Dose-intensive chemotherapy with growth factor or autologous bone marrow/stem cell transplant support in first-line treatment of advanced or metastatic adult soft tissue sarcoma : A systematic review
✍ Scribed by Shailendra Verma; Jawaid Younus; Denise Stys-Norman; Adam E. Haynes; Martin Blackstein
- Publisher
- John Wiley and Sons
- Year
- 2008
- Tongue
- English
- Weight
- 108 KB
- Volume
- 112
- Category
- Article
- ISSN
- 0008-543X
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✦ Synopsis
Abstract
A systematic review was performed to determine whether first‐line dose‐intensive chemotherapy supported by growth factor or autologous bone marrow/stem cell transplantation improves response rate, time‐to‐disease progression, or survival compared with standard‐dose chemotherapy in patients with inoperable, locally advanced, or metastatic soft tissue sarcoma. The MEDLINE, EMBASE, and Cochrane Library databases were searched. Three randomized trials (2 phase 3, 1 phase 2), 12 phase 2, and 5 phase 1 dose‐escalation trials were located. One randomized trial (N = 314) did not detect significant differences in response rate (P = .65) or survival (log‐rank P = .98) between high‐dose doxorubicin plus ifosfamide with granulocyte macrophage colony‐stimulating factor and doxorubicin plus ifosfamide at standard doses. Progression‐free survival, however, was significantly longer in the high‐dose arm (log‐rank P = .03). Higher rates of thrombocytopenia, infection, grade 3 of 4 asthenia, and stomatitis were observed with high‐dose compared with standard‐dose chemotherapy. Preliminary results from a second randomized trial (N = 162) indicated no benefit with respect to tumor response for an intensified mesna, doxorubicin (Adriamycin), ifosfamide, and dacarbazine regimen with granulocyte colony‐stimulating factor support compared with standard doxorubicin, ifosfamide, and dacarbazine. Grade 4 thrombocytopenia was significantly higher with the high‐dose regimen. Four phase 2 trials of high‐dose regimens observed tumor response rates greater than 50%. Phase 1 trials reported dose‐limiting toxicity for dose‐intensive chemotherapy regimens. On the basis of the available evidence, high‐dose chemotherapy with growth factor or autologous bone marrow/stem cell transplantation should not be used in the routine treatment of patients with inoperable, locally advanced, or metastatic soft tissue sarcoma. Cancer 2008. © 2008 American Cancer Society.