Biologic response modifiers in pediatric cancer

Many advances have been made in the development of chemotherapeutic agents, surgical approaches, and radiotherapy for cancer. Despite these advances, several tumors rapidly become resistant to chemotherapy, other tumors grow too close to critical structures to allow their complete surgical removal, and the administration of radiotherapy can be limited by the number of tumo r sites involved or the tolerance of the normal tissues in the radiation fi eld. Consequently, new therapeutic approaches are being explored, including the use of biologic response modifiers. The goal of biologic response modifiers is to stimulate the body's own immu ne system to help eradicate tumor cells. This stimulation is important beca use many tumor cells have low or absent major histocompatibility complex (M HC) class I or class Il molecules, which allows them to escape from immune surveillance.(7, 10, 11) The use of immunotherapy in the management of canc er began in 1884,(12) With the observation of a "spontaneous regression" of a tumor at the site of an infection. A round cell sarcoma was noted to rec ur repeatedly after every "complete" surgical resection. After one surgical excision, an erysipelas infection at the surgical resection site occurred, and the tumor did not recur. This infection was thought to have stimulated the body's immune system to help eradicate the residual disease. Based on this observation, Cooley(12) directly inoculated an infectious agent to a t umor site in hopes of stimulating an immune response and eradicating the tu mor. Immunotherapy has evolved considerably since these early days. The use of so-called biologic response modifiers has become an attractive alternat ive. Some biologic response modifiers, such as cytokines, are considered na tural because the human body produces them. Many biologic response modifier s are less toxic than standard chemotherapeutic agents and result in less d amage to the kidneys and liver. Because of their growing importance in the treatment of cancer, biologic response modifiers are now considered the fou rth treatment modality, after chemotherapy, radiotherapy, and surgery. This article is divided into three main sections. The first section address es some of the unique aspects of developing and assessing the effects of bi ologic response modifiers for clinical trials. The second section looks at biologic response modifiers used in pediatric solid tumors. The final secti on describes how biologic response modifiers are being used in the treatmen t of pediatric leukemias and lymphomas.