Difference between revisions of "Bone sarcoma"
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===References=== | ===References=== | ||
# Strauss SJ, McTiernan A, Driver D, Hall-Craggs M, Sandison A, Cassoni AM, Kilby A, Michelagnoli M, Pringle J, Cobb J, Briggs T, Cannon S, Witt J, Whelan JS. Single center experience of a new intensive induction therapy for ewing's family of tumors: feasibility, toxicity, and stem cell mobilization properties. J Clin Oncol. 2003 Aug 1;21(15):2974-81. [http://jco.ascopubs.org/content/21/15/2974.long link to original article] '''contains verified protocol''' [http://www.ncbi.nlm.nih.gov/pubmed/12885818 PubMed] | # Strauss SJ, McTiernan A, Driver D, Hall-Craggs M, Sandison A, Cassoni AM, Kilby A, Michelagnoli M, Pringle J, Cobb J, Briggs T, Cannon S, Witt J, Whelan JS. Single center experience of a new intensive induction therapy for ewing's family of tumors: feasibility, toxicity, and stem cell mobilization properties. J Clin Oncol. 2003 Aug 1;21(15):2974-81. [http://jco.ascopubs.org/content/21/15/2974.long link to original article] '''contains verified protocol''' [http://www.ncbi.nlm.nih.gov/pubmed/12885818 PubMed] | ||
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=Malignant fibrous histiocytoma (MFH) of bone= | =Malignant fibrous histiocytoma (MFH) of bone= | ||
*Malignant fibrous histiocytoma (MFH) of bone has been treated with [[#Osteosarcoma|osteosarcoma regimens]] | *Malignant fibrous histiocytoma (MFH) of bone has been treated with [[#Osteosarcoma|osteosarcoma regimens]] |
Revision as of 01:54, 6 September 2016
Use of this site is subject to you reading and agreeing with the terms set forth in the disclaimer.
Is there a regimen missing from this list? Would you like to share a different dosage/schedule or an additional reference for a regimen? Have you noticed an error? Do you have an idea that will help the site grow to better meet your needs and the needs of many others? You are invited to contribute to the site.
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Chondrosarcoma
- No standard chemotherapy for grades 1 to 3 conventional chondrosarcoma
- Mesenchymal chondrosarcoma has been treated with Ewing's sarcoma regimens
- Dedifferentiated chondrosarcoma has been treated with osteosarcoma regimens
Ewing's sarcoma
Cyclophosphamide & Topotecan
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Regimen #1, Saylors et al. 2001
Level of Evidence: Phase II
The NCCN, Bone Cancer version 2.2012, also says that Vincristine (Oncovin) can be added to this regimen. No primary reference for this is available.
- Cyclophosphamide (Cytoxan) 250 mg/m2 IV over 30 minutes on days 1 to 5, given first
- Topotecan (Hycamtin) 0.75 mg/m2 IV over 30 minutes on days 1 to 5, given second
21-day cycles x 12 to 14 cycles
Supportive medications:
- 500 mL/m/2 fluids PO/IV 2 to 4 hours before chemotherapy
- Antiemetics as premedication before chemotherapy
- 3 liters/m2 PO/IV over 24 hours after chemotherapy
- Filgrastim (Neupogen) 5 mcg/kg SC daily starting on day 6, to continue until ANC is at least 1500 after the nadir period
Regimen #2, Hunold et al. 2006
Level of Evidence: Phase II
The NCCN, Bone Cancer version 2.2012, also says that Vincristine (Oncovin) can be added to this regimen. No primary reference for this is available.
- Cyclophosphamide (Cytoxan) 250 mg/m2 IV over 30 minutes on days 1 to 5
- Topotecan (Hycamtin) 0.75 mg/m2 IV over 30 minutes on days 1 to 5
21-day cycles x 12 to 14 cycles
Supportive medications:
- Mesna (Mesnex), antiemetics, fluids, and Filgrastim (Neupogen) "according to institutional standards"
Local therapy:
- Surgical removal of tumors is done when possible.
- Radiation therapy for all other lesions.
References
- Saylors RL 3rd, Stine KC, Sullivan J, Kepner JL, Wall DA, Bernstein ML, Harris MB, Hayashi R, Vietti TJ; Pediatric Oncology Group. Cyclophosphamide plus topotecan in children with recurrent or refractory solid tumors: a Pediatric Oncology Group phase II study. J Clin Oncol. 2001 Aug 1;19(15):3463-9. link to original article contains verified protocol PubMed
- Hunold A, Weddeling N, Paulussen M, Ranft A, Liebscher C, Jürgens H. Topotecan and cyclophosphamide in patients with refractory or relapsed Ewing tumors. Pediatr Blood Cancer. 2006 Nov;47(6):795-800. link to original article contains verified protocol PubMed
Cyclophosphamide & Topotecan - high dose
back to top |
Regimen
Level of Evidence: Non-randomized
The NCCN, Bone Cancer version 2.2012, also says that Vincristine (Oncovin) can be added to this regimen. No primary reference for this is available.
