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Adjuvant and neoadjuvant chemotherapy for soft tissue sarcoma of the extremities

Author
Robert Maki, MD, PhD
Section Editor
Thomas F DeLaney, MD
Deputy Editor
Diane MF Savarese, MD

INTRODUCTION

Soft tissue sarcomas (STS) are uncommon malignant tumors that arise from extraskeletal connective tissues, including the peripheral nervous system. They can arise at any body site, but are most common in the extremities, particularly the lower limbs. (See "Clinical presentation, histopathology, diagnostic evaluation, and staging of soft tissue sarcoma", section on 'Clinical presentation'.)

In treating STS of the extremities, the major therapeutic goals are long-term survival, avoidance of a local recurrence, maximizing function, and minimizing morbidity. Surgical resection is the cornerstone of potentially curative treatment. For nearly all patients with extremity sarcomas >5 cm, the addition of radiation therapy (RT) improves local control, and it has also had a significant impact on limb salvage. There are advantages to preoperative (neoadjuvant) as compared with postoperative (adjuvant) administration of RT, and for neoadjuvant therapy utilizing combinations of RT and chemotherapy, particularly for recurrent and large, high-grade primary tumors. These topics are discussed in detail elsewhere. (See "Local treatment for primary soft tissue sarcoma of the extremities and chest wall" and "Treatment of locally recurrent and unresectable, locally advanced soft tissue sarcoma of the extremities".)

Systemic chemotherapy is a routine component of treatment for several sarcomas that occur predominantly in children (eg, rhabdomyosarcoma, Ewing sarcoma, and osteogenic sarcoma). However, the value of adjuvant chemotherapy in patients undergoing resection of the adult-type localized extremity STS (eg, leiomyosarcoma, liposarcoma, synovial sarcoma) remains controversial due to the complexity of the group of diagnoses involved.

This topic review will discuss the use of adjuvant and neoadjuvant chemotherapy in the treatment of adult-type extremity STS. The role of chemotherapy in the treatment of retroperitoneal STS, rhabdomyosarcoma and the Ewing sarcoma family of tumors, and neoadjuvant combined modality approaches for patients with large, high-grade or recurrent extremity STS are discussed in detail elsewhere. (See "Clinical features, evaluation, and treatment of retroperitoneal soft tissue sarcoma", section on 'Adjuvant chemotherapy' and "Rhabdomyosarcoma in childhood, adolescence, and adulthood: Treatment" and "Treatment of the Ewing sarcoma family of tumors" and "Surgical treatment and other localized therapy for metastatic soft tissue sarcoma".)

ADJUVANT CHEMOTHERAPY

Pediatric-type sarcomas — The addition of systemic chemotherapy to local therapy significantly improves outcomes for the common pediatric types of sarcoma (rhabdomyosarcoma, osteogenic sarcoma, and the Ewing sarcoma family of tumors of both soft tissue and bone). Most modern treatment plans utilize initial (induction or neoadjuvant) chemotherapy followed by local treatment and additional (adjuvant) chemotherapy.

                

