Chemotherapy: the more, the better in malignant lymphoma?

Several clinical trials have demonstrated that high-dose chemotherapy (HDC) with autologous hematopoietic stem-cell transplantation is more effective than conventional-dose chemotherapy in some subsets of patients with malignant lymphoma, such as relapsed aggressive lymphoma patients showing a response to salvage chemotherapy and those with Hodgkin's disease who fail primary initial chemotherapy. This paper summarizes recent findings and the following issues remaining to be resolved: (1) whether HDC is superior to conventional-dose chemotherapy as initial therapy for aggressive lymphoma in unfavorable risk groups, (2) whether single HDC or multiple semi-HDC is better, (3) whether HDC has curative potential in indolent lymphoma or mantle-cell lymphoma, and (4) the HDC regimen that is most useful. To clarify these controversial issues, well-designed clinical trials are needed. To evaluate whether the concept "the more chemotherapy, the better in malignant lymphoma" is valid, the Lymphoma Study Group of the Japan Clinical Oncology Group is conducting two kinds of clinical trials in high- and high-intermediate-risk aggressive lymphoma patients, focusing on the dose intensity of key agents. One is a randomized phase II trial of dose-escalated cyclophosphamide, doxorubicin, vincristine, and prednisolone (high CHOP) versus shortened CHOP (biweekly CHOP) with prophylactic use of granulocyte colony-stimulating factor. The other is a phase II trial of HDC with peripheral blood stem-cell transplantation as a part of the initial therapy. If promising results are obtained from these trials a randomized phase III trial will be considered to compare the best dose-intensive regimen with standard CHOP.