- Cyclophosphamide (Cytoxan) 2100 mg/m2/day (4200 mg/m2 total dose) IV continuous 24-hour infusion on days 1 & 2; infusion starts second after mesna has started
- Children 10 years or younger received Cyclophosphamide (Cytoxan) 70 mg/kg/day (140 mg/kg total dose) IV continuous 24-hour infusion on days 1 & 2
- Cyclophosphamide is given in D5NS with 10 mEq potassium chloride (KCl) and 5 mg Furosemide (Lasix) per 500 mL fluid. 500 mL total volume is used for patients with body surface area <1 m2; 1000 mL total volume is used for patients with BSA of at least 1 m2
- Mesna (Mesnex) 2100 mg/m2/day (6300 mg/m2 total dose) IV continuous 24-hour infusion on days 1 to 3; infusion starts first
- Children 10 years or younger received Mesna (Mesnex) 70 mg/kg/day (210 mg/kg total dose) IV continuous 24-hour infusion on days 1 to 3
- If body surface area <1 m2, mesna is given in 500 mL NS over 24 hours
- If body surface area is at least 1 m2, mesna is given in 1000 mL NS over 24 hours
- Children 10 years or younger received Mesna (Mesnex) 70 mg/kg/day (210 mg/kg total dose) IV continuous 24-hour infusion on days 1 to 3
- Topotecan (Hycamtin) 2 mg/m2/day (6 mg/m2 total dose) IV continuous 24-hour infusion on days 1 to 3; suspended in D5W; infusion starts third after mesna and cyclophosphamide have started
subsequent cycles to start when ANC >1000 and platelets >75,000
Supportive medications:
- On day 1, prior to chemotherapy, 20 mL/kg normal saline IV bolus over 30 minutes, then D5 1/2 NS with 15 mEq KCl per 500 mL at 200 mL/m2/H until urine specific gravity <1.010, then start mesna & cyclophosphamide
- Additional hydration fluid on days 1 & 2 so that, when added to volumes of cyclophosphamide, mesna, and topotecan, total volume of fluids is 3000 mL/m2/24 hours
- Additional hydration fluid on day 3 at 150 mL/m2/hour for 6-12 hours after completion of cyclophosphamide infusion
- Filgrastim (Neupogen) 5 mcg/kg SC daily starting one day after completion of chemotherapy, to continue until ANC is at least 1000
References
- Kushner BH, Kramer K, Meyers PA, Wollner N, Cheung NK. Pilot study of topotecan and high-dose cyclophosphamide for resistant pediatric solid tumors. Med Pediatr Oncol. 2000 Nov;35(5):468-74. link to original article contains verified protocol PubMed
Docetaxel & Gemcitabine
back to top |
Regimen
Level of Evidence: Retrospective
The NCCN, Bone Cancer version 2.2012, also says that Vincristine (Oncovin) can be added to this regimen. No primary reference for this is available.
Only 2 of the 22 patients in this retrospective review had Ewing sarcoma.
- Docetaxel (Taxotere) 75-100 mg/m2 IV over 60 minutes on day 8, given after gemcitabine
- Gemcitabine (Gemzar) 675 mg/m2 IV over 90 minutes on days 1 & 8
21-day cycles
Supportive medications:
- Ondansetron (Zofran) prior to chemotherapy on days 1 & 8
- Dexamethasone (Decadron) starting either the day before or the day of docetaxel, and continued for 2 days after docetaxel
- H1 or H2 blockers such as Diphenhydramine (Benadryl) and Ranitidine (Zantac) prior to chemotherapy on days 1 & 8 per physician discretion
- Some patients received Filgrastim (Neupogen) starting on day 9
References
- Navid F, Willert JR, McCarville MB, Furman W, Watkins A, Roberts W, Daw NC. Combination of gemcitabine and docetaxel in the treatment of children and young adults with refractory bone sarcoma. Cancer. 2008 Jul 15;113(2):419-25. link to original article contains verified protocol PubMed
EVAIA
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EVAIA: Etoposide, Vincristine, Adriamycin (Doxorubicin), Ifosfamide, DActinomycin
Regimen
Study | Evidence | Comparator |
Paulussen et al. 2008 (EICESS-92) | Phase III | VAIA |
This regimen is intended for high-risk patients.
Initial therapy
- Etoposide (Vepesid) 150 mg/m2 IV once per day on days 1 to 3
- Vincristine (Oncovin) 1.5 mg/m2 IV once on day 1
- Doxorubicin (Adriamycin) 30 mg/m2 IV once per day on days 2 & 4
- Ifosfamide (Ifex) 2000 mg/m2 IV once per day on days 1 to 3; primary reference does not comment about the use of Mesna (Mesnex)
- Dactinomycin (Cosmegen) 0.5 mg/m2 IV once per day on days 1, 3, 5
21-day cycle x 4 cycles, then proceed to local therapy:
Local therapy
- Surgical removal of tumors is done when possible.
- For patients not undergoing surgery, with incomplete surgical resection, or poor histologic response, 54.4 Gy of radiation is administered
- For patients with a good histologic response, 44.8 Gy of radiation is administered
- Additional details about particular clinical scenarios can be found in the original reference
Chemotherapy after local therapy
- 10 additional cycles of EVAIA as described above
References
- Paulussen M, Craft AW, Lewis I, Hackshaw A, Douglas C, Dunst J, Schuck A, Winkelmann W, Köhler G, Poremba C, Zoubek A, Ladenstein R, van den Berg H, Hunold A, Cassoni A, Spooner D, Grimer R, Whelan J, McTiernan A, Jürgens H; European Intergroup Cooperative Ewing's Sarcoma Study-92. Results of the EICESS-92 Study: two randomized trials of Ewing's sarcoma treatment--cyclophosphamide compared with ifosfamide in standard-risk patients and assessment of benefit of etoposide added to standard treatment in high-risk patients. J Clin Oncol. 2008 Sep 20;26(27):4385-93. link to original article contains verified protocol PubMed
ICE - Ifosfamide, Carboplatin, Etoposide
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ICE: Ifosfamide, Carboplatin, Etoposide
Regimen
Level of Evidence: Phase II
The NCCN, Bone Cancer version 2.2012, also says that Vincristine (Oncovin) can be added to this regimen. No primary reference for this is available.
The reference did not mention Mesna (Mesnex) being used.
