Difference between revisions of "Osteosarcoma - historical"
Warner-admin (talk | contribs) m (Text replacement - ", <20 p" to ", fewer than 20 p") |
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[[#top|Back to Top]] | [[#top|Back to Top]] | ||
</div> | </div> | ||
− | The purpose of this page is to provide references to regimens that are obsolete, outdated, or of historical interest only | + | The purpose of this page is to provide references to regimens that are obsolete, outdated, or of historical interest only. Is there a regimen missing from this list? See the [[Osteosarcoma|main osteosarcoma page]] for current regimens. |
{| class="wikitable" style="float:right; margin-right: 5px;" | {| class="wikitable" style="float:right; margin-right: 5px;" | ||
|- | |- | ||
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==MA-BCD {{#subobject:f7c8d9|Regimen=1}}== | ==MA-BCD {{#subobject:f7c8d9|Regimen=1}}== | ||
MA-BCD: High-dose '''<u>M</u>'''ethotrexate, '''<u>A</u>'''driamycin (Doxorubicin), '''<u>B</u>'''leomycin, '''<u>C</u>'''yclophosphamide, '''<u>D</u>'''actinomycin | MA-BCD: High-dose '''<u>M</u>'''ethotrexate, '''<u>A</u>'''driamycin (Doxorubicin), '''<u>B</u>'''leomycin, '''<u>C</u>'''yclophosphamide, '''<u>D</u>'''actinomycin | ||
− | <div class="toccolours" style="background-color:# | + | <div class="toccolours" style="background-color:#ee6b6e"> |
===Regimen {{#subobject:fe9985|Variant=1}}=== | ===Regimen {{#subobject:fe9985|Variant=1}}=== | ||
{| class="wikitable sortable" style="width: 100%; text-align:center;" | {| class="wikitable sortable" style="width: 100%; text-align:center;" | ||
Line 49: | Line 49: | ||
**Cycles 2 to 4: 0.45 mg/m<sup>2</sup> IV bolus once per day on days 43 & 44 | **Cycles 2 to 4: 0.45 mg/m<sup>2</sup> IV bolus once per day on days 43 & 44 | ||
====Supportive therapy==== | ====Supportive therapy==== | ||
− | *[[Folinic acid | + | *[[Leucovorin (Folinic acid)]] 15 mg/m<sup>2</sup> PO every 6 hours x 12 hours once per day, starting 24 hours after the completion of each methotrexate infusion; additional leucovorin used for delayed methotrexate elimination |
*[[Sodium bicarbonate]] urine alkalinization prior to high-dose methotrexate | *[[Sodium bicarbonate]] urine alkalinization prior to high-dose methotrexate | ||
*[[Normal saline]] 4.5 L/m<sup>2</sup> on day 1 after methotrexate; NS 3 L/m<sup>2</sup> on day 2, with adjustments made to keep urine pH greater than 7.4 | *[[Normal saline]] 4.5 L/m<sup>2</sup> on day 1 after methotrexate; NS 3 L/m<sup>2</sup> on day 2, with adjustments made to keep urine pH greater than 7.4 | ||
Line 55: | Line 55: | ||
</div></div> | </div></div> | ||
===References=== | ===References=== | ||
− | # '''COSS-80:''' Winkler K, Beron G, Kotz R, Salzer-Kuntschik M, Beck J, Beck W, Brandeis W, Ebell W, Erttmann R, Göbel U, Havers W, Henze G, Hinderfeld L, Höcker P, Jobke A, Jürgens H, Kabisch H, Preusser P, Prindull G, Ramach W, Ritter J, Sekera J, Treuner J, Wist G, Landbeck G. Neoadjuvant chemotherapy for osteogenic sarcoma: results of a Cooperative German/Austrian study. J Clin Oncol. 1984 Jun;2(6):617-24. [https://doi.org/10.1200/jco.1984.2.6.617 link to original article] ''' | + | # '''COSS-80:''' Winkler K, Beron G, Kotz R, Salzer-Kuntschik M, Beck J, Beck W, Brandeis W, Ebell W, Erttmann R, Göbel U, Havers W, Henze G, Hinderfeld L, Höcker P, Jobke A, Jürgens H, Kabisch H, Preusser P, Prindull G, Ramach W, Ritter J, Sekera J, Treuner J, Wist G, Landbeck G. Neoadjuvant chemotherapy for osteogenic sarcoma: results of a Cooperative German/Austrian study. J Clin Oncol. 1984 Jun;2(6):617-24. [https://doi.org/10.1200/jco.1984.2.6.617 link to original article] '''dosing details in manuscript have been reviewed by our editors''' [https://pubmed.ncbi.nlm.nih.gov/6202851/ PubMed] |
==M-BCD {{#subobject:6f3563|Regimen=1}}== | ==M-BCD {{#subobject:6f3563|Regimen=1}}== | ||
M-BCD: High-dose '''<u>M</u>'''ethotrexate, '''<u>B</u>'''leomycin, '''<u>C</u>'''yclophosphamide, '''<u>D</u>'''actinomycin | M-BCD: High-dose '''<u>M</u>'''ethotrexate, '''<u>B</u>'''leomycin, '''<u>C</u>'''yclophosphamide, '''<u>D</u>'''actinomycin | ||
− | <div class="toccolours" style="background-color:# | + | <div class="toccolours" style="background-color:#ee6b6e"> |
===Regimen {{#subobject:8ea4f8|Variant=1}}=== | ===Regimen {{#subobject:8ea4f8|Variant=1}}=== | ||
{| class="wikitable sortable" style="width: 100%; text-align:center;" | {| class="wikitable sortable" style="width: 100%; text-align:center;" | ||
Line 84: | Line 84: | ||
*[[Dactinomycin (Cosmegen)]] 0.6 mg/m<sup>2</sup> IV bolus once per day on days 1 & 2 | *[[Dactinomycin (Cosmegen)]] 0.6 mg/m<sup>2</sup> IV bolus once per day on days 1 & 2 | ||
====Supportive therapy==== | ====Supportive therapy==== | ||
− | *[[Folinic acid | + | *[[Leucovorin (Folinic acid)]] 15 mg/m<sup>2</sup> PO every 6 hours x 12 hours once per day on days 16 & 23, starting 24 hours after the completion of methotrexate infusion; additional leucovorin used for delayed methotrexate elimination |
*[[Sodium bicarbonate]] urine alkalinization prior to high-dose methotrexate | *[[Sodium bicarbonate]] urine alkalinization prior to high-dose methotrexate | ||
*[[Normal saline]] 4.5 L/m<sup>2</sup> on day 1 after methotrexate; NS 3 L/m<sup>2</sup> on day 2, with adjustments made to keep urine pH greater than 7.4 | *[[Normal saline]] 4.5 L/m<sup>2</sup> on day 1 after methotrexate; NS 3 L/m<sup>2</sup> on day 2, with adjustments made to keep urine pH greater than 7.4 | ||
Line 96: | Line 96: | ||
</div></div> | </div></div> | ||
===References=== | ===References=== | ||
− | # '''COSS-82:''' Winkler K, Beron G, Delling G, Heise U, Kabisch H, Purfürst C, Berger J, Ritter J, Jürgens H, Gerein V, Graf N, Russe W, Gruemayer ER, Ertelt W, Kotz R, Preuzzer P, Prindull G, Brandeis W, Landbeck G. Neoadjuvant chemotherapy of osteosarcoma: results of a randomized cooperative trial (COSS-82) with salvage chemotherapy based on histological tumor response. J Clin Oncol. 1988 Feb;6(2):329-37. [https://doi.org/10.1200/jco.1988.6.2.329 link to original article] ''' | + | # '''COSS-82:''' Winkler K, Beron G, Delling G, Heise U, Kabisch H, Purfürst C, Berger J, Ritter J, Jürgens H, Gerein V, Graf N, Russe W, Gruemayer ER, Ertelt W, Kotz R, Preuzzer P, Prindull G, Brandeis W, Landbeck G. Neoadjuvant chemotherapy of osteosarcoma: results of a randomized cooperative trial (COSS-82) with salvage chemotherapy based on histological tumor response. J Clin Oncol. 1988 Feb;6(2):329-37. [https://doi.org/10.1200/jco.1988.6.2.329 link to original article] '''dosing details in manuscript have been reviewed by our editors''' [https://pubmed.ncbi.nlm.nih.gov/2448428/ PubMed] |
=Adjuvant therapy= | =Adjuvant therapy= | ||
