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Gender, body weight, disease activity, and previous radiotherapy influence the response to pegvisomant

Parkinson, Craig; Burman, Pia LU ; Messig, Michael and Trainer, Peter J. (2007) In Journal of Clinical Endocrinology and Metabolism 92(1). p.190-195
Abstract
Context/Objective: To effectively normalize IGF-I in patients with acromegaly, various covariates may affect dosing and plasma concentrations of pegvisomant. We assessed whether sex, age, weight, and previous radiotherapy influence dosing of pegvisomant in patients with active disease. Design: Data from 69 men and 49 women participating in multicenter, open-label trials of pegvisomant were retrospectively evaluated using multiple regression techniques. Sixty-nine subjects ( 39 men, 30 women) had undergone external beam pituitary radiotherapy. Serum IGF- I was at least 30% above age- related upper limit of normal in all patients at study entry. After a loading dose of pegvisomant ( 80 mg), patients were commenced on 10 mg/d. Pegvisomant... (More)
Context/Objective: To effectively normalize IGF-I in patients with acromegaly, various covariates may affect dosing and plasma concentrations of pegvisomant. We assessed whether sex, age, weight, and previous radiotherapy influence dosing of pegvisomant in patients with active disease. Design: Data from 69 men and 49 women participating in multicenter, open-label trials of pegvisomant were retrospectively evaluated using multiple regression techniques. Sixty-nine subjects ( 39 men, 30 women) had undergone external beam pituitary radiotherapy. Serum IGF- I was at least 30% above age- related upper limit of normal in all patients at study entry. After a loading dose of pegvisomant ( 80 mg), patients were commenced on 10 mg/d. Pegvisomant dose was adjusted by 5 mg every eighth week until serum IGF- I was normalized. Results: At baseline, men had significantly higher mean serum IGF- I levels than women despite similar GH levels. After treatment with pegvisomant, IGF- I levels were similar in men and women. A significant correlation between baseline GH, IGF- I, body weight, and the dose of pegvisomant required to normalize serum IGF- I was observed ( all P < 0.001). Women required an average of 0.04 mg/ kg more pegvisomant than men and a mean weight- corrected dose of 19.2 mg/ d to normalize serum IGF-I [14.5 mg/d ( men); P < 0.001]. Patients treated with radiotherapy required less pegvisomant to normalize serum IGF- I despite similar baseline GH/ IGF-I levels ( 15.2 vs. 18.5 mg/ d for no previous radiotherapy; P < 0.002). Conclusions: Sex, body weight, previous radiotherapy, and baseline GH/ IGF- I influence the dose of pegvisomant required to normalize serum IGF- I in patients with active acromegaly. (Less)
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author
organization
publishing date
type
Contribution to journal
publication status
published
subject
in
Journal of Clinical Endocrinology and Metabolism
volume
92
issue
1
pages
190 - 195
publisher
The Endocrine Society
external identifiers
  • wos:000243317500035
  • scopus:33846040409
ISSN
1945-7197
DOI
10.1210/jc.2006-1412
language
English
LU publication?
yes
id
ce6eba54-4701-4254-9a81-095733e2590e (old id 679355)
date added to LUP
2007-12-14 15:41:13
date last changed
2017-10-01 04:53:55
@article{ce6eba54-4701-4254-9a81-095733e2590e,
  abstract     = {Context/Objective: To effectively normalize IGF-I in patients with acromegaly, various covariates may affect dosing and plasma concentrations of pegvisomant. We assessed whether sex, age, weight, and previous radiotherapy influence dosing of pegvisomant in patients with active disease. Design: Data from 69 men and 49 women participating in multicenter, open-label trials of pegvisomant were retrospectively evaluated using multiple regression techniques. Sixty-nine subjects ( 39 men, 30 women) had undergone external beam pituitary radiotherapy. Serum IGF- I was at least 30% above age- related upper limit of normal in all patients at study entry. After a loading dose of pegvisomant ( 80 mg), patients were commenced on 10 mg/d. Pegvisomant dose was adjusted by 5 mg every eighth week until serum IGF- I was normalized. Results: At baseline, men had significantly higher mean serum IGF- I levels than women despite similar GH levels. After treatment with pegvisomant, IGF- I levels were similar in men and women. A significant correlation between baseline GH, IGF- I, body weight, and the dose of pegvisomant required to normalize serum IGF- I was observed ( all P &lt; 0.001). Women required an average of 0.04 mg/ kg more pegvisomant than men and a mean weight- corrected dose of 19.2 mg/ d to normalize serum IGF-I [14.5 mg/d ( men); P &lt; 0.001]. Patients treated with radiotherapy required less pegvisomant to normalize serum IGF- I despite similar baseline GH/ IGF-I levels ( 15.2 vs. 18.5 mg/ d for no previous radiotherapy; P &lt; 0.002). Conclusions: Sex, body weight, previous radiotherapy, and baseline GH/ IGF- I influence the dose of pegvisomant required to normalize serum IGF- I in patients with active acromegaly.},
  author       = {Parkinson, Craig and Burman, Pia and Messig, Michael and Trainer, Peter J.},
  issn         = {1945-7197},
  language     = {eng},
  number       = {1},
  pages        = {190--195},
  publisher    = {The Endocrine Society},
  series       = {Journal of Clinical Endocrinology and Metabolism},
  title        = {Gender, body weight, disease activity, and previous radiotherapy influence the response to pegvisomant},
  url          = {http://dx.doi.org/10.1210/jc.2006-1412},
  volume       = {92},
  year         = {2007},
}