- Ifosfamide (Ifex) 1800 mg/m2 IV once per day on days 1 to 5
- Carboplatin (Paraplatin) 400 mg/m2 IV "for 2 days"--the reference did not explicitly say which 2 days carboplatin should be given on
- Etoposide (Vepesid) 100 mg/m2 IV once per day on days 1 to 5
- Resection of disease was allowed after 4 cycles based on patient's response to ICE
21-day cycles, with next cycle starting as soon as ANC is at least 1000 and platelet count is at least 100,000
Supportive medications:
- Depending on the study the patients were enrolled on, they received one of the following:
- CCG-0894: Filgrastim (Neupogen) 5 or 10 mcg/kg/day SC daily, starting 24 hours after completing ICE, and to continue until day 18 if ANC is at least 1000, or until ANC is at least 1000 post nadir, whichever comes later
- CCG-0924: PIXY 321 at doses of 500/750/1000 mcg/m2 daily or 500 mcg/m2 BID SQ, starting on day 5 and to continue until day 18 unless ANC reached 20,000 or platelet count is at least 900,000 for 2 days between days 13-18, or until ANC is at least 1000 and platelet count is at least 100,000, whichever comes later
- CCG-0931: Filgrastim (Neupogen) 5 mcg/kg/day SC daily and IL-6 at 2.5, 3.75, or 5.0 mcg/kg SC BID, starting 24 hours after completing ICE. Filgrastim is continued until ANC is at least 1000, and IL-6 is continued until platelets are at least 100,000 for 2 consecutive days or until day 35, whichever comes sooner.
References
- Van Winkle P, Angiolillo A, Krailo M, Cheung YK, Anderson B, Davenport V, Reaman G, Cairo MS. Ifosfamide, carboplatin, and etoposide (ICE) reinduction chemotherapy in a large cohort of children and adolescents with recurrent/refractory sarcoma: the Children's Cancer Group (CCG) experience. Pediatr Blood Cancer. 2005 Apr;44(4):338-47. link to original article contains verified protocol PubMed
IE - Ifosfamide & Etoposide
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IE: Ifosfamide, Etoposide
Regimen
Level of Evidence: Phase II
The NCCN, Bone Cancer version 2.2012, also says that Vincristine (Oncovin) can be added to this regimen. No primary reference for this is available.
- Ifosfamide (Ifex) 1800 mg/m2 IV once per day on days 1 to 5, given second, together with loading dose of mesna
- Mesna (Mesnex) 2880 mg/m2 total dose on days 1 to 5, given second with irinotecan as follows
- Mesna 360 mg/m2 IV loading dose over 1 hour
- Then Mesna 120 mg/m2/hour IV continuous infusion x 3 hours
- Then Mesna 360 mg/m2 over 15 minutes Q3hours (given at hours 5, 8, 11, 14, 17, 20) x 6 doses; doses after hour 5 can be given PO or IV
- Etoposide (Vepesid) 100 mg/m2 IV over 1 hour on days 1 to 5, given first
- For patients responding to therapy after 4 cycles, local therapy with surgery or radiation is used to try to achieve a complete remission
- Radiation therapy consisted of 1.8 Gy fractions given for a total dose of 50-55 Gy
21-day cycles x 12 cycles
References
- Miser JS, Kinsella TJ, Triche TJ, Tsokos M, Jarosinski P, Forquer R, Wesley R, Magrath I. Ifosfamide with mesna uroprotection and etoposide: an effective regimen in the treatment of recurrent sarcomas and other tumors of children and young adults. J Clin Oncol. 1987 Aug;5(8):1191-8. link to original article contains verified protocol PubMed
TC -> IE, VDoxoC, VEC - POG 9457
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TC -> IE, VDoxoC, VEC: Topotecan, Cyclophosphamide -> Ifosfamide, Etoposide; Vincristine, Doxorubicin, Cyclophosphamide; Vincristine, Etoposide, Cyclophosphamide
POG: Pediatric Oncology Group
Regimen
Level of Evidence: Phase II
This is a complex regimen, and it is suggested to refer to the primary reference and figure 1 for the protocol schema. One arm of patients in this trial received Amifostine (Ethyol), but its usage is not described below since it did not result in improved outcomes.
Optional initial window for stable patients without significantly impaired function or life-threatening disease:
- Topotecan (Hycamtin) 2.4 mg/m2/day IV once per day on days 1 to 5
Supportive medications:
- Filgrastim (Neupogen) 5 mcg/kg SC daily starting on day 6, to continue until ANC is at least 5000 after nadir
5-day course
TC upfront window (starts at week 0):
- Topotecan (Hycamtin) 0.75 mg/m2 IV over 30 minutes on days 1 to 5
- Cyclophosphamide (Cytoxan) 250 mg/m2 IV over 30 minutes on days 1 to 5; given first
Supportive medications:
- Prehydration with 500 mL/m2 D5 1/4 NS
- 1500 mL/m2 PO/IV hydration continuous for 24 hours after chemotherapy
- Filgrastim (Neupogen) 5 mcg/kg SC daily starting on day 6, to continue until ANC is at least 5000 after nadir
21-day cycles x up to 2 cycles--patients with progression after the first cycle moved immediately to induction therapy
High-dose induction therapy (starts at week 6):
IE for cycles 1, 3, 5 (starts at week 6):
- Ifosfamide (Ifex) 3600 mg/m2 IV over 2 hours on days 1 to 5, given second, after etoposide; administered in 200 mL/m2 D5 1/2 NS
- Mesna (Mesnex) 4000 mg/m2 IV once per day on days 1 to 5
- Etoposide (Vepesid) 100 mg/m2 IV over 45 minutes on days 1 to 5, given first, before ifosfamide; administered in 250 mL/m2 of D5 1/2 NS
Supportive medications:
- "Vigorous hydration," antiemetics
- Filgrastim (Neupogen) 5 mcg/kg SC daily starting 24-48 hours after completion of chemotherapy
21-day cycles x a total of 3 cycles of IE, alternating with VDoxoC
VDoxoC for cycles 2 & 4 (starts at week 9):
- Vincristine (Oncovin) 2 mg/m2 (maximum dose per cycle is 2mg) IV bolus on days 1, 8, 15, given first, prior to cyclophosphamide
- Doxorubicin (Adriamycin) 37.5 mg/m2/day (75 mg/m2 total dose) IV continuous 24-hour infusion on days 1 & 2, given third; administered in 2400 mL/m2/day (4800 mL/m2 total volume) of D5 1/2 NS
