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D Couanet

Publications and source records attributed to D Couanet.

At least 37 records · Page 2Linked to original sources
PubMed1998

Phase II study of high-dose thiotepa and hematopoietic stem cell transplantation in children with solid tumors.

From 1987 to 1995, 22 children with refractory solid tumors entered a phase II study of high-dose thiotepa (HDT) (900 mg/m2) followed by stem cell transplantation (SCT) in the Pediatrics Department of the Institut Gustave Roussy. Tumor types were rhabdomyosarcoma (eight), osteosarcoma (seven), neuroblastoma (three), Ewing's sarcoma (three) and Burkitt's lymphoma (one). Before HDT, all had been extensively treated with conventional chemotherapy, surgical resection of the primary tumor (13/22) and of metastases (6/22), and radiotherapy of the primary tumor in three patients. All had measurable disease, at the site of the primary tumor (3 patients), of the metastases (9 patients) or both (10 patients). Toxicity from the HDT was severe but acceptable. No toxicity-related death occurred. The median duration of neutropenia and thrombocytopenia was 18 days (5-37) and 30 days (7-377), respectively. Septicemia was documented in four patients. Severe diarrhea was observed in seven patients. Mild hepatic toxicity occurred 18 times. No CR and 11/22 PR were documented: osteosarcoma 4/7, rhabdomyosarcoma 4/8, Ewing's sarcoma 2/3; 1/1 Burkitt's lymphoma progressed. We conclude that at a dose of 900 mg/m2 followed by SCT support in these heavily pretreated children, the main toxicity induced by thiotepa was digestive. The response rate observed, especially in sarcoma, is particularly encouraging. Thiotepa should be further evaluated in HDC regimens either in combination with other alkylating agents or in rapidly cycled courses of HDC with SCT.

Adolescent↗
PubMed1998

Long-term follow up of 69 patients treated for optic pathway tumours before the chemotherapy era.

AIM: To analyse the long-term results of conservative management with radiotherapy in patients with optic pathway tumours. DESIGN: All 69 patients were symptomatic at diagnosis and most neoplasms involved the optic chiasm and hypothalamus. RESULTS: At 10 years, overall survival and progression free survival were 83% and 65.5%, respectively. After radiotherapy, vision improved in 18 patients and remained stable in 29 other patients. Cerebrovascular complications occurred in nine of 53 patients treated with radiotherapy after a median interval of two and a half years. These complications were five times more frequent in patients with neurofibromatosis type 1 (NF1). Severe intellectual disabilities were present in 18 children, most of whom underwent irradiation at a very young age (median age, 4 years). IMPLICATIONS: Radiotherapy is a valuable treatment in terms of tumour response, visual outcome, and progression free survival. However, in young children and in patients with NF1, major sequelae are encountered and new treatment strategies should be proposed for these patients.

Adolescent↗
PubMed1997

Nonmetastatic intracranial germinoma: the experience of the French Society of Pediatric Oncology.

BACKGROUND: Standard treatment of localized intracranial germinoma is focal irradiation of the primary tumor (45-50 grays [Gy]) combined with craniospinal radiotherapy (RT). To decrease late effects related to extensive fields of RT, the French Society of Pediatric Oncology decided in 1990 to replace prophylactic RT with chemotherapy (CT) and to deliver focal RT at 40 Gy. METHODS: Twenty-nine patients with localized, biopsy proven germinoma were included in this study between January 1990 and December 1994. CT consisted of 2 cycles of carboplatin 600 mg/m2 on Day 1, etoposide 150 mg/m2 on Days 1-3, ifosfamide 1.8 g/m2 on Days 22-26, and etoposide 150 mg2 on Days 22-24, followed by RT delivered to the initial tumor volume (40 Gy). RESULTS: The median age of the 19 boys and 10 girls was 12.8 years; 25 patients had a unifocal tumor in the pineal (13), suprasellar (10), or thalamic (2) area, and 4 patients had a bifocal tumor. Three patients initially had complete surgery. Of the 26 patients evaluable for CT response, 11 had a small amount of tumor residue and 15 no residue; no patient underwent surgery after CT or RT. One patient recurred 3 years after diagnosis and is in his second complete remission. Twenty-eight patients are in their first complete remission after a median follow-up of 32 months (range, 7-68 months); 9 of the 28 have a small amount of tumor residue that is considered nonevolving. Overall survival at 4 years is 100% and event free survival is 93.3% (+/- 6%) after a median follow-up of 32 months. CONCLUSIONS: This treatment strategy avoids craniospinal RT and reduces focal RT, with results equivalent to those achieved with extensive RT. Thus, the authors consider it a valid treatment of nonmetastatic germinoma.

