History of Cancer Chemotherapy - A Period of Quiet

A Period of Quiet

With the successes of combination chemotherapy and the discovery of many new agents, there was a feeling at this time that all cancers could be treated, if only one could administer the correct combination of drugs, at the correct doses and at the correct intervals. A search continued, with the pharmaceutical industry screening for new compounds and clinical scientists performing elaborate clinical trials with ever more complex combinations and higher doses.

One important contribution during this period was the discovery of a means that allowed the administration of previously lethal doses of chemotherapy. The patient's bone marrow was first harvested, the chemotherapy administered, and the harvested marrow then returned to patient a few days later. This approach, termed autologous bone marrow transplantation, was initially thought to be of benefit to a wide group of patients, including those with advanced breast cancer. However, rigorous studies have failed to confirm this benefit, and autologous transplantation is no longer widely used for solid tumors. The proven curative benefits of high doses of chemotherapy afforded by autologous bone marrow rescue are limited to both Hodgkin's and selected non-Hodgkin's lymphoma patients who have failed therapy with conventional combination chemotherapy. Autologous transplantation continues to be used as a component of therapy for a number of other hematologic malignancies.

The hormonal contribution to several categories of breast cancer subtypes was recognized during this time, leading to the development of pharmacological modulators (e.g. of oestrogen) such as tamoxifen.

Although clinical oncologists appeared to have hit a wall at this point in terms of results, under the surface something extraordinary was happening: namely, elucidation of the mechanisms underlying cancer. Understanding of the machinery of the cell and advances in techniques to probe perturbations in its function allowed researchers to understand the genetic nature of cancer. It is important to realize that prior to this point, chemotherapeutic agents had been discovered essentially by chance, or by inhibiting the metabolic pathways crucial to cell division, but none were particularly specific to the cancer cell.