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Biomedical subjects

M Brunat-Mentigny

Publications and source records attributed to M Brunat-Mentigny.

At least 37 records · Page 2Linked to original sources
PubMed1997

Ifosfamide and etoposide in childhood osteosarcoma. A phase II study of the French Society of Paediatric Oncology.

The aim of this phase II study was to determine the efficacy of high-dose ifosfamide with moderate dose etoposide in childhood osteosarcoma. From January 1992 to January 1995, 27 children (15 male, 12 female) with relapsed or refractory evaluable osteosarcoma were included in a phase II study of two courses of ifosfamide 3g/m2/day and etoposide 75 mg/m2/day for 4 days. Median age was 14 years (7-19 years). All but one had received high-dose methotrexate and doxorubicin as first-line treatment. 22 patients had previously received ifosfamide. This regimen was given as first-line in 1 patient, second-line in 23 and third-line in 3. Evaluable disease was lung metastases in 21 patients, local relapse in 5 and adenopathy in 1. There were six complete responses, seven partial responses, three minor responses, six stable disease and five progressive disease (including one mixed response). Response rate was 48% (95% confidence interval, 29-67%). Duration of response was not available (10 responding patients had other treatments). Response rate was equivalent in the subgroup of 22 patients who had previously received ifosfamide (4 CR, 6 PR). Among 3 patients who received the phase II regimen as third-line chemotherapy, there was 1 PR. All but 4 patients had a well tolerated grade 4 neutropenia. Transient mild confusion or seizures were each observed once. 5 patients are alive 15-31 months after the beginning of chemotherapy. This combination of drugs at this dosage has tolerable toxicity, is efficient and deserves evaluation in phase III studies.

Adolescent↗
PubMed1997

Phase I study of interleukin-6 in children with solid tumours in relapse.

The aim of this study was to evaluate the feasibility, toxicity and efficacy of escalating doses of subcutaneous recombinant interleukin-6 (IL-6) in children with solid tumours in relapse. Recombinant IL-6 was administered subcutaneously once daily for 14 consecutive days, with a 14 day follow-up period. The starting dose for IL-6 was 1 microgram/kg/day and was escalated in subsequent patients groups until 10 micrograms/kg. Doses were escalated every 3 patients, provided that grade III or IV organ toxicity did not occur at the preceding dose level. Twelve patients were treated, three at each dose level. No grade 3-4 major organ toxicity was observed. Flu-like symptoms and fatigue were the most common side effects. All these symptoms resolved after the end of IL-6 administration. Significant increases in acute-phase proteins (CRP [C reactive protein], fibrinogen) and ESR (Erthrocyte sedimentation rate) were observed in all patients. Stimulatory effects on thrombocytopoiesis were observed at every dose level, and were maximal at 5 micrograms/kg and 10 microgram/kg. There was no tumour response observed during IL-6 administration. Pharmacokinetic profiles performed in 3 patients are consistent with previous reports in adults. IL-6 is a promising new cytokine for paediatric oncology, in particular to increase thrombocyte counts. We recommend that further studies in children proceed at a dose of 5-10 micrograms/kg/day in a once or, better, twice daily administration.

Acute-Phase Proteins↗
PubMed1996

A 5-year (1990-1994) neuroblastoma screening feasibility study in France. Methodology and preliminary observations.

INTRODUCTION: Following the pioneering Japanese experience, several European and North American groups implemented pilot studies on screening infants for neuroblastoma, considering the possibility of demonstrating a decrease in mortality rate. In France, a 5-year (1990-1994) feasibility study on neuroblastoma screening at the age of 4 months was initiated in the Rhône district (1.5 M inhabitants, 26,000 births per year). METHODS: Vanillylmandelic (VMA) and homovanillic (HVA) acids were measured by HPLC, and creatinine (Cr) by the Jaffé's kinetic method on Technicon RA-XT. VMA and HVA were expressed as microgram/mg of Cr. The method was assessed with both a daily intra-laboratory control and a sample of urine obtained from a national quality control organism. RESULTS AND DISCUSSION: The overall participation rate for the 5-year period was 82.2%. Out of 105,293 infants tested from 128,126 births, 12 NB cases were discovered with screening (screened cases) and 1 case was discovered with a late performed test (at 13 months of age). Six neuroblastomas were found clinically before the age of 4 m. Two cases were missed because the parents did not perform the test. Three children with normal tests at screening were false-negative cases: two of them were found secreting at diagnosis, while one remained non-secretory at diagnosis and later on. Otherwise, thirty-five false-positive tests were found. Biochemical observations are discussed. It is too early to reach clinical conclusions from this screening program on neuroblastomas as it is presently being followed up.

