| | Taken
together, these studies indicate that "low" levels
of cortisol are associated with an increased incidence and magnitude
of nausea and vomiting and perhaps account for the efficacy
of endogenous cortisol as an anti-emetic. The site and mechanism
of action is not known, but among those suggested (Seymour,
1993) are:
- Reduction in cerebral
edema and blood brain barrier permeability;
- Reduction in prostanoid
turnover;
- Increased endorphin
release;
- Reduction in 5-HT
metabolism; and
- Modulation of neuronal
membrane ion permeability.
There is also evidence
that chemotherapy drugs may directly or indirectly influence
the activity of the hypothalamic-pituitary-adrenal (HPA) axis.
Figure 3.2 characterizes the temporal changes in blood cortisol
concentrations in 23 women with carcinoma of the ovary treated
with platinum-based chemotherapy and administered dexamethasone
as part of antiemetic prophylaxis (Morrow
et al., 2000). A significantly reduced level of serum cortisol
was present immediately following the infusion of either cisplatin
or carboplatin, suggesting that the effect is present by the end
of the chemotherapy administration.
(Click
on the image to view animation popup window)
| Figure
3.2: Cortisol Levels Following Treatment
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The serum cortisol
levels for both Treatment 1 and 2 days were significantly lower
for the first four hours following chemotherapy than on the non-treatment
baseline day. Since the reduction in cortisol was seen only in
the presence of the cytotoxic drug, it is likely that the effect
is "direct" and does not involve any overt psychological
or circadian mechanism.
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