Can we predict long-term remission after somatostatin analog withdrawal in patients with acromegaly? Results from a multicenter prospective trial

Abstract

Somatostatin analogs (SSAs) represent the mainstay of therapy in acromegaly. One of the potential disadvantages is the expected need to maintain therapy indefinitely in previously non-irradiated patients. The aim of this multicenter prospective open trial was to evaluate the likelihood of successful discontinuation of SSA therapy in well-controlled acromegalic patients who fulfilled very strict criteria: two or more years of treatment with the long-acting SSA octreotide LAR (OCT-LAR), a stable dose and injections interval every 4 weeks or longer for the previous year, GH levels <2.5 ng/ml and normal IGF-1 levels for age, a tumor remnant <10 mm, no history of radiotherapy, and no use of cabergoline or pegvisomant over the previous 6 months. Disease recurrence was defined as an increase of IGF-1 to levels above 1.2-fold the upper limit of normal (ULN). Out of 220 patients, 20 patients (12 women and 8 men; mean age, 48.1 ± 10.3 years; age range, 27-64) treated for 2.74 ± 0.64 years (range, 2.0-4.4) were included in this prospective study and OCT-LAR therapy was stopped. Four patients (20 %) remained without clinical and biochemical/neuroradiological evidence of disease recurrence after 12-18 months of follow-up. Sixteen patients (80 %) relapsed biochemically within 9 months after drug withdrawal and restarted OCT-LAR at the same previous dose. Compared to recurring subjects, non-recurring patients had significantly lower mean IGF-1 (× ULN) levels but there were some overlapping values in both groups. No other characteristic could be identified as a predictor of successful OCT-LAR discontinuation. Our findings demonstrated that OCT-LAR withdrawal, though rare, is possible in well-selected acromegalic patients treated for at least 2 years and considered optimally controlled in hormonal and neuroradiological terms.

Patients lost to follow-up in acromegaly: results of the ACROSPECT study

“…These treatments usually control the disease effectively, and normalising levels of GH and insulin-like growth factor 1 (IGF1) should reduce the excess morbidity and mortality associated with acromegaly (4,7,8). However, recent studies have shown that there was a relatively low percent of patients with acromegaly who might be cured after withdrawal of somatostatin analogues (up to 20%) (9,10). This means that these treatments should be monitored regularly on a lifelong basis, and as a consequence, that acromegaly has become a chronic disease requiring regular follow-up.…”

Somatostatin analog withdrawal in patients with acromegaly: an elusive goal?

“…In this issue of Endocrine Vilar and colleagues from four Brazilian centers report a study in which octreotide LAR was withheld in 20 patients with acromegaly (four on primary treatment) who had been adequately controlled for at least 2 years [8]. They carefully followed these subjects with serial IGF-1 measurements and defined recurrence as the rise of IGF-1 to above 1.29 the upper limit of normal (ULN).…”

“…They carefully followed these subjects with serial IGF-1 measurements and defined recurrence as the rise of IGF-1 to above 1.29 the upper limit of normal (ULN). Within 9 months of octreotide LAR discontinuation, 16 of the 20 patients recurred and were started back on the SA; the four remaining patients (one on primary treatment) continued to be on remission after 12-18 months follow up [8]. The only distinctive feature of the patients who remained on remission was having a lower IGF-1 at the moment of drug discontinuation [8].…”

“…In support of this concept, in a more recent prospective study, octreotide LAR was stopped in 12 patients with acromegaly who had been very well controlled on 20 mg injected every 8 or more weeks; 40 % of them remain in remission after over 3 years of follow up [12]. Of the 20 subjects included in Vilar's study, 12 were being injected every 4 weeks and 6 every 6 weeks, so it is no surprise that the injection interval did not turn out to be a predictive factor of successful discontinuation [8]. Furthermore, the 4 patients who remained in remission had very low baseline IGF-1 values (below 0.6 9 ULN), almost in the GH deficiency range, and were probably receiving inappropriately high doses of the SA [8].…”

“…Of the 20 subjects included in Vilar's study, 12 were being injected every 4 weeks and 6 every 6 weeks, so it is no surprise that the injection interval did not turn out to be a predictive factor of successful discontinuation [8]. Furthermore, the 4 patients who remained in remission had very low baseline IGF-1 values (below 0.6 9 ULN), almost in the GH deficiency range, and were probably receiving inappropriately high doses of the SA [8].…”