Chromatography, High Pressure Liquid↗
PubMed1996

[Prolonged remission in a child with late brain metastasis of retinoblastoma].

BACKGROUND: Outcome of patients with retinoblastoma is strongly related to the extent of the disease at diagnosis. Thus, prognosis of extra-ocular retinoblastoma is poor and metastases to central nervous system are usually fatal. CASE REPORT: An 8-year-old child presented with a late recurrence of bilateral retinoblastoma. Initial treatment had associated enuclation of the left eye and radiation therapy on the right. At time of tumour recurrence, clinical examination showed cervical lymph nodes. There was a large frontal metastasis on the CT scan and bone marrow examination showed a minimal involvement by malignant cells. The patient achieved complete remission with high dose etoposide and carboplatin; he subsequently underwent massive chemotherapy followed by bone marrow rescue, and received additional radiation therapy on the frontal and cervical areas. He is well, five years after relapse. CONCLUSIONS: This case highlights efficacy of chemotherapy in advanced retinoblastomas. Intensive chemotherapy is a promising and potentially curative approach in the management of advanced or metastatic retinoblastomas.

Brain Neoplasms↗
PubMed1996

[Wilms tumor and Bloom syndrome].

UNLABELLED: Bloom syndrome is characterized by growth failure, skin anomalies with sun sensitivity, minor anatomic defects, excessive chromosomic fragility and usually severe immune deficiency. The chromosome fragility predisposes these children to the development of hematologic malignancies and solid tumors. CASE REPORT: Morgan, a 4-year-old boy with Bloom syndrome, developed a Wilms tumor. Chemotherapy was poorly tolerated. Two years later, the child died from an uncontrolled progressive disease. CONCLUSION: This is the fourth reported case of Wilms tumor occurring in a child with Bloom syndrome. This possibility requires repeated abdominal ultrasonography in such patients.

Antineoplastic Combined Chemotherapy Protocols↗
PubMed1996

[School at the end of life. What objectives what hope?].

BACKGROUND: School intervention programs for children and adolescents with cancer have been developed in France during the last years. Their primary objective is to improve the pschychosocial adaptation of these children to normal life through school integration. These programs are however inadequate for these children who will ultimately die from their disease and may require a specific school intervention. MATERIAL AND METHODS: School data from 30 children requiring palliative care were prospectively collected. School interest, its evolution and specific adaptations according to the child's status were analysed. RESULTS: Sixty per cent of the children showed a continuous desire for school education throughout their life's end. Reading, mathematics and computer work were the most favorite topics. Physical disability and fatigue may change their request during the evolution of the disease. School refusal occurred in 40% of the children and is mainly due to other extra-academic topics, or related to uncontrolled pain. CONCLUSION: Objectives of life's end school are different from educational programs proposed for children with cancer. They must be part of palliative care and have to be defined as a specific entity.

Adolescent↗
PubMed1996

Loss of heterozygosity of the RB gene is a poor prognostic factor in patients with osteosarcoma.

