9 - Circumvention of drug resistance by high-dose chemotherapy in solid tumors

Summary

Introduction

Drug resistance is a major problem in the treatment of patients with chemotherapeutic drugs. The roots of this problem lie in part in the presence of tumor cells that are intrinsically resistant to chemotherapeutic drugs, or that have become so in the course of treatment. One of the ways to circumvent drug resistance is to administer the chemotherapeutic drugs in a higher dose. Initially, studies on the treatment of breast cancer and ovarian cancer with high-dose chemotherapy and bone marrow support dealt with patients having a large tumor load at the time of treatment. In similar situations of high tumor load, other malignancies including acute leukemia, germ cell tumors, small cell lung cancer and ovarian cancer have been shown to be incurable with standard dose chemotherapy. Several malignancies in complete remission, however, can be cured by high-dose therapy. These include acute leukemia, aggressive non-Hodgkin's lymphoma and occasional germ cell tumors. The fact that supportive care improved has made this procedure less dangerous. Therefore, it is more acceptable to enter this type of treatment earlier in the stage of disease of solid tumors.

Myelo-, cardio-, pulmonal- and neurotoxicity are the main toxicities that make dose intensification difficult. Cardio-, pulmonal- and neurotoxicity are difficult to circumvent. It is however possible to circumvent bone marrow toxicity without long-term untoward effects for the patient.