of resected metastases (1, 2-4, and > or = 5) were performed. The log-rank test was used to compare survival curves. RESULTS: Among 575 adult patients operated on with curative intent before December 1991, the first operation allowed the complete resection of a known number of histologically proven viable pulmonary metastases in 230 and 151 patients with metastases from carcinoma and sarcoma, respectively. The 5- and 10-year probabilities of survival (Kaplan-Meier) were 37 and 23%, respectively in carcinoma patients, and 31 and 28%, respectively in sarcoma patients (log-rank test: ns). Only the difference between patients with 1 versus 2-4 metastases from carcinoma proved statistically significant (P = 0.02), with 5-year survival estimates of 41 and 25%, respectively. Beside survival, the only significant difference between the subgroups of patients with different numbers of resected metastases was the mean interval between the diagnosis of pulmonary metastases and the resection of pulmonary metastases, which was significantly longer in patients with several metastases in both histologic groups. CONCLUSIONS: In patients with resectable pulmonary metastases from sarcoma or carcinoma, the number of metastases should have little influence on the surgical decision, except for delaying this decision in patients with several metastases until a significant interval, with or without treatment, has shown that metastatic disease remains resectable and confined to the lungs.

Adult↗
PubMed1997

[Optimization of combined radiotherapy and chemotherapy in treatment of non-small cell lung carcinoma].

PURPOSE: To report the results of CEBI 140 and 142 trials. These trials were aimed at improving the local control in stage III non-small cell carcinoma with concomitant chemotherapy and radiotherapy in the CEBI 140 trial, and with concomitant chemotherapy and radiotherapy followed by local excision in the CEBI 142 trial. MATERIAL AND METHODS: Thirty-four patients presenting with stage III non-small cell lung carcinoma were included into the CEBI 140 trial from December 1989 to December 1992. Patients were treated with a combination of daily cisplatin (6 mg/m2 per day, 144 mg/m2 in total), vindesine once a week (2.5 mg/m2, 15 mg/m2 in total) and bifractionated radiotherapy (60 Gy/48 fractions/6 weeks) followed by two cycles of cisplatin 120 mg/m2 (at d18 and d45 after completion of radiochemotherapy) and three cycles of vindesine (6 mg/m2 at d24, d31, and d38 after completion of radiochemotherapy). Twenty-eight patients presenting with stage IIIB non-small cell carcinoma-were included into the CEBI 142 trial since January 1993. Patients received a combination of cisplatin (100 mg/m2 at d1 and d24, 200 mg/m2 in total), vinblastine (4 mg/m2 at d1 and d24, 8 mg/m2 in total), 5-fluorouracil in continuous infusion (1,000 mg/m2 from d1 to d3, and from d24 to 26, 6,000 mg/m2 in total) and bifractionated radiotherapy (two series of 21 Gy/14 fractions/9 days, 11 days apart) followed by a new evaluation and surgical excision. RESULTS: In the CEBI 140 trial, all patients received a complete course of radiotherapy, but the dose of cisplatin was decreased in 27% of the cases, and the dose of vindesine in 88%. There were two toxicity-related deaths. Three months after completion of the protocol, there were 50% of complete responders. The overall survival rates at 1, 2 and 3 years were 53, 33, and 11%, respectively, and disease-free survival rates 21 11, and 11%, respectively. In the CEBI 142 trial the immediate tolerance was good. Twenty-one patients (75%) underwent surgical resection. Four tumors could not be resected. Resection was histologically incomplete in one case, and complete in the 16 remaining cases. With a median follow-up of 14 months, ten patients were alive and disease-free. CONCLUSION: Preliminary results of the CEBI 142 trial are encouraging. More patients and longer follow-up are needed for definitive conclusion. It would be of interest to implement a randomized trial comparing the CEBI 142 scheme and classical radiation therapy.

Adult↗
PubMed1997

Ca125 and neuron-specific enolase (NSE) as tumour markers for intra-abdominal desmoplastic small round-cell tumours.

Seven consecutive patients with intra-abdominal desmoplastic small round-cell tumours were screened at presentation for carcinoembryonic antigen (CEA), Ca19-9, Ca15-3, Ca125, alpha-fetoprotein (AFP), human chorionic gonadotrophin (hCG) and neuron-specific enolase (NSE). Initially elevated tumour markers were used to monitor therapy and follow-up. Tumour marker assays were all in the normal range, with the exception of Ca125 and NSE. The Ca125 level was initially high in six of the seven patients (86%) with a median value of 200 U ml-1 and a range of 22-735 U ml-1. The NSE value was elevated before therapy in three of the five patients (60%) for whom assay results were available, with a median of 19 ng ml-1 and a range of 6.8-37.5 ng ml-1 . Ca1 25 normalized in five out of six cases and NSE always normalized during chemotherapy, but neither of these two tumour markers correlated specifically with response, as only one patient experienced a partial response, five tumour stabilization and the remaining patient tumour progression. At progression, Ca125 was again elevated in two out of four cases several weeks before clinical relapse and NSE in only one out of three cases. Ca125 and NSE are frequently raised in the serum of patients with intra-abdominal desmoplastic small round-cell tumours before therapy, but are not reliable monitors of the course of the disease. However, normalization is frequently associated with an improvement of symptoms or a moderate clinical response.

