Difference between revisions of "Soft tissue sarcoma"
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# Northfelt DW, Dezube BJ, Thommes JA, Miller BJ, Fischl MA, Friedman-Kien A, Kaplan LD, Du Mond C, Mamelok RD, Henry DH. Pegylated-liposomal doxorubicin versus doxorubicin, bleomycin, and vincristine in the treatment of AIDS-related Kaposi's sarcoma: results of a randomized phase III clinical trial. J Clin Oncol. 1998 Jul;16(7):2445-51. [http://jco.ascopubs.org/content/16/7/2445.long link to original article] '''contains verified protocol''' [https://www.ncbi.nlm.nih.gov/pubmed/9667262 PubMed] | # Northfelt DW, Dezube BJ, Thommes JA, Miller BJ, Fischl MA, Friedman-Kien A, Kaplan LD, Du Mond C, Mamelok RD, Henry DH. Pegylated-liposomal doxorubicin versus doxorubicin, bleomycin, and vincristine in the treatment of AIDS-related Kaposi's sarcoma: results of a randomized phase III clinical trial. J Clin Oncol. 1998 Jul;16(7):2445-51. [http://jco.ascopubs.org/content/16/7/2445.long link to original article] '''contains verified protocol''' [https://www.ncbi.nlm.nih.gov/pubmed/9667262 PubMed] | ||
− | ==Bevacizumab | + | ==Bevacizumab monotherapy {{#subobject:25316e|Regimen=1}}== |
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Revision as of 03:12, 19 August 2017
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19 regimens on this page
28 variants on this page
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Guidelines
ESMO
- Soft tissue and visceral sarcomas: ESMO Clinical Practice Guidelines for diagnosis, treatment and follow-up. (2014) PubMed
NCCN
Neoadjuvant therapy
Epirubicin & Ifosfamide
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Regimen
Study | Evidence | Comparator | Efficacy |
Gronchi et al. 2017 (ISG-STS 1001) | Phase III | Histotype-tailored therapy | Seems not superior |
Chemotherapy
- Epirubicin (Ellence) 60 mg/m2 IV once per day on days 1 & 2
- Ifosfamide (Ifex) 3000 mg/m2 IV once per day on days 1 to 3
Supportive medications
- Mesna (Mesnex) with Ifosfamide (Ifex); abstract does not list dosage/schedule
21-day cycle for 3 cycles, followed by surgery
References
- Gronchi A, Ferrari S, Quagliuolo V, Broto JM, Pousa AL, Grignani G, Basso U, Blay JY, Tendero O, Beveridge RD, Ferraresi V, Lugowska I, Merlo DF, Fontana V, Marchesi E, Donati DM, Palassini E, Palmerini E, De Sanctis R, Morosi C, Stacchiotti S, Bagué S, Coindre JM, Dei Tos AP, Picci P, Bruzzi P, Casali PG. Histotype-tailored neoadjuvant chemotherapy versus standard chemotherapy in patients with high-risk soft-tissue sarcomas (ISG-STS 1001): an international, open-label, randomised, controlled, phase 3, multicentre trial. Lancet Oncol. 2017 Jun;18(6):812-822. Epub 2017 May 9. link to original article contains protocol PubMed
Single-agent regimens
Dacarbazine (DTIC)
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Regimen #1
Study | Evidence | Comparator | Efficacy |
Buesa et al. 1991 | Phase II | ||
Schöffski et al. 2016 | Phase III | Eribulin | Seems to have inferior OS |
Details below are for Buesa et al. 1991.
Chemotherapy
- Dacarbazine (DTIC) 1200 mg/m2 in 200 mL normal saline IV over 20 minutes once on day 1
Supportive medications
- Calcium gluconate (10% solution) 5 mL IV every 10 minutes x 3 doses (total of 15 mL) after the start of dacarbazine; 2 additional doses of calcium gluconate (10% solution) 5 mL IV every 10 minutes were given to patients whose systolic blood pressure decreased below 80 mmHg or heart rate ≥160 beat/minute.
21-day cycles, given until progression of disease
Regimen #2
Study | Evidence | Comparator | Efficacy |
Demetri et al. 2015 | Phase III | Trabectedin | Inferior PFS |
Note: this is listed as a "starting dose," but no adjustment instructions were provided in the manuscript.
Chemotherapy
- Dacarbazine (DTIC) 1000 mg/m2 IV over 20 to 120 minutes once on day 1
21-day cycles
References
- Buesa JM, Mouridsen HT, van Oosterom AT, Verweij J, Wagener T, Steward W, Poveda A, Vestlev PM, Thomas D, Sylvester R. High-dose DTIC in advanced soft-tissue sarcomas in the adult. A phase II study of the E.O.R.T.C. Soft Tissue and Bone Sarcoma Group. Ann Oncol. 1991 Apr;2(4):307-9. link to original article contains verified protocol PubMed
- Demetri GD, von Mehren M, Jones RL, Hensley ML, Schuetze SM, Staddon A, Milhem M, Elias A, Ganjoo K, Tawbi H, Van Tine BA, Spira A, Dean A, Khokhar NZ, Park YC, Knoblauch RE, Parekh TV, Maki RG, Patel SR. Efficacy and safety of trabectedin or dacarbazine for metastatic liposarcoma or leiomyosarcoma after failure of conventional chemotherapy: results of a phase III randomized multicenter clinical trial. J Clin Oncol. 2016 Mar 10;34(8):786-93. Epub 2015 Sep 14. link to original article contains verified protocol link to PMC article PubMed
- Schöffski P, Chawla S, Maki RG, Italiano A, Gelderblom H, Choy E, Grignani G, Camargo V, Bauer S, Rha SY, Blay JY, Hohenberger P, D'Adamo D, Guo M, Chmielowski B, Le Cesne A, Demetri GD, Patel SR. Eribulin versus dacarbazine in previously treated patients with advanced liposarcoma or leiomyosarcoma: a randomised, open-label, multicentre, phase 3 trial. Lancet. 2016 Apr 16;387(10028):1629-37. Epub 2016 Feb 10. link to original article PubMed
Doxorubicin (Adriamycin)
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Regimen
Study | Evidence | Comparator | Efficacy |
Mouridsen et al. 1987 | Phase III | Epirubicin | Seems not superior |
Lorigan et al. 2007 | Phase III | Ifos 3 | Seems not superior |
Ifos 9 | Seems not superior | ||
Judson et al. 2014 (EORTC 62012) | Phase III | Intensified Doxorubicin & Ifosfamide | Might have inferior OS |
Tap et al. 2016 | Randomized Phase II | Doxorubicin & Olaratumab | Inferior OS |
Chemotherapy
- Doxorubicin (Adriamycin) 75 mg/m2 IV bolus once on day 1
Supportive medications
- In Tap et al. 2016, Dexrazoxane (Zinecard) (dose not specified) could be used on day 1 of every cycle to reduce the potential for doxorubicin-related cardiotoxicity in cycles 5 to 8
21-day cycle for up to 6 to 8 cycles, until progression of disease, unacceptable toxicity, or patient refusal
Note: in Mouridsen et al. 1987, treatment was given until progression of disease, unacceptable toxicity, or cumulative doxorubicin dosage of 550 mg/m2, though the ultimate decision to stop treatment based on cumulative doxorubicin dosage was at the discretion of the treating physician.
