A Textbook of Clinical Pharmacology and Therapeutics

Table 48.10: Monoclonal antibodies used to treat cancer
Figure 48.9: Three-dimensional structure of a monoclonal antibody.
• acute hypersensitivity reactions;
• heart failure, especially in patients who have received
prior anthracyclines or cyclophosphamide.
HORMONES
DRUGS USED IN CANCER CHEMOTHERAPY 383
Drug a Therapeutic use Pharmacodynamics/pharmacokinetics Side effects Additional comments
Alemtuzumab B-cell lymphoma Binds to CD52 on neutrophils and lymphs, Infusion reactions, Early efficacy in mycosis
Causes apoptosis via ADCC. Plasma opportunistic fungoides and T-cell
t1/2 � 12 days, dose-dependent kinetics infections,
pancytopenia
lymphoma
Bevacizumab Colorectal and ? Binds to circulating VEGF, inhibits Hypertension, Used as single agent or in
lung cancer angiogenesis neovascularization, pulmonary and combinations in colorectal
plasma t1/2 � mean 20 days gastro-intestinal cancer. It improves median
(range 11–50) bleeds, proteinuria,
cardiac failure
survival by 5 months
Cetuximab Colorectal and Targets EGFR (Erb-1), inhibits Infusion reactions, Prolongs survival in colon
pancreatic and EGFR-mediated signal transduction. skin rashes – 75%, cancer
NSCL and ?
breast cancer
Plasma t1/2 � 3–8 days electrolyte losses
Gemtuzumab Acute myeloid Targets CD33 on T cells, plasma Infusion reactions,
leukaemia t1/2 � 10–20 days bone marrow
suppression, VOD
and skin rash
Rituximabb B-cell lymphoma Binds to CD20 on B-cells and activates Infusion reactions:
and CLL (also used TK, c-myc and MHC class II molecules, fever, rash, dyspnoea,
for ITP) plasma t1/2 � 10–14 days delayed neutropenia
a Dosing of all monoclonal antibodies is intravenous. Usually a loading dose is followed by weekly or biweekly treatments.
b Radioisotope labelled versions of other antibodies to the same target are available.
ADCC, antibody-directed cellular cytotoxicity; EGFR, epidermal growth factor receptor; CLL, chronic lymphatic leukaemia; ITP, idiopathic thrombocytopenia;
NSCL, non-small cell lung; TK, tyrosine kinase; VEGF, vascular endothelial growth factor; VOD, vascular occlusive disease.
Hormones can cause remission of sensitive tumours (e.g. lymphomas),
but do not eradicate the disease. They often alleviate
symptoms over a long period and they do not cause bone marrow
suppression. Sex hormones or their antagonists (Chapter 41)
are effective in tumours arising from cells that are normally hormone
dependent (breast, prostate).
There are several ways in which hormones can affect malignant
cells:
• A hormone may stimulate growth of a malignant cell.
For example, if a breast carcinoma is oestrogen
receptor-positive, oestrogen antagonists can inhibit
these cells.
• A hormone may suppress the production of other
hormones by a feedback mechanism. This will change the
hormonal milieu surrounding the malignant cells and
may suppress their proliferation. In breast cancer, patients
who respond to one form of endocrine therapy are more
likely to respond to subsequent hormone treatment than
those who fail to respond initially.