==Doxorubicin monotherapy {{#subobject:681e0f|Regimen=1}}== | ==Doxorubicin monotherapy {{#subobject:681e0f|Regimen=1}}== | ||
− | <div class="toccolours" style="background-color:# | + | <div class="toccolours" style="background-color:#ee6b6e"> |
===Regimen {{#subobject:81ee7b|Variant=1}}=== | ===Regimen {{#subobject:81ee7b|Variant=1}}=== | ||
− | {| class="wikitable" style="width: | + | {| class="wikitable sortable" style="width: 60%; text-align:center;" |
− | !style="width: | + | !style="width: 33%"|Study |
− | !style="width: | + | !style="width: 33%"|Dates of enrollment |
+ | !style="width: 33%"|[[Levels_of_Evidence#Evidence|Evidence]] | ||
|- | |- | ||
|[https://doi.org/10.1056/NEJM197411072911903 Cortes et al. 1974] | |[https://doi.org/10.1056/NEJM197411072911903 Cortes et al. 1974] | ||
+ | |Not reported | ||
|style="background-color:#91cf61"|Non-randomized | |style="background-color:#91cf61"|Non-randomized | ||
|- | |- | ||
Line 119: | Line 121: | ||
</div></div> | </div></div> | ||
===References=== | ===References=== | ||
− | # Cortes EP, Holland JF, Wang JJ, Sinks LF, Blom J, Senn H, Bank A, Glidewell O. Amputation and adriamycin in primary osteosarcoma. N Engl J Med. 1974 Nov 7;291(19):998-1000. [https://doi.org/10.1056/NEJM197411072911903 link to original article] ''' | + | # Cortes EP, Holland JF, Wang JJ, Sinks LF, Blom J, Senn H, Bank A, Glidewell O. Amputation and adriamycin in primary osteosarcoma. N Engl J Med. 1974 Nov 7;291(19):998-1000. [https://doi.org/10.1056/NEJM197411072911903 link to original article] '''dosing details in abstract have been reviewed by our editors''' [https://pubmed.ncbi.nlm.nih.gov/4528415/ PubMed] |
==IP-BCD {{#subobject:b45a8a|Regimen=1}}== | ==IP-BCD {{#subobject:b45a8a|Regimen=1}}== | ||
IP-BCD: '''<u>I</u>'''fosfamide, '''<u>P</u>'''latinol (Cisplatin), '''<u>B</u>'''leomycin, '''<u>C</u>'''yclophosphamide, '''<u>D</u>'''actinomycin | IP-BCD: '''<u>I</u>'''fosfamide, '''<u>P</u>'''latinol (Cisplatin), '''<u>B</u>'''leomycin, '''<u>C</u>'''yclophosphamide, '''<u>D</u>'''actinomycin | ||
− | <div class="toccolours" style="background-color:# | + | <div class="toccolours" style="background-color:#ee6b6e"> |
===Regimen {{#subobject:c70abe|Variant=1}}=== | ===Regimen {{#subobject:c70abe|Variant=1}}=== | ||
{| class="wikitable sortable" style="width: 60%; text-align:center;" | {| class="wikitable sortable" style="width: 60%; text-align:center;" | ||
Line 136: | Line 138: | ||
<div class="toccolours" style="background-color:#cbd5e8"> | <div class="toccolours" style="background-color:#cbd5e8"> | ||
====Preceding treatment==== | ====Preceding treatment==== | ||
− | *[[Osteosarcoma#MAP| | + | *Neoadjuvant [[Osteosarcoma#MAP|MAP]], then [[Surgery#Surgical_resection|surgery]], with poor response |
</div> | </div> | ||
<div class="toccolours" style="background-color:#b3e2cd"> | <div class="toccolours" style="background-color:#b3e2cd"> | ||
Line 151: | Line 153: | ||
</div></div> | </div></div> | ||
===References=== | ===References=== | ||
− | # '''COSS-82:''' Winkler K, Beron G, Delling G, Heise U, Kabisch H, Purfürst C, Berger J, Ritter J, Jürgens H, Gerein V, Graf N, Russe W, Gruemayer ER, Ertelt W, Kotz R, Preuzzer P, Prindull G, Brandeis W, Landbeck G. Neoadjuvant chemotherapy of osteosarcoma: results of a randomized cooperative trial (COSS-82) with salvage chemotherapy based on histological tumor response. J Clin Oncol. 1988 Feb;6(2):329-37. [https://doi.org/10.1200/jco.1988.6.2.329 link to original article] ''' | + | # '''COSS-82:''' Winkler K, Beron G, Delling G, Heise U, Kabisch H, Purfürst C, Berger J, Ritter J, Jürgens H, Gerein V, Graf N, Russe W, Gruemayer ER, Ertelt W, Kotz R, Preuzzer P, Prindull G, Brandeis W, Landbeck G. Neoadjuvant chemotherapy of osteosarcoma: results of a randomized cooperative trial (COSS-82) with salvage chemotherapy based on histological tumor response. J Clin Oncol. 1988 Feb;6(2):329-37. [https://doi.org/10.1200/jco.1988.6.2.329 link to original article] '''dosing details in manuscript have been reviewed by our editors''' [https://pubmed.ncbi.nlm.nih.gov/2448428/ PubMed] |
==MA-BCD/AP {{#subobject:2ce305|Regimen=1}}== | ==MA-BCD/AP {{#subobject:2ce305|Regimen=1}}== | ||
MA-BCD/AP: High-dose '''<u>M</u>'''ethotrexate, '''<u>A</u>'''driamycin (Doxorubicin), '''<u>B</u>'''leomycin, '''<u>C</u>'''yclophosphamide, '''<u>D</u>'''actinomycin alternating with '''<u>A</u>'''driamycin (Doxorubicin) & '''<u>P</u>'''latinol (Cisplatin) | MA-BCD/AP: High-dose '''<u>M</u>'''ethotrexate, '''<u>A</u>'''driamycin (Doxorubicin), '''<u>B</u>'''leomycin, '''<u>C</u>'''yclophosphamide, '''<u>D</u>'''actinomycin alternating with '''<u>A</u>'''driamycin (Doxorubicin) & '''<u>P</u>'''latinol (Cisplatin) | ||
− | <div class="toccolours" style="background-color:# | + | <div class="toccolours" style="background-color:#ee6b6e"> |
===Regimen {{#subobject:59841a|Variant=1}}=== | ===Regimen {{#subobject:59841a|Variant=1}}=== | ||
{| class="wikitable sortable" style="width: 100%; text-align:center;" | {| class="wikitable sortable" style="width: 100%; text-align:center;" | ||
Line 190: | Line 192: | ||
==M-BCD {{#subobject:67c944|Regimen=1}}== | ==M-BCD {{#subobject:67c944|Regimen=1}}== | ||
M-BCD: High-dose '''<u>M</u>'''ethotrexate, '''<u>B</u>'''leomycin, '''<u>C</u>'''yclophosphamide, '''<u>D</u>'''actinomycin | M-BCD: High-dose '''<u>M</u>'''ethotrexate, '''<u>B</u>'''leomycin, '''<u>C</u>'''yclophosphamide, '''<u>D</u>'''actinomycin | ||
− | <div class="toccolours" style="background-color:# | + | <div class="toccolours" style="background-color:#ee6b6e"> |
===Regimen {{#subobject:3696a1|Variant=1}}=== | ===Regimen {{#subobject:3696a1|Variant=1}}=== | ||
{| class="wikitable sortable" style="width: 100%; text-align:center;" | {| class="wikitable sortable" style="width: 100%; text-align:center;" | ||
Line 215: | Line 217: | ||
<div class="toccolours" style="background-color:#cbd5e8"> | <div class="toccolours" style="background-color:#cbd5e8"> | ||
====Preceding treatment==== | ====Preceding treatment==== | ||
− | *[[#M-BCD| | + | *Neoadjuvant [[#M-BCD|M-BCD]], then [[Surgery#Surgical_resection|surgery]], with good response |
</div> | </div> | ||
<div class="toccolours" style="background-color:#b3e2cd"> | <div class="toccolours" style="background-color:#b3e2cd"> | ||
Line 225: | Line 227: | ||
*[[Dactinomycin (Cosmegen)]] 0.6 mg/m<sup>2</sup> IV bolus once per day on days 1 & 2 | *[[Dactinomycin (Cosmegen)]] 0.6 mg/m<sup>2</sup> IV bolus once per day on days 1 & 2 | ||
====Supportive therapy==== | ====Supportive therapy==== | ||
− | *[[Folinic acid | + | *[[Leucovorin (Folinic acid)]] 15 mg/m<sup>2</sup> PO every 6 hours x 12 hours once per day on days 16 & 23, starting 24 hours after the completion of methotrexate infusion; additional leucovorin used for delayed methotrexate elimination |