References
- Mouridsen HT, Bastholt L, Somers R, Santoro A, Bramwell V, Mulder JH, van Oosterom AT, Buesa J, Pinedo HM, Thomas D et al. Adriamycin versus epirubicin in advanced soft tissue sarcomas. A randomized phase II/phase III study of the EORTC Soft Tissue and Bone Sarcoma Group. Eur J Cancer Clin Oncol. 1987 Oct;23(10):1477-83. link to original article contains verified protocol PubMed
- Meta-analysis Bramwell VH, Anderson D, Charette ML. Doxorubicin-based chemotherapy for the palliative treatment of adult patients with locally advanced or metastatic soft-tissue sarcoma: a meta-analysis and clinical practice guideline. Sarcoma. 2000;4(3):103-12. link to original article link to PMC article PubMed
- Lorigan P, Verweij J, Papai Z, Rodenhuis S, Le Cesne A, Leahy MG, Radford JA, Van Glabbeke MM, Kirkpatrick A, Hogendoorn PC, Blay JY; European Organisation for Research and Treatment of Cancer Soft Tissue and Bone Sarcoma Group Study. Phase III trial of two investigational schedules of ifosfamide compared with standard-dose doxorubicin in advanced or metastatic soft tissue sarcoma: a European Organisation for Research and Treatment of Cancer Soft Tissue and Bone Sarcoma Group Study. J Clin Oncol. 2007 Jul 20;25(21):3144-50. link to original article contains verified protocol PubMed
- Judson I, Verweij J, Gelderblom H, Hartmann JT, Schöffski P, Blay JY, Kerst JM, Sufliarsky J, Whelan J, Hohenberger P, Krarup-Hansen A, Alcindor T, Marreaud S, Litière S, Hermans C, Fisher C, Hogendoorn PC, dei Tos AP, van der Graaf WT; European Organisation and Treatment of Cancer Soft Tissue and Bone Sarcoma Group. Doxorubicin alone versus intensified doxorubicin plus ifosfamide for first-line treatment of advanced or metastatic soft-tissue sarcoma: a randomised controlled phase 3 trial. Lancet Oncol. 2014 Apr;15(4):415-23. Epub 2014 Mar 5. link to original article PubMed
- Tap WD, Jones RL, Van Tine BA, Chmielowski B, Elias AD, Adkins D, Agulnik M, Cooney MM, Livingston MB, Pennock G, Hameed MR, Shah GD, Qin A, Shahir A, Cronier DM, Ilaria R Jr, Conti I, Cosaert J, Schwartz GK. Olaratumab and doxorubicin versus doxorubicin alone for treatment of soft-tissue sarcoma: an open-label phase 1b and randomised phase 2 trial. Lancet. 2016 Jul 30;388(10043):488-97. link to original article contains verified protocol PubMed
Epirubicin (Ellence)
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Regimen
Study | Evidence | Comparator | Efficacy |
Mouridsen et al. 1987 | Phase III | Doxorubicin | Seems not superior |
Chemotherapy
- Epirubicin (Ellence) 75 mg/m2 IV bolus once on day 1
21-day cycles, given until progression of disease, unacceptable toxicity, or cumulative epirubicin dosage of 550 mg/m2 (though the ultimate decision to stop treatment based on cumulative epirubicin dosage was at the discretion of the treating physician)
References
- Mouridsen HT, Bastholt L, Somers R, Santoro A, Bramwell V, Mulder JH, van Oosterom AT, Buesa J, Pinedo HM, Thomas D et al. Adriamycin versus epirubicin in advanced soft tissue sarcomas. A randomized phase II/phase III study of the EORTC Soft Tissue and Bone Sarcoma Group. Eur J Cancer Clin Oncol. 1987 Oct;23(10):1477-83. link to original article contains verified protocol PubMed
Eribulin (Halaven)
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Regimen
Study | Evidence | Comparator | Efficacy |
Schöffski et al. 2016 | Phase III | Dacarbazine | Seems to have superior OS |
Chemotherapy
- Eribulin (Halaven) 1.4 mg/m2 IV once per day on days 1 & 8
21-day cycles until progression
References
- Schöffski P, Chawla S, Maki RG, Italiano A, Gelderblom H, Choy E, Grignani G, Camargo V, Bauer S, Rha SY, Blay JY, Hohenberger P, D'Adamo D, Guo M, Chmielowski B, Le Cesne A, Demetri GD, Patel SR. Eribulin versus dacarbazine in previously treated patients with advanced liposarcoma or leiomyosarcoma: a randomised, open-label, multicentre, phase 3 trial. Lancet. 2016 Apr 16;387(10028):1629-37. Epub 2016 Feb 10. link to original article contains protocol PubMed
Ifosfamide monotherapy
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Regimen #1, short infusion (Ifos 3)
Study | Evidence | Comparator | Efficacy |
