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.
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.
Verma
Shailendra
S
Ottawa Hospital, Ottawa, Ontario, Canada.
Younus
Jawaid
J
Stys-Norman
Denise
D
Haynes
Adam E
AE
Blackstein
Martin
M
D000971:Antineoplastic Combined Chemotherapy Protocols / Q000008:administration & dosage*; D016026:Bone Marrow Transplantation; D003131:Combined Modality Therapy; D004305:Dose-Response Relationship, Drug; D006133:Growth Substances / Q000008:administration & dosage*; D006801:Humans; D012509:Sarcoma / Q000188:drug therapy / Q000601:surgery / Q000628:therapy*; D033581:Stem Cell Transplantation
D006133:Growth Substances