BACKGROUNDA Phase II trial in children with advanced neuroblastoma was carried out in five Italian institutions to evaluate the antitumor activity and tolerability of topotecan followed by vincristine and doxorubicin.METHODSChildren older than age 1 year with Stage III or Stage IV neuroblastoma, all of whom had been treated previously with chemotherapy and were diagnosed with either refractory or recurrent disease, were treated with topotecan at an intravenous dose of 1.5 mg/m2 (the dose was 0.75 mg/m2 for patients who were treated within 1 year of previous megatherapy) per day for 5 days followed by 48‐hour intravenous infusions of 2 mg/m2 vincristine and 45 mg/m2 doxorubicin. Cycles of therapy were repeated every 3 weeks.RESULTSTwenty‐five patients (2 with Stage III disease and 23 with Stage IV disease; 19 with refractory disease and 6 with recurrent disease) were treated with a total of 115 cycles. Four patients had complete responses, 12 patients had partial responses, 4 patients had minor responses or stable disease, and 5 patients had tumor progression. The overall response rate (including complete and partial responses) was 64% (95% confidence interval, 43–82%). Fifteen patients were alive at the time of the current report and were progression free at 4–16 months (median, 9 months) after the first course of this treatment. Toxicity generally was limited to the hematopoietic system. Dose‐limiting toxicity was observed in only 1 patient (Grade 4 liver toxicity). There were no deaths due to infectious or toxic causes.CONCLUSIONSThe topotecan‐vincristine‐doxorubicin combination was active and well tolerated in previously treated patients with advanced neuroblastoma. Cancer 2003. © 2003 American Cancer Society.

A novel approach is presented for the solution of production planning problems for multiproduct processes. A mixed‐integer programming (MIP) scheduling model is analyzed off‐line to obtain a convex approximation of feasible production levels and a convex underestimation of total production cost as a function of production levels. The two approximating functions are expressed via linear inequalities that involve only planning variables yet provide all the relevant scheduling information necessary to solve the planning problem with high quality. A rolling horizon algorithm is also presented for generation (if necessary) of detailed schedules. © 2007 American Institute of Chemical Engineers AIChE J, 2007

Summary:Despite the use of aggressive chemotherapy, stage 4 high risk neuroblastoma still has very poor prognosis which is estimated at 25%. Metabolic radiotherapy with I 131 MIBG appears a feasible option to enhance the effects of chemotherapy. Seventeen patients having MIBGpositive residual disease received 4.1-11.1 mCi/kg of I 131 MIBG 7-10 days before initiating the high-dose chemotherapy cycle consisting of busulphan 16 mg/kg and melphalan 140 mg/m 2 followed by PBSC infusion. We compared the toxicity in these patients to that seen in 15 control subjects with neuroblastoma who underwent a PBSC transplant without MIBG therapy. We observed greater toxic involvement of the gastrointestinal system in children treated with I strategy includes inductive chemotherapy, mainly based on ozaphorines and platine derivatives followed by surgery and a consolidation phase including megatherapy with stem cell rescue. Conditioning regimens combining high-dose chemotherapy with total body irradiation have been abandoned due to unsatisfactory results and severe late effects. In a Children's Cancer Group (CCG) study, the event-free survival (EFS) of children receiving high-dose (HD) chemotherapy with peripheral blood stem cell transplantation (PBSC) rescue was 34% reaching 46% when followed by further therapy with 13 cis-retinoic acid treatment. 1 Targeted radiotherapy with I 131 metaiodobenzylguanidine (MIBG) has proven to be active in advanced neuroblastoma (NB) and insertion in the megatherapy regimen is promising. In fact, I 131 MIBG, that concentrates in the neuroblastoma cells, is potentially capable of selectively delivering a substantial radiation dose to neoplastic cells while sparing normal tissues. We report on the feasibility of this approach in 17 patients with advanced NB. Fifteen children with NB receiving a similar myeloablative conditioning regimen without I 131 MIBG are evaluated and reported as controls. Our experience suggests that including I 131 MIBG in the conditioning regimen followed by PBSC rescue in children taking up MIBG is a feasible therapeutic strategy, although attention should be paid to avoiding lung complications. Patients and methods Patients' characteristics and first line therapyFrom October 1994 to February 2000 17 patients suffering from either stage 3 (one patient) or 4 (16 patients) neuroblastoma and having positive MIBG residual disease were treated with MIBG megatherapy followed by high-dose chemotherapy with PBSC rescue. Ten were females and seven were males. Median age at diagnosis was 3 years (range 1-9). Median time between diagnosis and megatherapy was 7 months (range 4-46). NB origin was adrenal in seven cases, retroperitoneal gangliar in seven cases, abdominal in two, and unknown in one.