Lorigan et al. 2007 | Phase III | Doxorubicin | Seems not superior |
Ifos 9 | Seems not superior |
Chemotherapy
- Ifosfamide (Ifex) 3000 mg/m2 IV over 4 hours on days 1 to 3
- Each day's dose of ifosfamide is mixed together with Mesna (Mesnex) in 1 liter of normal saline
Supportive medications
- Mesna (Mesnex) as follows:
- 600 mg/m2 IV bolus once on day 1, given immediately prior to mesna/ifosfamide infusion, then
- 1500 mg/m2 IV over 4 hours on days 1 to 3, given together with Ifosfamide (Ifex), then
- 1200 mg/m2 IV two times per day on days 1 to 3, given at 4 and 8 hours after completion of ifosfamide and mesna
- An alternative is to use oral mesna instead of intravenous: Mesna (Mesnex) 1200 mg/m2 PO two times per day on days 1 to 3, given at 2 and 6 hours after completion of ifosfamide and mesna
- Sodium bicarbonate 150 mmol IV once per day on days 1 to 3
- Patient with somnolence or other signs of encephalopathy with ifosfamide received methylene blue 50 mg IV every 4 hours until resolution of symptoms. During cycles thereafter, patients would receive methylene blue 50 mg IV every 4 hours, starting 4 hours prior to ifosfamide on day 1, continuing until 72 hours after completion
21-day cycle for up to 6 cycles, progression of disease, unacceptable toxicity, or patient refusal
Regimen #2, continuous infusion (Ifos 9)
Study | Evidence | Comparator | Efficacy |
Lorigan et al. 2007 | Phase III | Doxorubicin | Seems not superior |
Ifos 3 | Seems not superior |
Chemotherapy
- Ifosfamide (Ifex) 3000 mg/m2/day IV continuous infusion over 72 hours (total dose per cycle: 9000 mg/m2) on days 1 to 3, given together with mesna
- Each day's dose is mixed together with mesna in 3 liters of normal saline
Supportive medications
- Mesna (Mesnex) as follows:
- 600 mg/m2 IV bolus once on day 1, immediately prior to mesna/ifosfamide infusion, then
- 3000 mg/m2/day IV continuous infusion over 72 hours (total dose per cycle: 9000 mg/m2) on days 1 to 3, given together with Ifosfamide (Ifex), then
- 1800 mg/m2 IV over 12 hours once on day 4, starting after completion of ifosfamide and mesna
- An alternative is to use oral mesna instead of intravenous: Mesna (Mesnex) 1200 mg/m2 PO three times on day 4, given 0, 2, and 6 hours after completion of ifosfamide and mesna
- Sodium bicarbonate 150 mmol IV once per day on days 1 to 3
- Patient with somnolence or other signs of encephalopathy with ifosfamide received methylene blue 50 mg IV every 4 hours until resolution of symptoms. During cycles thereafter, patients would receive methylene blue 50 mg IV every 4 hours, starting 4 hours prior to ifosfamide on day 1, continuing until 72 hours after completion
21-day cycle for up to 6 cycles, progression of disease, unacceptable toxicity, or patient refusal
Regimen #3
Study | Evidence |
van Oosterom et al. 2002 | Phase II |
Chemotherapy
- Ifosfamide (Ifex) 3000 mg/m2 IV over 4 hours once per day on days 1 to 3
- Each day's dose is dissolved in 125 mL sterile water per 1000 mg of ifosfamide, mixed together with Mesna (Mesnex) in an additional 1 liter of dextrose/saline
Supportive medications
- Mesna (Mesnex) as follows:
- 600 mg/m2 IV bolus once on day 1, immediately prior to mesna/ifosfamide infusion, then
- 1500 mg/m2 IV over 4 hours on days 1 to 3, given together with Ifosfamide (Ifex), then
- 500 mg/m2 IV two times per day on days 1 to 3, given at 4 and 8 hours after completion of ifosfamide and mesna
- "Antiemetics were prescribed according to local conventions"
- 1 liter of fluid PO two times per day on days 1 to 3, taken 4 and 8 hours after completion of ifosfamide and mesna
21-day cycle for at least 2 cycles, except in cases of rapid disease progression; continued until disease progression or unacceptable toxicity or patient refusal
References
- van Oosterom AT, Mouridsen HT, Nielsen OS, Dombernowsky P, Krzemieniecki K, Judson I, Svancarova L, Spooner D, Hermans C, Van Glabbeke M, Verweij J; EORTC Soft Tissue and Bone Sarcoma Group. Results of randomised studies of the EORTC Soft Tissue and Bone Sarcoma Group (STBSG) with two different ifosfamide regimens in first- and second-line chemotherapy in advanced soft tissue sarcoma patients. Eur J Cancer. 2002 Dec;38(18):2397-406 link to original article contains verified protocol PubMed content property of HemOnc.org
