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The role of combination medical therapy in the treatment of acromegaly

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Abstract

Purpose

Uncontrolled acromegaly results in approximately 2-fold excess mortality. Pituitary surgery is first-line therapy, and medical treatment is indicated for persistent disease. While cabergoline and pegvisomant are used in select patients, somatostatin receptor ligands (SRLs) remain the cornerstone of medical treatment. Management of patients poorly responsive to SRLs is therefore, challenging. The purpose of this review is to highlight the options for combination medical therapy in the treatment of acromegaly, with an emphasis on efficacy and safety.

Methods

All original articles/abstracts detailing combination medical therapy in acromegaly were identified from a PubMed search.

Results

Studies reviewed included retrospective and open-label prospective studies. While the combination of SRL and cabergoline was generally well tolerated, a lower baseline insulin-like growth factor-1 (IGF-1) level was the best predictor of efficacy; this combination may be most effective in patients with mildly elevated IGF-1. SRL-pegvisomant combination normalized IGF-1 in the majority of patients; continued efficacy despite individual drug dosing reduction was also reported. The risk of significant liver enzyme elevation was, however, higher than that reported with SRL monotherapy; close monitoring is recommended. Data on pegvisomant-cabergoline combination is limited, but this may be an option in the setting of SRL intolerance. Reports on temozolomide used in combination with other medical therapies in patients with aggressive GH-secreting tumors are also summarized.

Conclusion

While more prospective, randomized controlled trials on long-term efficacy and safety are needed, combination medical therapy remains a treatment strategy that should be considered for acromegaly patients poorly responsive to SRLs.

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Acknowledgments

The authors thank Shirley McCartney, Ph.D., Oregon Health & Science University, for editorial assistance with the manuscript.

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  1. Departments of Medicine (Endocrinology) and Neurological Surgery, and Northwest Pituitary Center, Oregon Health & Science University, 3303 SW Bond Ave, Mail Code CH8N, Portland, OR, 97239, USA

    Dawn Shao Ting Lim & Maria Fleseriu

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  1. Dawn Shao Ting Lim
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Correspondence to Maria Fleseriu.

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The authors did not receive support for writing of this manuscript. Dr. Fleseriu is the principal investigator on research grants to Oregon Health & Science University from Chiasma, Ipsen, Novartis and Pfizer and an ad-hoc scientific consultant to Chiasma, Ipsen, Novartis and Pfizer. Dr. Dawn Shao Ting Lim has no conflict of interest.

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Lim, D.S.T., Fleseriu, M. The role of combination medical therapy in the treatment of acromegaly. Pituitary 20, 136–148 (2017). https://doi.org/10.1007/s11102-016-0737-y

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