Eur J Endocrinol
HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS
QUICK SEARCH:   [advanced]


     

DOI: 10.1530/eje.1.01825
European Journal of Endocrinology, Vol 152, Issue 1, 161-162
Copyright © 2005 by European Society of Endocrinology
This Article
Right arrow Full Text (PDF)
Right arrow Alert me when this article is cited
Right arrow Alert me if a correction is posted
Services
Right arrow Similar articles in this journal
Right arrow Similar articles in ISI Web of Science
Right arrow Similar articles in PubMed
Right arrow Alert me to new issues of the journal
Right arrow Download to citation manager
Citing Articles
Right arrow Citing Articles via HighWire
Right arrow Citing Articles via ISI Web of Science (2)
Right arrow Citing Articles via Google Scholar
Google Scholar
Right arrow Articles by Drake, W M
Right arrow Articles by Hutson, R K
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Drake, W M
Right arrow Articles by Hutson, R K
LETTER TO THE EDITOR

Effect of treatment with pegvisomant on meningioma growth in vivo

W M Drake, A B Grossman and R K Hutson1

Department of Endocrinology, St Bartholomew’s Hospital, London EC1A 7BE, UK and 1 Department of Radiology, University of Tennessee Medical Center, 1924 Alcoa Highway, Knoxville, Tennessee 37920, USA

(Correspondence should be addressed to W M Drake; Email: w.m.drake{at}qmul.ac.uk)

Pegvisomant is a pegylated analogue of human growth hormone (GH) that functions as a GH receptor antagonist. Although its use is currently limited to patients with acromegaly (1), there exists considerable interest in the potential use of pegvisomant for the treatment of a variety of tumours whose growth may be promoted by insulin-like growth factor-I (IGF-I). We report the case of a 74-year-old woman with acromegaly, treated with pegvisomant, in whom we have documented the growth rate of a meningioma noted incidentally during the course of routine radiological imaging.

The patient’s acromegaly was diagnosed in 1992 on the basis of failure of suppression of serum GH during a 75 g oral glucose load (nadir serum GH 10 mU/l) and an elevated serum IGF-I concentration (489 ng/ml, age-adjusted normal range 109–269). Magnetic resonance imaging (MRI) of the pituitary demonstrated a 9 mm intrasellar pituitary mass lesion. She declined surgical adenomectomy or pituitary irradiation and was successfully treated with thrice-daily s.c. octreotide (serum IGF-I within age-adjusted normal range). In 1998, she enrolled in a 12 week placebo-controlled study of pegvisomant in the treatment of acromegaly (2) and was randomised to receive pegvisomant 10 mg daily. At its conclusion, she continued pegvisomant in an open-label study, but therapy was suspended after 9 months because of a shortage of drug. Eight weeks after cessation of pegvisomant, depot octreotide 10 mg four-weekly was commenced and continued for 26 months. In December 2001, she enrolled in an open-label study of patients with acromegaly converting from stable treatment with depot octreotide to therapy with pegvisomant and continued this drug at a dose of 10 mg daily until May 2004.

Regular surveillance pituitary imaging was performed during both clinical trials. Incidental note was made, at the start of the first trial, of a dural-based homogeneously enhancing mass related to the greater wing of the sphenoid, typical of a meningioma (Fig. 1AGo). She reported no symptoms referable to the mass and declined any surgical intervention. Axial, sagittal and coronal dimensions of the mass were recorded at each scan and the volume calculated, for a prolate ellipsoid, using the formula 4/3{pi}(height/2) (width/2)(depth/2) (3). The volume of the meningioma increased from 470 to 4810 mm3 5 years later (Fig. 1BGo), with no discernible inhibitory effect of pegvisomant therapy (Fig. 2Go).



View larger version (94K):
[in this window]
[in a new window]
  		Figure 1 Sagittal MRI scan showing a dural-based homogeneously enhancing mass related to the greater wing of the sphenoid in 1998 (A) and 2003 (B).

 


View larger version (15K):
[in this window]
[in a new window]
  		Figure 2 Meningioma volume (mm3) vs time and the relationship to medical therapy for acromegaly.