- Lorigan P, Verweij J, Papai Z, Rodenhuis S, Le Cesne A, Leahy MG, Radford JA, Van Glabbeke MM, Kirkpatrick A, Hogendoorn PC, Blay JY; European Organisation for Research and Treatment of Cancer Soft Tissue and Bone Sarcoma Group Study. Phase III trial of two investigational schedules of ifosfamide compared with standard-dose doxorubicin in advanced or metastatic soft tissue sarcoma: a European Organisation for Research and Treatment of Cancer Soft Tissue and Bone Sarcoma Group Study. J Clin Oncol. 2007 Jul 20;25(21):3144-50. link to original article contains verified protocol PubMed
Pazopanib (Votrient)
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Regimen
Study | Evidence | Comparator | Efficacy |
van der Graaf et al. 2012 (PALETTE) | Phase III | Placebo | Superior PFS |
Chemotherapy
- Pazopanib (Votrient) 800 mg PO once per day
Given until progression of disease, unacceptable toxicity, withdrawal of consent, or death
References
- van der Graaf WT, Blay JY, Chawla SP, Kim DW, Bui-Nguyen B, Casali PG, Sch?ffski P, Aglietta M, Staddon AP, Beppu Y, Le Cesne A, Gelderblom H, Judson IR, Araki N, Ouali M, Marreaud S, Hodge R, Dewji MR, Coens C, Demetri GD, Fletcher CD, Dei Tos AP, Hohenberger P; EORTC Soft Tissue and Bone Sarcoma Group; PALETTE study group. Pazopanib for metastatic soft-tissue sarcoma (PALETTE): a randomised, double-blind, placebo-controlled phase 3 trial. Lancet. 2012 May 19;379(9829):1879-86. Epub 2012 May 16. link to original article contains verified protocol PubMed
Placebo
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Regimen
Study | Evidence | Comparator | Efficacy |
van der Graaf et al. 2012 (PALETTE) | Phase III | Pazopanib | Inferior PFS |
Kawai et al. 2015 | Randomized Phase II | Trabectedin | Inferior PFS |
Mir et al. 2016 (REGOSARC) | Randomized Phase II | Regorafenib | Inferior PFS (*) |
No active antineoplastic treatment. Used as a comparator arm and here for reference purposes only. Note: reported efficacy in REGOSARC is for the leiomyosarcoma, synovial sarcoma, and other sarcoma cohorts; there was no significant difference in outcome for the liposarcoma cohort.
References
- van der Graaf WT, Blay JY, Chawla SP, Kim DW, Bui-Nguyen B, Casali PG, Sch?ffski P, Aglietta M, Staddon AP, Beppu Y, Le Cesne A, Gelderblom H, Judson IR, Araki N, Ouali M, Marreaud S, Hodge R, Dewji MR, Coens C, Demetri GD, Fletcher CD, Dei Tos AP, Hohenberger P; EORTC Soft Tissue and Bone Sarcoma Group; PALETTE study group. Pazopanib for metastatic soft-tissue sarcoma (PALETTE): a randomised, double-blind, placebo-controlled phase 3 trial. Lancet. 2012 May 19;379(9829):1879-86. Epub 2012 May 16. link to original article contains verified protocol PubMed
- Kawai A, Araki N, Sugiura H, Ueda T, Yonemoto T, Takahashi M, Morioka H, Hiraga H, Hiruma T, Kunisada T, Matsumine A, Tanase T, Hasegawa T, Takahashi S. Trabectedin monotherapy after standard chemotherapy versus best supportive care in patients with advanced, translocation-related sarcoma: a randomised, open-label, phase 2 study. Lancet Oncol. 2015 Apr;16(4):406-16. Epub 2015 Mar 18. link to original article contains protocol PubMed
- Mir O, Brodowicz T, Italiano A, Wallet J, Blay JY, Bertucci F, Chevreau C, Piperno-Neumann S, Bompas E, Salas S, Perrin C, Delcambre C, Liegl-Atzwanger B, Toulmonde M, Dumont S, Ray-Coquard I, Clisant S, Taieb S, Guillemet C, Rios M, Collard O, Bozec L, Cupissol D, Saada-Bouzid E, Lemaignan C, Eisterer W, Isambert N, Chaigneau L, Cesne AL, Penel N. Safety and efficacy of regorafenib in patients with advanced soft tissue sarcoma (REGOSARC): a randomised, double-blind, placebo-controlled, phase 2 trial. Lancet Oncol. 2016 Dec;17(12):1732-1742. Epub 2016 Oct 14. link to original article contains protocol PubMed
Regorafenib (Stivarga)
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Regimen
Study | Evidence | Comparator | Efficacy |
Mir et al. 2016 (REGOSARC) | Randomized Phase II | Placebo | Superior PFS |
Note: reported efficacy is for the leiomyosarcoma, synovial sarcoma, and other sarcoma cohorts; there was no significant difference in outcome for the liposarcoma cohort.
