Cancer, treatment rituximab

Reactions following initial infusions of antibody are common, but these can usually be handled by a cautious rate of infusion, appropriate hydration and diuresis, and, if necessary, praned-ication. Twenty six percent of initial reactions are reported to be mild, 48 % moderate, and 26 % severe. The initial infusion reaction to some mAbs, for example, rituximab (see below), may provoke tumor lysis syndrome, cytokine release syndrome, and systemic inflammatory response syndrome. Tumor lysis syndrome, noted particularly with rituximab, can occur following cancer treatment and sometimes without treatment. It is believed to be the result of breakdown products of cancer cells leading to increased levels of some metabolites and reflected in conditions such as hypercalcemia, hyperkalemia, hyperphosphatemia, acute uric acid nephropathy, and acute renal failure. The syndrome can occur in the early stages of mAb therapy and is potentially life-threatening. Cytokine release syndrome, also called cytokine storm, is commonly seen after... 

Based on these data, rituximab was approved by the FDA in 1998 for the treatment of relapsed or refractory low-grade or follicular, CD20(+), B-cell NHL. Rituximab was the first mAh to receive approval for the treatment of cancer. 

Monoclonal antibodies may be used as passive immunotherapy to treat malignancies. They react with specific antigens present on the surface of tumor cells and result in cell destruction. Rituximab was the first MoAb approved in the United States for the treatment of cancer. It is a chimeric MoAb directed against cluster differentiation 20 (CD20) markers, which are expressed on over 90% of B-cell NHL tumors. Rituximab is thought to result in B-cell depletion by a number of mechanisms, including complement-mediated and antibody-dependent cell lysis and induction of apoptosis. 

In general, the MoAbs used in treating cancer are relatively well tolerated compared with conventional cytotoxic chemotherapy. The main adverse effect associated with rituximab use is infusion-related or hypersensitivity reactions. Patients may experience fever, rigors, dyspnea, hypotension, and rarely anaphylactoid reactions. Premedication with acetaminophen, diphenhydramine, and corticosteroids can reduce these reactions. Patients with significant tumor burden at the time of first treatment with rituximab may experience tumor lysis syndrome, and appropriate measures should be implemented to prevent this complication in these patients. 

The rituximab presentation to the Biologies Response Modifiers Advisory Committee (BRMAC) of the FDA took place on July 25, 1997 and the final approval was granted on November 26,1997 (Fig. 4) [55-58]. The EMEA granted approvi to rituximab in Europe in June 1998. Rituximab became the first monoclonal antibody approved for the treatment of cancer and specifically for patients with NHL. 

Rituximab represents the most important scientific achievement of the past decade. It was the first therapeutic antibody approved for the treatment of cancer and specifically for N H L. The current IWRC for N H L had their origin with the rituximab response criteria. Clinical development was completed in record time. Dossiers were filed simultaneously in the United States and in Europe. The US fihng utilized an electronic format (computer-aided product license application, CAPLA). These and many other achievements during clinical development served to provide tremendous impetus to the monoclonal antibody research area. The renewed enthusiasm in this area has yielded many new Mabs with activity in both hematologic malignancies and in autoimmune diseases. Several of these have been approved (e.g. herceptin, alemtuzumab, mylotarg, others) and many others are under active investigation. 

In 2002, rituximab became the number one, brand name, cancer therapeutic in the world. It is an important component of the current curative combination for aggressive NHL (R + CHOP). In the future, rituximab may become a part of other curative treatment regimens for hematologic malignancies and will also find utility in the treatment of major diseases such as rheumatoid arthritis and other autoimmune disorders. 

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