Adolescent↗
PubMed1997

Phase II trial of raltitrexed ('Tomudex') in advanced small-cell lung cancer.

Raltitrexed, a thymidylate synthase inhibitor, was given to 21 patients with advanced small-cell lung cancer, at a dose of 3 mg m(-2) as a 15-min intravenous infusion at 21-day intervals. All of the patients had extensive disease and 17 had received prior therapy. Patients with disease refractory to primary chemotherapy were excluded. Forty-one treatment cycles were given (median two, range one to four). The drug was well tolerated. No objective tumour response was documented. The patients had chemoresistant disease, as shown by a response in only one of ten patients who went on to receive alternative cytotoxic regimens. We conclude that raltitrexed given in this schedule is inactive as second line therapy for small-cell lung cancer.

Adult↗
PubMed1997

Dose-intensity of a four-drug chemotherapy regimen with or without recombinant human granulocyte-macrophage colony-stimulating factor in extensive-stage small-cell lung cancer: a multicenter randomized phase III study.

PURPOSE AND METHODS: We investigated whether a high-dose chemotherapy regimen of cyclophosphamide 1,800 mg/m2, 4'-epidoxorubicin 60 mg/m2, etoposide 330 mg/m2, and cisplatin 120 mg/m2 given monthly for four cycles with recombinant human granulocyte-macrophage colony-stimulating factor (rhGM-CSF) support (5 micrograms/kg daily for 10 days) could improve the survival of patients with extensive-stage small-cell lung cancer (SCLC) compared with a standard-dose regimen (cyclophosphamide 1,200 mg/m2, 4'-epidoxorubicin 40 mg/m2, etoposide 225 mg/m2, and cisplatin 100 mg/m2) given monthly for six cycles. Planned cumulative doses of the drugs were the same in both treatment arms except for cisplatin (which was 80% in the higher-dose plus rhGM-CSF group). RESULTS: At the time of the preplanned interim analysis, 125 patients, 60 in the standard-dose group and 65 in the higher-dose plus rhGM-CSF group, had entered the study; 116 were eligible, 55 in the standard-dose group and 61 in the higher-dose group. All patients were included in the analyses. The cumulative doses of each drug actually delivered were significantly higher in the standard-dose group. No difference in response rates was observed between the two groups. There were significantly greater hematologic toxicities, documented infections, and transfusions of RBCs and platelets in the higher-dose plus rhGM-CSF group. Patients in this group proved to have a shorter survival duration and a shorter time to relapse than patients in the standard-dose group (median overall survival: standard-dose, 10.8 months; higher-dose, 8.9 months; log-rank test with adjustment for prognostic variables, P = .0005; respective probabilities of relapse at 1 year, 77 +/- 0.6 and 96 +/- 2.2; log-rank test, P = .013). CONCLUSION: A 50% increase in dose-intensity for this four-drug regimen could not be achieved with GM-CSF due to excessive toxicity in patients with extensive-stage SCLC.

Antineoplastic Combined Chemotherapy Protocols↗
PubMed1997

[Angiosarcoma of the breast. Apropos of 8 cases and review of the literature].

The 8 cases of primary breast angiosarcoma which were diagnosed, treated and had their follow-up at the Gustave-Roussy Institute between 1954 and 1995 are reported. The age at presentation ranged from 32 to 68 years. In 4 patients the vascular nature of their mammary lesion was conspicuous by a violaceous discolorations of the overlying skin. No patient had enlarged ipsilateral axillary lymph nodes. One patient had metastases. In 2 out of 5 patients who had a partial surgical or fine-needle biopsy before treatment, the diagnosis was missed, and adequate treatment was unduly delayed. The tumor most often presents as an ill defined area made of dense endothelium-lined papillae. A remarkable picture of "soap bubbles" has been identified in 4 cases. The "meshes" of fatty areas appear to be reinforced as they are infiltrated by tumor cells. This appearance may be specific of mammary angiosarcoma. By the French Cancer Centers' grading system for soft tissue sarcomas in general, grade is III in 3 tumors, II in 2 tumors, I in 3 tumors. Five tumors were treated by total mastectomy only. In 3 cases a total mastectomy was followed by radiation therapy to the chest wall. At diagnosis a chemotherapy was administered only to the patient who had metastases. Median disease-free survival was 9 months. Median overall survival was 13 months. From a review of the literature a simple mastectomy appears to be necessary as well as enough for local treatment. Patients with a grade III angiosarcoma of the breast should be included into a therapeutical trial of adjuvant chemotherapy for soft tissue sarcomas in general.