Chemotherapy
- Regorafenib (Stivarga) 160 mg PO once per day on days 1 to 21
28-day cycles, given until progression of disease or unacceptable toxicity
References
- Mir O, Brodowicz T, Italiano A, Wallet J, Blay JY, Bertucci F, Chevreau C, Piperno-Neumann S, Bompas E, Salas S, Perrin C, Delcambre C, Liegl-Atzwanger B, Toulmonde M, Dumont S, Ray-Coquard I, Clisant S, Taieb S, Guillemet C, Rios M, Collard O, Bozec L, Cupissol D, Saada-Bouzid E, Lemaignan C, Eisterer W, Isambert N, Chaigneau L, Cesne AL, Penel N. Safety and efficacy of regorafenib in patients with advanced soft tissue sarcoma (REGOSARC): a randomised, double-blind, placebo-controlled, phase 2 trial. Lancet Oncol. 2016 Dec;17(12):1732-1742. Epub 2016 Oct 14. link to original article contains protocol PubMed
Temozolomide (Temodar)
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Regimen #1
Study | Evidence |
Talbot et al. 2003 | Phase II |
Chemotherapy
- Temozolomide (Temodar) 200 mg/m2 (doses rounded up if needed to next available dosage based on capsule doses) PO once on day 1, on an empty stomach; then 12 hours later, 90 mg/m2 PO once every 12 hours x 9 doses (total of 10 doses per cycle) on days 1 to 5, on an empty stomach
Supportive medications
- Antiemetics "prescribed as clinically indicated by the treating physician"
28-day cycles, given until progression of disease or 1 year; patients on study could be reconsented to receive therapy beyond 1 year
Regimen #2
Study | Evidence |
Garcia del Muro et al. 2005 | Phase II |
Chemotherapy
- Temozolomide (Temodar) 100 mg/m2 PO once per day on days 1 to 42 (6 weeks), with no food 1 hour before and after temozolomide doses
- Initial dose used in the study was 75 mg/m2, but due to lack of toxicity, protocol was amended to use 100 mg/m2 doses
Supportive medications
- "Antiemetics, mainly oral metoclopramide and ondansetron, were prescribed as clinically indicated by the treating physician"
9-week cycle for up to 3 cycles, progression of disease, or unacceptable toxicity
References
- Talbot SM, Keohan ML, Hesdorffer M, Orrico R, Bagiella E, Troxel AB, Taub RN. A phase II trial of temozolomide in patients with unresectable or metastatic soft tissue sarcoma. Cancer. 2003 Nov 1;98(9):1942-6. link to original article contains verified protocol PubMed
- Garcia del Muro X, Lopez-Pousa A, Martin J, Buesa JM, Martinez-Trufero J, Casado A, Poveda A, Cruz J, Bover I, Maurel J; Spanish Group for Research on Sarcomas. A phase II trial of temozolomide as a 6-week, continuous, oral schedule in patients with advanced soft tissue sarcoma: a study by the Spanish Group for Research on Sarcomas. Cancer. 2005 Oct 15;104(8):1706-12. link to original article contains verified protocol PubMed
Trabectedin (Yondelis)
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Regimen #1
Study | Evidence | Comparator | Efficacy |
Demetri et al. 2015 | Phase III | Dacarbazine | Superior PFS |
Note: this is listed as a "starting dose," but no adjustment instructions were provided in the manuscript.
Chemotherapy
- Trabectedin (Yondelis) 1.5 mg/m2 IV continuous infusion over 24 hours, starting on day 1
Supportive medications
- Dexamethasone (Decadron) 20 mg IV once prior to trabectedin
21-day cycles
Regimen #2
Study | Evidence | Comparator | Efficacy |
Kawai et al. 2015 | Randomized Phase II | Placebo | Superior PFS |
Chemotherapy
- Trabectedin (Yondelis) 1.2 mg/m2 IV continuous infusion over 24 hours, starting on day 1
21-day cycles
References
- Demetri GD, Chawla SP, von Mehren M, Ritch P, Baker LH, Blay JY, Hande KR, Keohan ML, Samuels BL, Schuetze S, Lebedinsky C, Elsayed YA, Izquierdo MA, Gómez J, Park YC, Le Cesne A. Efficacy and safety of trabectedin in patients with advanced or metastatic liposarcoma or leiomyosarcoma after failure of prior anthracyclines and ifosfamide: results of a randomized phase II study of two different schedules. J Clin Oncol. 2009 Sep 1;27(25):4188-96. Epub 2009 Aug 3. link to original article PubMed
- Kawai A, Araki N, Sugiura H, Ueda T, Yonemoto T, Takahashi M, Morioka H, Hiraga H, Hiruma T, Kunisada T, Matsumine A, Tanase T, Hasegawa T, Takahashi S. Trabectedin monotherapy after standard chemotherapy versus best supportive care in patients with advanced, translocation-related sarcoma: a randomised, open-label, phase 2 study. Lancet Oncol. 2015 Apr;16(4):406-16. Epub 2015 Mar 18. link to original article contains protocol PubMed
- Demetri GD, von Mehren M, Jones RL, Hensley ML, Schuetze SM, Staddon A, Milhem M, Elias A, Ganjoo K, Tawbi H, Van Tine BA, Spira A, Dean A, Khokhar NZ, Park YC, Knoblauch RE, Parekh TV, Maki RG, Patel SR. Efficacy and safety of trabectedin or dacarbazine for metastatic liposarcoma or leiomyosarcoma after failure of conventional chemotherapy: results of a phase III randomized multicenter clinical trial. J Clin Oncol. 2016 Mar 10;34(8):786-93. Epub 2015 Sep 14. link to original article contains verified protocol link to PMC article PubMed
Combination regimens
AIM
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AIM: Adriamycin, Ifosfamide, Mesna
Regimen #1, 5-day course, lower dose doxorubicin - AI 75/10
Study | Evidence |
Patel et al. 1998 | Pilot, <20 patients reported |
Chemotherapy
- Doxorubicin (Adriamycin) 25 mg/m2/day IV continuous infusion over 72 hours on days 1 to 3 (total dose per cycle: 75 mg/m2)
- Ifosfamide (Ifex) 2000 mg/m2 IV over 2 hours once per day on days 1 to 5 (total dose per cycle: 10,000 mg/m2)
Supportive medications
- Mesna (Mesnex) 400 mg/m2 IV once on day 1, given simultaneously with the first dose of Ifosfamide (Ifex)
