Prediction of Tumor Shrinkage in Acromegaly

Acromegaly Clinical Trial

Official title:

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT00616408
• Other study ID #: NeuroendoUnit-8
• Status: Completed
• Phase: N/A
• First received: February 5, 2008
• Last updated: February 5, 2008
• Start date: January 1997
• Est. completion date: December 2007

Study information

• Verified date: December 2007
• Source: Federico II University
• Contact: n/a
• Is FDA regulated: No
• Health authority: Italy: National Institute of HealthItaly: National Monitoring Centre for Clinical Trials - Ministry of Health
• Study type: Observational

Clinical Trial 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.

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).

Recruitment information / eligibility

• Status: Completed
• Enrollment: 61
• Est. completion date: December 2007
• Est. primary completion date: December 2007
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 18 Years to 85 Years

Eligibility

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

Study Design

Observational Model: Cohort, Time Perspective: Retrospective

Related Conditions & MeSH terms

• Acromegaly

Intervention

Drug:
• Octreotide-LAR
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

Locations

Country	Name	City	State
Italy	Department of Molecular and Clinical Endocrinology and Oncology, University Federico II of Naples	Naples

Sponsors (1)

Lead Sponsor	Collaborator
Federico II University

Country where clinical trial is conducted

Italy, 

References & Publications (6)

Colao A, Pivonello R, Auriemma RS, Briganti F, Galdiero M, Tortora F, Caranci F, Cirillo S, Lombardi G. Predictors of tumor shrinkage after primary therapy with somatostatin analogs in acromegaly: a prospective study in 99 patients. J Clin Endocrinol Meta — View Citation

Colao A, Pivonello R, Auriemma RS, Galdiero M, Savastano S, Lombardi G. Beneficial effect of dose escalation of octreotide-LAR as first-line therapy in patients with acromegaly. Eur J Endocrinol. 2007 Nov;157(5):579-87. — View Citation

Cozzi R, Montini M, Attanasio R, Albizzi M, Lasio G, Lodrini S, Doneda P, Cortesi L, Pagani G. Primary treatment of acromegaly with octreotide LAR: a long-term (up to nine years) prospective study of its efficacy in the control of disease activity and tum — View Citation

Mercado M, Borges F, Bouterfa H, Chang TC, Chervin A, Farrall AJ, Patocs A, Petersenn S, Podoba J, Safari M, Wardlaw J; SMS995B2401 Study Group. A prospective, multicentre study to investigate the efficacy, safety and tolerability of octreotide LAR (long- — View Citation

Resmini E, Dadati P, Ravetti JL, Zona G, Spaziante R, Saveanu A, Jaquet P, Culler MD, Bianchi F, Rebora A, Minuto F, Ferone D. Rapid pituitary tumor shrinkage with dissociation between antiproliferative and antisecretory effects of a long-acting octreotid — View Citation

Sheppard MC. Primary medical therapy for acromegaly. Clin Endocrinol (Oxf). 2003 Apr;58(4):387-99. Review. — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	GH and IGF-I age-normalized levels, percent GH and IGF-I suppression and percent tumor shrinkage after 3 months		12 months	No
Secondary	baseline age, gender, estimated disease duration, GH and IGF-I levels, tumor size		12 months	No