Does partial surgical tumour removal influence the response to octreotide-LAR in acromegalic patients previously resistant to the somatostatin analogue?

• Published in: Clinical endocrinology (Oxford) 2007-08, Vol.67 (2), p.310-315
• Main Authors: Jallad, Raquel S., Musolino, Nina R., Kodaira, Sergio, Cescato, Valter A., Bronstein, Marcello D.
• Format: Article
• Language: English
• Subjects: Acromegaly - drug therapy; Acromegaly - metabolism; Acromegaly - pathology; Adult; Aged; Antineoplastic Agents, Hormonal - therapeutic use; Biological and medical sciences; Delayed-Action Preparations; Drug Resistance, Neoplasm; Endocrinopathies; Female; Fundamental and applied biological sciences. Psychology; Growth Hormone - blood; Growth Hormone-Secreting Pituitary Adenoma - blood; Growth Hormone-Secreting Pituitary Adenoma - pathology; Growth Hormone-Secreting Pituitary Adenoma - surgery; Humans; Hypothalamus. Hypophysis. Epiphysis (diseases); Insulin-Like Growth Factor I - analysis; Magnetic Resonance Imaging; Male; Medical sciences; Middle Aged; Multivariate Analysis; Non tumoral diseases. Target tissue resistance. Benign neoplasms; Octreotide - therapeutic use; Pituitary Neoplasms - blood; Pituitary Neoplasms - pathology; Pituitary Neoplasms - surgery; Prospective Studies; Somatostatin - metabolism; Treatment Outcome; Vertebrates: endocrinology
• ISSN: 0300-0664; 1365-2265
• DOI: 10.1111/j.1365-2265.2007.02885.x

Summary Objective  To compare the intrapatient response to the same dose of slow‐release octreotide (OCT‐LAR) before and after noncurative surgery in acromegalic patients who did not attain disease control after primary treatment with OCT‐LAR. Design  Prospective clinical study. Patients  Eleven acromegalic patients (eight men, aged 42·45 ± 11·15 years, 10 macroadenomas) received OCT‐LAR (20 mg, n = 1; 30 mg, n = 10) every 28 days as the primary treatment (1stOCT‐LAR) for 11·3 ± 4·2 months, without IGF‐I normalization. They were subsequently submitted to surgery without cure and were then treated with the same dose of OCT‐LAR for 8·0 ± 6·5 months (2ndOCT‐LAR). Measurements  GH and IGF‐I serum concentrations were obtained under basal conditions as well as during treatment. Pituitary tumour volume was assessed by magnetic resonance imaging (MRI) of the sella. IGF‐I was also expressed as a percentage of the upper limit of the normal age‐ and sex‐matched range (%ULNR IGF‐I). Results  After 1stOCT‐LAR, there was a decrease in GH levels (P = 0·003) and %ULNR IGF‐I (P = 0·009) compared to baseline (B), but no IGF‐I normalization. Tumour shrinkage was observed in eight of 10 patients with macroadenomas (median 63·7%, range 24·5–75·5%). After surgery, mean levels of GH and %ULNR IGF‐I were lower than those at baseline (P = 0·0004 and P = 0·003, respectively), but not when compared to values during 1stOCT‐LAR (P = 1·000 and P = 0·957, respectively). MRI confirmed surgical tumour removal (median 64%, range 4·9–96·6%) in eight of the 10 patients. Comparing the 2ndOCT‐LAR results with postsurgical results, there were no significant decrease in %ULNR IGF‐I (P = 0·061) and GH levels (P = 0·414). Nine patients (82%) achieved IGF‐I normalization. The degree of surgical tumour reduction did not correlate with IGF‐I normalization (P = 0·794). When comparing the results between 1stOCT‐LAR and 2ndOCT‐LAR, there was a decrease, albeit not statistically significant, in serum GH levels (P = 0·059) and a significant decrease in %ULNR IGF‐I (P = 0·011). Conclusions  Using strict criteria (same patient, same drug, same dose) our results strongly suggest that the surgical reduction of tumour mass can improve the outcome of OCT‐LAR treatment in acromegalic patients resistant to primary therapy with SA.