- Mesna (Mesnex) 1200 mg/m2/day IV continuous infusion over 5 days on days 1 to 5 (total dose per cycle: 6000 mg/m2)
- Each day's dose is given in 2 liters of D5W with 100 mEq/L sodium acetate, 20 mEq/L potassium acetate, and 4 mEq/L magnesium sulfate
- If febrile neutropenia occurs, G-CSF is used in subsequent cycles
21-day cycles, given until maximum response, 6 cycles of therapy, progression of disease, or unacceptable toxicity
Regimen #2, 4-day course, higher dose doxorubicin - AI 90/10
Study | Evidence |
Patel et al. 1998 | Pilot, <20 patients reported |
Chemotherapy
- Doxorubicin (Adriamycin) 30 mg/m2/day IV continuous infusion over 72 hours on days 1 to 3 (total dose per cycle: 90 mg/m2)
- Ifosfamide (Ifex) 2500 mg/m2 IV over 3 hours once per day on days 1 to 4 (total dose per cycle: 10,000 mg/m2)
Supportive medications
- Mesna (Mesnex) 500 mg/m2 IV once on day 1, given simultaneously with the first dose of Ifosfamide (Ifex)
- Mesna (Mesnex) 1500 mg/m2/day IV continuous infusion over 4 days on days 1 to 4 (total dose per cycle: 6000 mg/m2)
- Each day's dose is given in 2 liters of D5W with 100 mEq/L sodium acetate, 20 mEq/L potassium acetate, and 4 mEq/L magnesium sulfate
- G-CSF 5 mcg/kg (dose rounded to 300 or 480 mcg) SC once per day, starting on day 5, given until ANC is at least 10,000/uL
21-day cycles, given until maximum response, 6 cycles of therapy, progression of disease, or unacceptable toxicity
References
- Patel SR, Vadhan-Raj S, Burgess MA, Plager C, Papadopolous N, Jenkins J, Benjamin RS. Results of two consecutive trials of dose-intensive chemotherapy with doxorubicin and ifosfamide in patients with sarcomas. Am J Clin Oncol. 1998 Jun;21(3):317-21. link to original article contains verified protocol PubMed
Docetaxel & Gemcitabine
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Regimen #1, no prior radiation
Study | Evidence |
Hensley et al. 2002 | Phase II |
Chemotherapy
- Docetaxel (Taxotere) 100 mg/m2 IV over 1 hour once on day 8, given second
- Gemcitabine (Gemzar) 900 mg/m2 IV over 90 minutes once per day on days 1 & 8, given first
Supportive medications
- Dexamethasone (Decadron) 8 mg PO BID on days 7 to 9 (the day before, the day of, and day after Docetaxel (Taxotere))
- Patients could receive diuretics at physician discretion for peripheral edema related to docetaxel
- One of the following growth factors (varies depending on reference):
- G-CSF 150 mcg/m2 (dose rounded to 300 or 480 mcg) SC once per day on days 9 to 15 as primary neutropenia prophylaxis; could be stopped before day 15 if ANC greater than 1200/uL on two separate measurements
- Pegfilgrastim (Neulasta) 6 mg SC once on either day 9 or 10 (only one dose given)
21-day cycle for 6 to 8 cycles, given until progression of disease or unacceptable toxicity; Hensley et al. 2008 did not specify a maximum number of cycles
Regimen #2, patients who received prior radiation
Study | Evidence |
Hensley et al. 2002 | Phase II |
Chemotherapy
- Docetaxel (Taxotere) 75 mg/m2 IV over 1 hour once on day 8, given second
- Gemcitabine (Gemzar) 675 mg/m2 IV over 90 minutes once per day on days 1 & 8, given first
Supportive medications
- Dexamethasone (Decadron) 8 mg PO BID on days 7-9 (the day before, the day of, and day after Docetaxel (Taxotere))
- Patients could receive diuretics at physician discretion for peripheral edema related to docetaxel
- One of the following growth factors (varies depending on reference):
- G-CSF 150 mcg/m2 (dose rounded to 300 or 480 mcg) SC once per day on days 9 to 15 as primary neutropenia prophylaxis; could be stopped before day 15 if ANC greater than 1200/uL on two separate measurements
- Pegfilgrastim (Neulasta) 6 mg SC once on either day 9 or 10 (only one dose given)
21-day cycle for 6 to 8 cycles, given until progression of disease or unacceptable toxicity; Hensley et al. 2008 did not specify a maximum number of cycles
References
- Hensley ML, Maki R, Venkatraman E, Geller G, Lovegren M, Aghajanian C, Sabbatini P, Tong W, Barakat R, Spriggs DR. Gemcitabine and docetaxel in patients with unresectable leiomyosarcoma: results of a phase II trial. J Clin Oncol. 2002 Jun 15;20(12):2824-31. link to original article contains verified protocol PubMed
- Hensley ML, Blessing JA, Mannel R, Rose PG. Fixed-dose rate gemcitabine plus docetaxel as first-line therapy for metastatic uterine leiomyosarcoma: a Gynecologic Oncology Group phase II trial. Gynecol Oncol. 2008 Jun;109(3):329-34. link to original article contains verified protocol link to PMC article PubMed
Doxorubicin & Olaratumab
Regimen
Study | Evidence | Comparator | Efficacy |
Tap et al. 2016 | Randomized Phase II | Doxorubicin | Superior OS |
Chemotherapy
- Doxorubicin (Adriamycin) as follows:
- Cycles 1 to 8: 75 mg/m2 IV once on day 1
- Olaratumab (Lartruvo) 15 mg/kg IV once per day on days 1 & 8
21-day cycles, given until progression of disease
Supportive medications
- In Tap et al. 2016, Dexrazoxane (Zinecard) (dose not specified) could be used on day 1 of every cycle to reduce the potential for doxorubicin-related cardiotoxicity in cycles 5 to 8
References
- Tap WD, Jones RL, Van Tine BA, Chmielowski B, Elias AD, Adkins D, Agulnik M, Cooney MM, Livingston MB, Pennock G, Hameed MR, Shah GD, Qin A, Shahir A, Cronier DM, Ilaria R Jr, Conti I, Cosaert J, Schwartz GK. Olaratumab and doxorubicin versus doxorubicin alone for treatment of soft-tissue sarcoma: an open-label phase 1b and randomised phase 2 trial. Lancet. 2016 Jul 30;388(10043):488-97. Epub 2016 Jun 9. Erratum in: Lancet. 2016 Jul 30;388(10043):464. link to original article contains verified protocol PubMed
