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T Le Chevalier

Publications and source records attributed to T Le Chevalier.

At least 145 records · Page 8Linked to original sources

[Metastases from cancers of unknown primary site. Data from 302 autopsies].

The autopsies of 302 patients who had metastases from cancers of unknown primary site were studied. In two-thirds of the cases the metastases were located in the lymph nodes, the lungs and the bones. The primary tumour was found in 82 patients when still alive (27 percent) and in 173 patients (57 percent) at autopsy. It could not be identified in 16 percent of the cases. The primary tumours most often discovered were in the pancreas (26.5 percent), the lungs (17.2 percent), the kidneys (4.6 percent) and the colorectal bowel (3.6 percent). On the whole, the paraclinical examinations performed for diagnostic purposes had been disappointing. The survival rate was the same whether or not the primary tumour had been identified. The number of inaugural metastases seems to be a major prognostic factor. These highly progressive tumours must represent a very distinct clinical and biological neoplastic entity. A simple approach and a unicist practical management are suggested.

Adolescent↗

A phase II study of the combination of carboplatin and ifosfamide in previously untreated metastatic small cell lung carcinoma.

This Phase II study evaluated the combination of two active agents in small cell lung carcinoma (SCLC): carboplatin and ifosfamide. Thirty previously untreated patients (27 men and 3 women) with a median age of 59 years were included in this study. Twelve patients had one metastatic site and 18 had two or more metastatic sites. The median performance status was 80%. The chemotherapy (CT) regimen administered during the course of this study consisted of carboplatin (300 mg/m2) and ifosfamide (4 g/m2) plus mesna every 4 weeks. All 30 patients were evaluable: 1 achieved a complete remission (CR) and 18 achieved a partial remission (PR) (objective response rate, 63%). The median response time was 3 months and the median survival time was 8 months (range, 1 to 25+ months). Bone marrow toxicity was Grade III in three patients and Grade IV in four patients. The carboplatin and ifosfamide combination was well tolerated. No cross-resistance with the doxorubicin and etoposide regimen was established because 4 of 11 patients responded to this combination (+/- cisplatin) after failing to respond to the ifosfamide and carboplatin regimen. The ifosfamide and carboplatin combination may be considered for inclusion in non-cross-resistant alternating CT schedules.

Adult↗

Radiotherapy alone versus combined chemotherapy and radiotherapy in nonresectable non-small-cell lung cancer: first analysis of a randomized trial in 353 patients.

We report the results observed in a large, randomized study that compared the effects of radiotherapy alone (the standard therapy) with those of a combination of radiotherapy and chemotherapy in nonresectable squamous cell and large-cell lung carcinoma. The radiation dose was 65 Gy in each group, and chemotherapy included vindesine, cyclophosphamide, cisplatin, and lomustine. In this study, 177 patients received radiotherapy alone (group A), and 176 patients received the combined treatment (group B). The 2-year survival rate was 14% in group A and 21% in group B (P = .08). The distant metastasis rate was significantly lower in group B (P less than .001). Local control was poor in both groups (17% and 15%, respectively) and remained the major problem.

Antineoplastic Combined Chemotherapy Protocols↗

[Phase I trial of a recombinant human interleukin 2. Results in patients with disseminated solid tumors].

A phase I trial of Roussel-Uclaf recombinant human interleukin 2 (IL 2) was performed on 31 cancer bearing patients of the Institut Gustave-Roussy, Villejuif, and the Institut Curie, Paris. This study allowed to define a schedule for administration of IL 2 in continuous infusion over 5 day cycles. This schedule is manageable in patients without major visceral failure. It is reproducibly feasible in conventional medical oncology units, without specialized intensive care facilities. Toxicities, although numerous, are acceptable for IL 2 doses below 24,000,000 IU/m2/day. There is a close relationship between secondary effect severity and IL 2 doses received. Main toxicities were: fever with chills, fatigue and general discomfort in 23 patients, nauseas and vomiting in 12, diarrhea in 10 and cutaneous rashes with erythema and dermal vascularitis in 13. One peculiar feature of this study was the minimal occurrence of manifestation related to leaky capillary syndrome prominant in other studies. Oliguria, functional renal failure and edema were observed in only 4 patients with functionally unique kidney. Five patients had severe anemia, 2 grade III thrombocytopenia, 1 grade IV hepatic cytolysis, 4 severe confusion episodes and 2 hypothyroidism with anti-thyroid microsome auto-antibodies. All these toxicities were reversible after withdrawal of IL 2 treatment. During this phase I trial, 3 therapeutic objective responses were observed, all 3 occurring in patients with metastatic melanoma treated with IL 2 doses equal to, or above 16,000,00 IU/m2/d. Recombinant IL 2 Roussel-Uclaf thus can be administered through a simple, manageable and efficient regimen.