*[[Sodium bicarbonate]] urine alkalinization prior to high-dose methotrexate | *[[Sodium bicarbonate]] urine alkalinization prior to high-dose methotrexate | ||
*[[Normal saline]] 4.5 L/m<sup>2</sup> on day 1 after methotrexate; NS 3 L/m<sup>2</sup> on day 2, with adjustments made to keep urine pH greater than 7.4 | *[[Normal saline]] 4.5 L/m<sup>2</sup> on day 1 after methotrexate; NS 3 L/m<sup>2</sup> on day 2, with adjustments made to keep urine pH greater than 7.4 | ||
Line 233: | Line 235: | ||
# Eilber F, Giuliano A, Eckardt J, Patterson K, Moseley S, Goodnight J. Adjuvant chemotherapy for osteosarcoma: a randomized prospective trial. J Clin Oncol. 1987 Jan;5(1):21-6. [https://doi.org/10.1200/JCO.1987.5.1.21 link to original article] [https://pubmed.ncbi.nlm.nih.gov/3543236/ PubMed] | # Eilber F, Giuliano A, Eckardt J, Patterson K, Moseley S, Goodnight J. Adjuvant chemotherapy for osteosarcoma: a randomized prospective trial. J Clin Oncol. 1987 Jan;5(1):21-6. [https://doi.org/10.1200/JCO.1987.5.1.21 link to original article] [https://pubmed.ncbi.nlm.nih.gov/3543236/ PubMed] | ||
## '''Update:''' Bernthal NM, Federman N, Eilber FR, Nelson SD, Eckardt JJ, Eilber FC, Tap WD. Long-term results (>25 years) of a randomized, prospective clinical trial evaluating chemotherapy in patients with high-grade, operable osteosarcoma. Cancer. 2012 Dec 1;118(23):5888-93. Epub 2012 May 30. [https://doi.org/10.1002/cncr.27651 link to original article] [https://pubmed.ncbi.nlm.nih.gov/22648705/ PubMed] | ## '''Update:''' Bernthal NM, Federman N, Eilber FR, Nelson SD, Eckardt JJ, Eilber FC, Tap WD. Long-term results (>25 years) of a randomized, prospective clinical trial evaluating chemotherapy in patients with high-grade, operable osteosarcoma. Cancer. 2012 Dec 1;118(23):5888-93. Epub 2012 May 30. [https://doi.org/10.1002/cncr.27651 link to original article] [https://pubmed.ncbi.nlm.nih.gov/22648705/ PubMed] | ||
− | # '''COSS-82:''' Winkler K, Beron G, Delling G, Heise U, Kabisch H, Purfürst C, Berger J, Ritter J, Jürgens H, Gerein V, Graf N, Russe W, Gruemayer ER, Ertelt W, Kotz R, Preuzzer P, Prindull G, Brandeis W, Landbeck G. Neoadjuvant chemotherapy of osteosarcoma: results of a randomized cooperative trial (COSS-82) with salvage chemotherapy based on histological tumor response. J Clin Oncol. 1988 Feb;6(2):329-37. [https://doi.org/10.1200/jco.1988.6.2.329 link to original article] ''' | + | # '''COSS-82:''' Winkler K, Beron G, Delling G, Heise U, Kabisch H, Purfürst C, Berger J, Ritter J, Jürgens H, Gerein V, Graf N, Russe W, Gruemayer ER, Ertelt W, Kotz R, Preuzzer P, Prindull G, Brandeis W, Landbeck G. Neoadjuvant chemotherapy of osteosarcoma: results of a randomized cooperative trial (COSS-82) with salvage chemotherapy based on histological tumor response. J Clin Oncol. 1988 Feb;6(2):329-37. [https://doi.org/10.1200/jco.1988.6.2.329 link to original article] '''dosing details in manuscript have been reviewed by our editors''' [https://pubmed.ncbi.nlm.nih.gov/2448428/ PubMed] |
==Methotrexate & Vincristine {{#subobject:606364|Regimen=1}}== | ==Methotrexate & Vincristine {{#subobject:606364|Regimen=1}}== | ||
− | <div class="toccolours" style="background-color:# | + | <div class="toccolours" style="background-color:#ee6b6e"> |
===Regimen {{#subobject:8f64e5|Variant=1}}=== | ===Regimen {{#subobject:8f64e5|Variant=1}}=== | ||
− | {| class="wikitable" style="width: | + | {| class="wikitable sortable" style="width: 60%; text-align:center;" |
− | !style="width: | + | !style="width: 33%"|Study |
− | !style="width: | + | !style="width: 33%"|Dates of enrollment |
+ | !style="width: 33%"|[[Levels_of_Evidence#Evidence|Evidence]] | ||
|- | |- | ||
|[https://doi.org/10.1056/NEJM197411072911902 Jaffe et al. 1974] | |[https://doi.org/10.1056/NEJM197411072911902 Jaffe et al. 1974] | ||
+ | |1972-06 to NR | ||
|style="background-color:#91cf61"|Non-randomized | |style="background-color:#91cf61"|Non-randomized | ||
|- | |- | ||
Line 251: | Line 255: | ||
<div class="toccolours" style="background-color:#b3e2cd"> | <div class="toccolours" style="background-color:#b3e2cd"> | ||
====Chemotherapy==== | ====Chemotherapy==== | ||
− | *[[Methotrexate (MTX)]] | + | *[[Methotrexate (MTX)]] 1500 mg/m<sup>2</sup> IV over 6 hours once on day 1 |
− | *[[Vincristine (Oncovin)]] | + | *[[Vincristine (Oncovin)]] 2 mg/m<sup>2</sup> IV once on day 1, '''given 30 minutes prior to methotrexate''' |
====Supportive therapy==== | ====Supportive therapy==== | ||
− | *[[Folinic acid | + | *[[Leucovorin (Folinic acid)]] |
− | '''21-day cycle for up to | + | '''14-day cycle until therapeutic goal achieved, then 21-day cycle for up to 33 cycles (2 years total)''' |
</div></div> | </div></div> | ||
===References=== | ===References=== | ||
− | # Jaffe N, Frei E 3rd, Traggis D, Bishop Y. Adjuvant methotrexate and citrovorum-factor treatment of osteogenic sarcoma. N Engl J Med. 1974 Nov 7;291(19):994-7. [https://doi.org/10.1056/NEJM197411072911902 link to original article] [https://pubmed.ncbi.nlm.nih.gov/4606174/ PubMed] | + | # Jaffe N, Frei E 3rd, Traggis D, Bishop Y. Adjuvant methotrexate and citrovorum-factor treatment of osteogenic sarcoma. N Engl J Med. 1974 Nov 7;291(19):994-7. [https://doi.org/10.1056/NEJM197411072911902 link to original article] '''dosing details in manuscript have been reviewed by our editors''' [https://pubmed.ncbi.nlm.nih.gov/4606174/ PubMed] |
+ | |||
=Relapsed, refractory, or metastatic= | =Relapsed, refractory, or metastatic= | ||
==Doxorubicin monotherapy {{#subobject:8a4535|Regimen=1}}== | ==Doxorubicin monotherapy {{#subobject:8a4535|Regimen=1}}== | ||
− | <div class="toccolours" style="background-color:# | + | <div class="toccolours" style="background-color:#ee6b6e"> |
===Regimen {{#subobject:dc69eb|Variant=1}}=== | ===Regimen {{#subobject:dc69eb|Variant=1}}=== | ||
− | {| class="wikitable" style="width: | + | {| class="wikitable sortable" style="width: 60%; text-align:center;" |
− | !style="width: | + | !style="width: 33%"|Study |
− | !style="width: | + | !style="width: 33%"|Dates of enrollment |
+ | !style="width: 33%"|[[Levels_of_Evidence#Evidence|Evidence]] | ||
|- | |- | ||
− | |[https:// | + | |[https://doi.org/10.1001/jama.1972.03200230020005 Cortes et al. 1972] |
+ | |Not reported | ||
| style="background-color:#ffffbe" |Non-randomized, fewer than 20 pts | | style="background-color:#ffffbe" |Non-randomized, fewer than 20 pts | ||
|- | |- | ||
Line 276: | Line 283: | ||
</div></div> | </div></div> | ||
===References=== | ===References=== | ||
− | # Cortes EP, Holland JF, Wang JJ, Sinks LF. Doxorubicin in disseminated osteosarcoma. JAMA. 1972 Sep 4;221(10):1132-8. [https:// | + | # Cortes EP, Holland JF, Wang JJ, Sinks LF. Doxorubicin in disseminated osteosarcoma. JAMA. 1972 Sep 4;221(10):1132-8. [https://doi.org/10.1001/jama.1972.03200230020005 link to original article] [https://pubmed.ncbi.nlm.nih.gov/4512088/ PubMed] |
