Long-term renal and hearing toxicity of carboplatin in infants treated for localized and unresectable neuroblastoma: results of the SFOP NBL90 study.

BACKGROUND: A secondary end point of the NBL90 protocol (Rubie H et al. Pediatr Oncol 2001;36:247-250) was the concern in this infant population for possible carboplatin-(CBDCA) induced late side effects including impaired renal and hearing functions. PROCEDURE: Glomerular filtration rate (GFR), tubular function (TF), pure tone audiometry (PTA), high-frequency, and transient evoked-otoacoustic emission were prospectively assessed in 30 children alive and disease-free 6 years after the end of the treatment. RESULTS: Median age at diagnosis and at assessment was 4.7 months and 7 years, respectively. Blood pressure was < or =97.5 centile in all children. The mean estimated GFR was 114 +/- 13 ml/min/1.73 m(2) by Schwartz formula [range 87-145]. TF assessment failed to demonstrate any impairment. 29/30 children had grade 0 ototoxicity and all transient evoked otoacoustic emission were normal. CONCLUSIONS: With a 6-year follow-up the combination of VP16 and carboplatin given at conventional doses is safe on renal and hearing functions in infants with unresectable neuroblastomas treated according to SFOP NB90.

NB87 induction protocol for stage 4 neuroblastoma in children over 1 year of age: a report from the French Society of Pediatric Oncology.

PURPOSE: NB87 was designed to test the efficacy of a short, non cross-resistant, induction protocol for unselected patients over 1 year of age with stage 4 neuroblastoma. A secondary objective was to compare in a randomized study the toxicity of two modalities of cisplatin administration. PATIENTS AND METHODS: A total of 183 patients received two cycles of alternating sequences: cyclophosphamide 300 mg/m2/d on days 1 to 5, vincristine 1.5 mg/m2/d on days 1 and 5, and doxorubicin 60 mg/m2/d on day 5 (CADO); and cisplatin 40 mg/m2/d and etoposide 100 mg/m2/d on days 1 to 5 (CVP), followed by surgery of the primary tumor (126 patients). Ninety-one were randomized to receive cisplatin either as bolus (BO; n = 48) or continuous infusion (CI; n = 43). International Neuroblastoma Staging System (INSS) and Response Criteria (INRC) were used with emphasis on skeletal evaluation by meta-iodobenzylguanidine (MIBG). RESULTS: Hematotoxicity was predominant, with a higher incidence of neutropenia (P = .01) for CADO and of thrombocytopenia for CVP (P < .001). Severe infections, as well as nonhematologic toxicities, occurred more often after the first sequence. Gastrointestinal complications were predominant during both courses of CVP. The toxic death rate, including surgery, was 3%. Complete remissions (CRs) were less frequent on MIBG (45%) compared with marrow (66%) or other metastases (61%). Combining all metastatic sites resulted in a 39% CR rate. After surgery, the final CR rate was 42%. Nephrotoxicity was minimal in both arms (92% normal clearance for CI v 82% for BO). Hearing loss greater than 40 dB at 6,000 to 8,000 Hz was reported equally in both arms (n = 6 for CI v n = 5 for BO). CONCLUSION: Intensified chemotherapy using CADO/CVP increases CR rates despite a shorter induction duration. However, the rate of MIBG normalization remains unsatisfactory and could be raised through the dose-intensive use of agents such as cyclophosphamide.

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.

[A case of intrauterine dwarfism with enlargement of the cortex of the long bones]. / Une observation de nanisme à début intra-utérin avec élargissement de la corticale des os longs.

The case of a girl with severe, predominantly mesomelic, intrauterine dwarfism with acromicria is reported. Other anomalies included ligamentary hyperlaxity, clinodactyly of the fifth fingers, and narrow dental arches. Roentgenograms failed to disclose any metaphyseal or epiphyseal anomalies; long bones were narrow and short with thick cortices and the pelvis had an unusual appearance. This case is reminiscent of a constitutional disease with elective involvement of the cortices but distinctive features include the very early onset and the severity of statural growth failure.

[Mirror-image osteosarcoma of the radius. A case]. / Ostéosarcome en miroir du radius. Une observation.

Multiple osteosarcoma is a rare tumour which usually has a poor prognosis. We report the case of a 14-year old girl who developed successively, at 2 1/2 years' interval, one osteosarcoma of the right radius bone, then one of the left radius bone. The tumours were strictly symmetrical. Each time, the patient was treated with chemotherapy of the Rosen type and underwent conservative surgery. At present, 5 years after the first treatment, she is in good health. This case is remarkable on several scores: chemotherapy was feasible and well tolerated, the multiple osteosarcoma had a favourable outcome, and conservative surgery of both radius bones gave satisfactory functional results.

[Neonatal pulmonary fibrosarcoma]. / Fibrosarcome pulmonaire néo-natal.

The authors report a case of pulmonary fibrosarcoma in a newborn. The respiratory distress imposed an urgent thoracotomy at the fifth hour of live. A lobectomy was performed. Three months later a relapse occurred. A second thoracotomy permitted an incomplete resection. The total involution was achieved after 6 months of chemotherapy. Actually no recidive is shown after 20 months of follow up. Its an exceptional case. A unique one was published in 1977.

[Cancer chemotherapy and fertility in women]. / Chimiothérapie anticancéreuse et fertilité chez la femme.

Therapeutic advances for certain cancers raise now the problem of long-term toxicity of the chemotherapy, especially on the gonads. The risk of involvement of the gonadic function in women depends on the type of medication used, the dose and duration of the treatment and mostly the age of the patient. After the age of 35, amenorrhea is almost constant and often irreversible. The younger the woman, the better the prognosis. Finally, it seems that post-chemotherapy pregnancies are normal, and so are the children born. However, the carcinogenic risks of the descendants and the risks of mutation of other generations are not well known at the present time.