A Textbook of Clinical Pharmacology and Therapeutics

DRUGSUSED INCANCERCHEMOTHERAPY 383

• acute hypersensitivity reactions;


• heart failure, especially in patients who have received
  prior anthracyclines or cyclophosphamide.

HORMONES

Hormones can cause remission of sensitive tumours (e.g. lymph-

omas), but do not eradicate the disease. They often alleviate

symptoms over a long period and they do not cause bone mar-

row suppression. Sex hormones or their antagonists (Chapter 41)

are effective in tumours arising from cells that are normally hor-

mone dependent (breast, prostate).

There are several ways in which hormones can affect malig-

nant 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.

Figure 48.9:Three-dimensional structure of a monoclonal antibody.

Table 48.10:Monoclonal antibodies used to treat cancer

Druga 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

t1/212 days, dose-dependent kinetics infections, lymphoma

pancytopenia

Bevacizumab Colorectal and? Binds to circulating VEGF, inhibits Hypertension, Used as single agent or in

lung cancer angiogenesis neovascularization, pulmonary and combinations in colorectal

plasmat1/2mean 20 days gastro-intestinal cancer. It improves median

(range 11–50) bleeds, proteinuria, survival by 5 months

cardiac failure

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? Plasma t1/23–8 days electrolyte losses

breast cancer

Gemtuzumab Acute myeloid Targets CD33 on T cells, plasma Infusion reactions,

leukaemia t1/210–20 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 t1/210–14 days delayed neutropenia

aDosing of all monoclonal antibodies is intravenous. Usually a loading dose is followed by weekly or biweekly treatments.
bRadioisotope 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.