Epirubicin & Ifosfamide
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Regimen
Study | Evidence |
Reichardt et al. 1998 | Phase II |
Chemotherapy
- Epirubicin (Ellence) 45 mg/m2/day IV continuous infusion over 2 days on days 2 & 3 (total dose per cycle: 90 mg/m2)
- Ifosfamide (Ifex) 2500 mg/m2/day IV continuous infusion over 5 days on days 1 to 5 (total dose per cycle: 12,500 mg/m2)
- Each day's dose is mixed together with Mesna (Mesnex) in 3 liters of "fluids with electrolytes"
Supportive medications
- Mesna (Mesnex) 1500 mg/m2 IV continuous infusion over 5 days on days 1 to 5, given together with Ifosfamide (Ifex) (total dose per cycle: 7500 mg/m2)
- G-CSF 5 mcg/kg SC once per day on days 6 to 15 or "until recovery of leukocytes"
- Ondansetron (Zofran) 8-24 mg per day prn nausea
- Dexamethasone (Decadron) (dose/schedule not specified) for antiemesis if necessary
21-day cycles
References
- Reichardt P, Tilgner J, Hohenberger P, D?rken B. Dose-intensive chemotherapy with ifosfamide, epirubicin, and filgrastim for adult patients with metastatic or locally advanced soft tissue sarcoma: a phase II study. J Clin Oncol. 1998 Apr;16(4):1438-43. link to original article contains verified protocol PubMed
Gemcitabine & Vinorelbine
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Regimen
Study | Evidence |
Dileo et al. 2007 | Phase II |
Chemotherapy
- Gemcitabine (Gemzar) 800 mg/m2 IV over 90 minutes once per day on days 1 & 8
- Vinorelbine (Navelbine) 25 mg/m2 IV over 10 minutes once per day on days 1 & 8
21-day cycles, given until progression of disease or unacceptable toxicity
Reference
- Dileo P, Morgan JA, Zahrieh D, Desai J, Salesi JM, Harmon DC, Quigley MT, Polson K, Demetri GD, George S. Gemcitabine and vinorelbine combination chemotherapy for patients with advanced soft tissue sarcomas: results of a phase II trial. Cancer. 2007 May 1;109(9):1863-9. link to original article contains verified protocol PubMed
Giant-cell tumor of bone
Denosumab (Xgeva)
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Regimen
Study | Evidence |
Thomas et. al 2010 | Phase II |
Primary therapy
- Denosumab (Xgeva) as follows:
- Cycle 1: 120 mg SC once per day on days 1, 8, 15
- Cycle 2 onwards: 120 mg SC once on day 1
Supportive medications
- (per Thomas, et. al 2010):
- Calcium 500 mg PO once per day
- Vitamin D 400 IU PO once per day
28-day cycles, given until complete tumor resection, progression of disease, or patient choice
References
- Thomas D, Henshaw R, Skubitz K, Chawla S, Staddon A, Blay JY, Roudier M, Smith J, Ye Z, Sohn W, Dansey R, Jun S. Denosumab in patients with giant-cell tumour of bone: an open-label, phase 2 study. Lancet Oncol. 2010 Mar;11(3):275-80. link to original article contains verified protocol PubMed
Gastrointestinal Stromal Tumor (GIST)
These regimens have been moved to their own page, which can be found here.
Angiosarcoma
Bevacizumab monotherapy
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Regimen
Study | Evidence |
Agulnik et al. 2013 | Phase II |
Chemotherapy
- Bevacizumab (Avastin) 15 mg/kg IV once on day 1
21-day cycles, given until progression of disease, intolerance, unacceptable toxicity, patient refusal, or physician discretion
References
- Agulnik M, Yarber JL, Okuno SH, von Mehren M, Jovanovic BD, Brockstein BE, Evens AM, Benjamin RS. An open-label, multicenter, phase II study of bevacizumab for the treatment of angiosarcoma and epithelioid hemangioendotheliomas. Ann Oncol. 2013 Jan;24(1):257-63. link to original article contains verified protocol PubMed
Paclitaxel (Taxol)
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Regimen
Study | Evidence |
Penel et al. 2008 (ANGIOTAX) | Phase II |
Chemotherapy
- Paclitaxel (Taxol) 80 mg/m2 IV over 60 minutes once per day on days 1, 8, 15
Supportive medications
- Dexamethasone (Decadron) 8 mg IV once prior to paclitaxel
- Cimetidine (Tagamet) 200 mg IV once prior to paclitaxel
- Dexchlorpheniramine (note: was spelled as dexchloropheramine in the Penel et al. 2008) (Polaramine) 5 mg IV once prior to paclitaxel
- "Standard antiemetics (mainly metoclopramide) were prescribed as clinically indicated by the treating physician"
28-day cycle for 6 cycles, given until progression of disease or unacceptable toxicity
References
- Penel N, Bui BN, Bay JO, Cupissol D, Ray-Coquard I, Piperno-Neumann S, Kerbrat P, Fournier C, Taieb S, Jimenez M, Isambert N, Peyrade F, Chevreau C, Bompas E, Brain EG, Blay JY. Phase II trial of weekly paclitaxel for unresectable angiosarcoma: the ANGIOTAX Study. J Clin Oncol. 2008 Nov 10;26(32):5269-74. Epub 2008 Sep 22. link to original article contains verified protocol PubMed
HIV/AIDS-associated Kaposi's Sarcoma
ABV
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ABV: Adriamycin (Doxorubicin), Bleomycin, Vincristine
Regimen #1
Study | Evidence | Comparator | Efficacy |
Northfelt et al. 1998 | Phase III | Pegylated liposomal doxorubicin | Inferior ORR |
Chemotherapy
- Doxorubicin (Adriamycin) 20 mg/m2 IV once on day 1
- Bleomycin (Blenoxane) 10 mg/m2 IV once on day 1
- Vincristine (Oncovin) 1 mg IV once on day 1
Supportive medications
- "Colony-stimulating factors (CSFs) were prescribed at the discretion of the investigators."
14-day cycle for up to 6 cycles
Regimen #2
Study | Evidence | Comparator | Efficacy |
Gill et al. 1996 | Phase III | Liposomal daunorubicin | Seems not superior |
Gill et al. 1996 described doses but did not clearly say in the paper when these drugs were given, but this schedule is assumed based on the Northfelt et al. 1998 ABV regimen.