- Cyclophosphamide (Cytoxan) 2100 mg/m2/day (4200 mg/m2 total dose) IV over 30 minutes on days 1 & 2, given second after vincristine; administered in 200 mL/m2 D5 1/2 NS
- Mesna (Mesnex) 2400 mg/m2 total dose IV; exact schedule not specified by reference
Supportive medications:
- Filgrastim (Neupogen) 5 mcg/kg SC daily starting on day 4, 24 hours after chemotherapy is complete
21-day cycles x a total of 2 cycles of VDoxoC, alternating with IE
Local therapy for primary disease and ongoing chemotherapy (starts at week 21):
VDoxoC:
- Vincristine (Oncovin) 2 mg/m2 (maximum dose per cycle is 2mg) IV once per day on days 1 & 8
- Doxorubicin (Adriamycin) 37.5 mg/m2/day (75 mg/m2 total dose) IV continuous 24-hour infusion on days 1 & 2
- Cyclophosphamide (Cytoxan) 1500 mg/m2 IV on day 1
- Mesna (Mesnex), dosage & schedule not specified by reference
Supportive medications:
- Filgrastim (Neupogen) 5 mcg/kg SC daily starting 24-48 hours after completion of chemotherapy
21-day cycle x 1 cycle, followed by local control
Local control (after week 21):
- Choice of modality between surgical and radiation therapy options is at the discretion of the provider
- Patients treated with radiation along received 45 Gy in 1.8 Gy fractions to the initial tumor volume; additional treatment up to a total of 55.8 Gy was administered to original bony tumors and the postinduction chemotherapy soft tissue volumes plus a 2 cm margin
- See primary reference for details about radiation therapy in a variety of clinical scenarios
Further VEC chemotherapy after local control (starts at "week 24," but depending on what local therapy precedes it, may be at a different point in the schedule):
- Vincristine (Oncovin) 2 mg/m2 (maximum dose per cycle is 2mg) IV once per day on days 1 & 8
- Etoposide (Vepesid) 150 mg/m2 IV once per day on days 1 to 3
- Cyclophosphamide (Cytoxan) 1500 mg/m2 IV on day 1
- Use of Mesna (Mesnex) not specified by reference
Supportive medications:
- Filgrastim (Neupogen) 5 mcg/kg SC daily starting 24-48 hours after completion of chemotherapy
21-day cycles x 2 cycles
Continuation therapy (starts at week 30):
IE:
- Ifosfamide (Ifex) 2100 mg/m2/day IV once per day on days 1 to 5
- Mesna (Mesnex), dosage & schedule not specified by reference
- Etoposide (Vepesid) 100 mg/m2 IV once per day on days 1 to 5
Supportive medications:
- Filgrastim (Neupogen) 5 mcg/kg SC daily starting 24-48 hours after completion of chemotherapy
21-day cycle x 1 cycle
VDoxoC:
- Vincristine (Oncovin) 2 mg/m2 (maximum dose per cycle is 2mg) IV once per day on days 1, 8, 15
- Doxorubicin (Adriamycin) 37.5 mg/m2/day (75 mg/m2 total dose) IV continuous 24-hour infusion on days 1 & 2
- Cyclophosphamide (Cytoxan) 2100 mg/m2/day (4200 mg/m2 total dose) IV once per day on days 1 & 2
- Mesna (Mesnex) dosage & schedule not specified by reference
Supportive medications:
- Filgrastim (Neupogen) 5 mcg/kg SC daily starting 24-48 hours after completion of chemotherapy
21-day cycle x 1 cycle
IE:
- Ifosfamide (Ifex) 2100 mg/m2/day IV once per day on days 1 to 5
- Mesna (Mesnex), dosage & schedule not specified by reference
- Etoposide (Vepesid) 100 mg/m2 IV once per day on days 1 to 5
Supportive medications:
- Filgrastim (Neupogen) 5 mcg/kg SC daily starting 24-48 hours after completion of chemotherapy
21-day cycle x 1 cycle
Local therapy for metastatic disease and ongoing chemotherapy (starts at week 39):
VDoxoC (starts at week 39):
- Vincristine (Oncovin) 2 mg/m2 (maximum dose per cycle is 2mg) IV once per day on days 1 & 8; note: the day 8 dose is not described in the text but is described in figure 1
- Doxorubicin (Adriamycin) 37.5 mg/m2/day (75 mg/m2 total dose) IV continuous 24-hour infusion on days 1 & 2
- Cyclophosphamide (Cytoxan) 2100 mg/m2/day (4200 mg/m2 total dose) IV once per day on days 1 & 2
- Mesna (Mesnex) dosage & schedule not specified by reference
Supportive medications:
- Filgrastim (Neupogen) 5 mcg/kg SC daily starting 24-48 hours after completion of chemotherapy
21-day cycle x 1 cycle, then local control of metastatic disease
Local control of metastatic disease (after week 39):
- Choice of modality between surgical and radiation therapy options is at the discretion of the provider
- Radiation therapy could be used to treat up to three sites of metastatic disease
- See primary reference for details about radiation therapy in a variety of clinical scenarios
Further VEC chemotherapy after local control (starts at "week 42," but depending on what local therapy precedes it, may be at a different point in the schedule):
- Vincristine (Oncovin) 2 mg/m2 (maximum dose per cycle is 2mg) IV once per day on days 1 & 8
- Etoposide (Vepesid) 150 mg/m2 IV once per day on days 1 to 3
- Cyclophosphamide (Cytoxan) 1500 mg/m2 IV on day 1
- Use of Mesna (Mesnex) not specified by reference
Supportive medications:
- Filgrastim (Neupogen) 5 mcg/kg SC daily starting 24-48 hours after completion of chemotherapy
21-day cycles x 2 cycles
References
- Bernstein ML, Devidas M, Lafreniere D, Souid AK, Meyers PA, Gebhardt M, Stine K, Nicholas R, Perlman EJ, Dubowy R, Wainer IW, Dickman PS, Link MP, Goorin A, Grier HE; Pediatric Oncology Group; Children's Cancer Group Phase II Study 9457; Children's Oncology Group. Intensive therapy with growth factor support for patients with Ewing tumor metastatic at diagnosis: Pediatric Oncology Group/Children's Cancer Group Phase II Study 9457--a report from the Children's Oncology Group. J Clin Oncol. 2006 Jan 1;24(1):152-9. link to original article contains verified protocol PubMed
Temozolomide & Irinotecan
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Regimen #1, Casey, et al., 2009
Level of Evidence: Retrospective
The NCCN, Bone Cancer version 2.2012, also says that Vincristine (Oncovin) can be added to this regimen. No primary reference for this is available.
