Prediction of Tumor Shrinkage in Acromegaly

Study Overview
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Brief Summary
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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
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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).

Official Title
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Predictive Value of 3 Months Results on 12 Months Tumor Shrinkage After First-Line Octreotide-LAR Therapy in Patients With Acromegaly

Conditions
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Acromegaly

Intervention / Treatment
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* Drug: Octreotide-LAR


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: No previous treatment for acromegaly Exclusion Criteria: primary surgery concomitant hyperprolactinemia requiring combined somatostatin analogues and dopamine-agonist treatment primary treatment with lanreotide

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 85 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| A<br>Newly diagnosed active acromegaly out of the 297 patients coming to our Department for acromegaly who received first-line treatment with LAR | Drug: Octreotide-LAR<br>* 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<br>* Other names: Sandostatin (Novartis Pharma);|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| GH and IGF-I age-normalized levels, percent GH and IGF-I suppression and percent tumor shrinkage after 3 months |  | 12 months | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| baseline age, gender, estimated disease duration, GH and IGF-I levels, tumor size |  | 12 months | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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GH, IGF-I, GH-secreting tumors, Octreotide