Bone Cancer Treatment Regimens Clinical Trials: The NCCN recommends cancer patient participation in clinical trials as the gold standard for treatment. Cancer therapy selection, dosing, administration, and the management of related adverse events can be a complex process that should be handled by an experienced health care team. Clinicians must choose and verify treatment options based on the individual patient; drug dose modifications and supportive care interventions should be administered accordingly. The cancer treatment regimens below may include both U.S. Food and Drug Administration-approved and unapproved indications/regimens. These regimens are provided only to supplement the latest treatment strategies. These Guidelines are a work in progress that may be refined as often as new significant data become available. The NCCN Guidelines® are a consensus statement of its authors regarding their views of currently accepted approaches to treatment. Any clinician seeking to apply or consult any NCCN Guidelines® is expected to use independent medical judgment in the context of individual clinical circumstances to determine any patient’s care or treatment. The NCCN makes no warranties of any kind whatsoever regarding their content, use, or application and disclaims any responsibility for their application or use in any way. Note: All recommendations are category 2A unless otherwise indicated. uSystemic Therapy for MSI-H/dMMR Tumors1 REGIMEN DOSING Preferred Regimens Pembrolizumab2-6,a Day 1: Pembrolizumab 200mg IV over 30 minutes. Repeat cycle every 3 weeks for up to 2 years. OR Day 1: Pembrolizumab 400mg IV over 30 minutes. Repeat cycle every 6 weeks for up to 2 years. uSystemic Therapy for TMB-H (≥10 mutations/megabase) Tumors1 Useful in Certain Circumstances Pembrolizumab2-6,b Day 1: Pembrolizumab 200mg IV over 30 minutes. Repeat cycle every 3 weeks for up to 2 years. OR Day 1: Pembrolizumab 400mg IV over 30 minutes. Repeat cycle every 6 weeks for up to 2 years. uSystemic Therapy for Chondrosarcoma: Metastatic and Widespread Disease Other Recommended Regimens Dasatinib7-9,c Days 1-28: Dasatinib 70mg-100mg orally twice daily. Repeat cycle every 4 weeks. Pazopanib10,11,c Days 1-28: Pazopanib 800mg orally daily. Repeat cycle every 4 weeks. uSystemic Therapy for Chondrosarcoma Conventional (Grades 1-3)1 Preferred Regimens No known standard chemotherapy options1 Useful in Certain Circumstances Ivosidenib Days 1-28: Ivosidenib 500mg orally daily. (for susceptible IDH1 mutations)12,13,c Repeat cycle every 4 weeks. uSystemic Therapy for Chondrosarcoma Dedifferentiated1 Preferred Regimens Follow osteosarcoma regimens (Category 2B)1 Useful in Certain Circumstances Ivosidenib Days 1-28: Ivosidenib 500mg orally daily. (for susceptible IDH1 mutations)12-13,c Repeat cycle every 4 weeks. uSystemic Therapy for Chondrosarcoma Mesenchymal1 Preferred Regimens Follow Ewing Sarcoma Regimens (category 2B)1 continued 1 CancerTherapyAdvisor.com Bone Cancer Treatment Regimens uSystemic Therapy for Chordoma1 REGIMEN DOSING Other Recommended Regimens Dasatinib7-9,c Days 1-28: Dasatinib 