PURPOSE: The usual therapy of osteosarcoma is neoadjuvant chemotherapy, followed by surgery, then by postoperative chemotherapy. There is no prognostic factor to predict, at diagnosis, the histologic response and final outcome. Inactivation of the retinoblastoma-susceptibility gene RB is associated with the pathogenesis of several human cancers. In primary osteosarcomas, loss of heterozygosity (LOH) at the RB locus has been found in greater than 60% of cases. The aim of this study was to determine the potential early prognostic value of LOH of RB gene on the biopsy material at diagnosis. PATIENTS AND METHODS: Forty-seven patients with primary osteosarcoma, treated in four French institutions, were studied. LOH was studied by polymerase chain reaction (PCR) of an informative RB DNA polymorphism. RESULTS: Assessment of LOH at the RB gene could be completed on 34 heterozygous patients only. LOH was found in 24 cases (70%). The event-free survival (EFS) rate at 60 months is 100% for patients without LOH, 43% for all patients with RB LOH, and 65% for nonmetastatic patients with RB LOH. The difference in EFS is highly significant at P = .008 and P = .024, respectively. Histologic response after preoperative chemotherapy did not show significant correlation with LOH status. CONCLUSION: RB gene LOH appears to be an early predictive feature for osteosarcomas that indicates a potential unfavorable outcome. RB LOH study might shortly help to identify high-risk patients earlier. If this is verified, therapy could then be adapted earlier to the individual's real risk of relapse.

Adolescent↗
PubMed1996

[Prognostic factors of survival in infiltrating urothelial bladder carcinoma. A retrospective study of 158 patients treated by radical cystectomy].

The clinical files of 158 patients who were treated by radical cystectomy for infiltrating bladder carcinoma were retrospectively reviewed to define prognostic factors. PATIENTS AND METHODS.--All patients had a radical cystectomy with bilateral pelvic lymph node dissection for an infiltrating operable bladder urothelial tumor. Each tumor was classified according the pTNM staging system and were analysed for the presence of vascular invasion, carcinoma in situ and tumor grade. Twenty-three patients (14.5%) had an irradiation. Sixty-seven patients (42%) received chemotherapy (neoadjuvant in 31, adjuvant in 30, both in 6). RESULTS.--The median overall survival of the whole group was 19 months. The 5 years disease free survival (DFS) and overall survival (OS) were 44% and 31%, respectively. In the univariate analysis, the factors with significant prognostic value were: pT stage and the tumor size for OS, age and lymph node involvement for DFS, presence of carcinoma in situ (CIS) and tumor size for local recurrence free survival (LRFS) and sex and lymph node involvement for metastatic free survival (MFS). The following variables attained significant prognostic value in the multivariate analysis: pT stage and an interaction between lymph node involvement and vascular invasion for OS, pT stage and presence of CIS for LRFS, pT stage for MFS. CONCLUSION.--The pT stage, lymph node involvement and vascular invasion are the most important prognostic factors of survival in infiltrating bladder cancer.

Adult↗
PubMed1995

The C5R protocol: a regimen of high-dose chemotherapy and radiotherapy in primary cerebral non-Hodgkin's lymphoma of patients with no known cause of immunosuppression.

In most reported series, less than 20% of patients with primary cerebral non-Hodgkin's lymphoma (PCL) and no known cause of immunodepression are alive and disease-free 5 years after the initial diagnosis. Whether chemotherapy improves the outcome of these patients remains unclear. We report a pilot study of a protocol (C5R) with 5 courses of chemotherapy followed by cranial radiotherapy in 25 adult patients with PCL and no known cause of immunodepression. The median age was 51 years (range, 16 to 70 years) and the median performance status was 2 (range, 1 to 4) in this series. Fourteen patients (56%) achieved a complete response and 4 (16%) achieved a partial response 1 month after the completion of the treatment. Four patients died in the first month of treatment because of progression (n = 1) or toxicity (n = 3). In 3 patients, the treatment could not be performed because of patient refusal (n = 1) or severe infections (n = 2). Myelosuppression was the most frequent side effect; febrile neutropenia occurred in 96%, 89%, 69%, and 74% of the patients after the second, third, fourth, and fifth courses of chemotherapy, respectively. Grade 4 thrombocytopenia occurred in 20% of the patients. With a median follow-up of 24 months, the projected survival of the group at 2 and 5 years is 70% and 56%, respectively. The 4 early deaths occurred in the subgroup of 6 patients greater than 60 years of age with an international prognostic index (IPI) greater than 3. In the 19 remaining patients (76% of this series) less than 61 years of age or with an IPI less than 4, the projected overall survival at 2 and 5 years is 88% and 70%, respectively. The C5R protocol is a highly efficient regimen in nonimmunosuppressed patients with PCL less than 61 years of age or with an IPI less than 4.

