Clinical and Scientific Considerations in Preoperative (Neoadjuvant) Chemotherapy

Abstract

Thirty years ago, chemotherapy had little to offer patients with solid tumors and in general patients were treated after failure of surgery or radiotherapy when advanced overt metastatic disease was already present. As progress was made in the chemotherapy of the childhood solid tumors, and of certain adult tumors, such as metastatic breast cancer, the investigation of chemotherapy in the adjuvant situation developed. This was stimulated by the fact that, for example, patients with stage II breast cancer or osteogenic sarcoma are at high risk of having micrometastatic dissemination at the time of diagnosis, so that potentially definitive treatment must include not only control of the primary with surgery and/ or radiotherapy (S/R), but also systemic chemotherapy (C), the latter to control disseminated micrometastatic disease. The experimental basis for this was the observation that chemotherapy for in vivo transplanted tumors was capable of cytoeradication (cure) in inverse relationship to the tumor burden. Thus chemotherapy which produced only partial regression of advanced tumor was frequently curative when applied to the same tumor in microscopic form (Goldin et al. 1956). This was also demonstrated in experimental in vivo systems, wherein the primary in the extremity was controlled by amputation, following which the cure rate could be increased in many circumstances by chemotherapy addressed to micrometastatic disease (Skipper 1978).