PMID- 19438906
OWN - NLM
STAT- MEDLINE
DCOM- 20091123
LR  - 20161125
IS  - 1365-2265 (Electronic)
IS  - 0300-0664 (Linking)
VI  - 71
IP  - 4
DP  - 2009 Oct
TI  - A randomized, controlled, multicentre trial comparing pegvisomant alone with 
      combination therapy of pegvisomant and long-acting octreotide in patients with 
      acromegaly.
PG  - 549-57
LID - 10.1111/j.1365-2265.2009.03620.x [doi]
AB  - OBJECTIVE: For patients with acromegaly who are suboptimally controlled on 
      long-acting octreotide (LAR), treatment options are to switch to pegvisomant 
      monotherapy (PM) or add pegvisomant to LAR (P-LAR). Our objective was to evaluate 
      if the safety and efficacy of these regimens differ. DESIGN: This was an 
      open-label, multicentre, randomized, 40-week outpatient study. The control arm 
      consisted of patients controlled on LAR (n = 28). PATIENTS: A total of 27 
      patients with suboptimally controlled acromegaly [as indicated by a serum IGF-I 
      level > or = 1.3 x upper limit of normal (ULN) of the age-related reference 
      range] were randomized to PM (10 mg once daily initially, then adjusted in 5-mg 
      increments every 8 weeks based on IGF-I levels) and 29 to P-LAR (LAR dosing 
      remained fixed). MEASUREMENTS: The primary end-point was adverse events (AEs). 
      The secondary end-point was biochemical IGF-I-based efficacy. The RIA for IGF-I 
      was discontinued by the manufacturer during the study and a chemiluminescent 
      assay was subsequently used. Previously obtained IGF-I levels were re-analysed. 
      RESULTS: PM and P-LAR were well tolerated and there were no differences in the 
      number of AEs. Patients receiving P-LAR tended to be more likely to have 
      clinically significant increases in hepatic transaminase levels, especially those 
      receiving high-dose LAR. Normalization of IGF-I was similar with both regimens 
      (56% and 62% of patients for PM and P-LAR respectively). The change in IGF-I 
      assay resulted in lower rates of IGF-I normalization than expected. Reductions in 
      fasting glucose levels were greater with PM than with P-LAR (-0.8 mmol/l; 95% 
      confidence interval -1.16, -0.53 mmol/l). CONCLUSIONS: In patients suboptimally 
      controlled on LAR, PM and P-LAR were equally well tolerated and effective in 
      normalizing IGF-I, and overall clinical improvement was observed with both 
      regimens. Thus, pegvisomant monotherapy and adjunctive therapy are equally viable 
      options for the treatment of LAR-resistant acromegaly.
FAU - Trainer, Peter J
AU  - Trainer PJ
AD  - Department of Endocrinology, Christie Hospital, Wilmslow Road, Manchester, UK. 
      Peter.Trainer@manchester.ac.uk
FAU - Ezzat, Shereen
AU  - Ezzat S
FAU - D'Souza, Gwyn A
AU  - D'Souza GA
FAU - Layton, Gary
AU  - Layton G
FAU - Strasburger, Christian J
AU  - Strasburger CJ
LA  - eng
PT  - Journal Article
PT  - Multicenter Study
PT  - Randomized Controlled Trial
PT  - Research Support, Non-U.S. Gov't
DEP - 20090502
PL  - England
TA  - Clin Endocrinol (Oxf)
JT  - Clinical endocrinology
JID - 0346653
RN  - 0 (Delayed-Action Preparations)
RN  - 12629-01-5 (Human Growth Hormone)
RN  - 67763-96-6 (Insulin-Like Growth Factor I)
RN  - N824AOU5XV (pegvisomant)
RN  - RWM8CCW8GP (Octreotide)
SB  - IM
MH  - Acromegaly/*drug therapy
MH  - Adult
MH  - Delayed-Action Preparations
MH  - Drug Therapy, Combination
MH  - Female
MH  - Human Growth Hormone/administration & dosage/adverse effects/*analogs & 
      derivatives
MH  - Humans
MH  - Insulin-Like Growth Factor I/metabolism
MH  - Liver/enzymology
MH  - Male
MH  - Middle Aged
MH  - Octreotide/*administration & dosage/adverse effects
EDAT- 2009/05/15 09:00
MHDA- 2009/12/16 06:00
CRDT- 2009/05/15 09:00
PHST- 2009/05/15 09:00 [entrez]
PHST- 2009/05/15 09:00 [pubmed]
PHST- 2009/12/16 06:00 [medline]
AID - CEN3620 [pii]
AID - 10.1111/j.1365-2265.2009.03620.x [doi]
PST - ppublish
SO  - Clin Endocrinol (Oxf). 2009 Oct;71(4):549-57. doi: 
      10.1111/j.1365-2265.2009.03620.x. Epub 2009 May 2.