Dana Farber癌症研究所与Salk研究所合作开展的临床试验表明，维生素D类似物帕立骨化醇可能破坏胰腺癌的保护性纤维组织微环境，从而提高肿瘤对化疗的敏感性。1该试验纳入36名未经治疗的转移性胰腺癌患者，所有患者接受标准化疗（吉西他滨与白蛋白结合型紫杉醇），其中部分患者同时给予帕立骨化醇或安慰剂。1
接受帕立骨化醇治疗的患者显示更优的治疗反应。1在24名接受该药物的患者中，部分缓解率达42%（10人），而安慰剂组（12人）的部分缓解率仅为9%（1人）。1此外，使用帕立骨化醇的患者中有5人在一年时仍无疾病进展，而安慰剂组未见此类情况。1研究发现该药物通过减少肿瘤内成纤维细胞的激活并增加T细胞浸润来发挥作用。1
帕立骨化醇已获FDA批准用于慢性肾脏病患者的继发性甲状旁腺功能亢进症的预防和治疗。1试验中5名口服该药物的患者出现血钙升高的不良反应。1相关研究已发表于《Nature Cancer》期刊。1
A clinical trial led by Dana Farber Cancer Institute and based on foundational research from Salk Institute has found that a vitamin D analog called paricalcitol may help dismantle the protective fibrous tissue surrounding pancreatic tumors, making them more susceptible to chemotherapy.1 The study enrolled 36 previously untreated patients with metastatic pancreatic cancer who received standard chemotherapy—gemcitabine plus albumin-bound paclitaxel—either combined with paricalcitol or placebo.1
Patients receiving paricalcitol demonstrated significantly higher treatment response rates, with a partial response rate of 42 percent compared to 9 percent in the placebo group.1 Among the 24 patients treated with paricalcitol, 10 achieved partial remission, while only 1 of 12 placebo recipients did so.1 Additionally, five patients in the paricalcitol group remained disease-free at one year, whereas none in the placebo arm achieved this outcome.1
The drug, which has already received FDA approval for preventing and treating secondary hyperparathyroidism in patients with chronic kidney disease, reduced the activation of cancer-associated fibroblasts within tumors while simultaneously increasing T cell infiltration.1 However, elevated blood calcium levels were observed in five patients taking oral paricalcitol.1
The research, published in Nature Cancer, suggests that tumors expressing high levels of vitamin D receptor may benefit most from this combination approach.1
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