Scientific basis for cancer chemotherapy and models of tumour response

Abstract

Chemotherapy is a much more complex mode of cancer treatment than radiotherapy, mainly due to the variety of drugs available for use that differ among themselves in molecular structure, mode of action, pharmacological properties and side effect. The widely accepted tenets of cancer chemotherapy have been largely arrived at with empiricism. Although a number of models for chemotherapeutic effects have been proposed, most of them had no profound impact on practical clinical situations. Again, generally, they have serious limitations in application due to non-availability of treatment and tumour parameters in human cancers. Nevertheless, they do attempt to provide an insight in intricacies of chemotherapy. This paper presents the underlying scientific basis for cancer chemotherapy and a few models. The paper also proposes a clinically applicable model based upon tumour volume known by CT scan films during chemotherapy protocol of Cisplatinum and Cyclophosphamide in 51 patients of epithelial ovarian cancer. Tumour volume regression pattern during treatment was found to follow exponential from. The regression rate could be used to distinguish patients with the risk of shorter survival. Patients with fast regressing tumour (n=29, mean regression constant - 0.026) had median survival of 29.2 months, as opposed to 18.9 months (pc0.05) in case of moderately regressing tumours (n=16, mean regression constant = -0.012). It was also found that if "percent reduction in tumour volume after first cycle of chemotherapy" was less than 15%, the tumour was likely to be inherently resistant to on-going chemotherapy as was the case with 83.3% (5 out of 6 inherently resistant) tumours with median survival of 8.5 months. This may help in identifying such inherently resistant tumours just after the first cycle of chemotherapy and hence save time, money and unnecessary toxicity.