Adolescent↗
PubMed1995

Renal function following unilateral nephrectomy for neuroblastoma and Wilms' tumour.

To estimate the side effects of chemotherapy and the influence of age at the time of nephrectomy on renal function, we investigated renal function in 34 uninephrectomised children with neuroblastoma (NB) or Wilms' tumour (WT). The results were compared with 6 controls who underwent nephrectomy for non-malignant disease. Study of renal function was primarily based on the clearance of inulin and para-aminohippuric acid (Cin and CPAH, ml/min per 1.73 m2). No significant differences in Cin/CPAH (mean +/- SD) were found between the NB group (90 +/- 24/421 +/- 95), WT group (85 +/- 17/386 +/- 104) and the controls (93 +/- 13/430 +/- 61). Children with NB and WT were divided into two subgroups according to the theoretical nephrotoxic risk. There was no significant difference in renal function between NB or between WT subgroups. Cumulative cisplatin doses in children with NB did not affect renal function significantly. The age at time of unilateral nephrectomy (< or = 2 years vs. > 2 years) was not associated with a higher risk of renal damage in WT children, whereas in NB children the filtration fraction (Cin:CPAH) was higher in younger children (mean +/- SD: 0.243 +/- 0.023 vs. 0.191 +/- 0.041). In conclusion, uninephrectomised children with NB are supposed to have a higher risk of drug-induced renal impairment compared with those with WT. Our data do not confirm this hypothesis, since renal function was comparable to controls in both groups, except in younger patients with NB who show a high filtration fraction. Since the survival of children with NB has improved, a longer follow-up of their renal function in needed.

Age Factors↗
PubMed1995

Non-metastatic childhood ependymomas.

PURPOSE: Intracranial ependymomas of childhood are relatively infrequent. There are significant disagreements concerning optimal postoperative treatment as well as the patterns of relapse following treatment. The purpose of this retrospective study was the analysis of the recurrence pattern and therefore the implication on the extent of the radiotherapy fields. Data from 37 patients referred within 19 years were used for this study. PATIENTS AND METHODS: From April 1975 to July 1993, 37 children aged 1-14 years were referred for postoperative treatment of an intracranial ependymoma. Twenty-eight children received postoperative radiation therapy and 26 patients received chemotherapy. The median follow-up is 6 years (range 2 months to 19 years). RESULTS: Overall survival and event free survival at 5 and 10 years were 40%. Eighteen children relapsed. Relapses occurred from 1.5 months to 3.6 years post treatment. Relapses were distant in four cases and local in 14. Age, sex, extent of primary resection, chemotherapy and type of radiation therapy did not influence the outcome. Children with poorly differentiated tumors who did not receive postoperative radiation therapy had a higher relapse rate but this difference is not statistically significant. CONCLUSIONS: Despite doses of radiation > or = 50 Gy the majority of recurrences were local. Our results, despite the small number of patients are in accordance to those previously published, suggest that prophylactic craniospinal irradiation is superfluous. Better means of achieved local control are required, such as three-dimensional conformal radiation therapy with dose-escalation study or hyperfractionation regimen.

Adolescent↗
PubMed1995

[Radiotherapy and Ewing tumor in children].

Despite high local control rate in Ewing's sarcoma the exact indication of radiation therapy is still controversial as well as the choice of the target volume and the optimal dose of radiation. The importance of the quality of radiotherapy has been stressed in recently published data and has shown a significant impact on long term local control with adequate radiation therapy. The dramatic improvement of precision allowed by the conformal therapy and three dimensional dosimetry allow to expect a decrease of late effects expected for second malignancies. However, late sequellae and radio-induced osteosarcoma still remain the major side effects after radiotherapy. The authors discuss the results of the main trials on Ewing's sarcoma on the choice of dose and target volume. Surgery is still the preferred choice for small tumors if the foreseen outcome is identical.

Bone Neoplasms↗
PubMed1994

Desmoplastic small round cell tumors of the abdomen.

