Relevance of high-dose chemotherapy in solid tumours

Abstract

Drug resistance is a major problem in the treatment of solid tumours. Based on a steep dose-response relationship for especially alkylating agents on tumour cell survival, high-dose chemotherapy was considered of interest for the treatment of solid tumours. Results of phase 1 and 2 studies with high-dose chemotherapy in a variety of tumour types showed good response rates. Nowadays, several phase 3 studies are available especially in metastatic and high-risk breast cancer patients. The high expectations of high-dose chemotherapy did not come true. This review analyses results of randomised studies and comments on the discrepancy between findings in patients versus those in tissue culture. Potential factors involved are the presence of tumour stem cells with different characteristics from more mature tumour cells, limitations in drug escalation in the clinic, transplant mortality, trial design and tumour cell contamination of the haematopoietic stem cell transplant. Maturation of the results from recent studies indicating a more modest benefit in, e.g., adjuvant breast cancer balanced versus long-term side effects will ultimately determine the role of high-dose chemotherapy in certain solid tumours. In case of well-defined indications for high-dose chemotherapy, further selection of patients based on patient and tumour characteristics as well as the introduction of new agents will most likely play a role.