Lanreotide Autogel-120 mg as First-Line Treatment of Acromegaly
Lanreotide Autogel-120 mg as First-Line Treatment of Acromegaly
Recently, a new formulation of lanreotide, lanreotide Autogel (ATG) 60 mg, 90 mg and 120 mg
 was developed in order to further extend the duration of the release of the active
 ingredient. The ATG formulation consists of a solution of lanreotide in water with no
 additional excipients. ATG was found to have linear pharmacokinetics for the 60 to 120 mg
 doses and provided a prolonged dosing interval and good tolerability (1). In some previous
 studies, the ATG was demonstrated as effective as the micro-particle lanreotide (2,3) and as
 octreotide-LAR in patients with acromegaly (4-7).

 Data on the efficacy of ATG in newly diagnosed patients with acromegaly are still lacking.
 Similarly, the prevalence and amount of tumor shrinkage after ATG treatment is unknown. This
 information is particularly useful in the setting of first-line therapy of acromegaly that is
 currently becoming a more frequent approach to the disease (8). It is demonstrated that
 approximately 80% of the patients treated with depot somatostatin analogues as first line
 have a greater than 20% tumor shrinkage during the first 12 months of treatment (9). A
 definition of significant tumor shrinkage was provided in 14 studies (including a total
 number of patients of 424) and the results showed that 36.6% (weighted mean percentage) of
 patients receiving first-line somatostatin analogues therapy for acromegaly had a significant
 reduction in tumor size (10). About 50% of the patients were found to have a greater than 50%
 tumor shrinkage within the first year of treatment (10); in this study we found that percent
 decrease in IGF-I levels was the major determinant of tumor shrinkage (10).

 The current open, prospective study is designed to investigate the prevalence and amount of
 tumor shrinkage in newly diagnosed patients with acromegaly treated first-line with ATG.
This is an open, prospective, observational, clinical study to be performed in two University
 Hospitals (Naples and Genova, Italy). The primary objective is to evaluate the efficacy of
 the ATG 120 mg on control of GH and IGF-I excess in acromegaly according with the currently
 accepted criteria (12) and on tumor shrinkage. The secondary objectives are to assess
 improvement of clinical symptoms and safety profile. The study population will consist of at
 least 20 patients, enrolled in the two centers from Jan 1st 2003 to June 30th 2007. Patients
 give their written informed consent prior to entering into the study. The study was performed
 according to the principles defined by the declaration The safety population, as defined by
 the protocol, consists of patients who received at least one study drug dosing.

 Hormonal evaluation GH levels are assessed as a mean value of 5 samples at 30-min intervals
 (starting between 08:00 and 9:00 in the morning) taken at each visit before the injection of
 ATG. IGF-I levels are assessed as a single sample taken at each visit at the same time as the
 first GH sample. All hormonal parameters were assessed in a central laboratory (University of
 Genoa).

 Improvement in clinical symptoms is considered on the basis of a semiquantitative scale for
 asthenia, hyperhidrosis, headache, swelling of extremities, arthralgia, paraesthesia, carpal
 tunnel syndrome: symptoms were graded as 0 = absent, 1 = mild, 2 = moderate, 3 = severe.

 Any adverse event (AE) during the study is monitored and reported by the investigators.
 Safety, evaluated by local laboratory data, is assessed at inclusion and at the final visit
 by: hematology: erythrocytes, leukocytes, platelets, haemoglobin, hematocrit; biochemistry:
 glucose, creatinine, alkaline phosphatase, total bilirubin, alanine aminotransferase (ALT),
 aspartate aminotransferase (AST), electrolytes (sodium, potassium, calcium, phosphorous)
 glycosylated haemoglobin, triglycerides, total and high density lipoproteins (HDL)
 cholesterol, blood amylase, iron, transferrin, prothrombin; glucose and insulin
 concentrations; hormonal evaluation: thyroid-stimulating hormone (TSH), free triiodothyronine
 (FT3), free triiodothyronine (FT4), follicle stimulating hormone (FSH) and luteinizing
 hormone (LH) levels. Safety related to gallbladder is assessed by ultrasound examination
 performed at inclusion and at the end of the study.
Inclusion Criteria:

 -  Patients with active acromegaly [serum GH levels above 2.5 μg/liter and/or above 1
 μg/liter after oral glucose tolerance test (OGTT) and abnormal IGF-I values] with a
 micro- (<10 mm max tumor diameter) or macroadenoma (>10 mm max tumor diameter)

 -  Patients never treated before

 -  Patients who do not require immediate surgery because of neurological symptoms and/or
 emergency conditions

 -  Patients who signed an informed consent to participate to the study.

 Exclusion Criteria:

 -  Patients already treated before with surgery or radiotherapy or with medical treatment

 -  Patients with mixed GH-PRL adenomas who require combined somatostatin and dopamine
 treatment