Doxorubicin-Based Chemotherapy for the Palliative Treatment of Adult Patients with Locally Advanced or Metastatic Soft-Tissue Sarcoma: A Meta-Analysis and Clinical Practice Guideline

Purpose. To make recommendations for the use of doxorubicin-based chemotherapy in patients with soft-tissue sarcoma. Patients. The recommendations apply to patients with symptomatic unresectable locally advanced or metastatic soft-tissue sarcoma who are candidates for palliative chemotherapy. Methods. A systematic review of the published literature was combined with a consensus process around the interpretation of the evidence in the context of conventional practice to develop an evidence-based practice guideline. Results. Eight randomized trials comparing doxorubicin-based combination versus doxorubicin single-agent chemotherapy were reviewed. Response rates and overall survival were evaluated using pooled statistical analysis.The pooled response data in 2281 patients showed a slight trend favouring the combination therapy, although this did not reach statistical significance (odds ratio (OR), 0.79; 95% confidence interval (CI), 0.60–1.05; p=0.10). Survival data could only be abstracted from six studies involving 2097 patients, and showed no significant advantage for combination therapy (OR, 0.84; 95% CI, 0.67–1.06; p=0.13). Data on adverse effects could not be combined in a meta-analysis; however nausea, vomiting and myelosuppression were consistently more severe with combination chemotherapy than with single-agent chemotherapy. Discussion. Single-agent doxorubicin is an appropriate first-line chemotherapy option for advanced or metastatic soft-tissue sarcoma. Some doxorubicin-based combination chemotherapy regimens, given in conventional doses, produce only marginal increases in response rates, at the expense of increased adverse effects, and with no improvements in overall survival. Future randomized clinical trials should compare new regimens, whose activity has been established in single-arm studies, with single-agent doxorubicin, and include quality of life as an outcome measure.