Adolescent↗

Alternating radiotherapy and chemotherapy schedules in limited small cell lung cancer: analysis of local chest recurrences.

An analysis of the chest recurrences was conducted in 72 consecutive patients with limited small cell lung cancer treated in two successive phase II trials alternating six induction chemotherapy courses and three series of thoracic radiotherapy, followed by maintenance chemotherapy. The total radiation dose was 45 Gy (3 series of 15 Gy) in the first trial, and 55 (20, 20 and 15 Gy) in the second. The effect of the irradiated volume was investigated by comparing the local relapse rates in the group of patients treated by radiation fields encompassing the initial tumor volume to another group in which the initial target volume was not fully covered by radiation fields. The definition of these two groups was performed retrospectively by examination of radiological, fiberoptic bronchoscopy initial findings, technical radiation charts and check films. The local recurrence rate were 33 and 36% in each group (no significant difference). This finding could suggest that tumor shrinkage after chemotherapy might allow the use of "reduced" radiation volumes. However, the limited number of patients does not permit a definite conclusion. The effect of radiation dose was investigated by comparing the local control rates in the two consecutive trials which delivered 45 and 55 Gy, respectively. No difference in long-term local control was found: the addition of 10 Gy in the second trial only seemed to delay the appearance of local recurrences by 6 months. Twenty percent of patients died from a local relapse without evidence of distant metastases.(ABSTRACT TRUNCATED AT 250 WORDS)

Actuarial Analysis↗

ASTRO (American Society for Therapeutic Radiology and Oncology) plenary: Effect of chemotherapy on locally advanced non-small cell lung carcinoma: a randomized study of 353 patients. GETCB (Groupe d'Etude et Traitement des Cancers Bronchiques), FNCLCC (Féderation Nationale des Centres de Lutte contre le Cancer) and the CEBI trialists.

Most patients with locally advanced non small cell lung carcinoma are treated with external thoracic radiotherapy. Because of the high incidence of distant metastasis the addition of chemotherapy has been proposed. The present randomized study was conducted from June 1983 to February 1989 and included 353 patients. The trial compared arm A, thoracic megavoltage radiotherapy alone at a total dose of 65 Gy in 26 fractions and 45 days, to arm B that comprised the same radiotherapy preceded and followed by 3 monthly cycles of VCPC (vindesine 1.5 mg/m2 d 1-2, cyclophosphamide 200 mg/m2 d 2-4, cisplatinum 100 mg/m2 d 2 and lomustine 75 mg/m2 d 3). Disease was deemed unresectable but non-metastatic after bronchoscopic, radiologic, CAT, and nuclear scans and physical examinations. Only patients in clinical, radiological, endoscopic, and histological complete remission were considered as locally controlled; these patients were monitored by fiberoptic bronchoscopy and systematic biopsies to the primary site. One hundred seventy-seven patients received thoracic radiotherapy alone and 176 received the combined modality. Twenty-seven percent of arm B patients had an objective response after 2 VCPC cycles. At the time of final assessment, performed 3 months after the end of thoracic radiotherapy in both arms, there were 20% of complete responders in arm A versus 16% in arm B. The two-year survival rate was 14% in arm A versus 21% in arm B (p = 0.08, logrank test). The distant metastasis rate was 67% in arm A versus 45% in arm B (p less than 0.001). Local control at 1 year was poor in both groups (17% and 15%, respectively). The striking effect of VCPC chemotherapy on the incidence of distant metastasis did not have a significant impact on overall survival. We conclude that thoracic tumor control remains a significant problem in unresectable non small cell lung cancer.

