Rituximab: ongoing and future clinical development.

Monoclonal antibodies have been used as therapeutic agents for many years. In 1997, rituximab (Rituxan; Genentech, Inc, South San Francisco, CA, and IDEC Pharmaceuticals, San Diego, CA) became the first monoclonal antibody to be approved by the US Food and Drug Administration for a cancer indication. The use of rituximab in the treatment of low-grade or follicular, relapsed, or refractory CD20-positive B-cell non-Hodgkin's lymphoma was approved in November 1997 for United States marketing under the trade name Rituxan. In June 1998, rituximab was approved for all European Union countries under the trade name MabThera as therapy for patients with stage III/IV, follicular, chemoresistant, or relapsed (> or = 2 relapses) non-Hodgkin's lymphoma. To date, rituximab has been approved in 56 countries. Over 125,000 patients have been treated with this antibody in the United States alone. Rituximab served to heighten interest in the therapeutic applications of monoclonal antibodies. Literally dozens of antibodies are currently under investigation for a variety of malignant and non-neoplastic indications. The US Food and Drug Administration approved a new (revised) package insert in early 2001. These revisions have been communicated to physicians via a "Dear Doctor Letter" and will appear in the 2002 edition of the Physicians' Desk Reference. A significant amount of clinical research has been performed over the past 9 years, which has served to further our understanding of the potential clinical applications for this novel therapeutic agent. Ongoing and future clinical trials are reviewed in this article. However, much remains to be accomplished in key areas such as combinations with chemotherapy, biologics (including other antibodies), and radiotherapy/radioimmunotherapy; its role within multimodality regimens; and other malignant (beyond low-grade non-Hodgkin's lymphoma) and nonmalignant applications.