Soft tissue sarcoma

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19 regimens on this page
28 variants on this page


Guidelines

ESMO

NCCN

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

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

21-day cycles

References

  1. 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
  2. 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 PubMed
  3. 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 Phase III Intensified Doxorubicin & Ifosfamide Might have inferior OS
Tap et al. 2016 Randomized Phase II Doxorubicin & Olaratumab Inferior OS

Chemotherapy

21-day cycle for up to 6 to 8 cycles, until progression of disease, unacceptable toxicity, or patient refusal

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.

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

  1. 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
  2. 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 PubMed
  3. 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
  4. 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
  5. 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

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

  1. 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

21-day cycles until progression

References

  1. 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 (Ifex)

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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

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, 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 of ifosfamide 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, 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 of ifosfamide is dissolved in 125 mL sterile water per 1000 mg of ifosfamide, mixed together with mesna 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, 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

  1. 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
  2. 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

Given until progression of disease, unacceptable toxicity, withdrawal of consent, or death

References

  1. 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

No active antineoplastic treatment. Used as a comparator arm and here for reference purposes only.

References

  1. 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

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

  1. 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
  2. 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

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

Supportive medications

21-day cycles

References

  1. 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 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 of mesna 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 of mesna 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

21-day cycles, given until maximum response, 6 cycles of therapy, progression of disease, or unacceptable toxicity

References

  1. 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

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 >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

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 >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

  1. 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
  2. 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 PubMed

Doxorubicin & Olaratumab

Regimen

Study Evidence Comparator Efficacy
Tap et al. 2016 Randomized Phase II Doxorubicin Superior OS

Chemotherapy

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

  1. 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, given together with Mesna (Mesnex) (total dose per cycle: 12,500 mg/m2)
    • Each day's dose of ifosfamide is mixed together with mesna in 3 liters of "fluids with electrolytes"

Supportive medications

21-day cycles

References

  1. 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

21-day cycles, given until progression of disease or unacceptable toxicity

Reference

  1. 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

  1. 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

GIST (Gastrointestinal Stromal Tumor) - neoadjuvant therapy

Imatinib (Gleevec)

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Regimen

Study Evidence
Eisenberg et al. 2009 (RTOG 0132) Phase II

Chemotherapy

Given for 8 to 12 weeks prior to surgery, stopped on the day prior to surgery, resumed as soon as possible postoperatively, and continued for 2 years as postoperative adjuvant therapy

References

  1. Eisenberg BL, Harris J, Blanke CD, Demetri GD, Heinrich MC, Watson JC, Hoffman JP, Okuno S, Kane JM, von Mehren M. Phase II trial of neoadjuvant/adjuvant imatinib mesylate (IM) for advanced primary and metastatic/recurrent operable gastrointestinal stromal tumor (GIST): early results of RTOG 0132/ACRIN 6665. J Surg Oncol. 2009 Jan 1;99(1):42-7. link to PMC article contains verified protocol PubMed
    1. Update: Wang D, Zhang Q, Blanke CD, Demetri GD, Heinrich MC, Watson JC, Hoffman JP, Okuno S, Kane JM, von Mehren M, Eisenberg BL. Phase II trial of neoadjuvant/adjuvant imatinib mesylate for advanced primary and metastatic/recurrent operable gastrointestinal stromal tumors: long-term follow-up results of Radiation Therapy Oncology Group 0132. Ann Surg Oncol. 2012 Apr;19(4):1074-80. Epub 2011 Dec 28. Erratum in: Ann Surg Oncol. 2012 Jul;19(7):2420. link to PMC article PubMed

GIST (Gastrointestinal Stromal Tumor) - adjuvant therapy

Imatinib (Gleevec)

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Regimen #1, 3 years of treatment

Study Evidence Comparator Efficacy
Joensuu et al. 2012 Phase III Imatinib x 12 mos Seems to have superior OS

Treatment is to be started within 12 weeks after surgery.

Chemotherapy

36-month course

Regimen #2, 1 year of treatment

Study Evidence Comparator Efficacy
Dematteo et al. 2009 Phase III Placebo Superior RFS
Joensuu et al. 2012 Phase III Imatinib x 36 mos Seems to have inferior OS

Treatment is started within 12 weeks after surgery.'

