The importance of dose: lymphomas as a model of chemosensitive malignancies

Chemotherapy dose intensity is probably important to the success of treatment for some human malignancies. Recombinant human haemopoietic growth factors have recently become available to clinicians to ameliorate the myelosuppression that follows cytotoxic chemotherapy. Their use to increase the dose intensity of treatment, either by simply allowing the administration of the planned dose on schedule or by increasing the dose or dose rate above the conventional ones, is being actively investigated by several European and American groups. In several reported studies, neutropenia is no longer dose limiting when granulocyte colony-stimulating factor is used to help to intensify cytotoxic chemotherapy, but thrombocytopenia or mucositis are. The use of circulating haemopoietic progenitor cells, released into the blood stream by growth factors and infused with or without autologous bone marrow, has been reported to consistently reduce the overall period and severity of thrombocytopenia following intensive chemotherapy in patients without pre-existing severe bone marrow damage. However, no clear improvements in survival have yet been documented with the use of these techniques. Difficulties in study design include a number of variables potentially involved (tumour model, patient population, adjuvant or advanced disease, dose of cytotoxics, intervals, end-points, etc.), and there is clearly a need for more studies and longer follow-up. Lymphomas, both non-Hodgkin and Hodgkin's disease, are the prototypes of chemosensitive malignancies curable by chemotherapy alone even in disseminated disease. Therefore, they would seem to be adequate models to test the dose intensity hypothesis in the clinic. However, there are important differences between these two types of disorder. The success of conventional therapies in these conditions suggests that further improvements in outcome and long-term survival by further increases in dose intensity with current drugs will require careful study designs, due attention to prognostic factors, and reasonable expectations.