Clinical impact of chemotherapy dose escalation in patients with hematologic malignancies and solid tumors

To review published controlled clinical trials examining the benefit of escalated chemotherapy in patients with hematologic and solid malignancies.

Studies were obtained by searching Medline and CancerLit and by review of bibliographies of published trials. We reviewed studies that examined dose-intense (DI) chemotherapy alone, in combination with hematopoietic colony-stimulating factors (CSFs), or high-dose therapy (HDT) with autologous bone marrow support (ABMT).

DI therapy without CSF or ABMT has not been shown to improve overall outcome in any tumor except consolidative therapy of acute myelogenous leukemia (AML). In solid tumors, many published studies suggest that less than standard-intensity chemotherapy is suboptimal, but few studies that examined higher compared with standard-dose therapy have shown a significant difference in outcome. No studies have convincingly demonstrated improved overall survival (OS) with DI therapy with CSF support. The use of HDT with ABMT has been shown to improve survival in multiple myeloma (MM), as well as relapsed intermediate- and high-grade non-Hodgkin's lymphoma (NHL). High-dose chemotherapy with ABMT is promising in patients with metastatic breast cancer (MBC), but it should not yet be considered a standard approach for these patients.

DI chemotherapy is an acceptable and standard therapeutic maneuver for patients with AML in first remission, MM, and relapsed aggressive NHL. In solid tumors, the use of DI chemotherapy either alone or with cytokine support has not been shown to improve outcome and should not be considered standard therapy. Current randomized trials should provide definitive answers about the role of DI therapy in solid tumors.