Antineoplastic Combined Chemotherapy Protocols↗

[Chemotherapy of soft tissue sarcoma in adults].

The results of several studies of chemotherapy in treatment of soft tissue sarcomas of adults (except embryonic rhabdomyosarcoma) are presented. Most of these studies have been performed and published by the EORTC Bone and Soft tissue sarcoma group. In advanced disease, a randomized trial including 551 evaluable patients and comparing doxorubicin alone (75 mg/m2 q. 3 weeks), and two combination regimens: DI (Doxorubicin (50 mg/m2) + Ifosfamide (5 g/m2 + mesnum q. 3 weeks), and Cyvadic (Doxorubicin 50 mg/m2 d1, DTIC 750 mg/m2 d1, VCR 1.5 mg/m2 d1 (maximum 2 mg/m2), Cyclophosphamide 500 mg/m2 d1 q. 3 weeks), failed to prove any significant difference between these 3 treatments for response rate (25%, 31%, 28%), quality of the response and survival. There is a dose/effect relationship doxorubicin, it is possible that if combination is not superior to a single agent, the reason could be that the dose of doxorubicin is too low when used in combination as compared with the dose when used alone. So, in a phase II trial including 48 evaluable patients, optimal dose of doxorubicin (75 mg/m2 and Ifosfamide (5 g/m2) was given in association with rhGM-CSF. The response rate observed with this combination was 50%. For localized disease, in a randomized trial of the EORTC including 374 evaluable patients with resectable tumors with a mean follow-up of 44 months, the interest of 8 Cyvadic as adjuvant chemotherapy after adequate locoregional treatment (surgery with or without radiotherapy) was demonstrated only for locoregional relapse free survival but no for metastatic disease free survival or overall survival.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗

A phase I trial with recombinant interferon gamma (Roussel UCLAF) in advanced cancer patients.

A total of 29 patients with advanced malignancy were treated with recombinant interferon gamma (rIFN gamma, specific activity = 2.10(7) units/mg, purity greater than 95%) given by intravenous bolus at doses escalating from 0.01 mg/m2 to 5 mg/m2 (2 x 10(5) - 10(8) IU/m2) in nine successive steps (at least 3 patients/step). Injections of rIFN gamma were repeated every 72 h for 15 days. Toxicity was evaluated according to the WHO scale. Fever and chills occurred in all patients treated without clear dose effect. Nausea and vomiting appeared at the fifth dose level and their frequency seemed to be dose-related. Cardiovascular side-effects (first-degree atrioventricular reversible block) were observed at the 2 mg/m2 and 5 mg/m2 levels (3 patients). Hematological toxicities were mild (2 grade 1 and 1 grade II cases of granulocytopenia). Minor biological modifications included a transitory rise in hepatic enzymes (12 patients), which correlated with the presence of liver metastasis. Hypocholesterolemia was observed in 18 patients. The appearance of antibodies against rIFN gamma was not detected. One partial clinical response was observed in a patient receiving 2 mg/m2. During rIFN gamma therapy this patient had the highest scores in this series for peripheral T lymphocytes with an activated phenotype (HLA DR+, TAC+) = 15% and for natural killer (NK) cells (NKH1, Leu19+) = 17%. rIFN gamma appears as a well-tolerated and promising therapeutic agent with toxicities and mode of action probably distinct from IFN alpha and beta.

Adult↗

Pilot study of neoadjuvant ifosfamide, cisplatin, and etoposide in locally advanced non-small cell lung cancer.