Chemotherapy
- Doxorubicin (Adriamycin) 10 mg/m2 IV once on day 1
- Bleomycin (Blenoxane) 15 units IV once on day 1
- Vincristine (Oncovin) 1 mg IV once on day 1
Supportive medications
- "No routine premedication was established by the protocol, but it could be provided at the discretion of the investigator"
14-day cycle for minimum of 2 cycles; given until complete remission, unacceptable toxicity, disease progression, patient refusal, or death
References
- Gill PS, Wernz J, Scadden DT, Cohen P, Mukwaya GM, von Roenn JH, Jacobs M,Kempin S, Silverberg I, Gonzales G, Rarick MU, Myers AM, Shepherd F, Sawka C, Pike MC, Ross ME. Randomized phase III trial of liposomal daunorubicin versus doxorubicin, bleomycin, and vincristine in AIDS-related Kaposi's sarcoma. J Clin Oncol. 1996 Aug;14(8):2353-64. link to original article contains verified protocol PubMed
- Northfelt DW, Dezube BJ, Thommes JA, Miller BJ, Fischl MA, Friedman-Kien A, Kaplan LD, Du Mond C, Mamelok RD, Henry DH. Pegylated-liposomal doxorubicin versus doxorubicin, bleomycin, and vincristine in the treatment of AIDS-related Kaposi's sarcoma: results of a randomized phase III clinical trial. J Clin Oncol. 1998 Jul;16(7):2445-51. link to original article contains verified protocol PubMed
Bevacizumab monotherapy
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Regimen
Study | Evidence |
Uldrick et al. 2012 | Phase II |
Loading dose
- Bevacizumab (Avastin) 15 mg/kg IV once as a loading dose; start regular therapy 7 days later after this loading dose
Regular therapy
- Bevacizumab (Avastin) 15 mg/kg IV once on day 1
Supportive medications
- "Antihypertensive therapy was initiated for systolic blood pressure greater than 160 mmHg or diastolic blood pressure greater than 95 mmHg persisting for more than 1 week or for systolic blood pressure greater than 210 mmHg or diastolic blood pressure greater than 120 mmHg at any time."
- "HIV-positive patients with CD4 count of less than 200 cells/µL received Pneumocystis jiroveci prophylaxis."
- "Mycobacterium avium prophylaxis was considered if CD4 count was less than 75 cells/µL."
- Patients with HIV/AIDS continued HAART
- Filgrastim (Neupogen) "used as clinically indicated"
21-day cycles, given until progression of disease requiring cytotoxic therapy, lack of adherence to protocol (including HAART), or patient-requested discontinuation
References
- Uldrick TS, Wyvill KM, Kumar P, O'Mahony D, Bernstein W, Aleman K, Polizzotto MN, Steinberg SM, Pittaluga S, Marshall V, Whitby D, Little RF, Yarchoan R. Phase II study of bevacizumab in patients with HIV-associated Kaposi's sarcoma receiving antiretroviral therapy. J Clin Oncol. 2012 May 1;30(13):1476-83. Epub 2012 Mar 19. link to original article contains verified protocol link to PMC article PubMed
Daunorubicin liposomal (DaunoXome)
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Regimen
Study | Evidence | Comparator | Efficacy |
Gill et al. 1996 | Phase III | ABV | Seems not superior |
Chemotherapy
- Daunorubicin liposomal (DaunoXome) 40 mg/m2 IV over 30 to 60 minutes once on day 1
Supportive medications
- "No routine premedication was established by the protocol, but it could be provided at the discretion of the investigator"
14-day cycle for minimum of 2 cycles; given until complete remission, unacceptable toxicity, disease progression, patient refusal, or death
References
- Gill PS, Wernz J, Scadden DT, Cohen P, Mukwaya GM, von Roenn JH, Jacobs M,Kempin S, Silverberg I, Gonzales G, Rarick MU, Myers AM, Shepherd F, Sawka C, Pike MC, Ross ME. Randomized phase III trial of liposomal daunorubicin versus doxorubicin, bleomycin, and vincristine in AIDS-related Kaposi's sarcoma. J Clin Oncol. 1996 Aug;14(8):2353-64. link to original article contains verified protocol PubMed
Doxorubicin liposomal (Doxil)
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Regimen
Study | Evidence | Comparator | Efficacy |
Northfelt et al. 1998 | Phase III | ABV | Superior ORR |
Chemotherapy
- Doxorubicin liposomal (Doxil) 20 mg/m2 IV over 30 minutes once on day 1
Supportive medications
- "Colony-stimulating factors (CSFs) were prescribed at the discretion of the investigators."
14-day cycle for up to 6 cycles
References
- Northfelt DW, Dezube BJ, Thommes JA, Miller BJ, Fischl MA, Friedman-Kien A, Kaplan LD, Du Mond C, Mamelok RD, Henry DH. Pegylated-liposomal doxorubicin versus doxorubicin, bleomycin, and vincristine in the treatment of AIDS-related Kaposi's sarcoma: results of a randomized phase III clinical trial. J Clin Oncol. 1998 Jul;16(7):2445-51. link to original article contains verified protocol PubMed
Etoposide (Vepesid)
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Regimen
Study | Evidence |
Evans et al. 2002 | Phase II |
Chemotherapy
- Etoposide (Vepesid) 50 mg PO once per day on days 1 to 7
14-day cycles
References
- Evans SR, Krown SE, Testa MA, Cooley TP, Von Roenn JH. Phase II evaluation of low-dose oral etoposide for the treatment of relapsed or progressive AIDS-related Kaposi's sarcoma: an AIDS Clinical Trials Group clinical study. J Clin Oncol. 2002 Aug 1;20(15):3236-41. link to original article contains verified protocol PubMed