The roots of modern oncology: from discovery of new antitumor anthracyclines to their clinical use.

In May 1960, the Farmitalia CEO Dr. Bertini and the director of the Istituto Nazionale dei Tumori of Milan Prof. Bucalossi (talent scout and city's Mayor) signed a research agreement for the discovery and development up to clinical trials of new natural antitumor agents. This agreement can be considered as a pioneering and fruitful example of a translational discovery program with relevant transatlantic connections. Owing to an eclectic Streptomyces, found near Castel del Monte (Apulia), and to the skilled and motivated participants of both institutions, a new natural antitumor drug, daunomycin, was ready for clinical trials within 3 years. Patent interference by the Farmitalia French partner was overcome by the good quality of the Italian drug and by the cooperation between Prof. Di Marco, director of the Istituto Ricerche Farmitalia Research Laboratories for Microbiology and Chemotherapy, and Prof. Karnofsky, head of the Sloan-Kettering Cancer Institute of New York, leading to the first transatlantic clinical trials. The search for daunomycin's sister anthracyclines led to the discovery and development of adriamycin, one of the best drugs born in Milan. This was the second act prologue of the history of Italian antitumor discovery and clinical oncology, which started in July 1969 when Prof. Di Marco sent Prof. Bonadonna the first vials of adriamycin (doxorubicin) to be tested in clinical trials. This article reviews the Milan scene in the 1960s, a city admired and noted for the outstanding scientific achievements of its private and public institutions in drugs and industrial product discovery.

A historical perspective of anthracycline cardiotoxicity.

Anthracyclines remain important agents in the treatment of solid and hematological malignancy. Early experience with these drugs reported cardiac failure as an adverse event. Later, clinical recognition of cell injury at the time of administration was appreciated. This article explores the evolution of our understanding about anthracycline-associated cardiotoxicity, including the various strategies for the pretreatment assessment of patients for whom anthracyclines are contemplated, the frustrations associated with the lack of specific tests that could identify patients at risk of developing problems with their next 1 or 2 cycles, the concept of balancing oncologic benefit with cardiac risk in the treatment of cancer patients, and the newer strategies for reducing the potentially devastating complications of the treatment of malignant disease with anthracyclines.