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 Clinical Practice Guideline

摘要

Questions 1. In patients with inoperable locally advanced or metastatic soft tissue sarcoma, does first line dose-intensive chemotherapy supported by growth factor or autologous bone marrow/stem cell transplantation improve response rate, time-to-disease progression or survival compared with standard dose chemotherapy? 2. What are the effects of first line dose-intensive chemotherapy supported by growth factor or autologous bone marrow/stem cell transplantation on toxicity and quality of life? Perspectives Since therapeutic options for adult patients with advanced or metastatic soft tissue sarcoma are scarce and the possibility of cure for these patients is extremely limited, the Sarcoma Disease Site Group (DSG) felt it was important to review the available literature on dose-intensive chemotherapy for adult patients with locally advanced or metastatic soft tissue sarcoma and to subsequently develop a clinical practice guideline based on this evidence. Methodology A systematic review was developed and clinical recommendations relevant to patients in Ontario were drafted. The practice guideline report was reviewed and approved by the Sarcoma DSG which comprises medical oncologists, radiation oncologists, surgeons, a pathologist, a methodologist and community representatives. External review by Ontario practitioners was obtained through a mailed survey, the results of which were incorporated into the practice guideline. Final review and approval of the practice guideline was obtained from the Report Approval Panel. Practice Guideline Based on the systematic review, consensus, and external review the Sarcoma DSG has made the following recommendations: ? Dose-intensive chemotherapy with growth factor support is not recommended in the first-line treatment of patients with inoperable locally advanced or metastatic soft tissue sarcoma. ? There is insufficient data to support the use of high dose chemotherapy with autologous bone marrow/stem cell transplantation as first-line treatment in this group of patients. ? Eligible patients should be encouraged to enter clinical trials assessing novel approaches or compounds. Qualifying Statements ? High-dose chemotherapy with growth factor or autologous bone marrow/stem cell transplantation and standard-dose chemotherapy have similar adverse effects. The incidence of grade 3/4 thrombocytopenia is significantly higher; neutropenic fever and febrile neutropenia occur more frequently with high-dose regimens. Compared to standard treatment, the rate of treatment related deaths is also higher with high-dose regimens. Key Words: Soft tissue sarcoma, dose-intensive chemotherapy, growth factor, autologous bone marrow/stem cell transplantation, clinical practice guideline.