- Temozolomide (Temodar) 100 mg/m2 PO on days 1 to 5, used 1 hour prior to irinotecan
- Irinotecan (Camptosar) 20 mg/m2 IV over 1 hour on days 1 to 5, 8 to 12, given after temozolomide
21-day cycles, given until progression of disease or unacceptable toxicity
Supportive medications:
- Cefixime (Suprax) prophylaxis starting 1 to 2 days prior to irinotecan, continuing until the completion of each cycle
- Activated charcoal, with 5x the dose in mg of the irinotecan dose, maximum of 260 mg PO TID during irinotecan therapy
- Loperamide (Imodium) prn diarrhea
- Patient "advised to maintain hydration"
Regimen #2, Wagner, et al., 2004 & Wagner, et al., 2007
Level of Evidence: Pilot, <20 patients reported
The NCCN, Bone Cancer version 2.2012, also says that Vincristine (Oncovin) can be added to this regimen. No primary reference for this is available.
- Temozolomide (Temodar) 100 mg/m2 PO on days 1 to 5, used 1 hour prior to irinotecan
- Irinotecan (Camptosar) 10 mg/m2 IV over 1 hour on days 1 to 5, 8 to 12, given after temozolomide
- Irinotecan (Camptosar) 15 mg/m2 was also studied, but this dose was not recommended due to dose-limiting toxicities of diarrhea and infection
28-day cycles
Supportive medications:
- Loperamide (Imodium) prn diarrhea
References
- Wagner LM, Crews KR, Iacono LC, Houghton PJ, Fuller CE, McCarville MB, Goldsby RE, Albritton K, Stewart CF, Santana VM. Phase I trial of temozolomide and protracted irinotecan in pediatric patients with refractory solid tumors. Clin Cancer Res. 2004 Feb 1;10(3):840-8. link to original article contains verified protocol PubMed
- Wagner LM, McAllister N, Goldsby RE, Rausen AR, McNall-Knapp RY, McCarville MB, Albritton K. Temozolomide and intravenous irinotecan for treatment of advanced Ewing sarcoma. Pediatr Blood Cancer. 2007 Feb;48(2):132-9. link to original article PubMed
- Casey DA, Wexler LH, Merchant MS, Chou AJ, Merola PR, Price AP, Meyers PA. Irinotecan and temozolomide for Ewing sarcoma: the Memorial Sloan-Kettering experience. Pediatr Blood Cancer. 2009 Dec;53(6):1029-34. link to original article contains verified protocol PubMed
VAC, CVD
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VAC: Vincristine, Adriamycin, Cyclophosphamide
CVD: Cyclophosphamide, Vincristine, Doxorubicin or Dactinomycin
Regimen
- Vincristine (Oncovin) 2 mg/m2 IV on day 1; primary reference does not say the dose is capped at a maximum dose of 2 mg per cycle, but note that Grier et al. 2003 uses a capped dose in the VAC/IE regimen
- Doxorubicin (Adriamycin) 75 mg/m2 IV on day 1
- Cyclophosphamide (Cytoxan) 1200 mg/m2 IV on day 1
21-day cycles x 3 cycles, then local therapy
Local therapy:
- Surgical removal of tumors is done when possible.
- Radiation therapy to all metastatic sites of disease in addition to any radiation planned for primary tumor.
- If only radiation therapy is used, 4500 cGy of radiation is administered to the tumor volume plus a 3 cm margin, followed by 1080 cGy to only the preradiation tumor volume, for a total dose of 5580 cGy
- Residual tumor after surgery and lung metastases are treated with "dose-volume guidelines for gross residual disease"
After local therapy is complete, 2 more cycles of VAC as above are given, for a total of 5 cycles. This is then followed by:
- Cyclophosphamide (Cytoxan) 1200 mg/m2 IV on day 1
- Vincristine (Oncovin) 2 mg/m2 IV on day 1; primary reference does not say the dose is capped at a maximum dose of 2 mg per cycle, but note that Grier et al. 2003 uses a capped dose in the VAC/IE regimen
- Dactinomycin (Cosmegen) 1.25 mg/m2 IV on day 1
21-day cycles x 12 additional cycles
References
- Miser JS, Krailo MD, Tarbell NJ, Link MP, Fryer CJ, Pritchard DJ, Gebhardt MC, Dickman PS, Perlman EJ, Meyers PA, Donaldson SS, Moore S, Rausen AR, Vietti TJ, Grier HE. Treatment of metastatic Ewing's sarcoma or primitive neuroectodermal tumor of bone: evaluation of combination ifosfamide and etoposide--a Children's Cancer Group and Pediatric Oncology Group study. J Clin Oncol. 2004 Jul 15;22(14):2873-6. link to original article contains verified protocol PubMed
VACA
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VACA: Vincristine, Adriamycin, Cyclophosphamide, DActinomycin
Regimen #1, Paulussen et al. 2001
Level of Evidence: Phase III
- Vincristine (Oncovin) 1.5 mg/m2 IV once per day on days 1, 8, 15, 22
- Doxorubicin (Adriamycin) 30 mg/m2 IV once per day on days 1, 2, 43, 44
- Cyclophosphamide (Cytoxan) 1200 mg/m2 IV once per day on days 1 & 43; Cyclophosphamide (Cytoxan) 400 mg/m2 IV once per day on days 22, 23, 24
- Mesna (Mesnex) "as appropriate"
- Dactinomycin (Cosmegen) 0.5 mg/m2 IV once per day on days 22, 23, 24
9-week cycles x 1 initial cycle, then proceed to local therapy
Local therapy:
- Complete surgical removal of tumors is done when possible.