Chemotherapy

1-year course

References

  1. Dematteo RP, Ballman KV, Antonescu CR, Maki RG, Pisters PW, Demetri GD, Blackstein ME, Blanke CD, von Mehren M, Brennan MF, Patel S, McCarter MD, Polikoff JA, Tan BR, Owzar K; American College of Surgeons Oncology Group (ACOSOG) Intergroup Adjuvant GIST Study Team. Adjuvant imatinib mesylate after resection of localised, primary gastrointestinal stromal tumour: a randomised, double-blind, placebo-controlled trial. Lancet. 2009 Mar 28;373(9669):1097-104. link to original article contains verified protocol PubMed
  2. Joensuu H, Eriksson M, Sundby Hall K, Hartmann JT, Pink D, Sch?tte J, Ramadori G, Hohenberger P, Duyster J, Al-Batran SE, Schlemmer M, Bauer S, Wardelmann E, Sarlomo-Rikala M, Nilsson B, Sihto H, Monge OR, Bono P, Kallio R, Vehtari A, Leinonen M, Alveg?rd T, Reichardt P. One vs three years of adjuvant imatinib for operable gastrointestinal stromal tumor: a randomized trial. JAMA. 2012 Mar 28;307(12):1265-72. link to original article contains verified protocol PubMed

Placebo

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Regimen

Study Evidence Comparator Efficacy
Dematteo et al. 2009 Phase III Imatinib x 12 mos Inferior RFS

No active antineoplastic treatment. Used as a comparator arm and here for reference purposes only.

References

  1. Dematteo RP, Ballman KV, Antonescu CR, Maki RG, Pisters PW, Demetri GD, Blackstein ME, Blanke CD, von Mehren M, Brennan MF, Patel S, McCarter MD, Polikoff JA, Tan BR, Owzar K; American College of Surgeons Oncology Group (ACOSOG) Intergroup Adjuvant GIST Study Team. Adjuvant imatinib mesylate after resection of localised, primary gastrointestinal stromal tumour: a randomised, double-blind, placebo-controlled trial. Lancet. 2009 Mar 28;373(9669):1097-104. link to PMC article contains verified protocol PubMed

GIST (Gastrointestinal Stromal Tumor) - metastatic or unresectable disease

Imatinib (Gleevec)

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Regimen #1, standard-dose (400 mg/day)

Study Evidence Comparator Efficacy
Demetri et al. 2002 Phase III Higher-dose imatinib (600 mg/day) Seems not superior
Blanke et al. 2015 (SWOG S0502) Phase III Bevacizumab & Imatinib Not reported

Chemotherapy

Given until progression of disease or unacceptable toxicity

Regimen #2, high-dose (800 mg/day)

Study Evidence Comparator Efficacy
Verweij et al. 2003 Phase II
Blanke et al. 2008 (SWOG S0033) Phase III Standard-dose imatinib with pre-planned dose-escalation at progression Seems not superior
Blanke et al. 2015 (SWOG S0502) Phase III Bevacizumab & Imatinib Not reported

Note: high-dose imatinib was offered to patients with KIT exon 9 mutations in SWOG S0502; all other patients received standard-dose imatinib.

Chemotherapy

Given until progression of disease or unacceptable toxicity

Regimen #3, standard-dose with pre-planned dose-escalation at progression

Study Evidence Comparator Efficacy
Blanke et al. 2008 (SWOG S0033) Phase III High-dose imatinib (800 mg/day) Seems not superior

Standard dose therapy

Given until progression of disease or unacceptable toxicity

Patients who progressed could receive high-dose therapy, as follows:

High-dose therapy

Given until progression of disease or unacceptable toxicity

Regimen #4, higher-dose (600 mg/day)

Study Evidence Comparator Efficacy
Demetri et al. 2002 Phase III Standard-dose imatinib (400 mg/day) Seems not superior