Adolescent↗
PubMed1997

Dural sinus thrombosis in children with cancer.

Dural sinus thrombosis (DST) has been reported in association with cancer in both adults and children. We describe the seven patients seen with this complication in our centre between 1981 and 1995. Diagnosis was confirmed by either cerebral CT scanning, MRI or angiography. Median age was 13 years (range 8-15). Six patients were boys. Six children were being treated for non-Hodgkin lymphoma and one for neuroblastoma. Presenting symptoms were seizures and transient neurologic deficit, often preceded by headaches. The probable cause of DST was found in two cases. Tumour localisation in the central nervous system (CNS) probably caused DST in one patient who was treated for ki 1 lymphoma. Dehydration in combination with a poor general condition seemed to be the cause of DST in the patient with neuroblastoma. In five children with stage III or IV non-Hodgkin lymphoma (three lymphoblastic lymphoma; two Burkitt's lymphoma), etiology remained unknown. In these children, DST occurred early in the course of therapy. The median interval between start of chemotherapy and onset of symptoms was 19 days (range 8-40). No child had received L-asparaginase. Prognosis was favourable, with symptoms completely disappearing without therapy within 1 to 5 days. The incidence of DST in patients with advanced stage non-Hodgkin lymphoma during induction and consolidation was calculated to be below 3%. We conclude that DST is rarely diagnosed in children with cancer. Occurrence during the initial phase of therapy for non-Hodgkin lymphoma is associated with a benign prognosis.

Adolescent↗
PubMed1996

A high-dose busulfan-thiotepa combination followed by autologous bone marrow transplantation in childhood recurrent ependymoma. A phase-II study.

Sixteen children with refractory or relapsed ependymoma were entered in a phase-II study of high-dose chemotherapy followed by autologous bone marrow transplantation (ABMT). The conditioning regimen consisted of busulfan 150 mg/m2/day for 4 days and thiotepa 300 mg/m2/day for the 3 following days. All patients had previously been treated by surgery and conventional chemotherapy. Eight of them had also received irradiation at doses ranging from 45 to 55 Gy at the tumor site. At the time of transplantation, 9 patients were in first relapse, 5 in second relapse and 2 in third relapse or more; all had measurable disease; 15 patients were evaluable for response. No radiologic response > 50% was observed. Stable disease and progressive disease were documented in 10 and 5 cases, respectively. The duration of response to this treatment, which lasted for a median time of 7 months (range: 5-8 months), was only evaluable in 5 patients who did not receive further treatment after ABMT. To date, there are 3 disease-free survivors at 15, 25 and 27 months all of whom were treated with second complete surgical resection and local radiotherapy (55 Gy). Toxicity was severe, mainly digestive and cutaneous, and 1 toxicity-related death occurred. Unlike medulloblastomas, ependymomas do not appear to be sensitive to this combination therapy. New therapeutic approaches are warranted.

Adolescent↗
PubMed1996

Phase I study of high-dose continuous intravenous infusion of VP-16 in combination with high-dose melphalan followed by autologous bone marrow transplantation in children with stage IV neuroblastoma.