70mg-100mg orally twice daily. Repeat cycle every 4 weeks. Imatinib14,c Days 1-28 : Imatinib 400mg orally twice daily. Repeat cycle every 4 weeks. Sunitinib17,18,c,e Days 1-28: Sunitinib 37.5mg orally daily. Repeat cycle every 4 weeks. Useful in Certain Circumstances Erlotinib19,20,c Days 1-28: Erlotinib 150mg orally once daily. Repeat cycle every 4 weeks. Imatinib + Cisplatin14,19,21,22,c,d Day 1: Cisplatin 25mg/m2 IV over 60 minutes. Days 1-7: Imatinibc 400mg orally daily. Repeat cycle every week. Imatinib + Sirolimus14,23,24,c Days 1-28: Imatinib 400mg orally once daily Days 1-28: Sirolimus 2mg orally once daily (dose is adjusted to keep concentration within therapeutic range of 15-20 ng/mL). Repeat cycle every 4 weeks. Lapatinib (for EGFR mutation-positive Days 1-28: Lapatinib 1500mg orally once daily. chordomas)25,26,c Repeat cycle every 4 weeks. Sorafenib27-30,c,e Days 1-28: Sorafenib 400mg orally twice daily. Repeat cycle every 4 weeks. uEwing Sarcoma First-line Therapy (Primary/Neoadjuvant/Adjuvant Therapy)1 Preferred Regimens VDC/IE Day 1: Vincristine 2mg/m2 (maximum 2mg) IV over 5-10 minutes (Vincristine + Doxorubicin/Dactinomycin Day 1: Doxorubicin 75mg/m2 IV push + Cyclophosphamide Alternate with OR Ifosfamide and Etoposide) Day 1: Dactinomycin 1,250mcg/m2 IV push (Category 1)31-36,f-i Day 1: Cyclophosphamide 1,200mg/m2 IV over 60 minutes Day 1: Mesna 240mg/m2 IV over 15 minutes three times daily (one dose before cyclophosphamide, then at 4 and 8 hours from the start of each cyclophosphamide dose) Repeat cycle every 3 weeks for cycles 1 and 3 (neoadjuvant) and cycles 5, 7, 9, 11, 13, 15, and 17 (adjuvant), or cycles 1, 3, 5, 7, 9, 11, 13, 15, and 17 (metastatic), alternating with: Days 1-5: Ifosfamide 1,800mg/m2 IV over 3 hours daily Days 1-5: Mesna 360mg/m2 IV over 15 minutes three times daily (one dose before ifosfamide, then at 4 and 8 hours from the start of each ifosfamide dose) Days 1-5: Etoposide 100mg/m2 IV over 60 minutes daily. Repeat cycle every 3 weeks for cycles 2 and 4 (neoadjuvant) and cycles 6, 8, 10, 12, 14, and 16 (adjuvant) or cycles 2, 4, 6, 8, 10, 12, 14, and 16 (metastatic), alternating with: VDC regimen (shown above). VDC/IE Day 1: Vincristine 2mg/m2 IV (maximum 2mg) IV over 5-10 minutes (as neoadjuvant/adjuvant therapy for Days 1-2: Doxorubicin 37.5mg/m2 IV over 5-10 minutes OR patients aged <50 years) Day 1: Doxorubicin 75mg/m2 IV push OR (Category 1)31-37,f-i Day 1: Dactinomycin 1,250mcg/m2 IV push Day 1: Cyclophosphamide 1,200mg/m2 IV over 60 minutes Day 1: Mesna 240mg/m2 IV over 15 minutes three times daily (one dose before cyclophosphamide, then at 4 and 8 hours from the start of each cyclophosphamide dose). Repeat cycle every 2 weeks for cycles 1, 3, and 5 (neoadjuvant) and cycles 7, 9, 11, and 13 (adjuvant), alternating with: Days 1-5: Ifosfamide 1,800mg/m2 IV over 3 hours daily Days 1-5: Mesna 360mg/m2 IV over 15 minutes three times daily (one dose before ifosfamide, then at 4 and 8 hours from the start of each ifosfamide dose). Days 1-5: Etoposide 100mg/m2 IV over 60 minutes daily. Repeat cycle every 2 weeks for cycles 2, 