Standard treatment options for metastatic childhood soft tissue sarcoma include the following:

• Combination therapy using chemotherapy, radiation therapy, and surgical resection of pulmonary metastases.

The prognosis for children with metastatic soft tissue sarcomas is poor,[1,2,3,4,5,6] and these children should receive combined treatment with chemotherapy, radiation therapy, and surgical resection of pulmonary metastases. In a prospective randomized trial, chemotherapy with vincristine, dactinomycin, doxorubicin, and cyclophosphamide with or without dacarbazine led to tumor responses in one-third of patients with unresectable or metastatic disease. The estimated 4-year survival rate, however, was poor, with fewer than one-third of children surviving.[6,7,8] Children with isolated pulmonary metastases should undergo exploratory thoracotomy in an attempt to resect all gross disease. The estimated 5-year survival rate after thoracotomy for pulmonary metastasectomy has ranged from 10% to 58% in adult studies. Formal segmentectomy, lobectomy, and mediastinal lymph node dissection are unnecessary.[9]

Treatment Options Under Clinical Evaluation

Vincristine, doxorubicin, and ifosfamide with granulocyte colony-stimulating factor have been used in patients with unresected or metastatic tumors. The Pediatric Oncology Group evaluated the combination of doxorubicin and ifosfamide in children with unresected or metastatic soft tissue sarcomas because several adult trials have suggested that ifosfamide-based regimens may be superior to other chemotherapeutic regimens for soft tissue sarcomas.[10] Table 3 shows other promising agents currently being evaluated in clinical trials for specific histologic subtypes of nonrhabdomyosarcomatous soft tissue sarcomas (NRSTS).

Table 3. Treatment Options Under Clinical Evaluation for Select NRSTS

Current Clinical Trials

Check for U.S. clinical trials from NCI's PDQ Cancer Clinical Trials Registry that are now accepting patients with metastatic childhood soft tissue sarcoma. The list of clinical trials can be further narrowed by location, drug, intervention, and other criteria.

General information about clinical trials is also available from the NCI Web site.

References:

1. Demetri GD, Elias AD: Results of single-agent and combination chemotherapy for advanced soft tissue sarcomas. Implications for decision making in the clinic. Hematol Oncol Clin North Am 9 (4): 765-85, 1995.
2. 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 7 (9): 1208-16, 1989.
3. Edmonson JH, Ryan LM, Blum RH, et al.: Randomized comparison of doxorubicin alone versus ifosfamide plus doxorubicin or mitomycin, doxorubicin, and cisplatin against advanced soft tissue sarcomas. J Clin Oncol 11 (7): 1269-75, 1993.
4. Rao BN: Nonrhabdomyosarcoma in children: prognostic factors influencing survival. Semin Surg Oncol 9 (6): 524-31, 1993 Nov-Dec.
5. deCou JM, Rao BN, Parham DM, et al.: Malignant peripheral nerve sheath tumors: the St. Jude Children's Research Hospital experience. Ann Surg Oncol 2 (6): 524-9, 1995.
6. Pappo AS, Rao BN, Jenkins JJ, et al.: Metastatic nonrhabdomyosarcomatous soft-tissue sarcomas in children and adolescents: the St. Jude Children's Research Hospital experience. Med Pediatr Oncol 33 (2): 76-82, 1999.
7. Pratt CB, Pappo AS, Gieser P, et al.: Role of adjuvant chemotherapy in the treatment of surgically resected pediatric nonrhabdomyosarcomatous soft tissue sarcomas: A Pediatric Oncology Group Study. J Clin Oncol 17 (4): 1219, 1999.
8. Pratt CB, Maurer HM, Gieser P, et al.: Treatment of unresectable or metastatic pediatric soft tissue sarcomas with surgery, irradiation, and chemotherapy: a Pediatric Oncology Group study. Med Pediatr Oncol 30 (4): 201-9, 1998.
9. Putnam JB Jr, Roth JA: Surgical treatment for pulmonary metastases from sarcoma. Hematol Oncol Clin North Am 9 (4): 869-87, 1995.
10. Pappo AS, Devidas M, Jenkins J, et al.: Phase II trial of neoadjuvant vincristine, ifosfamide, and doxorubicin with granulocyte colony-stimulating factor support in children and adolescents with advanced-stage nonrhabdomyosarcomatous soft tissue sarcomas: a Pediatric Oncology Group Study. J Clin Oncol 23 (18): 4031-8, 2005.
11. Grosso F, Jones RL, Demetri GD, et al.: Efficacy of trabectedin (ecteinascidin-743) in advanced pretreated myxoid liposarcomas: a retrospective study. Lancet Oncol 8 (7): 595-602, 2007.
12. Stacchiotti S, Tamborini E, Marrari A, et al.: Response to sunitinib malate in advanced alveolar soft part sarcoma. Clin Cancer Res 15 (3): 1096-104, 2009.
13. George S, Merriam P, Maki RG, et al.: Multicenter phase II trial of sunitinib in the treatment of nongastrointestinal stromal tumor sarcomas. J Clin Oncol 27 (19): 3154-60, 2009.
14. Maki RG, D'Adamo DR, Keohan ML, et al.: Phase II study of sorafenib in patients with metastatic or recurrent sarcomas. J Clin Oncol 27 (19): 3133-40, 2009.
15. Davies DM, Johnson SR, Tattersfield AE, et al.: Sirolimus therapy in tuberous sclerosis or sporadic lymphangioleiomyomatosis. N Engl J Med 358 (2): 200-3, 2008.
16. Johansson G, Mahller YY, Collins MH, et al.: Effective in vivo targeting of the mammalian target of rapamycin pathway in malignant peripheral nerve sheath tumors. Mol Cancer Ther 7 (5): 1237-45, 2008.
17. Sleijfer S, Ray-Coquard I, Papai Z, et al.: Pazopanib, a multikinase angiogenesis inhibitor, in patients with relapsed or refractory advanced soft tissue sarcoma: a phase II study from the European organisation for research and treatment of cancer-soft tissue and bone sarcoma group (EORTC study 62043). J Clin Oncol 27 (19): 3126-32, 2009.