Alternative Medicine Review 2001 (Feb); 6 (1): 304–329 ~ FULL TEXT
Davis W. Lamson, MS, ND and Matthew S. Brignall, ND
Introduction
Dietary and endogenous antioxidants prevent cellular damage by reacting
with and eliminating oxidizing free radicals. However, in cancer treatment,
a mode of action of certain chemotherapeutic agents involves the generation
of free radicals to cause cellular damage and necrosis of malignant cells.
So a concern has logically developed as to whether exogenous antioxidant
compounds taken concurrently during chemotherapy could reduce the beneficial
effect of chemotherapy on malignant cells. The importance of this concern
is underlined by a recent study which estimates 23 percent of cancer patients
take antioxidants. [ 1 ]
The study of antioxidant use in cancer treatment is a rapidly evolving
area. Antioxidants have been extensively studied for their ability to prevent
cancer in humans. [ 2 ] This paper reviews the
use of antioxidants as a therapeutic intervention in cancer patients, and
their potential interactions with radiation and chemotherapy. There has
been significant investigation of this area, with promising findings which
indicate continuing investigation is warranted. For further discussion
of the use of antioxidants as sole cancer therapy, refer to the review
article by Prasad published earlier this year. [ 3 ]
A number of reports show a reduction in adverse effects of chemotherapy
when given concurrently with antioxidants. These data are more completely
summarized by Weijl et al. [ 4 ]
Conflicting Views of Antioxidant Use in Cancer Therapy
It was suggested in a recent publication that no supplementary antioxidants
be given concurrently with chemotherapy agents which employ a free radical
mechanism. [ 5 ] The paper must be commended
for pointing out that the combination of antioxidants and chemotherapy
agents needs more investigation, and should serve as a wake-up call regarding
how much we need further definition of the actions of specific antioxidants
with chemotherapeutic agents. However, it should not serve as scientific
closure on an adjunctive treatment of possible great promise in cancer
therapy.
The present authors are by no means recommending any lack of caution
about use of antioxidants. On the contrary, published research indicates
the cautious and judicious use of a number of antioxidants can be helpful
in the treatment of cancer; as sole agents and as adjuncts to standard
radiation and chemotherapy protocols.
It was suggested that antioxidants might interfere with the oxidative
mechanisms of alkylating agents. [ 5 ] These
drugs create substantial DNA damage, resulting in cell necrosis. However,
recent evidence indicates a sizeable amount of chemotherapy damage is by
other mechanisms, which trigger apoptosis. [ 6 ]
Antioxidants have been shown to increase cell death by this mechanism. [ 7,8 ]
Given this, any argument that antioxidants are likely to interfere with
most chemotherapy is too simplistic and probably untrue.
Numerous animal studies have been published demonstrating decreased
tumor size and/or increased longevity with the combination of chemotherapy
and antioxidants. [ 7,9-16 ] A recent study
was conducted on small-cell lung cancer in humans using combination chemotherapy
of cyclophosphamide, Adriamycin (doxorubicin), and vincristine with radiation
and a combination of antioxidants, vitamins, trace elements, and fatty
acids. The conclusion was "antioxidant treatment, in combination with
chemotherapy and irradiation, prolonged the survival time of patients"
compared to expected outcome without the composite oral therapy. [ 17 ]
Two human studies found melatonin plus chemotherapy to induce greater tumor
response than chemotherapy alone. [ 18,19 ]
The treatments producing these positive results would have been advised
against by those advocating no antioxidant use during chemotherapy. These
studies will be discussed in more detail below.
It is the opinion of the authors of this paper that interactions between
antioxidants and chemotherapeutics cannot be predicted solely on the basis
of presumed mechanism of action. The fact remains that physicians must
be aware of the available research to help their patients take advantage
of positive interactions existing between antioxidants and chemotherapy
or radiation.
Additionally, physicians need to remain aware of the large body of evidence
showing a positive effect of antioxidants in the period following chemotherapy
administration. The general protocol with standard oncologic therapies
is to follow a watch-and-wait strategy after therapeutic administration
is concluded. This is a period when supplemental therapies are highly indicated
and have been demonstrated to result in a higher percentage of successful
outcomes. [ 20,21 ]
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