4, and 6 (neoadjuvant) and cycles 8, 10, 12, and 14 (adjuvant), alternating with: VDC regimen (shown above). continued 2 CancerTherapyAdvisor.com Bone Cancer Treatment Regimens uEwing Sarcoma First-line Therapy (Primary/Neoadjuvant/Adjuvant Therapy)1 (continued) REGIMEN DOSING Other Recommended Regimens VAI Day 1: Vincristine 1.5mg/m2 (maximum 2mg) IV over 5-10 minutes (Vincristine + Doxorubicin/Dactinomycin Days 1-2: Doxorubicin (even numbered cycles) 30mg/m2 IV push once daily + Ifosfamide)31,32,34,38,39,f,g,i Days 1-3: Dactinomycin (odd-numbered cycles) 500mcg/m2 IV push once daily Days 1-3: Ifosfamide 2,000mg/m2 IV over 3 hours once daily Days 1-3: Mesna 400mg/m2 IV over 15 minutes three times daily (once prior to ifosfamide, then at 4 and 8 hours from the start of each ifosfamide dose). Repeat cycle every 3 weeks for 4-8 cycles (neoadjuvant) and 5-12 cycles (adjuvant) or 14 cycles (metastatic). VIDE Day 1: Vincristine 1.5mg/m2 (maximum 2mg) IV over 5-10 minutes (Vincristine + Ifosfamide + Doxorubicin/ Days 1-3: Ifosfamide 3,000mg/m2 IV over 3 hours daily Dactinomycin + Etoposide)31,32,34,35,40,41,f,g,i Days 1-3: Mesna 600mg/m2 IV over 15 minutes 3 times daily (once prior to ifosfamide, then at 4 and 8 hours from the start of each ifosfamide dose) Days 1-3: Doxorubicin 20mg/m2 IV push daily OR Days 1-3: Dactinomycin 500mcg/m2 IV push daily Days 1-3: Etoposide 150mg/m2 IV over 60 minutes daily. Repeat cycle every 3 weeks for 4-8 cycles (neoadjuvant) and 5-12 cycles (adjuvant) for total of 9-16 cycles or 14 cycles total (metastatic). uEwing Sarcoma Primary Therapy for Metastatic Disease at Initial Presentation1 Preferred Regimens VDC/IE Day 1: Vincristine 2mg/m2 (maximum 2mg) IV over 5-10 minutes (Vincristine + Doxorubicin/Dactinomycin Day 1: Doxorubicin 75mg/m2 IV push OR + Cyclophosphamide Day 1: Dactinomycin 1,250mcg/m2 IV push Alternate with Ifosfamide and Day 1: Cyclophosphamide 1,200mg/m2 IV over 60 minutes Etoposide)31-37,f,g,i Day 1: Mesna 240mg/m2 IV over 15 minutes three times daily (one dose before cyclophosphamide, then at 4 and 8 hours from the start of each cyclophosphamide dose) Repeat cycle every 3 weeks for cycles 1, 3, 5, 7, 9, 11, 13, 15, and 17 (metastatic), alternating with: Days 1-5: Ifosfamide 1,800mg/m2 IV over 3 hours daily Days 1-5: Mesna 360mg/m2 IV over 15 minutes three times daily (one dose before ifosfamide, then at 4 and 8 hours from the start of each ifosfamide dose) Days 1-5: Etoposide 100mg/m2 IV over 60 minutes daily. Repeat cycle every 3 weeks for cycles 2, 4, 6, 8, 10, 12, 14, and 16 (metastatic), alternating with: VDC regimen (shown above). VAI Day 1: Vincristine 1.5mg/m2 (maximum 2mg) IV over 5-10 minutes (Vincristine + Doxorubicin/Dactinomycin Days 1-2: Doxorubicin (even numbered cycles) 30mg/m2 IV push once daily + Ifosfamide)31,32,34,38,39,f,g,i Days 1-3: Dactinomycin (odd-numbered cycles) 500mcg/m2 IV push once daily Days 1-3: Ifosfamide 2,000mg/m2 IV over 3 hours once daily Days 1-3: Mesna 400mg/m2 IV over 15 minutes three times daily (once prior to ifosfamide, then at 4 and 8 hours from the start of each ifosfamide dose).