==MAPifn [COG AOST0331]== | ==MAPifn [COG AOST0331]== | ||
<div class="toccolours" style="background-color:#c8a2c8"> | <div class="toccolours" style="background-color:#c8a2c8"> | ||
+ | {| class="wikitable sortable" style="width: 60%; text-align:center;" | ||
+ | !style="width: 33%"|Study | ||
+ | !style="width: 33%"|Dates of enrollment | ||
+ | !style="width: 33%"|[[Levels_of_Evidence#Evidence|Evidence]] | ||
+ | |- | ||
+ | |[https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5052459/ Marina et al. 2019 (COG AOST0331)] | ||
+ | |2005-04-14 to 2011-06-30 | ||
+ | | style="background-color:#91cf61" |Non-randomized part of phase 3 RCT | ||
+ | |- | ||
+ | |} | ||
''Note: Induction is received by all patients and consists of 2 cycles of MAP. The remainder of this protocol is for good responders.'' | ''Note: Induction is received by all patients and consists of 2 cycles of MAP. The remainder of this protocol is for good responders.'' | ||
− | <div class="toccolours" style="background-color:# | + | <div class="toccolours" style="background-color:#ee6b6e"> |
===Induction=== | ===Induction=== | ||
<div class="toccolours" style="background-color:#b3e2cd"> | <div class="toccolours" style="background-color:#b3e2cd"> | ||
Line 288: | Line 305: | ||
*[[Methotrexate (MTX)]] 12,000 mg/m<sup>2</sup> (maximum dose of 20,000 mg) IV over 4 hours once on day 1 of weeks 4, 5, 9, and 10. | *[[Methotrexate (MTX)]] 12,000 mg/m<sup>2</sup> (maximum dose of 20,000 mg) IV over 4 hours once on day 1 of weeks 4, 5, 9, and 10. | ||
====Supportive therapy==== | ====Supportive therapy==== | ||
− | *[[Folinic acid | + | *[[Leucovorin (Folinic acid)]] 15 mg/m<sup>2</sup> PO or IV every 6 hours beginning 24 hours after the beginning of the methotrexate infusion and continuing until the serum methotrexate level is less than 0.1 μM. |
− | '''10 | + | '''10-week course''' |
</div></div><br> | </div></div><br> | ||
− | <div class="toccolours" style="background-color:# | + | <div class="toccolours" style="background-color:#ee6b6e"> |
===Consolidation, Cycles 3-4=== | ===Consolidation, Cycles 3-4=== | ||
<div class="toccolours" style="background-color:#b3e2cd"> | <div class="toccolours" style="background-color:#b3e2cd"> | ||
Line 299: | Line 316: | ||
*[[Methotrexate (MTX)]] 12,000 mg/m<sup>2</sup> (maximum dose of 20,000 mg) IV over 4 hours once on day 1 of weeks 15, 16, 20, and 21. | *[[Methotrexate (MTX)]] 12,000 mg/m<sup>2</sup> (maximum dose of 20,000 mg) IV over 4 hours once on day 1 of weeks 15, 16, 20, and 21. | ||
====Supportive therapy==== | ====Supportive therapy==== | ||
− | *[[Folinic acid | + | *[[Leucovorin (Folinic acid)]] 15 mg/m<sup>2</sup> PO or IV every 6 hours beginning 24 hours after the beginning of the methotrexate infusion and continuing until the serum methotrexate level is less than 0.1 μM. |
− | '''10 | + | '''10-week course''' |
</div></div><br> | </div></div><br> | ||
− | <div class="toccolours" style="background-color:# | + | <div class="toccolours" style="background-color:#ee6b6e"> |
===Consolidation, Cycles 5-6=== | ===Consolidation, Cycles 5-6=== | ||
<div class="toccolours" style="background-color:#b3e2cd"> | <div class="toccolours" style="background-color:#b3e2cd"> | ||
Line 309: | Line 326: | ||
*[[Methotrexate (MTX)]] 12,000 mg/m<sup>2</sup> (maximum dose of 20,000 mg) IV over 4 hours once on day 1 of weeks 24, 25, 28, and 29 | *[[Methotrexate (MTX)]] 12,000 mg/m<sup>2</sup> (maximum dose of 20,000 mg) IV over 4 hours once on day 1 of weeks 24, 25, 28, and 29 | ||
====Supportive therapy==== | ====Supportive therapy==== | ||
− | *[[Folinic acid | + | *[[Leucovorin (Folinic acid)]] 15 mg/m<sup>2</sup> PO or IV every 6 hours beginning 24 hours after the beginning of the methotrexate infusion and continuing until the serum methotrexate level is less than 0.1 μM. |
− | '''10 | + | '''10-week course''' |
</div></div><br> | </div></div><br> | ||
− | <div class="toccolours" style="background-color:# | + | <div class="toccolours" style="background-color:#ee6b6e"> |
===Maintenance, Weeks 30-104=== | ===Maintenance, Weeks 30-104=== | ||
+ | ''Note: Peginterferon alfa-2b dose is increased only if the starting dose is well tolerated.'' | ||
<div class="toccolours" style="background-color:#b3e2cd"> | <div class="toccolours" style="background-color:#b3e2cd"> | ||
====Immunotherapy==== | ====Immunotherapy==== | ||
− | *[[Peginterferon alfa-2b (Sylatron)]] 0.5 mcg/kg | + | *[[Peginterferon alfa-2b (Sylatron)]] as follows: |
− | ** | + | **Cycles 1 to 4: 0.5 mcg/kg (maximum dose of 50 mcg) SC once on day 1 |
− | + | **Cycles 5 to 75: 1 mcg/kg (maximum dose of 100 mcg) SC once on day 1 | |
− | '''75 | + | '''7-day cycle for 75 cycles''' |
</div></div></div> | </div></div></div> | ||
===References=== | ===References=== | ||
− | #''' | + | # '''EURAMOS-1 poor response:''' Marina NM, Smeland S, Bielack SS, Bernstein M, Jovic G, Krailo MD, Hook JM, Arndt C, van den Berg H, Brennan B, Brichard B, Brown KL, Butterfass-Bahloul T, Calaminus G, Daldrup-Link HE, Eriksson M, Gebhardt MC, Gelderblom H, Gerss J, Goldsby R, Goorin A, Gorlick R, Grier HE, Hale JP, Hall KS, Hardes J, Hawkins DS, Helmke K, Hogendoorn PC, Isakoff MS, Janeway KA, Jürgens H, Kager L, Kühne T, Lau CC, Leavey PJ, Lessnick SL, Mascarenhas L, Meyers PA, Mottl H, Nathrath M, Papai Z, Randall RL, Reichardt P, Renard M, Safwat AA, Schwartz CL, Stevens MC, Strauss SJ, Teot L, Werner M, Sydes MR, Whelan JS. Comparison of MAPIE versus MAP in patients with a poor response to preoperative chemotherapy for newly diagnosed high-grade osteosarcoma (EURAMOS-1): an open-label, international, randomised controlled trial. Lancet Oncol. 2016 Oct;17(10):1396-1408. Epub 2016 Aug 25. [https://doi.org/10.1016/S1470-2045(16)30214-5 link to original article] [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5052459/ link to PMC article] '''dosing details in manuscript have been reviewed by our editors''' [https://pubmed.ncbi.nlm.nih.gov/27569442/ PubMed] [https://clinicaltrials.gov/study/NCT00134030 NCT00134030] |
+ | |||
==MAPIE [COG AOST0331]== | ==MAPIE [COG AOST0331]== | ||
<div class="toccolours" style="background-color:#c8a2c8"> | <div class="toccolours" style="background-color:#c8a2c8"> | ||
Line 340: | Line 359: | ||
|} | |} | ||
''Note: Induction is received by all patients and consists of 2 cycles of MAP; subsequent treatments in this protocol are for poor responders.'' | ''Note: Induction is received by all patients and consists of 2 cycles of MAP; subsequent treatments in this protocol are for poor responders.'' | ||
