Soft Tissue Sarcoma Treatment Regimens

Doxorubicin + dacarbazine (AD)2-5

Days 1–4: Doxorubicin 60mg/m2 + dacarbazine 750mg/m2 as a continuous IV infusion over 96 hours.

Repeat cycle every 3 weeks.

Doxorubicin + ifosfamide + mesna (AIM)4-7

Days 1 and 2: Doxorubicin 30mg/m2/day IV + ifosfamide 3,750mg/m2/day IV + mesna 750mg/m2 IV immediately preceding and then 4 and 8 hours after ifosfamide administration.

Repeat cycle every 3 weeks.

Mesna + doxorubicin + ifosfamide + dacarbazine (MAID)4,5,8,9

Days 1–3: Doxorubicin 20mg/m2/day + ifosfamide 2,500mg/m2/day + dacarbazine 300mg/m2/day as continuous IV infusion over 72 hours, plus

Mesna 2,500mg/m2/day IV for 84 to 96 hours.

Repeat cycle every 3 weeks.

Ifosfamide + epirubicin + mesna10

Days 1 and 2: Epirubicin 60mg/m2/day IV

Days 1–5: Ifosfamide 1.8g/m2/day IV over 1 hour + mesna at 20% of the ifosfamide dose IV immediately preceding and then 4 and 8 hours after ifosfamide administration.

Repeat cycle every 3 weeks for 5 cycles.

Gemcitabine + docetaxel11,12

Days 1 and 8: Gemcitabine 900mg/m2 IV

Day 8: Docetaxel 100mg/m2 IV.

Repeat cycle every 3 weeks.

Gemcitabine + vinorelbine13

Days 1 and 8: Vinorelbine 25mg/m2 IV over 10 minutes + gemcitabine 800mg/m2 IV over 90 minutes.

Repeat cycle every 3 weeks.

Gemcitabine + dacarbazine14

Day 1: Gemcitabine 1,800mg/m2 IV + dacarbazine 500mg/m2 IV.

Repeat cycle ever 2 weeks for a total of 12 cycles; continuation of treatment after 24 weeks was allowed at investigator discretion.

Doxorubicin + olaratumab15,e

Day 1: Doxorubicin 75mg/m2 IV

Days 1 and 8: Olaratumab 15mg/kg IV.

Repeat cycle every 3 weeks for up to 8 cycles.

Doxorubicin4,5,16

Doxorubicin 60–75mg/m2 IV every 3 weeks.

Ifosfamide10,17

Ifosfamide 2,000–3,000mg/m2/day IV for 3 to 4 days + mesna at 20% of the ifosfamide dose IV immediately preceding and then 4 and 8 hours after ifosfamide administration every 3 weeks.

OR

Ifosfamide 5,000mg/m2 + mesna 5,000mg/m2 as a continuous IV infusion over 24 hours followed by additional mesna 400–600mg/m2 IV over 2 hours after completion of ifosfamide administration.

Repeat every 3 weeks.

Epirubicin18

Epirubicin 160mg/m2 IV every 3 weeks.

Gemcitabine

Days 1 and 8: Gemcitabine 1,200mg/m2 IV over 90 to 120 minutes.

Repeat cycle every 3 weeks.

Dacarbazine

Dacarbazine 250mg/m2/day IV for 5 days every 3 weeks.

OR

Dacarbazine 800–1,000mg/m2 IV every 3 weeks.

Liposomal doxorubicin19

Liposomal doxorubicin 30–50mg/m2 IV every 4 weeks.

Temozolomide20,d

Day 1: Temozolomide 200mg/m2 oral bolus dose once followed by temozolomide 90mg/m2 after 12 hours.

Days 2–5: Temozolomide 90mg/m2 orally twice daily.
Repeat cycle every 4 weeks.

Vinorelbine21,d

Vinorelbine 30mg/m2 IV weekly for 6 weeks during an 8-week interval.

Pazopanib22,d,f

Pazopanib 800mg orally once daily without food until disease progression or unacceptable toxicity.

Eribulin23,d,g

Days 1 and 8: Eribulin mesylate 1.4mg/m2 IV.

Repeat every 3 weeks until disease progression or unacceptable toxicity.

Trabectedin24-26,d,h

Trabectedin 1.5mg/m2 as a 24-hour continuous IV infusion every 3 weeks.

a Alveolar soft part sarcomas (ASPS), well-differentiated liposarcoma/atypical lipomatous tumor, and clear cell sarcomas are generally non sensitive to cytotoxic chemotherapy.

b Anthracycline-based regimens are preferred in the neoadjuvant and adjuvant setting.

c Regimens appropriate for pleomorphic rhabdomyosarcoma.

d Recommended only for palliative therapy.

e For use in STS histologies for which an anthracycline-containing regimen is appropriate.

f Pazopanib should not be used for lipogenic sarcomas.

g Category 1 recommendation for liposarcoma.

h Category 1 recommendation for liposarcoma and leiomyosarcoma (L-types).

1. Referenced with permission from NCCN Clinical Practice Guidelines in Oncology™ Soft Tissue Sarcoma. V1.2018. Available at: http://www.nccn.org/professionals/physician_gls/pdf/sarcoma.pdf. Accessed February 2, 2018.

2. Zalupski M, Metch B, Balcerzak S, et al. Phase III comparison of doxorubicin and dacarbazine given by bolus versus infusion in patients with soft-tissue sarcomas: A Southwest Oncology Group Study. J Natl Cancer Inst. 1991;83:926–932.

3. Antman K, Crowley J, Balcerzak SP, et al. An intergroup phase Ill randomized study of doxorubicin and dacarbazine with or without ifosfamide and mesna in advanced soft tissue and bone sarcomas. J Clin Oncol. 1993;11:1276–1285.

