Unii-0343igh41u

Description

Tositumomab was launched as a new radioimmunotherapeutic antibody for the treatment of β-cell non-Hodgkin’s lymphoma (NHL). It is specifically indicated for patients with CD20-positive, follicular NHL, with or without transformation, whose disease is refractory to rituximab and has relapsed following chemotherapy. Tositumomab is an anti-CD20 murine IgG_2a lambda monoclonal antibody produced in an antibiotic-free culture of mammalian cells. The therapeutic regimen of the drug is composed of tositumomab and ¹³¹I-tositumomab. This dual-action therapy combines the tumor-targeting ability of a cytotoxic monoclonal antibody and the therapeutic potential of radiation with patient-specific dosing. The binding of tositumomab to CD20 antigen on NHL cells initiates an immune response to the cancer and the radiolabeled antibody, 131Itositumomab, delivers a dose of radiation directly to tumor cells. Iodine-131 has a physical half-life of eight days. It emits b particles and γ rays, but the primary antitumor effect results from the β particles. In contrast to the external beam radiation, ¹³¹Itositumomab delivers radiation to the tumor at a continuous low dose rate. The dose rate initially increases, as radiolabelled antibodies accumulate at the tumor site, with a maximal tumor dose rate of ＜0.10 Gy/h. The dose rate then decreases with physical decay of the radioisotope and clearance from the body. The tositumomab and ¹³¹Itositumomab therapeutic regimen is dosed in two steps: a dosimetric step followed 7–14 days later by a therapeutic step. The dosimetric step consists of successive infusions of tositumomab (450 mg) and ¹³¹I-tositumomab (5.0 mCi, 35 mg). The therapeutic step consists of 450 mg tositumomab infusion, followed by ¹³¹I-tositumomab as calculated to patient-specific activity. Since non-tumor localization of ¹³¹I is primarily in the thyroid, the patients are also treated with a thyro-protective agent such as potassium iodide throughout the therapeutic course. In a clinical study in patients who had an average of four prior chemotherapies and who did not respond to or relapsed from rituximab therapy, overall response to tositumomab and ¹³¹I-tositumomab treatment was achieved in 63% of the patients and complete response was achieved in 29% of the patients. The duration of response in this category of patients was 25 months. The most common adverse reactions associated tositumomab regimens are severe or life-threatening cytopenia, infections, hemorrhage, allergic reactions, secondary leukemia, and myelodysplasia.

Originator

Corixa (US)

brand name

Bexxar