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

Clin Endocrinol (Oxf). 2007 Aug;67(2):310-5. doi: 10.1111/j.1365-2265.2007.02885.x. Epub 2007 Jun 6.

Abstract

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.

Publication types

  • Comparative Study

MeSH terms

  • Acromegaly / drug therapy*
  • Acromegaly / metabolism
  • Acromegaly / pathology
  • Adult
  • Aged
  • Antineoplastic Agents, Hormonal / therapeutic use*
  • Delayed-Action Preparations
  • Drug Resistance, Neoplasm
  • Female
  • Growth Hormone / blood
  • Growth Hormone-Secreting Pituitary Adenoma / blood
  • Growth Hormone-Secreting Pituitary Adenoma / pathology
  • Growth Hormone-Secreting Pituitary Adenoma / surgery*
  • Humans
  • Insulin-Like Growth Factor I / analysis
  • Magnetic Resonance Imaging
  • Male
  • Middle Aged
  • Multivariate Analysis
  • Octreotide / therapeutic use*
  • Pituitary Neoplasms / blood
  • Pituitary Neoplasms / pathology
  • Pituitary Neoplasms / surgery*
  • Prospective Studies
  • Somatostatin / metabolism*
  • Treatment Outcome

Substances

  • Antineoplastic Agents, Hormonal
  • Delayed-Action Preparations
  • Somatostatin
  • Insulin-Like Growth Factor I
  • Growth Hormone
  • Octreotide