− | <div class="toccolours" style="background-color:# | + | <div class="toccolours" style="background-color:#ee6b6e"> |
===Induction=== | ===Induction=== | ||
<div class="toccolours" style="background-color:#b3e2cd"> | <div class="toccolours" style="background-color:#b3e2cd"> | ||
Line 348: | Line 367: | ||
*[[Methotrexate (MTX)]] 12,000 mg/m<sup>2</sup> (maximum dose of 20,000 mg) IV over 4 hours once on day 1 of weeks 4, 5, 9, and 10. | *[[Methotrexate (MTX)]] 12,000 mg/m<sup>2</sup> (maximum dose of 20,000 mg) IV over 4 hours once on day 1 of weeks 4, 5, 9, and 10. | ||
====Supportive therapy==== | ====Supportive therapy==== | ||
− | *[[Folinic acid | + | *[[Leucovorin (Folinic acid)]] 15 mg/m<sup>2</sup> PO or IV every 6 hours beginning 24 hours after the beginning of the methotrexate infusion and continuing until the serum methotrexate level is less than 0.1 μM. |
'''10 Week course''' | '''10 Week course''' | ||
</div></div><br> | </div></div><br> | ||
− | <div class="toccolours" style="background-color:# | + | <div class="toccolours" style="background-color:#ee6b6e"> |
===Consolidation, MAPIE Cycles 3 and 7=== | ===Consolidation, MAPIE Cycles 3 and 7=== | ||
<div class="toccolours" style="background-color:#b3e2cd"> | <div class="toccolours" style="background-color:#b3e2cd"> | ||
Line 359: | Line 378: | ||
*[[Methotrexate (MTX)]] 12,000 mg/m<sup>2</sup> (maximum dose of 20,000 mg) IV over 4 hours once on day 1 of weeks 15 and 31. | *[[Methotrexate (MTX)]] 12,000 mg/m<sup>2</sup> (maximum dose of 20,000 mg) IV over 4 hours once on day 1 of weeks 15 and 31. | ||
====Supportive therapy==== | ====Supportive therapy==== | ||
− | *[[Folinic acid | + | *[[Leucovorin (Folinic acid)]] 15 mg/m<sup>2</sup> PO or IV every 6 hours beginning 24 hours after the beginning of the methotrexate infusion and continuing until the serum methotrexate level is less than 0.1 μM. |
'''5-Week Courses''' | '''5-Week Courses''' | ||
</div></div><br> | </div></div><br> | ||
− | <div class="toccolours" style="background-color:# | + | <div class="toccolours" style="background-color:#ee6b6e"> |
===Consolidation, MAP Cycles 4, 6, and 8=== | ===Consolidation, MAP Cycles 4, 6, and 8=== | ||
<div class="toccolours" style="background-color:#b3e2cd"> | <div class="toccolours" style="background-color:#b3e2cd"> | ||
Line 371: | Line 390: | ||
====Supportive therapy==== | ====Supportive therapy==== | ||
*[[Mesna (Mesnex)]] 2.8 g/m<sup>2</sup>/24 hours IV continuous infusion over 24 hours on days 1 through 5 of weeks 16, 24, and 32. | *[[Mesna (Mesnex)]] 2.8 g/m<sup>2</sup>/24 hours IV continuous infusion over 24 hours on days 1 through 5 of weeks 16, 24, and 32. | ||
− | *[[Folinic acid | + | *[[Leucovorin (Folinic acid)]] 15 mg/m<sup>2</sup> PO or IV every 6 hours beginning 24 hours after the beginning of the methotrexate infusion and continuing until the serum methotrexate level is less than 0.1 μM. |
'''5-Week Courses''' | '''5-Week Courses''' | ||
</div></div><br> | </div></div><br> | ||
− | <div class="toccolours" style="background-color:# | + | <div class="toccolours" style="background-color:#ee6b6e"> |
===Consolidation, MAP Cycle 5=== | ===Consolidation, MAP Cycle 5=== | ||
<div class="toccolours" style="background-color:#b3e2cd"> | <div class="toccolours" style="background-color:#b3e2cd"> | ||
Line 383: | Line 402: | ||
====Supportive therapy==== | ====Supportive therapy==== | ||
*[[Mesna (Mesnex)]] 3 g/m<sup>2</sup>/24 hours IV continuous infusion over 24 hours on days 1, 2, and 3 of weeks 20. | *[[Mesna (Mesnex)]] 3 g/m<sup>2</sup>/24 hours IV continuous infusion over 24 hours on days 1, 2, and 3 of weeks 20. | ||
− | *[[Folinic acid | + | *[[Leucovorin (Folinic acid)]] 15 mg/m<sup>2</sup> PO or IV every 6 hours beginning 24 hours after the beginning of the methotrexate infusion and continuing until the serum methotrexate level is less than 0.1 μM. |
'''5-Week Courses''' | '''5-Week Courses''' | ||
</div></div><br> | </div></div><br> | ||
− | <div class="toccolours" style="background-color:# | + | <div class="toccolours" style="background-color:#ee6b6e"> |
===Consolidation, MAP Cycle 9=== | ===Consolidation, MAP Cycle 9=== | ||
<div class="toccolours" style="background-color:#b3e2cd"> | <div class="toccolours" style="background-color:#b3e2cd"> | ||
Line 395: | Line 414: | ||
====Supportive therapy==== | ====Supportive therapy==== | ||
*[[Mesna (Mesnex)]] 3 g/m<sup>2</sup>/24 hours IV continuous infusion over 24 hours on days 1, 2, and 3 of weeks 36. | *[[Mesna (Mesnex)]] 3 g/m<sup>2</sup>/24 hours IV continuous infusion over 24 hours on days 1, 2, and 3 of weeks 36. | ||
− | *[[Folinic acid | + | *[[Leucovorin (Folinic acid)]] 15 mg/m<sup>2</sup> PO or IV every 6 hours beginning 24 hours after the beginning of the methotrexate infusion and continuing until the serum methotrexate level is less than 0.1 μM. |
'''5-Week Courses''' | '''5-Week Courses''' | ||
</div></div></div> | </div></div></div> | ||
===References=== | ===References=== | ||
− | #'''EURAMOS-1 poor response:''' Marina NM, Smeland S, Bielack SS, Bernstein M, Jovic G, Krailo MD, Hook JM, Arndt C, Berg H, Brennan B, Brichard B, Brown | + | # '''EURAMOS-1 poor response:''' Marina NM, Smeland S, Bielack SS, Bernstein M, Jovic G, Krailo MD, Hook JM, Arndt C, van den Berg H, Brennan B, Brichard B, Brown KL, Butterfass-Bahloul T, Calaminus G, Daldrup-Link HE, Eriksson M, Gebhardt MC, Gelderblom H, Gerss J, Goldsby R, Goorin A, Gorlick R, Grier HE, Hale JP, Hall KS, Hardes J, Hawkins DS, Helmke K, Hogendoorn PC, Isakoff MS, Janeway KA, Jürgens H, Kager L, Kühne T, Lau CC, Leavey PJ, Lessnick SL, Mascarenhas L, Meyers PA, Mottl H, Nathrath M, Papai Z, Randall RL, Reichardt P, Renard M, Safwat AA, Schwartz CL, Stevens MC, Strauss SJ, Teot L, Werner M, Sydes MR, Whelan JS. Comparison of MAPIE versus MAP in patients with a poor response to preoperative chemotherapy for newly diagnosed high-grade osteosarcoma (EURAMOS-1): an open-label, international, randomised controlled trial. Lancet Oncol. 2016 Oct;17(10):1396-1408. Epub 2016 Aug 25. [https://doi.org/10.1016/S1470-2045(16)30214-5 link to original article] [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5052459/ link to PMC article] '''dosing details in manuscript have been reviewed by our editors''' [https://pubmed.ncbi.nlm.nih.gov/27569442/ PubMed] [https://clinicaltrials.gov/study/NCT00134030 NCT00134030] |
[[Category:Osteosarcoma regimens]] | [[Category:Osteosarcoma regimens]] | ||
[[Category:Historical regimens]] | [[Category:Historical regimens]] |
Latest revision as of 23:41, 15 July 2024
The purpose of this page is to provide references to regimens that are obsolete, outdated, or of historical interest only. Is there a regimen missing from this list? See the main osteosarcoma page for current regimens.