Chemotherapy

Given until progression of disease or unacceptable toxicity

References

  1. Demetri GD, von Mehren M, Blanke CD, Van den Abbeele AD, Eisenberg B, Roberts PJ, Heinrich MC, Tuveson DA, Singer S, Janicek M, Fletcher JA, Silverman SG, Silberman SL, Capdeville R, Kiese B, Peng B, Dimitrijevic S, Druker BJ, Corless C, Fletcher CD, Joensuu H. Efficacy and safety of imatinib mesylate in advanced gastrointestinal stromal tumors. N Engl J Med. 2002 Aug 15;347(7):472-80. link to original article contains verified protocol PubMed
  2. Verweij J, van Oosterom A, Blay JY, Judson I, Rodenhuis S, van der Graaf W, Radford J, Le Cesne A, Hogendoorn PC, di Paola ED, Brown M, Nielsen OS. Imatinib mesylate (STI-571 Glivec, Gleevec) is an active agent for gastrointestinal stromal tumours, but does not yield responses in other soft-tissue sarcomas that are unselected for a molecular target. Results from an EORTC Soft Tissue and Bone Sarcoma Group phase II study. Eur J Cancer. 2003 Sep;39(14):2006-11. link to original article contains verified protocol PubMed
  3. Blanke CD, Rankin C, Demetri GD, Ryan CW, von Mehren M, Benjamin RS, Raymond AK, Bramwell VH, Baker LH, Maki RG, Tanaka M, Hecht JR, Heinrich MC, Fletcher CD, Crowley JJ, Borden EC. Phase III randomized, intergroup trial assessing imatinib mesylate at two dose levels in patients with unresectable or metastatic gastrointestinal stromal tumors expressing the kit receptor tyrosine kinase: S0033. J Clin Oncol. 2008 Feb 1;26(4):626-32. link to original article contains verified protocol PubMed
  4. Meta-analysis: Gastrointestinal Stromal Tumor Meta-Analysis Group (MetaGIST). Comparison of two doses of imatinib for the treatment of unresectable or metastatic gastrointestinal stromal tumors: a meta-analysis of 1,640 patients. J Clin Oncol. 2010 Mar 1;28(7):1247-53. Epub 2010 Feb 1. link to original article PubMed
  5. Kang YK, Ryu MH, Yoo C, Ryoo BY, Kim HJ, Lee JJ, Nam BH, Ramaiya N, Jagannathan J, Demetri GD. Resumption of imatinib to control metastatic or unresectable gastrointestinal stromal tumours after failure of imatinib and sunitinib (RIGHT): a randomised, placebo-controlled, phase 3 trial. Lancet Oncol. 2013 Nov;14(12):1175-82. Epub 2013 Oct 18. link to original article link to PMC article PubMed
  6. Blanke CD, Rankin C, Corless C, Eary JF, Mulder K, Okuno SH, George S, Heinrich M. S0502: A SWOG Phase III Randomized Study of Imatinib, With or Without Bevacizumab, in Patients With Untreated Metastatic or Unresectable Gastrointestinal Stromal Tumors. Oncologist. 2015 Dec;20(12):1353-4. Epub 2015 Nov 17. link to PMC article contains verified protocol PubMed

Pazopanib (Votrient)

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Regimen

Study Evidence Comparator Efficacy
Mir et al. 2016 (PAZOGIST) Randomized Phase II Best supportive care Seems to have superior PFS

Chemotherapy

Given until progression of disease, unacceptable toxicity, withdrawal of consent, or death

References

  1. Mir O, Cropet C, Toulmonde M, Cesne AL, Molimard M, Bompas E, Cassier P, Ray-Coquard I, Rios M, Adenis A, Italiano A, Bouché O, Chauzit E, Duffaud F, Bertucci F, Isambert N, Gautier J, Blay JY, Pérol D; PAZOGIST study group of the French Sarcoma Groupe-Groupe d'Etude des Tumeurs Osseuses (GSF-GETO). Pazopanib plus best supportive care versus best supportive care alone in advanced gastrointestinal stromal tumours resistant to imatinib and sunitinib (PAZOGIST): a randomised, multicentre, open-label phase 2 trial. Lancet Oncol. 2016 May;17(5):632-41. Epub 2016 Apr 5. link to original article contains protocol PubMed

Placebo

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Regimen

Study Evidence Comparator Efficacy
Demetri et al. 2006 Phase III Sunitinib Inferior TTP
Demetri et al. 2012 (GRID) Phase III Regorafenib Inferior PFS
Mir et al. 2016 (PAZOGIST) Randomized Phase II Pazopanib Seems to have inferior PFS

No active antineoplastic treatment. Used as a comparator arm and here for reference purposes only.

References

  1. Demetri GD, van Oosterom AT, Garrett CR, Blackstein ME, Shah MH, Verweij J, McArthur G, Judson IR, Heinrich MC, Morgan JA, Desai J, Fletcher CD, George S, Bello CL, Huang X, Baum CM, Casali PG. Efficacy and safety of sunitinib in patients with advanced gastrointestinal stromal tumour after failure of imatinib: a randomised controlled trial. Lancet. 2006 Oct 14;368(9544):1329-38. link to original article contains verified protocol PubMed
  2. Demetri GD, Reichardt P, Kang YK, Blay JY, Rutkowski P, Gelderblom H, Hohenberger P, Leahy M, von Mehren M, Joensuu H, Badalamenti G, Blackstein M, Le Cesne A, Sch?ffski P, Maki RG, Bauer S, Nguyen BB, Xu J, Nishida T, Chung J, Kappeler C, Kuss I, Laurent D, Casali PG; GRID study investigators. Efficacy and safety of regorafenib for advanced gastrointestinal stromal tumours after failure of imatinib and sunitinib (GRID): an international, multicentre, randomised, placebo-controlled, phase 3 trial. Lancet. 2013 Jan 26;381(9863):295-302. Epub 2012 Nov 22. link to PMC article contains verified protocol PubMed
  3. Kang YK, Ryu MH, Yoo C, Ryoo BY, Kim HJ, Lee JJ, Nam BH, Ramaiya N, Jagannathan J, Demetri GD. Resumption of imatinib to control metastatic or unresectable gastrointestinal stromal tumours after failure of imatinib and sunitinib (RIGHT): a randomised, placebo-controlled, phase 3 trial. Lancet Oncol. 2013 Nov;14(12):1175-82. Epub 2013 Oct 18. link to original article link to PMC article PubMed
  4. Mir O, Cropet C, Toulmonde M, Cesne AL, Molimard M, Bompas E, Cassier P, Ray-Coquard I, Rios M, Adenis A, Italiano A, Bouché O, Chauzit E, Duffaud F, Bertucci F, Isambert N, Gautier J, Blay JY, Pérol D; PAZOGIST study group of the French Sarcoma Groupe-Groupe d'Etude des Tumeurs Osseuses (GSF-GETO). Pazopanib plus best supportive care versus best supportive care alone in advanced gastrointestinal stromal tumours resistant to imatinib and sunitinib (PAZOGIST): a randomised, multicentre, open-label phase 2 trial. Lancet Oncol. 2016 May;17(5):632-41. Epub 2016 Apr 5. link to original article contains protocol PubMed

