DRUGSUSED INCANCERCHEMOTHERAPY 385INTERFERON-ALFA 2B
Interferon-alfa 2b is a glycoprotein (molecular weight
15–27.6 kDa) produced by recombinant expression in E. coli.
It is used in the treatment of hairy cell leukaemia, refractory
chronic myeloid leukaemia, advanced malignant melanoma
and follicular lymphoma. Interferons bind to specific cell sur-
face receptors which initiate intracellular events relating to
effects on RNA and protein synthesis. Such processes include
enzyme induction, inhibition of cell proliferation enhancement
of immune effector cells, such as macrophage phagocytic activ-
ity and cytotoxic T lymphocytes. Interferons are administered
subcutaneously. Pegylated formulations allow once weekly
administration. Common adverse effects include flu-like ill-
nesses, fatigue, myalgias and arthralgias, injection site reac-
tions, rashes. Less frequent side effects are hypotension, cardiac
failure and CNS effects (memory loss and depression). Chronic
interferon therapy may downregulate CYP450s involved in
drug metabolism and lead to drug toxicity, e.g to theophylline.
Other immunostimulatory drugs that have been used with
some success include thalidomide, which has anti-angiogenesis
properties and decreases TNF production (effective in refrac-
tory malignant myeloma), and levamisole(as an adjuvant for
colon cancer). The optimal use of tumour vaccines is still being
actively researched.
FURTHER READING AND WEB MATERIAL
Baker SD, Grochow LB. Pharmacology of cancer chemotherapy in the
older person. Clinics in Geriatric Medicine1997; 13 : 169–83.
Chabner BA, Longo DL. Cancer chemotherapy and biotherapy, 2nd edn.
Philadelphia: Lippincott-Raven, 1996.
Douglas JT. Cancer gene therapy. Technology in Cancer Research and
Treatment2003; 2 : 51–64.
Frei E. Curative cancer chemotherapy. Cancer Research1985; 45 :
6523–37.
Kim R, Emi M, Tanabe K et al. The role of apoptotic or nonapoptotic
cell death in determining cellular response to anticancer treatment.
European Journal of Surgical Oncology2006; 32 : 269–77.
Krause DS, Van Etten RA. Tyrosine kinases as targets for cancer ther-
apy. New England Journal of Medicine2005; 353 : 172–87.
Mooi WJ, Peeper DS. Oncogene-induced cell senescence – halting on
the road to cancer. New England Journal of Medicine2006; 355 :
1037–46.
O’Driscoll L, Clynes M. Biomarkers and multiple drug resistance in
breast cancer. Current Cancer Drug Targets2006; 6 : 365–84.
Yong WP, Innocenti F, Ratain MJ. The role of pharmacogenetics in
cancer therapeutics. British Journal of Clinical Pharmacology2006;
62 : 35–46.
Useful websites: American Society of Clinical Oncology, http://www.asco.org;
National Cancer Institute of America, http://www.cancer.gov.Case history
A 19-year-old white male presented with palpable lumps
on both sides of his neck and profuse sweating at night.
Lymph node biopsy and computed tomography (CT) scan-
ning yielded a diagnosis of stage IVb Hodgkin’s disease. He
was started on combination chemotherapy with doxoru-
bicin 60 mg/m^2 , bleomycin 10 units/m^2 , vinblastine 5 mg/m^2
and dacarbazine 100 mg (ABVD). After four cycles of
chemotherapy, he developed abdominal pain that was
found to be due to acute appendicitis and he underwent
emergency appendicectomy and made a good recovery.
Four days after completing his fifth cycle of ABVD treat-
ment he noted increased dyspnoea on exertion. This pro-
gressed over 48 hours to dyspnoea at rest. Physical
examination revealed cyanosis. There was no palpable cer-
vical lymphadenopathy, but he had a sinus tachycardia and
bilateral basal and mid-zone late inspiratory crackles.
Further investigations revealed normal haemoglobin,
white blood count and platelets, normal coagulation
screen,PO 2 on air 50 mmHg and fluffy interstitial infiltrates
in both lower- and mid-lung fields on chest x-ray.
Pulmonary function tests showed an FEV 1 /FVC ratio of
80%, reduced FVC and a DLCOof 25% of the predicted
value. Bronchoalveolar lavage fluid was negative for bacte-
rial, viral and fungal pathogens, including Pneumocystis
carinii.Question
What was the cause of this patient’s respiratory problems?
How should he be treated?
Answer
In this patient, the possible causes of such pulmonary symp-
toms and radiographic findings include opportunistic infec-
tion, pulmonary oedema (secondary to fluid overload),
pulmonary haemorrhage, progression of disease or drug-
induced interstitial alveolitis. Here, with the exclusion of a
haemorrhagic diathesis and pulmonary infection, no fluid
overload and apparent regression of his cervical lymph-
adenopathy, the probable diagnosis is bleomycin-induced
interstitial pneumonitis. Although the patient had not
received more than 300 units of bleomycin, it is likely that
during his operation he received high inspired oxygen
concentrations, and this could have put him at higher
risk of developing ‘bleomycin lung’. Currently, he should
receive the lowest inspired oxygen concentration that
will yield a PO 2 of60 mmHg. Glucocorticosteroid therapy
may be of benefit, but the syndrome may not be fully
reversible. Bleomycin, and other cytotoxic agents which
cause a pneumonitis (e.g. cyclophosphamide, busulfan,
carmustine, methotrexate and mitomycin) and radiation
therapy (which can exacerbate bleomycin pulmonary
toxicity), should not be used for this patient’s future
therapy.