Protracted Etoposide During Induction Therapy for High Risk Neuroblastoma

Induction Phase Overview The induction phase is approximately 15 weeks long. Chemotherapy is generally given every 3 weeks, each 3 week block is called a "cycle". During these 15 weeks we will treat subjects with chemotherapy 5 times using combinations of 4 different chemotherapy drugs. All IV chemotherapy drugs will be given in the hospital. During this 15 weeks doctors will try to collect special blood cells called hematopoietic stem cells. If the subject's tumor has not been removed completely you will have a surgery to take the rest of the tumor out as soon as possible once it has shrunk with the first two cycles of chemotherapy. Induction Phase Chemotherapy During the first 2 cycles of chemotherapy all children will receive two drugs: cisplatin and etoposide. Cisplatin is given through an IV for everyone. If participating in the research treatment plan, etoposide by mouth mouth for 14 days. After the first two cycles we will repeat studies to see if the tumor has shrunk. Then all children will receive two other chemotherapy drugs called cyclophosphamide and adriamycin during the 3rd cycle. If the subject responded to the first two cycles, the 4th cycle will be IV cisplatin and oral etoposide again; if the subject did not respond to the first two cycles, the 4th cycle will be IV cisplatin with standard IV etoposide. The 5th cycle will again be adriamycin and cyclophosphamide. If subjects choose not to participate in the research treatment plan, or are not eligible for the research treatment plan, cycle 1, 2, and 4 will be IV Cisplatin and IV Etoposide. Here is the induction treatment: Treatment #1, 2, and 4: Cisplatin and etoposide: Cisplatin will be given once a day for 5 days through an IV. Etoposide will be given either by mouth once a day for 14 days (research treatment plan) or through an IV for 3 days (standard treatment plan). Treatment #3 and 5: Cyclophosphamide and adriamycin: Cyclophosphamide and adriamycin are given daily for 2 days, both drugs are given through an IV. Cyclophosphamide may cause irritation of the bladder so another drug called mesna will be given several times after each dose to help prevent this. After treatment #3 and #5 patients will receive a drug called G-CSF. It stimulates the body to make white blood cells (infection fighting cells) to help prevent infections that can happen because of chemotherapy. G-CSF is an injection that must be given daily. Surgery: If the primary tumor was not removed before chemotherapy,subjects will undergo a second surgery after receiving chemotherapy. Tumor reevaluation is after cycle #2 and if it is resectable subjects will have surgery at that time. If this is not possible images of the tumor will be taken after cycle #3 and again after cycle #5. Surgery will occur as soon as the tumor is resectable Stem Cell Harvest Stem cells are special cells that can make all the different types of blood cells. Usually they are found in the bone marrow, but after chemotherapy many more of them are in your blood stream. Between the third and fifth cycles of induction, stem cells will be collected from the blood using a procedure called apheresis. The central line or catheter is connected to a machine that draws some of the subjects blood out of one side of the catheter, filters out the stem cells, and returns the rest of the blood through the other side of the catheter. Each apheresis procedure takes about 4-6 hours. The procedure may need to be done several times to collect enough stem cells. The consolidation phase takes approximately 15 weeks to complete and consists of radiation to the tumor followed by high doses of chemotherapy and hematopoietic stem cell transplant. HERE IS THE TREATMENT PLAN: Local Tumor Radiation: Local radiation therapy is given daily for about 2 weeks. Radiation beams will be aimed at the sites of the tumor. Each child's treatment will be designed just for them. The doctor who gives radiation will discuss the therapy in detail. Some children require sedation for radiation therapy. Radiation therapy does not usually require admission to the hospital. High Dose Chemotherapy and Hematopoietic Stem Cell Transplant Carboplatin, etoposide and melphalan: Carboplatin and etoposide are given daily for 4 days followed by melphalan for 3 days. Stem cells will be infused after chemotherapy. After high dose therapy subjects will receive G-CSF to help stimulate the growth of white blood cells. Other drugs will be used during and after the chemotherapy to prevent or decrease side effects from this treatment. Until the stem cells restore safe levels of blood cells, subjects will need to be hospitalized. This treatment may require hospitalization for 3 to 4 weeks or longer. Maintenance Phase Starting approximately 3 months following stem cell transplant subjects will receive six monthly treatments with 13-cis-retinoic acid. 13-cis retinoic acid is a drug closely related to vitamin A and has been shown to help stop the multiplication of any remaining neuroblastoma cells in the body. This drug will be taken 2 times a day by mouth for 14 days and then not take it for the following 14 days. This 28-day cycle will be repeated 6 times. AFTER COMPLETING STUDY TREATMENT The consolidation phase of treatment for high risk neuroblastoma lasts about 4 months. The entire treatment will last about 12-14 months.