RC:
This can be defined as the use of an approved
drug for something other than what it was intended
for or what it was officially approved for.
This is to be distinguished from the investigational
use of unapproved drugs or compassionate import
of foreign drugs. It is a complex area because
it is not only a matter of therapeutic efficacy
but involves regulatory and legal liability
issues for the prescriber. Essentially, the
US FDA (or other FDAs) intend drugs to be used
according to the the details of the product's
labelling (as in the package insert) but in
reality, many oncology treatments (including
chemotherapy) are conducted "off-label".
"Off-label" does not necessarily imply unproven
or investigational, in fact there is usually
good scientific investigation backing such an
alternative use (at least in our practice).
The real problem lies with the reality of business:
gathering relevant data is very costly for manufacturers
and they would need a powerful financial incentive
to pursue a new indication. If the target population
is small (e.g. some exotic cancers), drug is
widely available as a generic (e.g. cimetidine),
then the incentive does not exist.
Reality is that many drugs are used off-label
or though this "side-usage" of approved drugs
does put an increased level of liability on
the presribing physician, especially if something
goes wrong. A recent example is the unexpected
cardiac side-effect of Fen-Phen diet pill combo
now leaves many physicians at the mercy of case
and money hungry attorneys. Fear of liability
is perhaps why fairly common drugs (eg Celebrex,
antibiotics, statins) with potential anticancer
activity is not presribed more often or widely
or aggressively by oncologists.
Although off-label prescription is not malpractice
or negligence, it is still imperative that prescribers
be able to justify their choice of off-label
treatments such that it will could not be used
as evidence for breech in standard of care.
Towards this end, one must make sure that patients
understands why they are prescribed a certain
off-label treatment and all possible side-effects
should be discussed and extra careful monitoring
should be conducted. In some cases where potential
side-effect is great, the patient should sign
an informed consent before starting treatment.
Alternative cancer treatment frequently involve
the off-label use of approved drugs and examples
abound: common antibiotics (Ciprofloxacin for
bladder cancer, biaxin for lung cancer, minocycline
or tetracycline as antiangiogenic), anti-inflammatory
cox-2 inhibitors such as celecoxib (Celebrex)
as adjuncts in cancer prevention or treatment,
cients ... to the use of the exotic orphan drug
phenylbutyrate, the inhaled delivery of Leukine
(GM-CSF) and so forth.
Patients or practitioners seeking to learn
more about the off-label prescribing of drugs
can read the dated by still insightful 1998
report
by Emalee Murphy, Esq. There is also a nice
official review on "Off-Label Use of Prescription
Drugs" by the office of the Secretary of the
US Dept of Health and Human Services published
in the American Family Physician from 2003 (See
Ref).
In the field of cancer, J. Boos from Germany
wrote an editorial "Off-label use - label off
use?" in the Annals
of Oncology in 2003 that
is worth reading for a review of the issue.
Below is a list of useful "off-label" drugs
in cancer treatment:
Accutane
Biaxin
Celecoxib (Celebrex)
Cimetidine (Tagamet)
Ciprofloxacin
Estrogen
Leukine
Interferons
Mumps vaccine
Phenylbutyrate
PPAR gamma agonists
Spironolactone
Syprine
Tamoxifen
Tetracyclines (Minocycline, Doxycycline)
Statins
Tetracyclines