DƯỢC LÍ Goodman & Gilman's The Pharmacological Basis of Therapeutics 12th, 2010

Table 62–1
Monoclonal Antibodies Approved for Hematopoietic and Solid Tumors
RADIOISOTOPE-
ANTIGEN AND TUMOR BASED TOXIN-BASED
CELL TARGETS ANTIGEN FUNCTION NAKED ANTIBODIES ANTIBODIES ANTIBODIES
Antigen: CD20
Tumor type: B-cell Proliferation/ Rituximab
131
I-tositumomab; None
lymphoma and CLL differentiation (chimeric)
90
Y-ibritumomab
tiuxetan
Antigen: CD52
Tumor type: B-cell Unknown Alemtuzumab None None
CLL and T-cell
(humanized)
lymphoma
Antigen: CD33
Tumor type: acute Unknown Gemtuzumab None Gemtuzumab
myelocytic (humanized) ozogamicin
leukemia
Antigen: HER2/neu (ErbB2)
Tumor type: Tyrosine kinase Trastuzumab None None
breast cancer
(humanized)
Antigen: EGFR (ErbB1)
Tumor type: colorectal, Tyrosine kinase Cetuximab None None
NSCLC, pancreatic,
(chimeric)
breast
Antigen: VEGF
Tumor type: Angiogenesis Bevacizumab None None
colorectal cancer
(humanized)
CLL, chronic lymphocytic leukemia; EGFR, epidermal growth factor receptor; NSCLC, non–small cell lung cancer; VEGF, vascular endothelial
growth factor.
and expression of major histocompatibility complex
class II molecules. CD20 also may regulate transmembrane
Ca 2+ conductance through its function as a Ca 2+
channel. It is unclear which of these actions relates to
the pharmacological effect of rituximab.
Rituximab is approved as a single agent for relapsed indolent
lymphomas and significantly enhances response and survival in
combination with chemotherapy for the initial treatment of diffuse
large B-cell lymphoma. It remains effective in patients who relapse
after initial treatment with rituximab-based combinations. Rituximab
improves response rates when added to combination chemotherapy
for other indolent B-cell non-Hodgkin’s lymphomas (NHLs),
including CLL, mantle cell lymphoma, Waldenström macroglobulinemia,
and marginal zone lymphomas (Cheson and Leonard,
2008). Maintenance of remission with rituximab delays time to progression
and improves overall survival in indolent NHL (van Oers et al.,
2006). It is increasingly used for treatment of autoimmune diseases
such as rheumatological disease, thrombotic thrombocytopenic purpura,
autoimmune hemolytic anemias, cryoglobulin-induced renal
disease and multiple sclerosis.
Pharmacokinetics and Dosing. Rituximab has a t 1/2
of ~22 days
(Maloney et al., 1997). The drug is administered by intravenous infusion
both as a single agent and in combination with chemotherapy at
a dose of 375 mg/m 2 . As a single agent, it is given weekly for 4 weeks,
with maintenance dosing every 3-6 months. In combination regimens,
the drug may be administered every 3-4 weeks, with
chemotherapy, for up to eight doses. As maintenance therapy following
6-8 cycles of combination chemotherapy, rituximab may be given
once weekly for four doses, at 6-month intervals, for up to 16 doses.
During the first administration, the rate of infusion should be
increased slowly to prevent serious hypersensitivity reactions.
Infusions should begin at 50 mg/h, and in the absence of infusion reactions,
the rate can increase in 50-mg/h increments every 30 minutes to a
maximum rate of 400 mg/h. On subsequent infusion in the absence of
reactions, infusions may start at 100 mg/hr and increase in 100-mg/h
increments every 30 minutes to a maximum rate of 400 mg/h.
Pretreatment with antihistamines, acetaminophen, and glucocorticoids
decreases the risk of hypersensitivity reactions.
Patients with large numbers of circulating tumor cells (as in
CLL) are at increased risk for tumor lysis syndrome; in these
patients, the initial dose should be no more than 50 mg/m 2 on day 1