Dosage
Dosage of chemotherapy can be difficult: if the dose is too low, it
will be ineffective against the tumor, while at excessive doses the toxicity
(side-effects,
neutropenia) will be intolerable to the patient. This has led to the
formation of detailed "dosing schemes" in most hospitals, which give guidance on
the correct dose and adjustment in case of toxicity. In immunotherapy, they are
in principle used in smaller dosages than in the treatment of malignant
diseases.
In most cases, the dose is adjusted for the patient's
body surface area, a measure that correlates with blood volume. The BSA
is usually calculated with a mathematical formula or a
omogram,
using a patient's weight and height, rather than by direct measurement.
Delivery
Most chemotherapy is
delivered
intravenously, although there are a number of agents that can be
administered orally (e.g.
elphalan,
usulfan,
capecitabine). In some cases,
isolated limb perfusion (often used in
elanoma),
or isolated infusion of chemotherapy into the liver or the lung have been used.
The main purpose of these approaches is to deliver a very high dose of
chemotherapy to tumour sites without causing overwhelming systemic damage.
Depending on the patient, the cancer, the stage of cancer, the type of
chemotherapy, and the dosage, intravenous chemotherapy may be given on either an
inpatient or
outpatient basis. For continuous, frequent or prolonged intravenous
chemotherapy administration, various systems may be surgically inserted into the
vasculature to maintain access. Commonly used systems are the
ickman
line, the
Port-a-Cath or the
PICC line. These have a lower infection risk, are much less prone to
hlebitis
or
extravasation, and abolish the need for repeated insertion of peripheral
cannulae.
Harmful and lethal toxicity from chemotherapy limits the dosage of
chemotherapy that can be given. Some tumours can be destroyed by sufficiently
high doses of chemotheraputic agents. Unfortunately, these high doses cannot be
given because they would be fatal to the patient.
Newer and experimental approaches
Hematopoietic stem cell transplant approaches Stem cell harvesting and autologous or allogeneic
stem cell transplant has been used to allow for higher doses of
chemotheraputic agents where dosages are primarily limited by hematopoietic
damage. Years of research in treating solid tumors, particularly breast cancer,
with hematopoeitic stem cell transplants, has yielded little proof of efficacy.
Hematological malignancies such as
myeloma,
lymphoma, and
eukemia
remain the main indications for stem cell transplants.
Isolated infusion approaches
Isolated limb perfusion (often used in
elanoma),
or isolated infusion of chemotherapy into the liver or the lung have been used
to treat some tumours. The main purpose of these approaches is to deliver a very
high dose of chemotherapy to tumor sites without causing overwhelming
systemic damage. These approaches can help control solitary or limited
metastases, but they are by definition not systemic and therefore do not
treat distributed metastases or
micrometastases.
Targeted delivery mechanisms Specially targeted delivery vehicles aim to increase effective levels of
chemotherapy for tumor cells while reducing effective levels for other cells.
This should result in an increased tumor kill and/or reduced toxicity.
Specially targeted delivery vehicles have a differentially higher affinity
for tumor cells by interacting with tumor specific or tumour associated
antigens.
In addition to their targeting component, they also carry a payload - whether
this is a traditional chemotherapeutic agent, or a radioisotope or an immune
stimulating factor. Specially targeted delivery vehicles vary in their
stability, selectivity and choice of target, but in essence they all aim to
increase the maximum effective dose that can be delivered to the tumor cells.
Reduced systemic toxicity means that they can also be used in sicker patients,
and that they can carry new chemotherapeutic agents that would have been far too
toxic to deliver via traditional systemic approaches.
Nanoparticles
Nanoparticles have emerged as a useful vehicle for poorly-soluble agents
such as
paclitaxel.
Protein-bound paclitaxel (e.g. Abraxane) or nab-paclitaxel was approved by
the US
DA
in January 2005 for the treatment of refractory
breast cancer, and allows reduced use of the
Cremophor vehicle usually found in paclitaxel. Nanoparticles made of
magnetic material can also be used to concentrate agents at tumour sites using
an externally applied magnetic field.
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