International Pleuropulmonary Blastoma (PPB) Treatment and Biology Registry. Types I, II and III PPB

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1 CHILDREN S HOSPITALS AND CLINICS of MINNESOTA 2525 Chicago Avenue South Minneapolis, Minnesota 55404, USA International Pleuropulmonary Blastoma (PPB) Treatment and Biology Registry Types I, II and III PPB APPENDIX VIII: TYPE II AND IIII PPB HYDRATION, TREATMENT GUIDELINES, AND ROADMAPS Pre-hydration for ADo courses: D5½NS at 200 ml/m2/hour, until patient is adequately hydrated (urine output exceeds 2 cc/kg/hr). Chemotherapy: Vincristine push day 1, then weekly until (including) week 7 then every 3 weeks. Actinomycin push day 1. Ifosfamide (I) over 3 hours, days 1, 2. MESNA with Ifosfamide and then 3, 6, and 9 hours after the start of the Ifosfamide dose. Doxorubicin over 30 min, days 1, 2. Pre-hydration for A courses: D5½NS at 200 ml/m2/hour, until patient is adequately hydrated (urine output exceeds 2 cc/kg/hr). Chemotherapy: Vincristine push day 1. Actinomycin push day 1. Ifosfamide (I) over 3 hours, day 1. MESNA with Ifosfamide and then 3, 6, and 9 hours after the start of the Ifosfamide dose. Post-hydration, all courses: D5½NS + 10 meq KCl/L at 125 ml/m2/hour beginning immediately after Ifosfamide and continuing until next Ifosfamide dose or until 24 hours after last dose.

2 Treatment Study Therapy: I 2 VADo 2 Courses 1 & 2 BSA m² Due Given Day Week VCR *IFOS DACT DOXO Mesna mg. 1 1 VCR *IFOS DACT DOXO Mesna 2 *IFOS DOXO 8 2 VCR 15 3 VCR 22 4** VCR *IFOS DACT DOXO Mesna 23 *IFOS DOXO 29 5 VCR 36 6** VCR Vincristine (VCR) Actinomycin D (DACT) Doxorubicin (DOXO) Dose Table DOXO: Mesna: < 6 months 15 mg/m² Dose per Table, push Days as above Dose per Table, over 3 hours, Days as above. Give with Mesna and hydration. Dose per Table, push Days as above Dose per Table, 6-hr continuous infusion, Days as above (Max. cumulative dose 375 mg/m² if no mediastinal radiation; max dose 300 mg/m² if mediastinal radiation used). Dose per Table, with Ifos over 1 hour; doses 2 and 3 push over 3-5 min. at hours 3 and mg/m² 30 mg/m² 300 mg/m² 400 mg/m² *Substitute CPM for IFOS for all subsequent cycles if significant Fanconi syndrome occurs. See Protocol A-XI: 1.2 for CPM, and

3 Treatment Study Therapy: I 2 VADo 2 Courses 3 & 4 BSA m² Due Given Day Week VCR *IFOS DACT DOXO Mesna mg. 1 7 VCR *IFOS DACT DOXO Mesna 2 *IFOS DOXO VCR 8 8 VCR * VCR *IFOS DACT DOXO Mesna 23 *IFOS DOXO VCR 36 12** VCR **Begin next course when Plt. Ct. > 100k and ANC > 1,000. Vincristine (VCR) Actinomycin D (DACT) Doxorubicin (DOXO) Dose Table DOXO: Mesna: < 6 months 15 mg/m² Dose per Table, push Days as above Dose per Table, over 3 hours, Days as above. Give with Mesna and hydration. Dose per Table, push Days as above Dose per Table, 6-hr continuous infusion, Days as above (Max. cumulative dose 375 mg/m² if no mediastinal radiation; max dose 300 mg/m² if mediastinal radiation used). Dose per Table, with Ifos over 1 hour; doses 2 and 3 push over 3-5 min. at hours 3 and mg/m² 30 mg/m² 300 mg/m² 400 mg/m² *Substitute CPM for IFOS for all subsequent cycles if significant Fanconi syndrome occurs. See Protocol A-XI: 1.2 for CPM, and

4 Therapy: A Courses 5 & ** VCR *IFOS DACT Mesna 22 16** VCR *IFOS DACT Mesna Vincristine (VCR) Dose per Table, push Days as above Dose per Table, over 3 hours, Days as above. Give with Mesna and hydration. Actinomycin D (DACT) Dose per Table, push Days as above Dose per Table, with Ifos over 1 hour; doses 2 and 3 push over 3-5 min. at hours 3 and 7. M: 300 mg/m² 400 mg/m²

5 Therapy: A Courses 7 & * VCR *IFOS DACT Mesna 22 22* VCR *IFOS DACT Mesna Vincristine (VCR) Dose per Table, push Days as above Dose per Table, over 3 hours, Days as above. Give with Mesna and hydration. Actinomycin D (DACT) Dose per Table, push Days as above Dose per Table, with Ifos over 1 hour; doses 2 and 3 push over 3-5 min. at hours 3 and 7. M: 300 mg/m² 400 mg/m²

6 Therapy: A Courses 9 & * VCR *IFOS DACT Mesna 22 28* VCR *IFOS DACT Mesna Vincristine (VCR) Dose per Table, push Days as above Dose per Table, over 3 hours, Days as above. Give with Mesna and hydration. Actinomycin D (DACT) Dose per Table, push Days as above Dose per Table, with Ifos over 1 hour; doses 2 and 3 push over 3-5 min. at hours 3 and 7. M: 300 mg/m² 400 mg/m²

7 Therapy: A Courses 11 & ** VCR *IFOS DACT Mesna 22 34** VCR *IFOS DACT Mesna Begin Follow up Vincristine (VCR) Dose per Table, push Days as above Dose per Table, over 3 hours, Days as above. Give with Mesna and hydration. Actinomycin D (DACT) Dose per Table, push Days as above Dose per Table, with Ifos over 1 hour; doses 2 and 3 push over 3-5 min. at hours 3 and 7. M: 300 mg/m² 400 mg/m²

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