BACKGROUND: Desmoplastic small round cell tumors (DSRCT) have been only recently identified. METHODS: The authors report DSRCT in two pediatric patients (an 8-year-old boy and 12-year-old boy). In both patients, the initial diagnosis was rhabdomyosarcoma. The resistance to standard chemotherapy and radiation therapy prompted the authors to review the initial biopsy specimens and perform complementary immunophenotypic characterization. RESULTS: These analyses revealed that the tumor cells were strongly positive for keratin epithelial marker antigen, desmin, vimentin, neurospecific enolase, and S100 protein, corresponding to pleomorphic differentiation, characteristic of DSRCT: CONCLUSIONS: The authors suggest that extensive immunohistologic characterization be performed in all cases of small round cell tumors of the abdomen so that the diagnosis of DSRCT is not overlooked. These rare tumors are refractory to chemotherapy, and initial aggressive surgery is warranted.

Antigens, Neoplasm↗
PubMed1994

High-dose VP16 cisplatinum in soft tissue sarcoma of children.

Nine children with soft tissue sarcomas, five of them rhabdomyosarcomas with initial metastatic disease, (one patient, partial response, one patient), refractory primary, (two patients, relapse, five patients) were treated with a combination of high-dose VP16 (100 mg/m2 daily for 5 days) and cisplatin (40 mg/m2 daily for 5 days). The response rate was five out of nine or 55% (+/- 32%) (two complete and three partial, responses). Three of the five responders had rhabdomyosarcomas. The duration of response was 4-58 months (median 11 months). The toxicity was mainly hematological. Thus, the high-dose VP16-cisplatin association warrants further evaluation in soft tissue sarcoma in children.

Adolescent↗
PubMed1994

Etoposide and carboplatin: a highly effective combination in relapsed or refractory Wilms' tumor--a phase II study by the French Society of Pediatric Oncology.

PURPOSE: Since we had previously demonstrated encouraging efficacy of etoposide in patients with relapsed or refractory Wilms' tumor (WT), the likely synergism between etoposide and platinum compounds prompted us to conduct a phase II study of a combination with carboplatin. PATIENTS AND METHODS: Twenty-six relapsed or refractory WT patients were included in a phase II study of two courses of combination etoposide 100 mg/m2/d for 5 days and carboplatin 160 mg/m2/d for 5 days, with a 21-day interval between the two courses. Initial stages were I (n = 2), II (n = 8), III (n = 6), IV (n = 6), V (n = 3), and unknown (n = 1). Sites of diseases were lung(s) (11 patients), abdomen-pelvis or liver or primary tumor (six patients), and multiple (eight patients). Histology was unfavorable in three of 26 patients. RESULTS: Complete response (CR) was documented in eight patients and partial remission (PR) in 11 (overall response rate, 73%). Stable disease (SD) was observed in five patients and progressive disease (PD) in two. Thrombocytopenia (grade IV) was the major toxicity, and platelet transfusions were required in all but two patients. Grade III anemia and grade III to IV neutropenia were seen in 19 and 23, respectively, of 25 assessable first courses. Venoocclusive disease of the liver was fatal in one child who had undergone irradiation to the whole abdomen, 8 weeks before study. CONCLUSION: Combination etoposide and carboplatin has impressive activity in refractory or relapsed WT at the cost of high-grade hematologic toxicity, especially thrombocytopenia. It is of great interest in second-line therapy, since eight of 26 patients are still alive in continuous CR (median follow-up duration, 40 months; range, 24 to 56). This combination deserves further investigation as first-line or consolidation treatment.

Adolescent↗
PubMed1994

[Effect of carboplatin on the pharmacokinetics of melphalan administered intravenously].

In order to perform melphalan dosage adjustment, the linearity of melphalan kinetics was studied, in the case of previous carboplatin administration. Eleven patients with various solid tumors entered the present study. Carboplatin was administered during 5 days over 1-hour infusions; the day after, the melphalan test-dose was administered and followed 24 hours after by the complement dose. Melphalan kinetics were determined from only three plasma samples by using bayesian estimation. The present study showed that previous carboplatin administrations induced wide variations of melphalan pharmacokinetic parameters between the two administrations. As part of this protocol, the order of drug administration should be taken into account, in order to perform melphalan dosage adjustment.

Adolescent↗