Use of the dopamine agonist cabergoline during conventional fractionated radiotherapy to treat Cushing’s disease may be associated with a higher disease recurrence rate after an initial remission, according to findings published in Clinical Endocrinology.
“Amidst the limited modalities of treatment for recurrent or persistent Cushing’s disease, conventional fractionated radiotherapy was largely considered to be a definitive modality, as recurrence after conventional fractionated radiotherapy was reportedly a rare phenomenon,” Swati Ramteke-Jadhav, MD, DM, assistant professor in the department of endocrinology at KEM Hospital in Mumbai, India, told Endocrine Today. “However, our long-term follow-up study demonstrates post-conventional fractionated radiotherapy recurrence in 20% of patients, with a possible radioprotective role for peri-radiotherapy use of cabergoline. Our study demonstrates that caution is warranted when considering the use of cabergoline, if radiotherapy is being considered for Cushing’s disease.”
In a retrospective study, Ramteke-Jadhav and colleagues analyzed data from 42 patients with Cushing’s disease who received conventional fractionated radiotherapy and had at least 12-month postradiotherapy follow-up (mean age at administration, 24 years). Patients received a 45 Gy dose in 25 fractions during 5 weeks. Medical treatment (n = 22) included cabergoline alone (n = 13) or with ketoconazole (n = 9). Mean follow-up after radiotherapy was 71.5 months. The researchers used a dexamethasone-suppressed cortisol cutoff of 1.8 g/dL to define remission or recurrence and analyzed possible predictors for remission and recurrence.
Within the cohort, 29 (69%) patients achieved remission at a median 18 months after radiotherapy (range, 3-120 months), whereas 13 (31%) patients had persistent disease at last follow-up. There were no between-group differences in patient characteristics, disease severity or tumor size among those who achieved remission compared with those who had persistent disease after conventional fractionated radiotherapy.
Six (20.7%) patients had disease recurrence at a median 74 months after an initial documented remission. Recurrence of the disease was exclusively seen among patients who received peri-radiotherapy cabergoline. The researchers found that peri-conventional fractionated radiotherapy use of cabergoline was associated with increased recurrence rates (P = .016).
“What we want to emphasize is the fact of post-radiotherapy recurrence of Cushing’s disease after documented remission was seen in six patients,” Ramteke-Jadhav said. “Intriguingly, peri-radiotherapy exposure to cabergoline was significantly associated with disease recurrence, and the association was independent of duration of follow-up or the use of adjuvant ketoconazole.”
Ramteke-Jadhav said further clinical studies with larger cohorts with longer follow-up are needed to explore the role of anti-cortisolemic drugs and validate the findings.
“Basic in vitro studies to elucidate the radioprotective effects of cabergoline are also needed,” Ramteke-Jadhav said. – by Regina Schaffer
For more information:
Swati Ramteke-Jadhav, MD, DM, can be reached at KEM Hospital, Parel, Mumbai-400012, Maharashtra, India; email: firstname.lastname@example.org.
Disclosures: The authors report no relevant financial disclosures.