- Patients not undergoing surgery receive 60 Gy radiation to the tumor bulk, with the tumor-bearing compartment receiving at least 44.8 Gy
- Patients with incomplete surgical resection or poor histologic response received 44.8 Gy of radiation
Chemotherapy after local therapy for high risk patients involves 3 additional cycles of VACA as described above.
Regimen #2, Paulussen et al. 2008
Level of Evidence: Phase III
In Paulussen et al. 2008, this regimen was only part of a larger treatment scheme. See how this is incorporated with VAIA below.
- Vincristine (Oncovin) 1.5 mg/m2 IV on day 1
- Doxorubicin (Adriamycin) 30 mg/m2 IV once per day on days 2 & 4
- Cyclophosphamide (Cytoxan) 1200 mg/m2 IV on day 1
- Dactinomycin (Cosmegen) 0.5 mg/m2 IV once per day on days 1, 3, 5
21-day cycles x 10 cycles
References
- Paulussen M, Ahrens S, Dunst J, Winkelmann W, Exner GU, Kotz R, Amann G, Dockhorn-Dworniczak B, Harms D, Müller-Weihrich S, Welte K, Kornhuber B, Janka-Schaub G, Göbel U, Treuner J, Voûte PA, Zoubek A, Gadner H, Jürgens H. Localized Ewing tumor of bone: final results of the cooperative Ewing's Sarcoma Study CESS 86. J Clin Oncol. 2001 Mar 15;19(6):1818-29. link to original article contains verified protocol PubMed
- Grier HE, Krailo MD, Tarbell NJ, Link MP, Fryer CJ, Pritchard DJ, Gebhardt MC, Dickman PS, Perlman EJ, Meyers PA, Donaldson SS, Moore S, Rausen AR, Vietti TJ, Miser JS. Addition of ifosfamide and etoposide to standard chemotherapy for Ewing's sarcoma and primitive neuroectodermal tumor of bone. N Engl J Med. 2003 Feb 20;348(8):694-701. link to original article contains verified protocol PubMed
- Miser JS, Krailo MD, Tarbell NJ, Link MP, Fryer CJ, Pritchard DJ, Gebhardt MC, Dickman PS, Perlman EJ, Meyers PA, Donaldson SS, Moore S, Rausen AR, Vietti TJ, Grier HE. Treatment of metastatic Ewing's sarcoma or primitive neuroectodermal tumor of bone: evaluation of combination ifosfamide and etoposide--a Children's Cancer Group and Pediatric Oncology Group study. J Clin Oncol. 2004 Jul 15;22(14):2873-6. link to original article contains verified protocol PubMed
- Paulussen M, Craft AW, Lewis I, Hackshaw A, Douglas C, Dunst J, Schuck A, Winkelmann W, Köhler G, Poremba C, Zoubek A, Ladenstein R, van den Berg H, Hunold A, Cassoni A, Spooner D, Grimer R, Whelan J, McTiernan A, Jürgens H; European Intergroup Cooperative Ewing's Sarcoma Study-92. Results of the EICESS-92 Study: two randomized trials of Ewing's sarcoma treatment--cyclophosphamide compared with ifosfamide in standard-risk patients and assessment of benefit of etoposide added to standard treatment in high-risk patients. J Clin Oncol. 2008 Sep 20;26(27):4385-93. link to original article contains verified protocol PubMed
VAC/IE
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VAC/IE: Vincristine, Adriamycin, Cyclophosphamide, alternating with Ifosfamide, Etoposide
Regimen #1, Grier et al. 2003
Level of Evidence: Phase III
VAC:
- Vincristine (Oncovin) 2 mg/m2 (maximum dose of 2 mg per cycle) IV on day 1
- Doxorubicin (Adriamycin) 75 mg/m2 IV bolus on day 1
- If total Doxorubicin (Adriamycin) dose received by the patient is at least 375 mg/m2, Dactinomycin (Cosmegen) 1.25 mg/m2 IV on day 1 is used instead
- Cyclophosphamide (Cytoxan) 1200 mg/m2 IV on day 1
- Mesna (Mesnex) after Cyclophosphamide (Cytoxan) for prevention of hemorrhagic cystitis; primary reference did not list dosage/schedule
21-day cycles, alternating with IE, for up to 17 total cycles of chemotherapy
IE:
- Ifosfamide (Ifex) 1800 mg/m2 IV once per day on days 1 to 5
- Mesna (Mesnex) with Ifosfamide (Ifex); primary reference did not list dosage/schedule
- Etoposide (Vepesid) 100 mg/m2 IV once per day on days 1 to 5
21-day cycles, alternating with VAC, for up to 17 total cycles of chemotherapy
Local control of disease:
Starting on week 12. Local control plan can include radiation therapy, surgery, or both depending on physician judgement.