The purpose of the study was to determine the maximum tolerated dose of continuous infusion of high-dose VP-16 in combination with high-dose melphalan (HDM) for conditioning before autologous bone marrow transplantation (ABMT). Thirteen children (median age 27 months) with stage IV neuroblastoma were treated with high-dose VP-16 and HDM followed by ABMT as consolidation treatment. All had previously received conventional chemotherapy with a mean number of six drugs. Surgery of the primary tumor had been performed in 12/13. We performed a dose-escalating study of VP-16 from 1800 mg/m2/72 h with 300 mg/m2/72 h dose increments according to toxicity. VP-16 was administered as a 72-h i.v. infusion. Melphalan (140 mg/m2/day) was administered once as an i.v. push. VP-16 pharmacokinetics were analyzed in 12 patients. Five children received 1800 mg/m2/72 h of VP-16, five received 2100 mg/m2/72 h and three, 2400 mg/m2/72 h. The mean duration of granulocytopenia (< 0.5 x 10(9)/1) was 24 days and thrombocytopenia (< 50 x 10(9)/1) was 36 days. No major infectious complications occurred. Gastrointestinal (GI) toxicity was the dose-limiting toxicity. Five severe manifestations of GI toxicity in three patients led us to consider 2400 mg/m2/72 h as the MTD. The mean VP-16 clearance rate was 17.3 ml/min/m2 with continuous infusion. A mean steady-state plasma concentration of 24.2 micrograms/ml (s.d. = 2) and 28.3 micrograms/ml (s.d. = 1.9) was achieved at the 1800 mg/ml and 2100 mg/m2 dose levels, respectively, GI toxicity is dose limiting when VP-16 at 2400 mg/m2/72 h, is associated with HDM. When given as a continuous i.v. infusion, at 2100 mg/m2/72 h, VP-16 associated with HDM is well tolerated before ABMT in young heavily pre-treated children.

Antineoplastic Combined Chemotherapy Protocols↗
PubMed1996

[Retrospective analysis of 44 adrenal puncture biopsies under x-ray computed tomographic guidance].

Fourty-four CT-guided adrenal biopsies were performed on 43 patients aged 12-74 years old (mean 57 years). The results (benign adrenal tissue, malignant tissue, and nondiagnostic) were compared with outcomes. Diagnostic samples were obtained in 86% of patients. Among the 37 proved cases with diagnostic results (10 benign, 27 malignant), there were 26 true-positives, 1 false-negatives and 10 true-negatives. CT-guided adrenal biopsy had an accuracy of 82%, a sensitivity of 96%, a negative predictive value of 83%. In the 6 patients with nondiagnostic samples 1 mass proved malignant and two masses proved benign. Seven minor complications occurred in 7 patients (6 pneumothoraces and 1 retroperitoneal hemorrhage). CT-guided adrenal biopsy is a simple safe and well tolerated technique. In oncologic patients, obtaining benign adrenal tissue was highly predictive of benignity.

Adolescent↗
PubMed1995

[Research on bone marrow involvement in the diagnosis of solid tumors in children. Methods, results and interpretation].

The assessment of bone marrow involvement by tumor cells remains an essential problem at diagnosis in pediatric solid tumors. Besides the conventional cytological and histological methods, some modern cell density separation techniques have been described in order to improve the detection of minimal or scattered bone marrow involvement. Immunological or genetical (molecular biology) tools can be used for the recognition of separated cells. In terms of investigations, MRI and MIBG radionucleide scan, although giving no definite proof, have the ability to macroscopically study the scattering of bone marrow invasion in the particular case of neuroblastoma. In some pediatric tumors, especially neuroblastomas and non Hodgkin lymphomas, an extensive bone marrow investigation is mandatory at diagnosis. Such an investigation is only necessary in case of particular criteria at diagnosis of Hodgkin's disease, Ewing' sarcomas, rhabdomyosarcomas and retinoblastomas. All other pediatric solid tumors do not need to be investigated in terms of bone marrow involvement at diagnosis, with the exceptions of advanced disseminated disease or if an autologous bone marrow transplantation is planned.

