Colao Annamaria, Pivonello Rosario, Auriemma Renata S, Galdiero Mariano, Savastano Silvia, Lombardi Gaetano
Section of Endocrinology, Department of Molecular and Clinical Endocrinology and Oncology, University Federico II of Naples, via S Pansini 5, 80131 Naples, Italy.
Eur J Endocrinol. 2007 Nov;157(5):579-87. doi: 10.1530/EJE-07-0383.
To evaluate the efficacy of dose escalation of Octreotide-long-acting repeatable (LAR) up to 40 mg/month we studied 56 newly diagnosed patients with acromegaly (24 women, 32 men; age 20-82 years).
Analytical, observational, open and prospective.
Three months after LAR treatment beginning with a dose of 20 mg /q28d (every 28 days), 24 patients maintained the same dose (Group A), while 32 required a dose of 30 mg/q28d (Group B). The dose was further increased to 40 mg/q28d in 17 out of the 32 patients of Group B for another 12 months (Group C).
After 24 months, serum GH and IGF-I levels decreased by 93.1 +/- 8.6% (95% confidence limit (CL) 90.8-95.4%) and 62.7 +/- 13.4% (95% CL 59.1-66.3%) respectively. Control of GH and IGF-I levels was achieved in 45 patients (80.3%). Tumor shrinkage after 12 months was 49.8 +/- 23%; the relative tumor shrinkage during the second 12 months of treatment was 35.3 +/- 13.1% and overall tumor volume was 68.1 +/- 16.5% (95% CL 63.7-72.5%). Glucose tolerance impaired in eight patients (14.3%): four in Group A and four in Group C (16.7% vs 36.4%, P=0.39). The final dose was predicted by the patient's age at diagnosis (t=-2.2; P=0.032) and baseline tumor volume (t=2.1; P=0.043).
An increase of the LAR dose up to 40 mg/q28d in patients resistant to 30 mg/q28d is followed by greater suppression of GH and IGF-I levels and tumor shrinkage without further significant impairment of glucose tolerance when compared with lower doses. These results suggest that a new dosage schedule of 40 mg every 28 days is applied in patients with acromegaly mostly of young age and with bigger tumors who are likely to be poorly responsive to standard doses of Octreotide-LAR.
为评估长效奥曲肽（LAR）剂量增至每月40mg的疗效，我们研究了56例新诊断的肢端肥大症患者（24例女性，32例男性；年龄20 - 82岁）。
分析性、观察性、开放性和前瞻性研究。
LAR治疗开始时剂量为20mg /每28天一次，三个月后，24例患者维持相同剂量（A组），而32例患者需要30mg /每28天一次的剂量（B组）。B组的32例患者中有17例剂量进一步增至40mg /每28天一次，持续12个月（C组）。
24个月后，血清生长激素（GH）和胰岛素样生长因子-I（IGF-I）水平分别下降了93.1±8.6%（95%置信区间（CL）90.8 - 95.4%）和62.7±13.4%（95% CL 59.1 - 66.3%）。45例患者（80.3%）实现了GH和IGF-I水平的控制。12个月后肿瘤缩小率为49.8±23%；治疗的第二个12个月期间相对肿瘤缩小率为35.3±13.1%，总体肿瘤体积为68.1±16.5%（95% CL 63.7 - 72.5%）。8例患者（14.3%）出现葡萄糖耐量受损：A组4例，C组4例（16.7%对36.4%，P = 0.39）。最终剂量可由诊断时患者年龄预测（t = -2.2；P = 0.032）和基线肿瘤体积预测（t = 2.1；P = 0.043）。
对于对30mg /每28天一次剂量耐药的患者，将LAR剂量增至40mg /每28天一次后，与较低剂量相比，GH和IGF-I水平受到更大抑制，肿瘤缩小，且葡萄糖耐量无进一步显著受损。这些结果表明，每28天40mg的新剂量方案适用于大多数年轻且肿瘤较大、可能对标准剂量长效奥曲肽反应不佳的肢端肥大症患者。