Regorafenib (Stivarga)

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Regimen

Study Evidence Comparator Efficacy
Demetri et al. 2012 (GRID) Phase III Placebo Superior PFS

Patients in this study already had treatment failure with imatinib and sunitinib.

Chemotherapy

28-day cycles, given until progression of disease or unacceptable toxicity

References

  1. Demetri GD, Reichardt P, Kang YK, Blay JY, Rutkowski P, Gelderblom H, Hohenberger P, Leahy M, von Mehren M, Joensuu H, Badalamenti G, Blackstein M, Le Cesne A, Sch?ffski P, Maki RG, Bauer S, Nguyen BB, Xu J, Nishida T, Chung J, Kappeler C, Kuss I, Laurent D, Casali PG; GRID study investigators. Efficacy and safety of regorafenib for advanced gastrointestinal stromal tumours after failure of imatinib and sunitinib (GRID): an international, multicentre, randomised, placebo-controlled, phase 3 trial. Lancet. 2013 Jan 26;381(9863):295-302. Epub 2012 Nov 22. link to PMC article contains verified protocol PubMed

Sunitinib (Sutent)

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Regimen

Study Evidence Comparator Efficacy
Demetri et al. 2006 Phase III Placebo Superior TTP

Patients in Demetri et al. 2006 had treatment failure with imatinib.

Chemotherapy

  • Sunitinib (Sutent) 50 mg PO once per day on days 1 to 28
    • Dose may be decreased to 37.5 mg or 25 mg depending on tolerability

42-day cycles, given until progression of disease or unacceptable toxicity

References

  1. Demetri GD, van Oosterom AT, Garrett CR, Blackstein ME, Shah MH, Verweij J, McArthur G, Judson IR, Heinrich MC, Morgan JA, Desai J, Fletcher CD, George S, Bello CL, Huang X, Baum CM, Casali PG. Efficacy and safety of sunitinib in patients with advanced gastrointestinal stromal tumour after failure of imatinib: a randomised controlled trial. Lancet. 2006 Oct 14;368(9544):1329-38. link to original article contains verified protocol PubMed
  2. Prior JO, Montemurro M, Orcurto MV, Michielin O, Luthi F, Benhattar J, Guillou L, Elsig V, Stupp R, Delaloye AB, Leyvraz S. Early prediction of response to sunitinib after imatinib failure by 18F-fluorodeoxyglucose positron emission tomography in patients with gastrointestinal stromal tumor. J Clin Oncol. 2009 Jan 20;27(3):439-45. Epub 2008 Dec 8. link to original article contains verified protocol PubMed

Temozolomide (Temodar)

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Angiosarcoma

Bevacizumab (Avastin)

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Regimen

Study Evidence
Agulnik et al. 2013 Phase II

Chemotherapy

21-day cycles, given until progression of disease, intolerance, unacceptable toxicity, patient refusal, or physician discretion

References

  1. 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

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

  1. 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

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

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

  1. 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
  2. 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 (Avastin)

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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

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

  1. 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 PubMed

Daunorubicin liposomal (DaunoXome)

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Regimen

Study Evidence Comparator Efficacy
Gill et al. 1996 Phase III ABV Seems not superior

Chemotherapy

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

  1. 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

Supportive medications

  • "Colony-stimulating factors (CSFs) were prescribed at the discretion of the investigators."

14-day cycle for up to 6 cycles

References

  1. 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

14-day cycles

References

  1. 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
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