8 regimens on this page
8 variants on this page
|
Neoadjuvant therapy
MA-BCD
MA-BCD: High-dose Methotrexate, Adriamycin (Doxorubicin), Bleomycin, Cyclophosphamide, Dactinomycin
Regimen
Study | Dates of enrollment | Evidence | Comparator | Comparative Efficacy |
---|---|---|---|---|
Winkler et al. 1984 (COSS-80) | 1979-1982 | Phase 3 (C) | MAP | Did not meet primary endpoint of CDF rate |
Note: The exact schedule is unclear based on limited/conflicting information in the reference. For example, Figure 1 appears to depict high-dose methotrexate starting 2 weeks after adriamycin, but the text says that methotrexate begins after a 3-week rest period. Additionally, the diagram in Figure 1 implies that the later therapies are given 4 times (once, then repeated x 3 cycles), but based on the cumulative doses listed, they are only given for a total of 3 cycles. The optional interferon arm is omitted given lack of benefit seen in the study.
Chemotherapy
- Doxorubicin (Adriamycin) as follows:
- Cycles 1, 3, 4: 45 mg/m2 IV bolus once per day on days 1 & 2
- Cycle 2: 45 mg/m2 IV bolus once per day on days 15 & 16 (delayed during cycle 2 until after surgery)
- Methotrexate (MTX) as follows:
- Cycle 1: 12,000 mg/m2 (maximum dose of 20,000 mg) IV over 4 hours once per day on days 22 & 29
- Cycles 2 to 4: 12,000 mg/m2 (maximum dose of 20,000 mg) IV over 4 hours once per day on days 1, 8, 29, 36
- MTX is dissolved at a concentration of 20,000 mg/L in a solution containing 5% glucose
- Bleomycin (Blenoxane) as follows:
- Cycle 1: 12 mg/m2 IV bolus once per day on days 36 & 37
- Cycles 2 to 4: 12 mg/m2 IV bolus once per day on days 43 & 44
- Cyclophosphamide (Cytoxan) as follows:
- Cycle 1: 600 mg/m2 IV bolus once per day on days 36 & 37
- Cycles 2 to 4: 600 mg/m2 IV bolus once per day on days 43 & 44
- Dactinomycin (Cosmegen) as follows:
- Cycle 1: 0.45 mg/m2 IV bolus once per day on days 36 & 37
- Cycles 2 to 4: 0.45 mg/m2 IV bolus once per day on days 43 & 44
Supportive therapy
- Leucovorin (Folinic acid) 15 mg/m2 PO every 6 hours x 12 hours once per day, starting 24 hours after the completion of each methotrexate infusion; additional leucovorin used for delayed methotrexate elimination
- Sodium bicarbonate urine alkalinization prior to high-dose methotrexate
- Normal saline 4.5 L/m2 on day 1 after methotrexate; NS 3 L/m2 on day 2, with adjustments made to keep urine pH greater than 7.4
8-week cycle for 4 cycles, with surgery done during cycle 2 before doxorubicin; surgery is done 9 to 18 weeks after the start of chemotherapy
References
- COSS-80: Winkler K, Beron G, Kotz R, Salzer-Kuntschik M, Beck J, Beck W, Brandeis W, Ebell W, Erttmann R, Göbel U, Havers W, Henze G, Hinderfeld L, Höcker P, Jobke A, Jürgens H, Kabisch H, Preusser P, Prindull G, Ramach W, Ritter J, Sekera J, Treuner J, Wist G, Landbeck G. Neoadjuvant chemotherapy for osteogenic sarcoma: results of a Cooperative German/Austrian study. J Clin Oncol. 1984 Jun;2(6):617-24. link to original article dosing details in manuscript have been reviewed by our editors PubMed
M-BCD
M-BCD: High-dose Methotrexate, Bleomycin, Cyclophosphamide, Dactinomycin
Regimen
Study | Dates of enrollment | Evidence | Comparator | Comparative Efficacy |
---|---|---|---|---|
Winkler et al. 1988 (COSS-82) | 1982-1984 | Phase 3 (C) | MAP | Inferior ORR |
Note: The exact schedule is unclear based on limited information in the reference, as schedule of doses is primarily extrapolated from Figure 1, which does not contain clear delineations in time.
Chemotherapy
- Methotrexate (MTX) 12,000 mg/m2 (maximum dose of 20,000 mg) IV over 4 hours once per day on days 15 & 22
- MTX is dissolved at a concentration of 20,000 mg/L in a solution containing 5% glucose
- Bleomycin (Blenoxane) 15 mg/m2 IV bolus once per day on days 1 & 2
- Cyclophosphamide (Cytoxan) 600 mg/m2 IV bolus once per day on days 1 & 2
- Dactinomycin (Cosmegen) 0.6 mg/m2 IV bolus once per day on days 1 & 2
Supportive therapy
- Leucovorin (Folinic acid) 15 mg/m2 PO every 6 hours x 12 hours once per day on days 16 & 23, starting 24 hours after the completion of methotrexate infusion; additional leucovorin used for delayed methotrexate elimination
- Sodium bicarbonate urine alkalinization prior to high-dose methotrexate
- Normal saline 4.5 L/m2 on day 1 after methotrexate; NS 3 L/m2 on day 2, with adjustments made to keep urine pH greater than 7.4
35-day cycle for 2 cycles
References
- COSS-82: Winkler K, Beron G, Delling G, Heise U, Kabisch H, Purfürst C, Berger J, Ritter J, Jürgens H, Gerein V, Graf N, Russe W, Gruemayer ER, Ertelt W, Kotz R, Preuzzer P, Prindull G, Brandeis W, Landbeck G. Neoadjuvant chemotherapy of osteosarcoma: results of a randomized cooperative trial (COSS-82) with salvage chemotherapy based on histological tumor response. J Clin Oncol. 1988 Feb;6(2):329-37. link to original article dosing details in manuscript have been reviewed by our editors PubMed
Adjuvant therapy
Doxorubicin monotherapy
Regimen
Study | Dates of enrollment | Evidence |
---|---|---|
Cortes et al. 1974 | Not reported | Non-randomized |
Preceding treatment
Chemotherapy
- Doxorubicin (Adriamycin) 30 mg/m2 IV once per day on days 1 to 3
4- to 6-week cycle for 6 cycles
References
- Cortes EP, Holland JF, Wang JJ, Sinks LF, Blom J, Senn H, Bank A, Glidewell O. Amputation and adriamycin in primary osteosarcoma. N Engl J Med. 1974 Nov 7;291(19):998-1000. link to original article dosing details in abstract have been reviewed by our editors PubMed
IP-BCD
IP-BCD: Ifosfamide, Platinol (Cisplatin), Bleomycin, Cyclophosphamide, Dactinomycin
Regimen
Study | Dates of enrollment | Evidence |
---|---|---|
Winkler et al. 1988 (COSS-82) | 1982-1984 | Non-randomized part of phase 3 RCT |
Chemotherapy
- Ifosfamide (Ifex) 2000 mg/m2 IV over 23.5 hours once per day on days 1 to 5, given second, with mesna
- Cisplatin (Platinol) 20 mg/m2 IV over 30 minutes once per day on days 1 to 5, given first
- Bleomycin (Blenoxane) 15 mg/m2 IV bolus once per day on days 22 & 23
- Cyclophosphamide (Cytoxan) 600 mg/m2 IV bolus once per day on days 22 & 23
- Dactinomycin (Cosmegen) 0.6 mg/m2 IV bolus once per day on days 22 & 23
Supportive therapy
- Mesna (Mesnex) 2000 mg/m2 IV over 23.5 hours once per day on days 1 to 5, given second, with ifosfamide, then 2000 mg/m2/day IV continuous infusion over 48 hours, started on day 6 (total dose: 14,000 mg/m2)
- Mannitol given with cisplatin; no further details provided
35-day cycle for 3 cycles
References
