Acromegaly: Review of Current Medical Therapy and New Drugs on the Horizon
Over the years newer therapeutic options have included combination therapies with DAs, SSAs, and the GHRA pegvisomant.
To overcome resistance to 1 agent, the combined use of SSAs and DAs has been extensively studied with various results. The addition of high doses of cabergoline to SSA treatment has been shown to improve the response to GH in patients whose GH levels were not previously controlled with a maximum dose of SSA. The beneficial effects of cabergoline in combination with SSAs occur even when pretreatment prolactin levels are normal and/or there is no tumor GH/prolactin coexpression. Randomized prospective controlled studies are needed to confirm the effects of this combined regimen.
The addition of weekly pegvisomant to SSA treatment has been shown to control disease in the majority of patients with no significant increase in adverse effects. A combination of long-acting SSAs once monthly and pegvisomant once weekly (up to 80 mg, median 60 mg) in 26 patients with active acromegaly normalized IGF-I in 18 (95%) of 19 patients who completed 42 weeks of treatment. This combination therapy has also been successfully used in patients resistant to SSAs. Long-term safety data are now available for 86 patients (follow-up 29.2 ± 20.2 months; median dose of 60 mg pegvisomant administered weekly), added to data for patients previously treated with SSA for at least 6 months. Transient elevation in liver enzymes was observed in 23 (27%) of 86 patients regardless of the cumulative dose of pegvisomant, but enzymes subsequently became normal after discontinuing the drug. This study also showed tumor shrinkage of > 20% in 19% of patients. The highest percentage of tumor shrinkage was observed in those who received primary medical treatment. The possibility of lower doses of both SSAs and GHRAs must be investigated further. The overall effects on the cost of this combination have been debated.
Elevation in liver enzymes is observed more frequently with combination therapy, and long-term safety should be established before definite treatment recommendations are made.
In our opinion, the decision to use monotherapy or combination treatment should depend on individual patient circumstances. Tumor shrinkage with SSAs would be a good reason to continue SSAs, whereas worsening glucose control could tip the balance toward GHRA use.
Combination Therapy
Over the years newer therapeutic options have included combination therapies with DAs, SSAs, and the GHRA pegvisomant.
Somatostatin Analogs and DAs
To overcome resistance to 1 agent, the combined use of SSAs and DAs has been extensively studied with various results. The addition of high doses of cabergoline to SSA treatment has been shown to improve the response to GH in patients whose GH levels were not previously controlled with a maximum dose of SSA. The beneficial effects of cabergoline in combination with SSAs occur even when pretreatment prolactin levels are normal and/or there is no tumor GH/prolactin coexpression. Randomized prospective controlled studies are needed to confirm the effects of this combined regimen.
Somatostatin Analogs and GHRAs
The addition of weekly pegvisomant to SSA treatment has been shown to control disease in the majority of patients with no significant increase in adverse effects. A combination of long-acting SSAs once monthly and pegvisomant once weekly (up to 80 mg, median 60 mg) in 26 patients with active acromegaly normalized IGF-I in 18 (95%) of 19 patients who completed 42 weeks of treatment. This combination therapy has also been successfully used in patients resistant to SSAs. Long-term safety data are now available for 86 patients (follow-up 29.2 ± 20.2 months; median dose of 60 mg pegvisomant administered weekly), added to data for patients previously treated with SSA for at least 6 months. Transient elevation in liver enzymes was observed in 23 (27%) of 86 patients regardless of the cumulative dose of pegvisomant, but enzymes subsequently became normal after discontinuing the drug. This study also showed tumor shrinkage of > 20% in 19% of patients. The highest percentage of tumor shrinkage was observed in those who received primary medical treatment. The possibility of lower doses of both SSAs and GHRAs must be investigated further. The overall effects on the cost of this combination have been debated.
Elevation in liver enzymes is observed more frequently with combination therapy, and long-term safety should be established before definite treatment recommendations are made.
In our opinion, the decision to use monotherapy or combination treatment should depend on individual patient circumstances. Tumor shrinkage with SSAs would be a good reason to continue SSAs, whereas worsening glucose control could tip the balance toward GHRA use.
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