MEDLINE (1982 to January Week 4, 2005), EMBASE (1980 to February Week 6, 2005), and the Cochrane Library (2005, Issue 1) databases were searched. Disease-specific search terms "sarcoma" (Medical subject heading [MeSH]), "soft tissue neoplasms" (MeSH), "*sarcoma/dt" (exploded MeSH term) and "soft tissue sarcoma" (text word) were combined with treatment-specific terms "drug therapy" (MeSH), "drug therapy, combined" (MeSH), "granulocyte-macrophage colony-stimulating factor" (MeSH), "granulocyte colony-stimulating factor" (MeSH), "bone marrow transplantation" (MeSH), "transplantation, autologous" (MeSH), "hematopoietic stem cell transplantation" (MeSH) and each of the following phrases used as text words: "chemotherapy," "high-dose," "dose-intense," "g-csf," "gm-csf," "growth factor," "abmt," "pbsc," "psct," "transplant". These terms were combined with search terms for the following publications types: practice guidelines, systematic reviews, meta-analyses, randomized controlled trials, controlled clinical trials, phase I clinical trials, phase II clinical trials, and phase III clinical trials.
In addition, the 1998-2004 conference proceedings of the American Society of Clinical Oncology (ASCO) were searched for abstracts of relevant trials. The Canadian Medical Association Infobase (http://mdm.ca/cpgsnew/cpgs/index.asp) and the National Guideline Clearinghouse (http://www.guideline.gov/) were also searched for existing evidence-based practice guidelines.
Relevant articles and abstracts were selected and reviewed by two reviewers, and the reference lists from these sources were searched for additional trials, as were the reference lists from relevant review articles.
Study Selection Criteria
Inclusion Criteria
Articles (full reports or abstracts) were eligible for inclusion in this systematic review of the evidence if they matched one of the following sets of criteria:
- They were first line randomized controlled trials (RCTs) comparing dose-intensive chemotherapy regimens, supported by growth factor (e.g., granulocyte-colony stimulating factor [G-CSF] or granulocyte-macrophage colony stimulating factor GM-CSF) or autologous bone marrow/stem transplantation, with a lower- or standard-dose chemotherapy regimen in adult patients with locally advanced or metastatic soft tissue sarcoma (STS). They reported data, by allocation group, on overall survival, time-to-progression, or tumour response rate. "Dose-intensive chemotherapy" was defined as regimens for which the investigators expressed intent to increase standard doses of chemotherapy supported by the use of hemopoietic growth factors and/or autologous bone marrow/stem cell transplant support. Comparator regimens were accepted as standard chemotherapy if they had been previously evaluated in a large phase II trial or a randomized phase III trial without growth-factor support.
- First-line single-arm non-comparative trials were also included if they were phase II trials that reported toxicity data, response rates, or survival rates or if they were phase I trials that reported dose-limiting toxicity (DLT) or maximum tolerable dose (MTD) for adult patients who received dose-intensive chemotherapy (as defined above) as first-line therapy for locally advanced or metastatic STS. The rationale for including the non-comparative trials was due to the paucity of randomized controlled trials and to permit as detailed a description as possible of the potential efficacy and toxicity of dose-intensive chemotherapy in STS.
Exclusion Criteria
Articles were excluded from the systematic review if:
- They included patients with pediatric sarcomas, bone sarcoma, or small round cell sarcomas including Ewing's sarcoma.
- They assessed dose-intensive chemotherapy in the second-line setting.
- They were letters or editorials.
- They were published in a language other than English.