Bone Marrow Diseases↗
PubMed1995

[Treatment of metastatic kidney neoplasms with a new interleukin 2 protocol: The experience of the Gustave-Roussy Institute].

Treatment of metastatic renal cell carcinoma with interleukin 2 (IL2) remains controversial despite the authorization from the French government for IL2 with the West schedule in this disease. We report herein the study of the Institute Gustave-Roussy of 73 patients, who received from 1989 to 1991 a new schedule of high dose IL2. Seventy three patients received high dose IL2 according to the following schedule: IL2 by continuous infusion at 24.10(6) IU/m2/d, on 2 consecutive days per week, during 5 weeks. This treatment was associated in the first 33 patients with gamma interferon at a dose of 5.10(6) IU/m2/d subcutaneously the days of IL2 infusion, during the 5 weeks of therapy. Immunotherapy was further continued in responding patients, either as an association of IL2 and LANAK (lymphokine-activated natural killer) cells, or as IL2 alone. Finally, when possible, surgery was performed on residual masses. Twenty five percent of objective responses (PR + CR) have been observed. Moreover, 12.3% CR has been obtained after the overall therapy. The global mean survival is 15 months, with a mean survival of 8, 18 and 24+ months depending on the status of the disease (progressive, stable or responding) after initial treatment with IL2. Tolerance of this schedule was good with an actual received dose of 90% of the planned doses, and patients could leave the hospital within 2 hours after the end of IL2 in 87% of the cycles. No toxic death was observed. Among the parameters observed for correlation with the clinical response, only performance status and level of sTNF-alpha R were significantly associated with the response.

Adult↗
PubMed1994

What is the prognostic value of osteomedullary uptake on MIBG scan in neuroblastoma patients under one year of age?

Twenty-seven infants under one year of age with metastatic neuroblastoma were studied for osteomedullary metastases. They were evaluated by at least two imaging procedures: X-ray films and MIBG scan. Taking into account the results of these investigations, 3 groups were defined: osteomedullary metastases were detected in 8 infants by both X-ray and MIBG scan, no osteomedullary sites were detected by either technique in 13 patients, and 6 had osteomedullary foci with positive MIBG uptake but no radiological abnormality. These three groups were apparently different in terms of median age, response to chemotherapy, and long-term survival. The third group, which has not been previously described, appears to have a better prognosis than patients with radiologically detectable bone lesions. Nevertheless it was necessary to use intensive chemotherapy to obtain remission in these particular patients. It should be mandatory to specify the investigatory technique used to describe osteomedullary metastases in infants and treatment should be adapted according to this grouping system.

3-Iodobenzylguanidine↗
PubMed1994

Super-high-risk germ-cell tumors: a clinical entity. Report of eleven cases.

Among patients suffering from nonseminomatous germ-cell tumor, with a poor prognosis, a subset underwent respiratory failure and died very early in the course of their treatment. Between 1982 and 1989, 11 out of 56 such patients (20%) died within the first 5 weeks of chemotherapy. The clinical, radiological, biological and infectious characteristics of these patients were analyzed. Nine patients had extensive pulmonary metastases and the 2 others presented a bulky mediastinal mass with pleural effusion. All patients experienced acute respiratory distress during chemotherapy and underwent mechanical ventilation. All patients were febrile, and septicemia was documented in 7 cases. WHO grade 4 and grade 1-2 renal toxicities occurred in 3 and 4 patients respectively. There was no tumor lysis syndrome. All patients died within 35 days from the start of therapy; 4 were autopsied. These 11 patients represent a clinical entity, having what we called super-high-risk germ cell tumors. Early death is related to pulmonary distress within the first 5 weeks of therapy. The origin of the pulmonary distress is multifactorial: bulky disease of the chest, infection, and interstitial fibrosis. Immediate full-dose standard chemotherapy in association with intensive supportive care is recommended in the management of these patients.