- Surgery can be performed for resectable tumors. No radiation therapy is given for completely resected primary tumors with negative margins.
- For residual tumor after surgery, 4500 cGy radiation is administered to the original tumor volume plus a 1 cm margin
- If only radiation therapy is used, 4500 cGy of radiation is administered to the tumor volume plus a 3 cm margin, followed by 1080 cGy to only the preradiation tumor volume, for a total dose of 5580 cGy
Regimen #2, Miser et al. 2004
Level of Evidence: Phase III
VAC:
- Vincristine (Oncovin) 2 mg/m2 IV on day 1; Miser et al. 2004 does not say the dose is capped at a maximum dose of 2 mg per cycle, but note that Grier et al. 2003 uses a capped dose
- Doxorubicin (Adriamycin) 75 mg/m2 IV on day 1
- Cyclophosphamide (Cytoxan) 1200 mg/m2 IV on day 1
21-day cycles, alternating with IE, for up to 17 total cycles of chemotherapy
IE:
- Ifosfamide (Ifex) 1800 mg/m2 IV once per day on days 1 to 5
- Mesna (Mesnex) with Ifosfamide (Ifex); primary reference did not list dosage/schedule
- Etoposide (Vepesid) 100 mg/m2 IV once per day on days 1 to 5
21-day cycles, alternating with VAC, for up to 17 total cycles of chemotherapy
Local therapy:
Starting on week 9.
- Surgical removal of tumors is done when possible.
- Radiation therapy to all metastatic sites of disease in addition to any radiation planned for primary tumor.
- If only radiation therapy is used, 4500 cGy of radiation is administered to the tumor volume plus a 3 cm margin, followed by 1080 cGy to only the preradiation tumor volume, for a total dose of 5580 cGy
- Residual tumor after surgery and lung metastases are treated with "dose-volume guidelines for gross residual disease"
References
- Grier HE, Krailo MD, Tarbell NJ, Link MP, Fryer CJ, Pritchard DJ, Gebhardt MC, Dickman PS, Perlman EJ, Meyers PA, Donaldson SS, Moore S, Rausen AR, Vietti TJ, Miser JS. Addition of ifosfamide and etoposide to standard chemotherapy for Ewing's sarcoma and primitive neuroectodermal tumor of bone. N Engl J Med. 2003 Feb 20;348(8):694-701. link to original article contains verified protocol PubMed
- Miser JS, Krailo MD, Tarbell NJ, Link MP, Fryer CJ, Pritchard DJ, Gebhardt MC, Dickman PS, Perlman EJ, Meyers PA, Donaldson SS, Moore S, Rausen AR, Vietti TJ, Grier HE. Treatment of metastatic Ewing's sarcoma or primitive neuroectodermal tumor of bone: evaluation of combination ifosfamide and etoposide--a Children's Cancer Group and Pediatric Oncology Group study. J Clin Oncol. 2004 Jul 15;22(14):2873-6. link to original article contains verified protocol PubMed
VAIA (VAI)
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VAIA: Vincristine, Adriamycin (Doxorubicin), Ifosfamide, DActinomycin
VAI: Vincristine, Adriamycin (Doxorubicin), Ifosfamide
Regimen #1
Study | Evidence | Comparator |
Paulussen et al. 2008 (EICESS-92) | Phase III | EVAIA (high-risk) VAIA -> VACA (standard-risk) |
Initial therapy
- Vincristine (Oncovin) 1.5 mg/m2 IV once on day 1
- Doxorubicin (Adriamycin) 30 mg/m2 IV once per day on days 2 & 4
- Ifosfamide (Ifex) 2000 mg/m2 IV once per day on days 1 to 3; primary reference does not comment about the use of Mesna (Mesnex)
- Dactinomycin (Cosmegen) 0.5 mg/m2 IV once per day on days 1, 3, 5
21-day cycle x 4 cycles, then proceed to local therapy:
Local therapy
- Surgical removal of tumors is done when possible.
- For patients not undergoing surgery, with incomplete surgical resection, or poor histologic response, 54.4 Gy of radiation is administered
- For patients with a good histologic response, 44.8 Gy of radiation is administered
- Additional details about particular clinical scenarios can be found in the original reference
Chemotherapy after local therapy for high risk patients involves 10 additional cycles of VAIA as described above. Standard risk patients receive:
- 10 cycles of VAIA as described above
- OR 10 cycles of VACA:
VACA: Vincristine, Adriamycin, Cyclophosphamide, DActinomycin
- Vincristine (Oncovin) 1.5 mg/m2 IV once on day 1
- Doxorubicin (Adriamycin) 30 mg/m2 IV once per day on days 2 & 4
- Cyclophosphamide (Cytoxan) 1200 mg/m2 IV once on day 1
- Dactinomycin (Cosmegen) 0.5 mg/m2 IV once per day on days 1, 3, 5
21-day cycle x 10 cycles
Regimen #2, Paulussen et al. 2001
Level of Evidence: Phase III
- Vincristine (Oncovin) 1.5 mg/m2 IV once per day on days 1, 8, 15, 22
- Doxorubicin (Adriamycin) 30 mg/m2 IV once per day on days 1, 2, 43, 44
- Ifosfamide (Ifex) 3000 mg/m2 IV once per day on days 1, 2, 22, 23, 43, 44
- Mesna (Mesnex) "as appropriate"
- Dactinomycin (Cosmegen) 0.5 mg/m2 IV once per day on days 22, 23, 24
9-week cycles x 1 initial cycle, then proceed to local therapy
Local therapy:
- Complete surgical removal of tumors is done when possible.
- Patients not undergoing surgery receive 60 Gy radiation to the tumor bulk, with the tumor-bearing compartment receiving at least 44.8 Gy
- Patients with incomplete surgical resection or poor histologic response received 44.8 Gy of radiation
Chemotherapy after local therapy for high risk patients involves 3 additional cycles of VAIA as described above.