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Literature review current through: Nov 2016. | This topic last updated: Thu Feb 04 00:00:00 GMT+00:00 2016.
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References
Top
  1. Ahmad SA, Patel SR, Ballo MT, et al. Extraosseous osteosarcoma: response to treatment and long-term outcome. J Clin Oncol 2002; 20:521.
  2. Goldstein-Jackson SY, Gosheger G, Delling G, et al. Extraskeletal osteosarcoma has a favourable prognosis when treated like conventional osteosarcoma. J Cancer Res Clin Oncol 2005; 131:520.
  3. Antman KH. Adjuvant therapy of sarcomas of soft tissue. Semin Oncol 1997; 24:556.
  4. Sarcoma Meta-analysis Collaboration (SMAC). Adjuvant chemotherapy for localised resectable soft tissue sarcoma in adults. Cochrane Database Syst Rev 2000; :CD001419.
  5. Adjuvant chemotherapy for localised resectable soft-tissue sarcoma of adults: meta-analysis of individual data. Sarcoma Meta-analysis Collaboration. Lancet 1997; 350:1647.
  6. Frustaci S, Gherlinzoni F, De Paoli A, et al. Adjuvant chemotherapy for adult soft tissue sarcomas of the extremities and girdles: results of the Italian randomized cooperative trial. J Clin Oncol 2001; 19:1238.
  7. Frustaci S, De Paoli A, Bidoli E, et al. Ifosfamide in the adjuvant therapy of soft tissue sarcomas. Oncology 2003; 65 Suppl 2:80.
  8. 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.
  9. Brodowicz T, Schwameis E, Widder J, et al. Intensified Adjuvant IFADIC Chemotherapy for Adult Soft Tissue Sarcoma: A Prospective Randomized Feasibility Trial. Sarcoma 2000; 4:151.
  10. Woll PJ, Reichardt P, Le Cesne A, et al. Adjuvant chemotherapy with doxorubicin, ifosfamide, and lenograstim for resected soft-tissue sarcoma (EORTC 62931): a multicentre randomised controlled trial. Lancet Oncol 2012; 13:1045.
  11. 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.
  12. Bramwell V, Rouesse J, Steward W, et al. Adjuvant CYVADIC chemotherapy for adult soft tissue sarcoma--reduced local recurrence but no improvement in survival: a study of the European Organization for Research and Treatment of Cancer Soft Tissue and Bone Sarcoma Group. J Clin Oncol 1994; 12:1137.
  13. Le Cesne A, Ouali M, Leahy MG, et al. Doxorubicin-based adjuvant chemotherapy in soft tissue sarcoma: pooled analysis of two STBSG-EORTC phase III clinical trials. Ann Oncol 2014; 25:2425.
  14. Italiano A, Delva F, Mathoulin-Pelissier S, et al. Effect of adjuvant chemotherapy on survival in FNCLCC grade 3 soft tissue sarcomas: a multivariate analysis of the French Sarcoma Group Database. Ann Oncol 2010; 21:2436.
  15. Le Cesne A, Van Glabbeke M, Woll PJ, et al. The end of adjuvant chemotherapy era with doxorubicin-based regimen in resected high-grade soft tissue sarcoma: Pooled analysis of the two STBSG-EORTC phase III clinical trials (abstract). J Clin Oncol 2008; 26:559s.
  16. Eilber FC, Eilber FR, Eckardt J, et al. The impact of chemotherapy on the survival of patients with high-grade primary extremity liposarcoma. Ann Surg 2004; 240:686.
  17. Ferrari A, Gronchi A, Casanova M, et al. Synovial sarcoma: a retrospective analysis of 271 patients of all ages treated at a single institution. Cancer 2004; 101:627.
  18. Cormier JN, Huang X, Xing Y, et al. Cohort analysis of patients with localized, high-risk, extremity soft tissue sarcoma treated at two cancer centers: chemotherapy-associated outcomes. J Clin Oncol 2004; 22:4567.
  19. Eilber FC, Brennan MF, Eilber FR, et al. Chemotherapy is associated with improved survival in adult patients with primary extremity synovial sarcoma. Ann Surg 2007; 246:105.
  20. Palmerini E, Staals EL, Alberghini M, et al. Synovial sarcoma: retrospective analysis of 250 patients treated at a single institution. Cancer 2009; 115:2988.
  21. Blay JY, Le Cesne A. Adjuvant chemotherapy in localized soft tissue sarcomas: still not proven. Oncologist 2009; 14:1013.
  22. Schuetze SM, Patel S. Should patients with high-risk soft tissue sarcoma receive adjuvant chemotherapy? Oncologist 2009; 14:1003.
  23. Casali PG, Blay JY, ESMO/CONTICANET/EUROBONET Consensus Panel of experts. Soft tissue sarcomas: ESMO Clinical Practice Guidelines for diagnosis, treatment and follow-up. Ann Oncol 2010; 21 Suppl 5:v198.
  24. Antman K, Crowley J, Balcerzak SP, et al. An intergroup phase III 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.
  25. Gronchi A, Frustaci S, Mercuri M, et al. Short, full-dose adjuvant chemotherapy in high-risk adult soft tissue sarcomas: a randomized clinical trial from the Italian Sarcoma Group and the Spanish Sarcoma Group. J Clin Oncol 2012; 30:850.
  26. Grobmyer SR, Maki RG, Demetri GD, et al. Neo-adjuvant chemotherapy for primary high-grade extremity soft tissue sarcoma. Ann Oncol 2004; 15:1667.
  27. Italiano A, Penel N, Robin YM, et al. Neo/adjuvant chemotherapy does not improve outcome in resected primary synovial sarcoma: a study of the French Sarcoma Group. Ann Oncol 2009; 20:425.
  28. Gortzak E, Azzarelli A, Buesa J, et al. A randomised phase II study on neo-adjuvant chemotherapy for 'high-risk' adult soft-tissue sarcoma. Eur J Cancer 2001; 37:1096.
  29. Gronchi A, Bui BN, Bonvalot S, et al. Phase II clinical trial of neoadjuvant trabectedin in patients with advanced localized myxoid liposarcoma. Ann Oncol 2012; 23:771.