 
Pegvisomant inhibits the functional dimerisation of cell surface GH receptors, thereby reducing IGF-I synthesis (4). Evidence that growth of a variety of tumours is promoted by IGF-I has generated interest in the possible role of pegvisomant as an anti-cancer agent. In particular, data in nude mice indicate that pegvisomant inhibits growth of meningioma cells in vivo (5), leading to speculation that this drug may have a role in patients with inoperable or recurrent meningioma (6). To the best of our knowledge, this is the first report of the effect of pegvisomant therapy on growth of a non-pituitary tumour in vivo in a human subject. No inhibitory effect of pegvisomant therapy on meningioma growth was evident, emphasising the need for caution in extrapolating in vitro and animal data to therapy in human subjects. Further reports of the effect of pegvisomant therapy for acromegaly on coincidentally noted non-pituitary tumours are encouraged.

Acknowledgements

We gratefully acknowledge the technical assistance of Shannon K Campbell. The Department of Endocrinology receives financial support from Pfizer Inc. for its research into growth and growth factors.

References

    1. Van der Lely AJ, Hutson RK, Trainer PJ, Besser GM, Barkan AL, Katznelson L, Klibanski A, Herman-Bonert V, Melmed S, Vance ML, Freda PU, Stewart PM, Friend KE, Clemmons DR, Johannsson G, Stavrou S, Cook DM, Phillips LS, Strasburger CJ, Hackett S, Zib KA, Davis RJ, Scarlett JA & Thorner MO. Long-term treatment of acromegaly with pegvisomant, a growth hormone receptor antagonist. Lancet 2001 358 1754–1759.[CrossRef][Web of Science][Medline]

    2. Trainer PJ, Drake WM, Katznelson L, Freda PU, Herman-Bonert V, van der Lely AJ, Dimaraki EV, Stewart PM, Friend KE, Vance ML, Besser GM, Scarlett JA, Thorner MO, Parkinson C, Klibanski A, Powell JS, Barkan AL, Sheppard MC, Malsonado M, Rose DR, Clemmons DR, Johannsson G, Bengtsson BA, Stavrou S, Kleinberg DL, Cook DM, Phillips LS, Bidlingmaier M, Strasburger CJ, Hackett S, Zib K, Bennett WF & Davis RJ. Treatment of acromegaly with the growth hormone receptor antagonist pegvisomant. New England Journal of Medicine 2000 342 1171–1177.[Abstract/Free Full Text]

    3. Machinery’s Handbook, edn 26. New York, NY: Industrial Press, Inc, 2000.

    4. Kopchick JJ, Parkinson C, Stevens EC & Trainer PJ. Growth hormone receptor antagonists: discovery, development, and use in patients with acromegaly. Endocrine Reviews 2002 5 623–646.

    5. Friend KE. Cancer and the potential place for growth hormone receptor antagonist therapy. Growth Hormone and IGF Research 2001; 11: (Suppl A) S121–S123.

    6. McCutcheon IE, Flyvbjerg A, Hill H, Li J, Bennett WF, Scarlett JA & Friend KE. Antitumor activity of the growth hormone receptor antagonist pegvisomant against human meningiomas in nude mice. Journal of Neurosurgery 2001 94 487–492.[Medline]

Received 29 September 2004
Accepted 6 October 2004




This article has been cited by other articles:


Home page
 Exp PhysiolHome page
C. E. Higham and P. J. Trainer
Growth hormone excess and the development of growth hormone receptor antagonists
Exp Physiol, November 1, 2008; 93(11): 1157 - 1169.
[Abstract] [Full Text] [PDF]

This Article
Right arrow Full Text (PDF)
Right arrow Alert me when this article is cited
Right arrow Alert me if a correction is posted
Services
Right arrow Similar articles in this journal
Right arrow Similar articles in ISI Web of Science
Right arrow Similar articles in PubMed
Right arrow Alert me to new issues of the journal
Right arrow Download to citation manager
Citing Articles
Right arrow Citing Articles via HighWire
Right arrow Citing Articles via ISI Web of Science (2)
Right arrow Citing Articles via Google Scholar
Google Scholar
Right arrow Articles by Drake, W M
Right arrow Articles by Hutson, R K
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Drake, W M
Right arrow Articles by Hutson, R K

HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS