Bisphosphonates in Clinical Oncology : The Development of Pamidronate

The book gives an overview of the clinical developments in the use of bisphosphonates in clinical oncology. The first part pre- sents the composition, physiology, and pathophysiology of bone. Next is a section giving insight into mechanisms of bone resorp- tion, bone formation, and bone remodeling, a field in which I was most influenced by O. L. M. Bijvoet and H. Fleisch. The sec- ond part summarizes the pharmacological treatments for disor- ders of bone remodeling. The clinical aspects of tumor-induced hypercalcemia and its management are described in detail, in- cluding our first prospective randomized crossover study testing pamidronate versus mithramycin. The bisphosphonates were in- troduced in clinical oncology by endocrinologists. The same was true for our institution in 1986, when P. Burckhardt proposed testing pamidronate in the above-mentioned trial in his institu- tion (CHUV) and in our department. The impressive results ob- tained in the hypercalcemia trial stimulated our interest, and we actively investigated the use of pamidronate to counteract osteo- lytic bone destruction in cancer patients. These investigations are presented and discussed in the third part. They represent the interdisciplinary work involving many co-workers of the Depart- ment of Internal Medicine C and other institutes of the Interdis- ciplinary Oncology Center St. Gallen (IOSG), which I was privi- leged to chair for 10 years. Initially, a pharmacokinetic study was performed in order to optimize and facilitate the administration of the drug to patients with malignant osteolytic bone disease.