Rastogi Ashu, Walia Rama, Dutta Pinaki, Bhansali Anil
Department of Endocrinology, PGIMER, Chandigarh, India.
Indian J Endocrinol Metab. 2012 Dec;16(Suppl 2):S294-6. doi: 10.4103/2230-8210.104064.
Cabergoline (CAB) is conventionally started at a dose of 0.25-0.5 mg once a week with dose escalation at 1to 3months intervals. Previously, we and others have shown that rapid escalation and high doses of CAB can lead to normalization of serum PRL as early as 8.2 weeks in 93% of the patients. We hypothesize that rapid escalation of CAB doses, may help in both the earlier normalization of PRL and also significant shrinkage of tumor mass.
Randomized, prospective, interventional trial.
Forty two patients (male or female) with macroprolactinoma were randomized to conventional (group A) or rapid escalation (group B) of CAB dosing. In group B, CAB was started at a dose of 0.5 mg twice a week followed by a weekly hike of 1 mg/week, based on serum PRL and then monthly. The end point of the present study was a composite of normoprolactinemia and tumor shrinkage ≥50% from baseline. PRL and visual field analysis (weekly), other hormonal work up periodically and magnetic resonance imaging (sella) was performed monthly.
A total of 19 patients in each group completed a minimum follow-up of 6 months. There was a reduction of 72.7 ± 26.2% in group A and 84.1 ± 15.0 in group B (P = 0.24) within a week of CAB therapy. The duration of CAB treatment to normalize PRL was 10.2 ± 9.2 week(2-36) in group A and 7.2 ± 6.2 weeks(1-24) in group B (P = 0.28). There was no difference in the tumor shrinkage in either of the groups (92.3% [46.7-100%] in group A and 90.5% [66.6-100%] reduction in group B). The composite end point was achieved in 14 patients in group A (73.6%) and 16 patients in group B (84.2%) (P = 0.69). The composite end point was achieved in 13.1 ± 9.5 weeks (group A) versus 16.5 ± 14.1 weeks (group B) (P = 0.61).
This is first head to head comparative trial showing that a rapid hike of CAB dose is not associated with earlier normalization of PRL or reduction in tumor volume as compared to conventional monthly hike. There is no difference in the number of patients or duration required to achieve the composite end point. We obtained much earlier PRL normalization (8.4 weeks) as compared to previous studies (36-72 weeks), probably because PRL was not assessed as frequently as in the present study. Rapid escalation of CAB was well tolerated.
A weekly or a conventional 4 weekly escalation of CAB have a similar efficacy with regards to the achievement of normoprolactinemia and significant tumor shrinkage for macroprolactinoma.
卡麦角林（CAB）传统上起始剂量为每周0.25 - 0.5毫克，每隔1至3个月增加剂量。此前，我们及其他研究人员已表明，快速增加剂量及高剂量的卡麦角林可使93%的患者血清泌乳素早在8.2周时就恢复正常。我们推测，快速增加卡麦角林剂量可能有助于泌乳素更早恢复正常，也有助于肿瘤体积显著缩小。
随机、前瞻性、干预性试验。
42例患有大泌乳素瘤的患者（男性或女性）被随机分为卡麦角林常规给药组（A组）或快速增加剂量组（B组）。在B组中，卡麦角林起始剂量为每周两次，每次0.5毫克，随后根据血清泌乳素水平每周增加1毫克/周，之后每月增加一次。本研究的终点是泌乳素正常血症和肿瘤体积较基线缩小≥50%的综合指标。每周进行泌乳素和视野分析，定期进行其他激素检查，每月进行磁共振成像（蝶鞍）检查。
每组各有19例患者完成了至少6个月的随访。卡麦角林治疗一周内，A组血清泌乳素降低了72.7±26.2%，B组降低了84.1±15.0%（P = 0.24）。A组使泌乳素恢复正常的卡麦角林治疗持续时间为10.2±9.2周（2 - 36周），B组为7.2±6.2周（1 - 24周）（P = 0.28）。两组的肿瘤缩小情况无差异（A组缩小92.3%[46.7 - 100%]，B组缩小90.5%[66.6 - 100%]）。A组14例患者（73.6%）和B组16例患者（84.2%）达到了综合终点（P = 0.69）。达到综合终点的时间，A组为13.1±9.5周，B组为16.5±14.1周（P = 0.61）。
这是第一项直接对比试验，结果表明与传统的每月增加剂量相比，快速增加卡麦角林剂量与泌乳素更早恢复正常或肿瘤体积缩小无关。在达到综合终点所需的患者数量或时间上没有差异。与之前的研究（36 - 72周）相比，我们使泌乳素恢复正常的时间要早得多（8.4周），可能是因为之前的研究中对泌乳素的评估频率不如本研究。卡麦角林快速增加剂量耐受性良好。
对于大泌乳素瘤患者，每周或传统的每四周增加一次卡麦角林剂量在实现泌乳素正常血症和显著缩小肿瘤体积方面具有相似的疗效。