- COSS-82: Winkler K, Beron G, Delling G, Heise U, Kabisch H, Purfürst C, Berger J, Ritter J, Jürgens H, Gerein V, Graf N, Russe W, Gruemayer ER, Ertelt W, Kotz R, Preuzzer P, Prindull G, Brandeis W, Landbeck G. Neoadjuvant chemotherapy of osteosarcoma: results of a randomized cooperative trial (COSS-82) with salvage chemotherapy based on histological tumor response. J Clin Oncol. 1988 Feb;6(2):329-37. link to original article dosing details in manuscript have been reviewed by our editors PubMed
MA-BCD/AP
MA-BCD/AP: High-dose Methotrexate, Adriamycin (Doxorubicin), Bleomycin, Cyclophosphamide, Dactinomycin alternating with Adriamycin (Doxorubicin) & Platinol (Cisplatin)
Regimen
Study | Dates of enrollment | Evidence | Comparator | Comparative Efficacy |
---|---|---|---|---|
Link et al. 1986 | 1982-1984 | Phase 3 (E-esc) | No further treatment | Superior RFS |
Preceding treatment
Chemotherapy, MA-BCD portion
- Methotrexate (MTX)
- Doxorubicin (Adriamycin)
- Bleomycin (Blenoxane)
- Cyclophosphamide (Cytoxan)
- Dactinomycin (Cosmegen)
Chemotherapy, AP portion
References
- Link MP, Goorin AM, Miser AW, Green AA, Pratt CB, Belasco JB, Pritchard J, Malpas JS, Baker AR, Kirkpatrick JA, Ayala AG, Shuster JJ, Abelson HT, Simone JV, Vietti TJ. The effect of adjuvant chemotherapy on relapse-free survival in patients with osteosarcoma of the extremity. N Engl J Med. 1986 Jun 19;314(25):1600-6. link to original article PubMed
M-BCD
M-BCD: High-dose Methotrexate, Bleomycin, Cyclophosphamide, Dactinomycin
Regimen
Study | Dates of enrollment | Evidence | Comparator | Comparative Efficacy |
---|---|---|---|---|
Eilber et al. 1987 | 1981-1984 | Randomized (E-esc) | Observation | Seems to have superior OS |
Winkler et al. 1988 (COSS-82) | 1982-1984 | Non-randomized part of phase 3 RCT |
Note: The exact schedule is unclear based on limited information in the references; schedule of doses is primarily extrapolated from Figure 1 of Winkler et al. 1988, which does not contain clear delineations in time.
Chemotherapy
- Methotrexate (MTX) 12,000 mg/m2 (maximum dose of 20,000 mg) IV over 4 hours once per day on days 15 & 22
- MTX is dissolved at a concentration of 20,000 mg/L in a solution containing 5% glucose
- Bleomycin (Blenoxane) 15 mg/m2 IV bolus once per day on days 1 & 2
- Cyclophosphamide (Cytoxan) 600 mg/m2 IV bolus once per day on days 1 & 2
- Dactinomycin (Cosmegen) 0.6 mg/m2 IV bolus once per day on days 1 & 2
Supportive therapy
- Leucovorin (Folinic acid) 15 mg/m2 PO every 6 hours x 12 hours once per day on days 16 & 23, starting 24 hours after the completion of methotrexate infusion; additional leucovorin used for delayed methotrexate elimination
- Sodium bicarbonate urine alkalinization prior to high-dose methotrexate
- Normal saline 4.5 L/m2 on day 1 after methotrexate; NS 3 L/m2 on day 2, with adjustments made to keep urine pH greater than 7.4
35-day cycle for 2 cycles
References
- Eilber F, Giuliano A, Eckardt J, Patterson K, Moseley S, Goodnight J. Adjuvant chemotherapy for osteosarcoma: a randomized prospective trial. J Clin Oncol. 1987 Jan;5(1):21-6. link to original article PubMed
- Update: Bernthal NM, Federman N, Eilber FR, Nelson SD, Eckardt JJ, Eilber FC, Tap WD. Long-term results (>25 years) of a randomized, prospective clinical trial evaluating chemotherapy in patients with high-grade, operable osteosarcoma. Cancer. 2012 Dec 1;118(23):5888-93. Epub 2012 May 30. link to original article PubMed
- COSS-82: Winkler K, Beron G, Delling G, Heise U, Kabisch H, Purfürst C, Berger J, Ritter J, Jürgens H, Gerein V, Graf N, Russe W, Gruemayer ER, Ertelt W, Kotz R, Preuzzer P, Prindull G, Brandeis W, Landbeck G. Neoadjuvant chemotherapy of osteosarcoma: results of a randomized cooperative trial (COSS-82) with salvage chemotherapy based on histological tumor response. J Clin Oncol. 1988 Feb;6(2):329-37. link to original article dosing details in manuscript have been reviewed by our editors PubMed
Methotrexate & Vincristine
Regimen
Study | Dates of enrollment | Evidence |
---|---|---|
Jaffe et al. 1974 | 1972-06 to NR | Non-randomized |
Preceding treatment
Chemotherapy
- Methotrexate (MTX) 1500 mg/m2 IV over 6 hours once on day 1
- Vincristine (Oncovin) 2 mg/m2 IV once on day 1, given 30 minutes prior to methotrexate
Supportive therapy
14-day cycle until therapeutic goal achieved, then 21-day cycle for up to 33 cycles (2 years total)
References
- Jaffe N, Frei E 3rd, Traggis D, Bishop Y. Adjuvant methotrexate and citrovorum-factor treatment of osteogenic sarcoma. N Engl J Med. 1974 Nov 7;291(19):994-7. link to original article dosing details in manuscript have been reviewed by our editors PubMed
Relapsed, refractory, or metastatic
Doxorubicin monotherapy
Regimen
Study | Dates of enrollment | Evidence |
---|---|---|
Cortes et al. 1972 | Not reported | Non-randomized, fewer than 20 pts |
Chemotherapy
References
- Cortes EP, Holland JF, Wang JJ, Sinks LF. Doxorubicin in disseminated osteosarcoma. JAMA. 1972 Sep 4;221(10):1132-8. link to original article PubMed
MAPifn [COG AOST0331]
Study | Dates of enrollment | Evidence |
---|---|---|
Marina et al. 2019 (COG AOST0331) | 2005-04-14 to 2011-06-30 | Non-randomized part of phase 3 RCT |
Note: Induction is received by all patients and consists of 2 cycles of MAP. The remainder of this protocol is for good responders.
Induction
Chemotherapy
- Cisplatin (Platinol) 60 mg/m2 IV infusion over 4 hours, started on day 1 of weeks 1 and 6
- Doxorubicin (Adriamycin) 37.5 mg/m2/day (total dose is 75 mg/m2 given as a 48 hour infusion) on days 1 to 2 of Weeks 1 and 6
- Methotrexate (MTX) 12,000 mg/m2 (maximum dose of 20,000 mg) IV over 4 hours once on day 1 of weeks 4, 5, 9, and 10.
Supportive therapy
- Leucovorin (Folinic acid) 15 mg/m2 PO or IV every 6 hours beginning 24 hours after the beginning of the methotrexate infusion and continuing until the serum methotrexate level is less than 0.1 μM.
10-week course
Consolidation, Cycles 3-4
Chemotherapy
- Cisplatin (Platinol) 60 mg/m2 IV infusion over 4 hours, started on day 1 of weeks 12 and 17
- Doxorubicin (Adriamycin) 37.5 mg/m2/day (total dose is 75 mg/m2 given as a 48 hour infusion) on days 1 to 2 of Weeks 12 and 17.
- Methotrexate (MTX) 12,000 mg/m2 (maximum dose of 20,000 mg) IV over 4 hours once on day 1 of weeks 15, 16, 20, and 21.
Supportive therapy
- Leucovorin (Folinic acid) 15 mg/m2 PO or IV every 6 hours beginning 24 hours after the beginning of the methotrexate infusion and continuing until the serum methotrexate level is less than 0.1 μM.
10-week course
Consolidation, Cycles 5-6
Chemotherapy
- Doxorubicin (Adriamycin) 37.5 mg/m2/day (total dose is 75 mg/m2 given as a 48 hour infusion) on days 1 to 2 of Weeks 22 and 26.