Adult↗
PubMed1994

Head and neck rhabdomyosarcomas in children: value of clinical and CT findings in the detection of loco-regional relapses.

Between 1984 and 1990, 16 children who had been treated for a histologically proven head and neck rhabdomyosarcoma developed 19 local recurrences. Fourteen relapses discovered in 11 children (group 1) were based on clinical data acquired 3 to 52 months after completion of treatment. Clinical symptoms (12 patients) or examination (2 patients) led to suspicion of a relapse. The clinical presentation of relapses and that of primary tumour were identical in eight cases. CT scans performed prior to recurrence revealed a stable 'post-therapeutic residue' without mass effect at the original site (12 patients) or was normal (2 patients). Six of these 11 children died at 1 to 15 months and five are alive 12 to 36 months after treatment of recurrence. Five relapses were discovered on CT studies 3 to 15 months after completion of treatment in the remaining five children (group 2). Clinical examination was normal in all cases. CT scans performed 3 months before recurrence showed a stable 'post-therapeutic residue' (4 patients) or was normal (1 patient). All of these five children died 3 to 23 months after the relapse.

Adolescent↗
PubMed1993

Bone metastases as the presenting manifestation of rhabdomyosarcoma in childhood.

Rarely, rhabdomyosarcoma can present with bone pain and bone lesions on radiographs without evidence of a primary tumor. Of 428 children with biopsy-proven rhabdomyosarcoma, four presented with radiographic evidence of bone metastases, but no primary tumor was found on subsequent evaluation. On radiographs, these metastases, located most commonly in the metaphyses of the extremities and in the spine, displayed a destructive or diffusely permeative pattern without sclerotic margins and mimicked the more common neuroblastoma. One patient also had diaphyseal cortical lytic metastases of the tibia. Radiographs defined metastases of the extremities better than the correlative bone scans. In the spine, on T2-weighted magnetic resonance (MR) images, metastases displayed high signal intensity which contrasted with the low-signal-intensity marrow in these pediatric patients. On histopathologic examination, metastatic rhabdomyosarcoma was composed of small cells of variable size, shape, and growth pattern similar to other round cell tumors. A positive desmin immunohistochemical test helped to establish the diagnosis. The radiologist, pathologist, and clinician should be aware of this unusual presentation of rhabdomyosarcoma so that suitable immunohistochemical tests are performed and appropriate chemotherapy given.

Adolescent↗
PubMed1993

Extraskeletal mesenchymal chondrosarcoma.

Among seven patients with extraskeletal mesenchymal chondrosarcoma (EMC), three children (aged 3-6 years) developed EMC in a central location and four adults (aged 38-54 years) developed EMC in both central and peripheral sites. Conventional radiography and tomography and computed tomography (CT) depicted EMC as a soft-tissue mass with ring, arc, stippled, and highly opaque calcifications in four patients. Contrast-enhanced CT showed lobulation and peripheral tumoral enhancement, sometimes with central low-attenuation areas. On magnetic resonance (MR) images, EMC was a lobulated mass with high signal intensity on T2-weighted images and enhancement with low-signal-intensity focal areas on contrast-enhanced T1-weighted images. All adults developed recurrences and/or metastases and died. Of the three children, two were living and free of disease at the end of the study and the third child died of chemotherapeutic-induced leukemia. Although imaging features of EMC are nonspecific, its chondroid-type calcifications and foci of low signal intensity within enhancing lobules may reflect its dual histopathologic morphologic characteristics of differentiated cartilage islands interspersed within vascular undifferentiated mesenchyme.

Adult↗
PubMed1992

High-dose busulfan and thiotepa with autologous bone marrow transplantation in childhood malignant brain tumors: a phase II study.