References
- Paulussen M, Ahrens S, Dunst J, Winkelmann W, Exner GU, Kotz R, Amann G, Dockhorn-Dworniczak B, Harms D, Müller-Weihrich S, Welte K, Kornhuber B, Janka-Schaub G, Göbel U, Treuner J, Voûte PA, Zoubek A, Gadner H, Jürgens H. Localized Ewing tumor of bone: final results of the cooperative Ewing's Sarcoma Study CESS 86. J Clin Oncol. 2001 Mar 15;19(6):1818-29. link to original article contains verified protocol PubMed
- Paulussen M, Craft AW, Lewis I, Hackshaw A, Douglas C, Dunst J, Schuck A, Winkelmann W, Köhler G, Poremba C, Zoubek A, Ladenstein R, van den Berg H, Hunold A, Cassoni A, Spooner D, Grimer R, Whelan J, McTiernan A, Jürgens H; European Intergroup Cooperative Ewing's Sarcoma Study-92. Results of the EICESS-92 Study: two randomized trials of Ewing's sarcoma treatment--cyclophosphamide compared with ifosfamide in standard-risk patients and assessment of benefit of etoposide added to standard treatment in high-risk patients. J Clin Oncol. 2008 Sep 20;26(27):4385-93. link to original article contains verified protocol PubMed
VIDE
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VIDE: Vincristine, Ifosfamide, Doxorubicin, Etoposide
Regimen
Level of Evidence: Phase II
- Vincristine (Oncovin) 1.5 mg/m2 (maximum dose per cycle is 2mg) IV push on day 1
- Ifosfamide (Ifex) 3000 mg/m2 IV over 1 to 3 hours on days 1 to 3
- Mesna (Mesnex) 1000 mg/m2 IV push 1 hour prior to ifosfamide on day 1, then 3000 mg/m2/day IV continuous 24-hour infusion on days 1 to 3
- Doxorubicin (Adriamycin) 20 mg/m2 IV over 4 hours on days 1 to 3
- Etoposide (Vepesid) 150 mg/m2 IV over 1 hour on days 1 to 3
21-day cycles x 6 initial cycles
Supportive medications:
- 2 to 3 liters/m2 hydration per day
- Recommended, but not required: Filgrastim (Neupogen) 5 mcg/kg SC daily x 10 days, starting 24 hours after completion of chemotherapy
- Further therapy is dictated by patient characteristics & response; details can be found in the primary reference
References
- Juergens C, Weston C, Lewis I, Whelan J, Paulussen M, Oberlin O, Michon J, Zoubek A, Juergens H, Craft A. Safety assessment of intensive induction with vincristine, ifosfamide, doxorubicin, and etoposide (VIDE) in the treatment of Ewing tumors in the EURO-E.W.I.N.G. 99 clinical trial. Pediatr Blood Cancer. 2006 Jul;47(1):22-9. link to original article contains verified protocol PubMed
VIDE -> VAI +/- HD SCT
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VIDE: Vincristine, Ifosfamide, Doxorubicin, Etoposide
VAI: Vincristine, DActinomycin, Ifosfamide
HD SCT: High Dose chemotherapy with busulphan and melphalan and Stem Cell Transplant
Regimen
Level of Evidence: Phase II
Initial therapy:
- Vincristine (Oncovin) 1.4 mg/m2 (maximum dose per cycle is 2mg) IV on day 1
- Ifosfamide (Ifex) 3000 mg/m2 IV once per day on days 1 to 3
- Mesna (Mesnex) 3000 mg/m2/day IV continuous 24-hour infusion on days 1 to 3
- Doxorubicin (Adriamycin) 20 mg/m2 IV once per day on days 1 to 3
- Etoposide (Vepesid) 150 mg/m2 IV once per day on days 1 to 3
21-day cycles x up to 6 initial cycles
Local therapy:
- Complete surgical removal of tumors is done when possible.
- Patients not undergoing surgery receive radiation therapy (dosage/schedule not specified) concurrent with consolidation chemotherapy with VAI per the scenarios below.
Patients who presented with localized disease received consolidation with VAI:
- Vincristine (Oncovin) 1.4 mg/m2 (maximum dose per cycle is 2mg) IV on day 1
- Dactinomycin (Cosmegen) 0.75 mg/m2 IV once per day on days 1 & 2
- Ifosfamide (Ifex) 3000 mg/m2 IV once per day on days 1 & 2
- Mesna (Mesnex) 3000 mg/m2/day IV continuous 24-hour infusion on days 1 & 2
- If appropriate, concurrent radiation therapy given sometime during the cycles 1 to 3
21-day cycles x up to 8 cycles
Patients who presented with metastatic disease received one or more cycles of VAI as described above, but were also considered for high-dose chemotherapy and peripheral blood stem cell support after VAI:
- Busulfan (Myleran) 150 mg/m2 IV once per day on days -6 to -3
- Melphalan (Alkeran) 140 mg/m2 IV on day 2
- Peripheral blood stem cell rescue on day 0, using at least 2 x 10^6 CD34+ cells/kg
- Radiation therapy given 2 months after recovery from high-dose treatment
References
- Strauss SJ, McTiernan A, Driver D, Hall-Craggs M, Sandison A, Cassoni AM, Kilby A, Michelagnoli M, Pringle J, Cobb J, Briggs T, Cannon S, Witt J, Whelan JS. Single center experience of a new intensive induction therapy for ewing's family of tumors: feasibility, toxicity, and stem cell mobilization properties. J Clin Oncol. 2003 Aug 1;21(15):2974-81. link to original article contains verified protocol PubMed
Malignant fibrous histiocytoma (MFH) of bone
- Malignant fibrous histiocytoma (MFH) of bone has been treated with osteosarcoma regimens