Results of induction chemotherapy in children older than 1 year with a stage 4 neuroblastoma treated with the NB 97 French Society of Pediatric Oncology (SFOP) protocol.

PURPOSE: To test the metastatic response rate in stage 4 neuroblastoma, using dose-intensive induction chemotherapy in a multi-institutional setting. PATIENTS AND METHODS: From 1998 to 1999, 47 consecutive children were treated according to N7 protocol. Children received cyclophosphamide 140 mg/kg, doxorubicin 75 mg/m(2), and vincristine 0.066 mg/kg (CAV) in cycles 1, 2, 4, and 6, and cisplatinum 200 mg/m(2) and etoposide 600 mg/m(2) (P/VP) in cycles 3, 5, and 7. The International Neuroblastoma Staging system was used with an emphasis on skeletal evaluation by 123-iodine-metaiodobenzylguanidine (MIBG) scintigraphy. A phase II study evaluating the metastasis complete response rate after induction chemotherapy was conducted in patients who had positive metastatic sites on MIBG scans at diagnosis. RESULTS: Forty-six patients were assessable for toxicity. Hematologic toxicity was the main toxicity observed. Neutropenia was more frequent after CAV than after P/VP (P < .001). A higher rate of thrombocytopenia was observed after P/VP (P = .03). Forty patients with positive MIBG were assessable for metastatic response, and complete regression of metastases was achieved in 17 patients (ie, 43%; 95% CI, 27% to 59%). Of all 47 patients, 21 achieved complete metastatic response. CONCLUSION: The N7 induction chemotherapy protocol was feasible in a multicentric setting. The observed metastasis complete response rate was similar to that obtained in our previous studies and significantly lower than that published in a previous series using the same regimen. In our hands, escalating doses of cyclophosphamide and prolonging conventional chemotherapy with the same drugs failed to improve the metastasis complete response rate.

Efficacy of a combination of pemetrexed and multiple redo-surgery in an 11-year-old girl with a recurrent multifocal abdominal mesothelioma.

We report the case of an 11-year-old girl with a recurrent progressive locally advanced abdominal mesothelioma. First, there was an incomplete surgical resection without any complementary chemotherapy, followed by a slow progression of the disease. Three years later, after two macroscopically complete surgical resections of peritoneal and ovarian tumors, she failed to respond to treatment with gemcitabin-carboplatin and gemcitabin-cisplatin, and developed splenic tumors and large multicystic hepatic tumors. She was then treated with pemetrexed. The schedule of chemotherapy was pemetrexed 400 mg intravenously plus cisplatin 60 mg once every 3 weeks associated with folic acid and vitamin B12. The tumor reduction was evaluated with positron emission tomography scan and tomodensitometry every three courses. Chemotherapy tolerance was good apart from a grade III neutropenia at the second course, a fever of unknown origin at the fifth course and a grade III thrombocytopenia at the sixth course. As tolerance and clinical responses were good, pemetrexed posology was increased up to 10%. After six courses, hepatic and splenic lesion tumors were initially diminished and then stablilized. Thus, a surgical resection was attempted: a first surgery followed by a second one 3 days later allowed completion of a difficult left hepatectomy, and resection of the hilum and splenic tumors. Fourteen months after the surgery, the girl remained in partial remission with stable disease. So far, pemetrexed associated with cisplatin revealed a good tolerance and promising results regarding its antitumoral efficacy in a progressive metastatic abdominal mesothelioma in childhood.

Phase II study of temozolomide in relapsed or refractory high-risk neuroblastoma: a joint Société Française des Cancers de l'Enfant and United Kingdom Children Cancer Study Group-New Agents Group Study.

PURPOSE: To determine the response rate (RR) of neuroblastoma (NB) in children to temozolomide (TMZ), and evaluate the duration of response and tolerance of the drug in this patient population. PATIENTS AND METHODS: A multicenter, phase II evaluation of an oral, daily schedule of TMZ (200 mg/m2/d x 5 days every 28 days) was undertaken in children with refractory or relapsed high-risk NB (metastatic or localized with Myc-N amplification). Response assessment was based on imaging with two-dimentional measurement of disease and meta-iodobenzylguanidine (MIBG) score. Activity was defined by a reduction in lesion size or isotope uptake at anytime. Methodology included a two-step design using Fleming's method with a first step of 15 patients and a second of 10 additional patients if two to four responses had been observed in the first cohort. All data was centrally reviewed by a panel. RESULTS: Twenty-five assessable patients were recruited over a 14-month period in 14 centers and received 94 cycles of chemotherapy. Twenty-three patients had metastatic NB either refractory (n = 9) or in relapse (n = 14). Grade 3 or 4 thrombocytopenia was the most frequent toxicity (16% of cycles). Myelosuppression resulted in treatment delays and dose reductions (24% and 21% of cycles, respectively). Response (complete response, very good partial response, or partial response) was observed in five patients (RR = 20% +/- 8%) with a median duration of 6 months and an objective or mixed response in five additional patients. CONCLUSION: Temozolomide shows activity in heavily pretreated patients with NB, and deserves further evaluation in combination with another drug.