In order to evaluate the effect of intensive combined chemotherapy in pediatric brain tumors, we designed a phase II study of high-dose busulfan and thiotepa followed by bone marrow transplantation (BMT) in children with measurable recurrent brain tumors. As alkylating agents, busulfan and thiotepa were expected to exhibit a steep dose effect and no overlapping extramedullary toxicity. Moreover, both drugs have an excellent distribution into the central nervous system in humans. Since May 1988, 20 children (median age 6 years) have been treated. Busulfan (150 mg/m2/day x 4) given orally was followed by thiotepa (350 mg/m2/day x 3), given as a 1 h i.v. infusion. Cryopreserved bone marrow was reinfused 48 h after completion of chemotherapy. Tumor response was assessed by computed tomography and magnetic resonance imaging 4 to 6 weeks after BMT. Five partial responses were observed (three of six medulloblastomas, one of five ependymomas, one of two primitive neuroectodermal tumors); two patients with medulloblastoma and one with brain stem tumor achieved an objective response. Ten patients had stable disease and one progressive disease. One patient is not evaluable because of early toxic death. Toxicity was high in terms of aplasia and cutaneous, hepatic and neurological complications. The overall response rate of 26% is encouraging since all patients had disease refractory to all conventional therapies.

Adolescent↗
PubMed1991

Childhood malignant lymphoma of bone.

From 1974 to 1987, 450 children with non-Hodgkins' lymphoma (NHL) were seen at the Institut Gustave Roussy (IGR); 14 children had malignant lymphoma of bone (MLB). Eleven of the 14 were newly diagnosed, whereas three presented in relapse. Nine patients presented with multifocal bone involvement. The median age of these eight girls and six boys was 9.5 years (range 1.25-15 years). Bone pain was present in all patients as the initial symptom. Evaluation included physical examination, routine serum chemistries, complete blood count, chest roentgenography, skeletal survey, radionuclide bone scan, lumbar puncture, bone marrow aspiration, and intravenous pyelography, and/or abdominal ultrasonography. Hypercalcemia was found in six patients. Biopsy was performed in 12 patients, revealing high-grade lymphoblastic lymphomas in all. In two patients diagnosis was made on cytological examination of bone marrow aspirate. Immunophenotyping in four cases, demonstrated non-B, non-T cell origin in three and pre-B cell origin in one. Three patients were treated prior to 1982 with Cyclophosphamide/Oncovin/Prednisone/ADriamycin (COPAD) and seven patients, seen after 1982, were treated with a modified LSA2L2 protocol (LMT). None of the previously untreated patients received radiotherapy. All patients treated with COPAD have died, whereas four out of seven treated with LMT are alive with a median follow up of 51 months (range 36-82 months). One child treated on a pilot study died. One of the three children seen at relapse is disease-free with a follow-up of 98 months after high-dose chemotherapy followed by autologous bone marrow transplantation (ABMT). Five out of six patients presenting with hypercalcemia have died. Results with LMT are encouraging and together with published results suggest that sufficiently intensive chemotherapy can result in complete remission and cure in MLB. Radiotherapy does not seem to be necessary, avoiding possible serious long-term effects. Hypercalcemia is a bad prognostic feature.

Adolescent↗
PubMed1989

Limited small cell lung cancer treated by combined radiotherapy and chemotherapy: evaluation of a grading system of lung fibrosis.

A grading system of radiological fibrosis was defined and applied by four observers for the reading of 218 posterior-anterior chest X-rays of 78 patients. These patients with limited small cell lung cancer were treated from May 1980 to July 1983 in two consecutive alternating radiotherapy-chemotherapy schedules. Chest X-rays performed at each 6-month interval were read by each observer. A second reading was performed the day after. The analysis of results showed that in spite of some systematic variations in intra- and inter-observations, the proposed grading system had a good reproducibility. The radiological lung fibrosis score progressed between 6 and 12 months but was stable after one year of follow-up. There was no difference in the score of lung fibrosis between the two protocols which delivered a total dose of 45 and 55 Gy to the mediastinum. There was no significant correlation between the radiological changes and clinical symptoms.

Antineoplastic Combined Chemotherapy Protocols↗