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


METHODS
Prospective clinical study.


METHODS
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).


METHODS
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.
Jallad
Raquel S
RS
Neuroendocrine Unit, Division of Endocrinology and Metabolism, Hospital das Clinicas, University of Sao Paulo Medical School, 01406-100 Sao Paulo, SP, Brazil.
Musolino
Nina R
NR
Kodaira
Sergio
S
Cescato
Valter A
VA
Bronstein
Marcello D
MD
D000172:Acromegaly / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology; D000328:Adult; D000368:Aged; D018931:Antineoplastic Agents, Hormonal / Q000627:therapeutic use*; D003692:Delayed-Action Preparations; D019008:Drug Resistance, Neoplasm; D005260:Female; D013006:Growth Hormone / Q000097:blood; D049912:Growth Hormone-Secreting Pituitary Adenoma / Q000097:blood / Q000473:pathology / Q000601:surgery*; D006801:Humans; D007334:Insulin-Like Growth Factor I / Q000032:analysis; D008279:Magnetic Resonance Imaging; D008297:Male; D008875:Middle Aged; D015999:Multivariate Analysis; D015282:Octreotide / Q000627:therapeutic use*; D010911:Pituitary Neoplasms / Q000097:blood / Q000473:pathology / Q000601:surgery*; D011446:Prospective Studies; D013004:Somatostatin / Q000378:metabolism*; D016896:Treatment Outcome
D018931:Antineoplastic Agents, Hormonal; D003692:Delayed-Action Preparations; D013004:Somatostatin; D007334:Insulin-Like Growth Factor I; D013006:Growth Hormone; D015282:Octreotide