- Methotrexate (MTX) 12,000 mg/m2 (maximum dose of 20,000 mg) IV over 4 hours once on day 1 of weeks 24, 25, 28, and 29
Supportive therapy
- Leucovorin (Folinic acid) 15 mg/m2 PO or IV every 6 hours beginning 24 hours after the beginning of the methotrexate infusion and continuing until the serum methotrexate level is less than 0.1 μM.
10-week course
Maintenance, Weeks 30-104
Note: Peginterferon alfa-2b dose is increased only if the starting dose is well tolerated.
Immunotherapy
- Peginterferon alfa-2b (Sylatron) as follows:
- Cycles 1 to 4: 0.5 mcg/kg (maximum dose of 50 mcg) SC once on day 1
- Cycles 5 to 75: 1 mcg/kg (maximum dose of 100 mcg) SC once on day 1
7-day cycle for 75 cycles
References
- EURAMOS-1 poor response: Marina NM, Smeland S, Bielack SS, Bernstein M, Jovic G, Krailo MD, Hook JM, Arndt C, van den Berg H, Brennan B, Brichard B, Brown KL, Butterfass-Bahloul T, Calaminus G, Daldrup-Link HE, Eriksson M, Gebhardt MC, Gelderblom H, Gerss J, Goldsby R, Goorin A, Gorlick R, Grier HE, Hale JP, Hall KS, Hardes J, Hawkins DS, Helmke K, Hogendoorn PC, Isakoff MS, Janeway KA, Jürgens H, Kager L, Kühne T, Lau CC, Leavey PJ, Lessnick SL, Mascarenhas L, Meyers PA, Mottl H, Nathrath M, Papai Z, Randall RL, Reichardt P, Renard M, Safwat AA, Schwartz CL, Stevens MC, Strauss SJ, Teot L, Werner M, Sydes MR, Whelan JS. Comparison of MAPIE versus MAP in patients with a poor response to preoperative chemotherapy for newly diagnosed high-grade osteosarcoma (EURAMOS-1): an open-label, international, randomised controlled trial. Lancet Oncol. 2016 Oct;17(10):1396-1408. Epub 2016 Aug 25. link to original article link to PMC article dosing details in manuscript have been reviewed by our editors PubMed NCT00134030
MAPIE [COG AOST0331]
Study | Dates of enrollment | Evidence | Comparator | Comparative Efficacy |
---|---|---|---|---|
Marina et al. 2016 (EURAMOS-1 poor response) | 2005-2011 | Phase 3 (E-esc) | MAP | Did not meet primary endpoint of EFS |
Note: Induction is received by all patients and consists of 2 cycles of MAP; subsequent treatments in this protocol are for poor responders.
Induction
Chemotherapy
- Cisplatin (Platinol) 60 mg/m2 IV infusion over 4 hours, started on day 1 of weeks 1 and 6
- Doxorubicin (Adriamycin) 37.5 mg/m2/day (total dose is 75 mg/m2 given as a 48 hour infusion) on days 1 to 2 of Weeks 1 and 6
- Methotrexate (MTX) 12,000 mg/m2 (maximum dose of 20,000 mg) IV over 4 hours once on day 1 of weeks 4, 5, 9, and 10.
Supportive therapy
- Leucovorin (Folinic acid) 15 mg/m2 PO or IV every 6 hours beginning 24 hours after the beginning of the methotrexate infusion and continuing until the serum methotrexate level is less than 0.1 μM.
10 Week course
Consolidation, MAPIE Cycles 3 and 7
Chemotherapy
- Cisplatin (Platinol) 60 mg/m2 IV infusion over 4 hours, started on day 1 of weeks 12 and 28
- Doxorubicin (Adriamycin) 37.5 mg/m2/day (total dose is 75 mg/m2 given as a 48 hour infusion) on days 1 to 2 of Weeks 12 and 28.
- Methotrexate (MTX) 12,000 mg/m2 (maximum dose of 20,000 mg) IV over 4 hours once on day 1 of weeks 15 and 31.
Supportive therapy
- Leucovorin (Folinic acid) 15 mg/m2 PO or IV every 6 hours beginning 24 hours after the beginning of the methotrexate infusion and continuing until the serum methotrexate level is less than 0.1 μM.
5-Week Courses
Consolidation, MAP Cycles 4, 6, and 8
Chemotherapy
- Ifosfamide (Ifex) 2.8 g/m2/dose IV over 4 hours once per day on days 1 through 5 of weeks 16, 24, and 32.
- Etoposide (Vepesid) 100 mg/m2/dose IV over 60 minutes once per day on days 1 through 5 of weeks 16, 24, and 32.
- Methotrexate (MTX) 12,000 mg/m2 (maximum dose of 20,000 mg) IV over 4 hours once on day 1 of weeks 19, 27, and 35.
Supportive therapy
- Mesna (Mesnex) 2.8 g/m2/24 hours IV continuous infusion over 24 hours on days 1 through 5 of weeks 16, 24, and 32.
- Leucovorin (Folinic acid) 15 mg/m2 PO or IV every 6 hours beginning 24 hours after the beginning of the methotrexate infusion and continuing until the serum methotrexate level is less than 0.1 μM.
5-Week Courses
Consolidation, MAP Cycle 5
Chemotherapy
- Doxorubicin (Adriamycin) 37.5 mg/m2/day (total dose is 75 mg/m2 given as a 48 hour infusion) on days 1 to 2 of Week 20.
- Ifosfamide (Ifex) 3 g/m2/dose IV over 4 hours once per day on days 1, 2, and 3 of weeks 20.
- Methotrexate (MTX) 12,000 mg/m2 (maximum dose of 20,000 mg) IV over 4 hours once on day 1 of weeks 23.
Supportive therapy
- Mesna (Mesnex) 3 g/m2/24 hours IV continuous infusion over 24 hours on days 1, 2, and 3 of weeks 20.
- Leucovorin (Folinic acid) 15 mg/m2 PO or IV every 6 hours beginning 24 hours after the beginning of the methotrexate infusion and continuing until the serum methotrexate level is less than 0.1 μM.
5-Week Courses
Consolidation, MAP Cycle 9
Chemotherapy
- Doxorubicin (Adriamycin) 37.5 mg/m2/day (total dose is 75 mg/m2 given as a 48 hour infusion) on days 1 to 2 of Week 36.
- Ifosfamide (Ifex) 3 g/m2/dose IV over 4 hours once per day on days 1, 2, and 3 of weeks 36.
- Methotrexate (MTX) 12,000 mg/m2 (maximum dose of 20,000 mg) IV over 4 hours once on day 1 of weeks 39 and 40.
Supportive therapy
- Mesna (Mesnex) 3 g/m2/24 hours IV continuous infusion over 24 hours on days 1, 2, and 3 of weeks 36.
- Leucovorin (Folinic acid) 15 mg/m2 PO or IV every 6 hours beginning 24 hours after the beginning of the methotrexate infusion and continuing until the serum methotrexate level is less than 0.1 μM.
5-Week Courses
References
- EURAMOS-1 poor response: Marina NM, Smeland S, Bielack SS, Bernstein M, Jovic G, Krailo MD, Hook JM, Arndt C, van den Berg H, Brennan B, Brichard B, Brown KL, Butterfass-Bahloul T, Calaminus G, Daldrup-Link HE, Eriksson M, Gebhardt MC, Gelderblom H, Gerss J, Goldsby R, Goorin A, Gorlick R, Grier HE, Hale JP, Hall KS, Hardes J, Hawkins DS, Helmke K, Hogendoorn PC, Isakoff MS, Janeway KA, Jürgens H, Kager L, Kühne T, Lau CC, Leavey PJ, Lessnick SL, Mascarenhas L, Meyers PA, Mottl H, Nathrath M, Papai Z, Randall RL, Reichardt P, Renard M, Safwat AA, Schwartz CL, Stevens MC, Strauss SJ, Teot L, Werner M, Sydes MR, Whelan JS. Comparison of MAPIE versus MAP in patients with a poor response to preoperative chemotherapy for newly diagnosed high-grade osteosarcoma (EURAMOS-1): an open-label, international, randomised controlled trial. Lancet Oncol. 2016 Oct;17(10):1396-1408. Epub 2016 Aug 25. link to original article link to PMC article dosing details in manuscript have been reviewed by our editors PubMed NCT00134030