Note: Some citations in the text of this section are followed by a level of evidence. The PDQ editorial boards use a formal ranking system to help the reader judge the strength of evidence linked to the reported results of a therapeutic strategy. (Refer to the PDQ summary on Levels of Evidence for more information.)

Treatment of recurrent soft tissue sarcomas depends on the type of initial presentation and treatment. Patients who develop a local recurrence often can only be salvaged by aggressive local therapy: local excision plus radiation therapy after previous minimal therapy or amputation after previous aggressive treatment.[1,2] For selected patients who received radiation therapy, preoperative radiation therapy and wide local excision may avoid the need for amputation.[3,4,5] Metastases to the lung as first recurrence usually occur within 2 to 3 years of initial diagnosis and should be treated as described under treatment for stage IV disease.[6,7,8] A 30% survival rate at 3 years is noted if limited pulmonary metastases are resectable.

Doxorubicin alone or with dacarbazine is one of the most frequently used chemotherapeutic regimens for advanced sarcoma.[9,10,11] When used as single agents, only doxorubicin and ifosfamide show response rates greater than 20%; less active drugs include dacarbazine, cisplatin, methotrexate, and vinorelbine.[12] In a small study, pegylated liposomal doxorubicin has shown similar activity to doxorubicin, with fewer toxic effects.[13][Level of evidence: 3iiiDiii] A randomized trial of 340 patients with advanced sarcoma showed a higher response rate (32% vs. 17%, P < .002) and longer time-to-progression (6 vs. 4 months, P < .02) for doxorubicin, dacarbazine, ifosfamide, and mesna versus doxorubicin and dacarbazine alone.[14][Level of evidence: 1iiDii] Sequential use of doxorubicin followed by ifosfamide or other drugs with each subsequent recurrence is frequently preferred. Clinical trials of phase I and II agents should be considered for subsequent recurrences. High-dose chemotherapy (with or without transplantation) has not influenced disease-free survival or overall survival in published studies, but it remains under clinical evaluation for patients with metastatic disease in first complete remission, after resection of pulmonary metastases, or for inoperable large primaries.[15,16,17] Information about ongoing clinical trials is available from the NCI Web site.

References:

1. Brennan M, Singer S, Maki R, et al.: Sarcomas of the soft tissues and bone. In: DeVita VT Jr, Hellman S, Rosenberg SA, eds.: Cancer: Principles and Practice of Oncology. 7th ed. Philadelphia, Pa: Lippincott Williams & Wilkins, 2005, pp 1581-1631.
2. Midis GP, Pollock RE, Chen NP, et al.: Locally recurrent soft tissue sarcoma of the extremities. Surgery 123 (6): 666-71, 1998.
3. Essner R, Selch M, Eilber FR: Reirradiation for extremity soft tissue sarcomas. Local control and complications. Cancer 67 (11): 2813-7, 1991.
4. Singer S, Antman K, Corson JM, et al.: Long-term salvageability for patients with locally recurrent soft-tissue sarcomas. Arch Surg 127 (5): 548-53; discussion 553-4, 1992.
5. Lewis JJ, Leung D, Heslin M, et al.: Association of local recurrence with subsequent survival in extremity soft tissue sarcoma. J Clin Oncol 15 (2): 646-52, 1997.
6. van Geel AN, Pastorino U, Jauch KW, et al.: Surgical treatment of lung metastases: The European Organization for Research and Treatment of Cancer-Soft Tissue and Bone Sarcoma Group study of 255 patients. Cancer 77 (4): 675-82, 1996.
7. Casson AG, Putnam JB, Natarajan G, et al.: Five-year survival after pulmonary metastasectomy for adult soft tissue sarcoma. Cancer 69 (3): 662-8, 1992.
8. Putnam JB Jr, Roth JA: Surgical treatment for pulmonary metastases from sarcoma. Hematol Oncol Clin North Am 9 (4): 869-87, 1995.
9. Santoro A, Tursz T, Mouridsen H, et al.: Doxorubicin versus CYVADIC versus doxorubicin plus ifosfamide in first-line treatment of advanced soft tissue sarcomas: a randomized study of the European Organization for Research and Treatment of Cancer Soft Tissue and Bone Sarcoma Group. J Clin Oncol 13 (7): 1537-45, 1995.
10. 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 83 (13): 926-32, 1991.
11. Borden EC, Amato DA, Rosenbaum C, et al.: Randomized comparison of three adriamycin regimens for metastatic soft tissue sarcomas. J Clin Oncol 5 (6): 840-50, 1987.
12. 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.
13. Judson I, Radford JA, Harris M, et al.: Randomised phase II trial of pegylated liposomal doxorubicin (DOXIL/CAELYX) 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 37 (7): 870-7, 2001.
14. 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 11 (7): 1276-85, 1993.
15. Buesa JM, López-Pousa A, Martín J, et al.: Phase II trial of first-line high-dose ifosfamide in advanced soft tissue sarcomas of the adult: a study of the Spanish Group for Research on Sarcomas (GEIS) Ann Oncol 9 (8): 871-6, 1998.
16. Patel SR, Vadhan-Raj S, Burgess MA, et al.: Results of two consecutive trials of dose-intensive chemotherapy with doxorubicin and ifosfamide in patients with sarcomas. Am J Clin Oncol 21 (3): 317-21, 1998.
17. Elias AD: High-dose therapy for adult soft tissue sarcoma: dose response and survival. Semin Oncol 25 (2 Suppl 4): 19-23; discussion 45-8, 1998.