High-dose chemotherapy in adult sarcomas: no standard yet

Abstract

The management of patients with sarcoma involves a multidisciplinary approach, with surgery, radiotherapy, and chemotherapy all playing their part. The role of high-dose chemotherapy in this heterogeneous and rare disease remains controversial and unproven. Adult soft tissue sarcomas (STS) generally are poorly responsive to standard chemotherapy, with doxorubicin (DOX) and ifosfamide (IFOS) being the only available agents showing response rates of greater than 20%. Combination regimens generally do not add efficacy, but do add toxicity. For both active agents, a dose-response relationship has been shown. Therefore, and in the absence of new and better drugs or schedules, dose-intensifying and even high-dose chemotherapy regimens (HDCT) with cellular support have been studied. Unfortunately, most of these trials were noncontrolled, studying heterogeneous patient groups. Furthermore, these strategies never resulted in a significantly longer overall survival (OS), and therefore remain highly investigational. Primarily, the search for new active drugs should be encouraged. Although HDCT cannot be considered common practice in STS, the role of this strategy as consolidation therapy in well-defined subsets of patients, using prognostic factors, could be explored further in carefully designed studies. The Ewing tumor family (ET), as a distinct entity, is more responsive to chemotherapy and considered a systemic disease. Results from small, noncontrolled studies indicate that consolidation therapy by megatherapy and hematologic support contributes to an improved outcome in "high-risk" Ewing patients compared with historical controls. However, the exact role of HDCT remains to be determined in properly designed randomized studies with well-defined patient groups and appropriate sample sizes. The collaboration between cooperative groups in the design and execution of randomized studies with appropriate sample sizes should be encouraged. This approach might provide us with essential answers enabling further progress. In addition, each sarcoma patient should, as much as possible, be treated within the context of a properly designed study.