Prediction of Tumor Shrinkage in Acromegaly
Condition: Acromegaly
MeSH terms: Acromegaly
Study type: Observational

Summary: 
      In the last two decades, somatostatin analogs have become a cornerstone of medical therapy
      for acromegaly. One year of treatment with octreotide-LAR (LAR) controls GH and IGF-I excess
      in 54% and 63% of unselected patients, with an increasing proportion of subjects achieving
      IGF-I normalization prolonging the treatment. Clinically significant tumor shrinkage (20-30%
      vs. baseline) has also been reported, with a higher proportion in patients treated first-line
      [231 of 448 patients (52%)] than in those treated after surgery and/or radiotherapy [52 of
      248 patients (21%)]. The highest rate of clinically significant shrinkage (>20%) occurred in
      patients treated first-line with LAR (80%) as compared to the short-lasting octreotide
      formulation (50%) or lanreotide slow-release formulation (35%. In 99 de novo patients with
      acromegaly, we recently reported control of GH levels in 57.6%, of IGF-I levels in 45.5% and
      a greater than 50% tumor shrinkage in 44.4% after 12 months of first-line treatment with
      somatostatin analogues, either LAR or lanreotide. Besides the different drug used, the
      duration of treatment also plays an important role on the shrinkage magnitude. In a
      homogeneous cohort of 56 patients treated with LAR only and continuously for 24 months, we
      noted an even more sustained effect on tumor shrinkage: overall, tumor volume decreased by
      68.1±16.5% using dosages up-titrated to 40 mg every 28 days.

      Despite this evidence, there is still a debate on the use of first-line treatment with
      somatostatin analogues. Of paramount importance would be the possibility to predict the
      results of one year treatment early after treatment beginning. Controversy has been reported
      on the predictive value of initial tumor size, inhibition of GH and IGF-I levels during
      treatment, and dose or type of the somatostatin analogue used during treatment. We found that
      percent suppression of IGF-I after 12 months of LAR treatment was the parameter that best
      predicted the amount of tumor shrinkage after the same period, but did not investigate the
      results of short-term treatment in the same series.

      This observational, analytical, open, retrospective study was designed to evaluate the
      predictive value of tumor shrinkage, GH and IGF-I suppression after 3 months of
      Octreotide-LAR (LAR) on tumor shrinkage obtained after 12 months. As secondary parameters we
      also studied baseline patients profile such as age of diagnosis, gender, estimated disease
      duration, GH and IGF-I levels and tumor size.
    

Detailed description: 
      From Jan 1st 1995 to December 31st 2006, all files of patients with newly diagnosed active
      acromegaly out of the 297 patients coming to our Department for acromegaly who received
      first-line treatment with LAR will be considered for this study.

      As our routine procedure, all patients signed an informed consent to approve diagnostic
      testing, treatment decision, methods for follow-up and data treatment for scientific
      purposes. This study has been conducted in accordance with the Helsinki II Declaration on
      human experimentation. This study takes advantage from data collected in a large, prospective
      study to investigate the effect of first-line surgery or medical therapy (with somatostatin
      analogues and/or dopamine/agonists) on GH, IGF-I, tumor mass, cardiovascular risk markers,
      cardiomyopathy, hypertension, metabolic profile and prostate diseases in all the patients
      coming for a diagnosis of acromegaly in our Department and approved by our Ethical Committee
      the 14/10/97 (no.60/97).
    

Intervention name(s): Octreotide-LAR
Intervention type(s): Drug
Intervention description(s): Initial dose is 20 mg every 28 d for three months, then the dose is down-titrated to 10 mg/q28d if GH levels are below 1 ng/ml, up-titrated to 30 mg/q28d if GH levels are above 10 ng/ml and remains to 20 mg/q28 d if GH is between 1-10 ng/ml
Other intervention name(s): Sandostatin (Novartis Pharma)
Intervention MeSH terms: Octreotide
Observational model: Cohort
Time perspective: Retrospective
Sampling method: Probability Sample
Study population: 
        Newly diagnosed patients with acromegaly treated first-line with octreotide-LAR
      
Keywords: GH; IGF-I; GH-secreting tumors; Octreotide