Response to Cabergoline and Pasireotide in Non-functioning Pituitary Adenomas and Resistant Prolactinomas
Response to Cabergoline and Pasireotide in Non-functioning Pituitary Adenomas and Resistant Prolactinomas
There are no available medical treatment options for patients with non-functioning pituitary
 adenomas (NFPA) or with resistant prolactinomas to dopamine agonists (DA) who are not cured
 by surgery. The study of the receptors by quantitative messenger ribonucleic acid (mRNA)
 expression levels and immunohistochemistry analysis might end with a better understanding of
 these tumors. Besides that, it will be assessed the in vitro and in vivo responses to
 pasireotide (for NFPA and prolactinomas) and cabergoline (for NFPA). These responses will be
 compared with the receptor expressions which may be a tool as a predicting element of the
 response to these compounds.
The goals of this study are: to verify whether cabergoline and pasireotide are effective in
 NFPA to control tumor re-growth as adjuvant therapy after neurosurgery and whether
 pasireotide is capable of normalizing the prolactin levels in patients with prolactinomas
 resistant to cabergoline; to assess the mRNA levels of dopamine receptor type 2 (DR2) and
 SSTR1-5 and their protein expression; to evaluate the in vitro hormonal response to
 cabergoline, octreotide and pasireotide; and to determine whether the mRNA DR2/SSTR1-5 and/or
 protein expression and/or in vitro hormonal response to cabergoline, octreotide and
 pasireotide correlates with the in vivo response to the former and to the last one. With this
 data the investigators intend to establish if the mRNA analysis and/or protein expression in
 NFPA and resistant prolactinomas might be predictive or foretelling factors concerning drug
 treatment in patients with this kind of pituitary tumors and also evaluate if there is any
 response in vitro or in vivo to the treatment with pasireotide in NFPA and resistant
 prolactinomas and with cabergoline in NFPA.
Inclusion Criteria

 -  Male or female patients aged 18 years or greater

 -  Patients with confirmed diagnosis of NFPA evidenced by: magnetic resonance imaging
 (MRI) confirmation of pituitary adenoma and No pituitary tumoral hormone
 hypersecretion

 -  Patients with no previous medical treatment

 -  Patients who had been submitted to surgery but not cured. Lack of cure is defined as
 presence of remnant tumor on MRI at least three months after surgery (without any
 possible misinterpretation of postsurgical changes)

 -  Patients with confirmed diagnosis of resistant prolactinoma by lack of prolactin
 normalization with a tolerated cabergoline dosage during 12 weeks

 -  Patients who had been submitted to surgery due to resistance to cabergoline and not
 cured. Lack of cure is defined as lack of serum prolactin normalization or complete
 removal of tumor load

 -  Patients who signed the informed consent

 Exclusion Criteria

 -  Previous pituitary radiotherapy

 -  High risk for transsphenoidal surgery

 -  Patients with symptomatic cholelithiasis

 -  Diabetic patients on antidiabetic medications those fasting blood glucose is poorly
 controlled as evidenced by HbA1C > 8%

 -  Patients with abnormal coagulation (prothrombin time (PT) or partial thromboplastin
 time (PTT) elevated by 30% above normal limits);

 -  Patients receiving anticoagulants that affect PT or PTT

 -  Patients who have congestive heart failure (NYHA Class III or IV), unstable angina,
 sustained ventricular tachycardia, clinically significant bradycardia, advanced heart
 block, history of acute MI less than one year prior to study entry or clinically
 significant impairment in cardiovascular function

 -  Patients with risk factors for torsade de pointes, i.e. patients with a baseline
 corrected QT interval (QTc) > 480 ms, hypokalemia, family history of long QT syndrome,
 and concomitant medications known to prolong QT interval

 -  Patients with liver disease such as cirrhosis, chronic active hepatitis, or chronic
 persistent hepatitis, or patients with (alanine aminotransferase) ALT/ (aspartate
 aminotransferase) AST more than 2 X upper limit of normal (ULN), serum creatinine >
 2.0 X ULN, serum bilirubin > 2.0 X ULN, serum albumin < 0.67 X lower limit of normal
 (LLN)

 -  Patients with white blood cell (WBC) < 3 X 109/L; Hgb < LLN; Platelet count (PLT) <
 100 X 109/L

 -  Patients who have any current or prior medical condition that can interfere with the
 conduct of the study or the evaluation of its results in the opinion of the
 investigator

 -  Female patients who are pregnant or lactating, or are of childbearing potential and
 not practicing a medically acceptable method for birth control. Female patients must
 use barrier contraception with condoms. If oral contraception is used, the patient
 must have been practicing this method for at least two months prior to enrollment and
 must agree to continue the oral contraceptive throughout the course of the study and
 for one month after the last dose of study drug. Male patients who are sexually active
 are required to use condoms during the study and for 1 month afterwards

 -  Patients who have a history of alcohol or drug abuse in the 6 month period prior to
 receiving pasireotide