4. Adjuvant chemotherapy for localized resectable soft-tissue sarcoma of adults: Meta-analysis of individual data. Sarcoma Meta-analysis Collaboration. Lancet. 1997;350:1647–1654.

5. Pervaiz N, Colterjohn N, Farrokhyar F, et al. A systematic meta-analysis of randomized controlled trials of adjuvant chemotherapy for localized resectable soft-tissue sarcoma. Cancer. 2008;113:573–581.

6. Grobmyer SR, Maki RG, Demetri GD, et al. Neo-adjuvant chemotherapy for primary high-grade extremity soft tissue sarcoma. Ann Oncol. 2004;15:1667–1672.

7. Edmonson J, Ryan L, Blum R, et al. Randomized comparison of doxorubicin alone versus ifosfamide plus doxorubicin or mitomycin, doxorubicin, and cisplatin against advanced soft tissue sarcomas. J Clin Oncol. 1993;11:1269–1275.

8. Elias A, Ryan L, Sulkes A, et al. Response to mesna, doxorubicin, ifosfamide, and dacarbazine in 108 patients with metastatic or unresectable sarcoma and no prior chemotherapy. J Clin Oncol. 1989;7:1208–1216.

9. Kraybill WG, Harris J, Spiro IJ, et al. Long-term results of a phase 2 study of neoadjuvant chemotherapy and radiotherapy in the management of high-risk, high-grade, soft tissue sarcomas of the extremities and body wall: Radiation Therapy Oncology Group Trial 9514. Cancer. 2010;116:4613–4621.

10. Frustaci S, Gherlinzoni F, De Paoli A, et al. Adjuvant chemotherapy for soft tissue sarcomas of the extremities and girdles: results of the Italian randomized cooperative trial. J Clin Oncol. 2001;19:1238–1247.

11. Hensley ML, Maki R, Venkatraman E, et al. Gemcitabine and docetaxel in patients with unresectable leiomyosarcoma: results of a phase II trial. J Clin Oncol. 2002;20:2824–2831.

12. Maki RG, Wathen JK, Patel SR, et al. Randomized phase II study of gemcitabine and docetaxel compared with gemcitabine alone in patients with metastatic soft tissue sarcomas: results of sarcoma alliance for research through collaboration study 002. J Clin Oncol. 2007; 25:2755–2763.

13. Dileo P, Morgan JA, Zahrieh D, et al. Gemcitabine and vinorelbine combination chemotherapy for patients with advanced soft tissue sarcomas: results of a phase II trial. Cancer. 2007;109:1863–1869.

14. Garcia-Del-Muro X, Lopez-Pousa A, Maurel J, et al. Randomized phase II study comparing gemcitabine plus dacarbazine versus dacarbazine alone in patients with previously treated soft tissue sarcoma: a Spanish Group for Research on Sarcomas study. J Clin Oncol. 2011;29:2528–2533.

15. Tap WD, Jones RL, Van Tine BA, et al. Olaratumab and doxorubicin versus doxorubicin alone for treatment of soft-tissue sarcoma: an open-label phase 1b and randomised phase 2 trial. Lancet. 2016;388:488-497.

16. Mack LA, Crowe PJ, Yang JL, et al. Preoperative chemoradiotherapy (modified Eilber protocol) provides maximum local control and minimal morbidity in patients with soft tissue sarcoma. Ann Surg Oncol. 2005;12:646–653.

17. Antman KH, Elias A. Dana-Farber Cancer Institute studies in advanced sarcoma. Semin Oncol. 1990;1(Suppl 2):7–15.

18. Petrioli R, Coratti A, Correale P, et al. Adjuvant epirubicin with or without Ifosfamide for adult soft-tissue sarcoma. Am J Clin Oncol. 2002;25:468–473.

19. Judson I, Radford J, Harris M, et al. Randomized phase II trial of pegylated liposomal doxorubicin versus doxorubicin in the treatment of advanced or metastatic soft tissue sarcoma: a study by the EORTC Soft Tissue and Bone Sarcoma Group. Eur J Cancer. 2001; 37:870–877.

20. Talbot SM, Keohan ML, Hesdorffer M, et al. A Phase II trial of temozolomide in patients with unresectable or metastatic soft tissue sarcoma. Cancer. 2003; 98:1942–1946.

21. Kuttesch JF Jr, Krailo MD, Madden T, et al. Phase II evaluation of intravenous vinorelbine (Navelbine) in recurrent or refractory pediatric malignancies: a Children’s Oncology Group study. Pediatr Blood Cancer. 2009; 53:590–593.

22. van der Graaf WT, Blay JY, Chawla SP, et al. Pazopanib for metastatic soft-tissue sarcoma (PALETTE): a randomised, double-blind, placebo-controlled phase 3 trial. Lancet. 2012;379:1879–1886.

23. Schöffski P, Ray-Coquard IL, Cioffi A, et al. Activity of eribulin mesylate in patients with soft-tissue sarcoma: a phase 2 study in four independent histological subtypes. Lancet Oncol. 2011;12(11):1045–1052.

24. Demetri GD, von Mehren M, Jones RL, et al. 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. 2015;33:1–8.

25. Kawai A, Araki N, Sugiura H, et al. 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;16(4):406–416.

26. Samuels BL, Chawla S, Patel S, et al. Clinical outcomes and safety with trabectedin therapy in patients with advanced soft tissue sarcomas following failure of prior chemotherapy: results of a worldwide expanded access program study. Ann Oncol. 2013;24(6):1703–1709.