In the Journals

Cabergoline may increase recurrence risk after remission in Cushing’s disease

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.

Swati Ramteke-Jadhav

“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: drswatijadhav1980@gmail.com.

Disclosures: The authors report no relevant financial disclosures.

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.

Swati Ramteke-Jadhav

“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: drswatijadhav1980@gmail.com.

Disclosures: The authors report no relevant financial disclosures.