High-dose therapy for adult soft tissue sarcoma: dose response and survival

The role for high-dose therapy in the treatment of sarcomas is controversial and limited. Numerous trials in soft tissue sarcomas have suggested dose-response relationships for doxorubicin (and epirubicin) and ifosfamide. Low doses of these agents are associated with lower response rates than aggressive doses that do not require cellular support. There is little evidence that doses high enough to require hematopoietic stem cell support achieve higher response rates. Complete responses remain rare, and no survival advantage has been documented. New drugs are needed urgently, particularly those with dose-response relationships and those achieving complete responses. In their absence, transplant therapy does not yet play a role in the treatment of soft tissue sarcomas, although further phase II trials could be performed to assess consolidation therapy for complete responders, patients requiring neoadjuvant therapy, and those with resectable oligometastatic disease. High-dose therapy has been evaluated more extensively in patients with pediatric histologies like Ewing's sarcoma, rhabdomyosarcoma, and osteosarcoma. Many more agents suited to transplant regimens have substantial activity against these histologies. Results from certain trials demonstrate improved, long-term, relapse-free survival compared with historical controls, whereas others suggest that selection biases may account for such "improvements." Development of new agents is needed. Carefully designed randomized trials to evaluate the role of high-dose therapy with cellular support should be strongly encouraged in these histologies.