Adult↗
PubMed1997

Single-agent gemcitabine in non-small cell lung cancer: the French experience.

Gemcitabine is a novel nucleoside analogue that has demonstrated activity against several solid tumors. A large phase II study has been performed in Europe and Canada with a total enrollment of 161 non-small cell lung cancer patients, 26 of whom were from the Institut Gustave-Roussy. Patient characteristics were the same for our patients and the whole study population. One hundred fifty-one patients, including 24 at our institution, were evaluable for response. We observed an objective response rate of 21.8% (95% confidence interval, 15.5% to 29.3%) and median survival of 9.4 months for the whole population (7.5 months at our institution), with a 1-year survival rate of 42% (38% at our institution). Tolerance was good in the majority of patients. These results suggest that gemcitabine can be considered a safe and active agent for the treatment of patients with advanced non-small cell lung cancer.

Antimetabolites, Antineoplastic↗
PubMed1997

Lung resection for recurrence after pneumonectomy for metastases.

Resection of pulmonary recurrences after pneumonectomy for metastases is exceptional. Nevertheless in carefully selected patients surgery on the residual lung might be successfully performed. From January 1987 to February 1996, 5 patients underwent metastasectomy on single lung after pneumonectomy performed for the same metastatic disease. There were 3 male and 2 female with a mean age of 38 years at the time of surgery on single lung. All patients had a FEV1 > 40%. One patient (n degree 1) had 2 consecutive operations (wedge resections) on the right lower lobe followed 17 months later by right inferior lobectomy for metastases of soft tissue sarcoma. Three patients had only an operation on the residual lung (patient n degree 2 had 2 wedge resections for carcinoma; patient n degree 3 had 7 wedge resections for carcinoma; patient n degree 4 had 6 wedge resections for osteogenic sarcoma). The last patient (n degree 5) had 2 wedge resections on the right upper lobe and a large wedge resection on the right lower lobe for metastases of malignant corticosurrenaloma using a cardiopulmonary femoro-femoral by-pass without cardiac arrest. She postoperatively developed a right lower lobe venous infarction treated subsequently with a completion right lower lobectomy. She died in the postoperative course from cardiorespiratory insufficiency. The other patients had an uneventful postoperative course. Two patients (n degree 2 and n degree 4) died of their disease 14 and 12 months respectively after the surgery on the residual lung; by contrast 2 patients (40%) (n degree 1 and n degree 3) are still alive without recurrences 36 and 27 months after the last resection. In selected patients aggressive surgery for metastases on the residual lung can be successfully performed but the benefits in terms of long-term disease-free survival remain to be determined.

Adult↗
PubMed1997

[A phase II multicenter study of gemcitabine in non small cell lung cancers].

Gemcitabine is a novel pyrimidine nucleoside whose activity has been demonstrated on solid tumors. We report here the results of a multicentre phase II trial of gemcitabine in chemonaive patients with inoperable non small cell lung cancer (NSCLC). Gemcitabine was given weekly at a dose of 1,250 mg/m2 administered as a 30 min intravenous infusion, for 3 weeks followed by 1 week of rest (1 cycle). All the 161 patients included were evaluable for toxicity and 151 of them were evaluable for efficacy. The majority of patients had a stage IIIb (31.1%) or stage IV (64.6%) disease; 10.6%, 83.2% and 6.2% of patients had a WHO performance status (PS) 0, 1, and 2, respectively. Adenocarcinoma accounted for 52.2% of cases and squamous cell carcinoma for 43.5% of cases. Three complete responses and 30 partial responses gave an objective response (OR) rate of 21.8% (95% confidence interval; 15.5-29.3%). All responses were validated by an independent Oncology Review Board. Median duration of response was 7.6 months. Median time to progression was 4.6 months (3.3 months in non responders and 7.6 months in responders). Median survival was 7.3 months in non responders and 13.4 months in responders (p < 0.001), which gave an overall median survival of 8.9 months (95% CI: 0.1-21.9 months) in the entire study population. An improvement of symptoms and personal state was also observed. Treatment was well tolerated. Neutropenia was the only dose limiting toxicity. WHO grade 3 or 4 neutropenia occurred in 19.6% and 5.7% of patients, respectively. With a 21.8% OR rate, this multicentre study confirms the activity of gemcitabine as a single agent in patients with inoperable NSCLC. Its good tolerance and original mode of action make gemcitabine a drug of choice in the therapeutic strategy of these tumors.

Adult↗