33 patients with locally advanced non-small cell lung cancer entered a study of neoadjuvant chemotherapy to evaluate the response rate with ifosfamide/cisplatin/etoposide and the complete resection rate and safety of surgery following chemotherapy. Chemotherapy with cisplatin 25 mg/m2, ifosfamide 1.5 g/m2, and etoposide 100 mg/m2 was given on days 1-4 of a 21 day cycle and repeated for three cycles. For responders, surgery was done 15-20 days after haematological recovery. Chemotherapy induced 5 complete responses (15%) and 18 partial responses (55%). 77% of the 33 patients had grade 3-4 neutropenia and 60% grade 3-4 thrombocytopenia. 1 patient died with a central nervous system haemorrhage. Thoracotomy was done in 21 patients but resection was only possible in 20 (61%). A complete resection was achieved in 18 patients (55%). Histology was negative for the 5 complete responses. Surgery induced no morbidity. A high response rate may be obtained with ifosfamide, cisplatin and etoposide neoadjuvant chemotherapy allowing a high complete resection rate.

Adult↗

[Combined radiotherapy-chemotherapy in inoperable bronchial carcinoma (small cell carcinoma excluded)].

When treated by irradiation alone, non small cell carcinomas of the lung usually experience a very poor outcome. Consequently, more interest is being focussed on radiotherapy and chemotherapy association. The analysis of a randomized trial comparing irradiation alone to a sequential or an alternated combination of radio and chemotherapy did not reveal any clear advantage of the association of both therapies on each technique used alone. It is only when using concurrent irradiation and chemotherapy that some encouraging results are reported. Several non randomized studies used radio and chemotherapy prior to surgery, aiming at increasing the resectability rate. However, the criteria for initial unresectability were not homogeneous and it is not yet clear if such an association really allowed the state of surgical resection to be improved. In the near future it could be worth considering the use of radiosensitizing drugs, synchroneously given with an irradiation delivered with a multiple daily fractionation. This technique would possibly lead to a therapeutic gain, by increasing the local control rate and reducing the metastasis rate, while keeping it to an acceptable level of toxicity.

Antineoplastic Combined Chemotherapy Protocols↗

Identification and measurement of calcitonin precursors in serum of patients with malignant diseases.

Previous studies have suggested that molecular species larger than the mature calcitonin (CT) are produced by tumors of different origin. In order to study these species, we developed a monoclonal immunoradiometric assay for calcitonin precursors (CT-pr). This assay was based on both monoclonal antibody KC01 directed to the 1-11 region of katacalcin and monoclonal antibody CT08 directed to the 11-17 portion of CT. The sensitivity of this monoclonal immunoradiometric assay for CT-pr was less than 100 pg/ml. Only one of 131 healthy subjects had CT-pr serum levels greater than 100 pg/ml; this value was therefore selected as the standard serum value in healthy individuals. CT-pr was present in the serum of seven of ten patients with advanced renal failure and in that of 21 of 52 patients (40%) with benign liver disease but was undetectable in sera of patients with other benign diseases. The serum CT-pr level was correlated with that of mature CT in patients with medullary carcinoma of the thyroid. In contrast, the serum CT-pr level was frequently elevated in the absence of a detectable CT level in patients with various malignant tumors and, particularly, in those with either tumors of the neuroendocrine system (60%) or hepatocellular carcinomas (62%). CT-pr was detected in tumor extract from a patient with a hepatocellular carcinoma. Moreover, hybridization experiments with total RNA extracted from this tumor demonstrated the presence of RNAs hybridizing with complementary DNA encoding for common region, calcitonin, and katacalcin sequences. These results show that CT precursors are excreted by numerous cancers and might well be useful biological markers for the follow-up of productive tumors.

Antibodies, Monoclonal↗

Ten-year results of a randomized trial comparing a conservative treatment to mastectomy in early breast cancer.

A randomized trial was conducted at the Institut Gustave-Roussy (IGR) between 1972 and 1980 comparing tumorectomy and breast irradiation with modified radical mastectomy. One hundred and seventy-nine patients with an infiltrating breast carcinoma up to 20 mm in diameter at macroscopic examination were included: 88 had conservative management, and 91 a mastectomy. All patients had a low-axillary dissection with immediate histological examination. For the patients with positive axillary nodes, a complete axillary dissection was undertaken. Overall survival, distant metastasis, contralateral breast cancer and locoregional recurrence rates were not significantly different between the two treatment groups.

Adenocarcinoma↗