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University Hospital UCL of Mont-Godinne 5530 Yvoir, Belgium
We read with interest the article by Colao et al. (1) reporting the effectiveness of the new long-acting dopamine agonist cabergoline (CAB) in patients with prolactinoma resistant to bromocriptine (BRC) and quinagolide (CV 205-502). This interesting study, including a large number of patients, is the first one assessing the effect of CAB in cases resistant to CV, a drug usually considered more effective than the widely used BRC (2). Nevertheless, the authors refer to BRC and CV as standard dopamine agonists without making a distinction between the two compounds. We would like to analyze separately the results obtained with CAB in cases resistant to BRC and to CV.
CAB therapy was successful in 23 of the 27 patients resistant to BRC. This confirms previous studies (3, 4), unmentioned by the authors. The criteria for recognizing BRC resistance can be more or less selective. We personally observed (4) that CAB was effective in 2 out of 3 patients with unequivocal resistance to BRC, defined by a lack of 50% reduction in serum prolactin (PRL) levels despite increasing the daily dose to at least 15 mg. Only 5 of the patients reported by Colao et al. (1) met this strict criteria. In this condition, CAB allowed normalization of serum PRL levels in 3 patients.
Twenty patients studied by Colao et al. (1) were previously shown to be resistant not only to BRC but also to CV. CAB achieved normalization of serum PRL levels in 17 of these patients (85%). This finding raises some concerns about the respective potency of the different dopamine agonists in view of the previous results obtained by the authors with the other dopamine agonists under discussion. Indeed, in their experience, the oral administration of BRC allows normalization of serum PRL levels in 98% of the patients (5), and CV normalizes serum PRL levels in 78% of the patients resistant to BRC (6). Thus, if CAB is effective in a large majority (85%) of the (very rare) prolactinomas resistant to CV, one could expect CAB to normalize serum PRL levels in nearly all patients with prolactinoma. Nevertheless, in previous reports, normoprolactinemia was achieved in no more than 90% of patients treated with CAB (3).
Another striking point in the present study is the effective CAB dosage: 13 of the 20 patients resistant to 600 µg of daily CV responded well to low doses of CAB (0.5–1 mg weekly). Biller et al. (7) recently reported that among 5 patients who failed to normalize PRL on BRC or CV, 3 achieved normalization of PRL with CAB; but data on the doses of the different dopamine agonists are lacking. We had the opportunity to compare the efficacy of CV and CAB in one BRC resistant prolactinoma and obtained a similar control of prolactinemia with 600 µg of CV daily and 4.5 mg of CAB weekly. A possible explanation for the discordant response observed by Colao et al. (1) with CV and CAB is that poor compliance or intolerance to therapy was the cause of apparent resistance in a significant number of cases. The authors will probably agree with this interpretation as they relate in part the better effectiveness of CAB to its greater tolerability.
Thus, CAB appears to be a safe and well-tolerated drug in patients resistant to other dopamine agonists. However, considering the high rate of response with a low CAB dosage in patients resistant to CV, a drug already effective in case of BRC resistance, the results might be overestimated because of better compliance and tolerance to CAB.
Footnotes
b Received April 30, 1997. Address correspondence to: Etienne Delgrange, Department of Internal Medicine and Endocrinology, University Hospital UCL of Mont-Godinne, Solidarité Mutualiste Chrétienne, Yvoir, Belgium 5530.
References
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