Tessari Roberto, Ossato Andrea, Realdon Francesca, Montresor Valentina, Giovagnoni Giuseppe, Giannini Michele, Gandini Debora, Modena Alessandra, Inno Alessandro, Gori Stefania
Hospital Pharmacy, IRCCS Sacro Cuore Don Calabria Hirccospital, Negrar di Valpolicella, Verona, Italy.
Department of Pharmaceutical and Pharmacological Sciences, University of Padova, Padova, Italy.
Hosp Pharm. 2024 Sep 5:00185787241278702. doi: 10.1177/00185787241278702.
Antitumoral drugs (ADs) can induce drug hypersensitivity reactions (DHRs). Rapid drug desensitization (RDD) protocols represent an important option to mitigate recurrent DHRs thus allowing the safe administration of ADs at therapeutic doses. The aim of this retrospective study was to assess the effectiveness of the RDD protocols performed at our institution. The "DESARCh" study was a retrospective, observational study that included consecutive patients who underwent RDD protocols from January 2011 to December 2022 at IRCCS Ospedale Sacro Cuore Don Calabria in Negrar di Valpolicella, Verona, Italy. The RDD protocol consisted of a 5-step protocol with 5 different concentrations of the drugs at 1:1, 1:10, 1:100, 1:1,000 and 1:10,000 dilution given intravenously over a 1-hour infusion each, with concentrations increasing from the most diluted to the most concentrated form, preceded by a 30-min premedication regimen. A total of 66 RDD protocols were administered to 25 female patients with ovarian (64%; n = 16/25), breast (12%; n = 3/25), endometrium (8%; n = 2/25), cervix (8%; n = 2/25), uterine (4%; n = 1/25) and fallopian tubes (4%; n = 1/25) cancers. A known history of atopy/allergy was reported by 36% (n = 9/25) of patients. Patients received RDD protocols because of DHRs to carboplatin (n = 23/66, 34.85%), paclitaxel (n = 18/66, 27.27%), pegylated liposomal doxorubicin (n = 3/66, 4.55%), and trastuzumab (n = 22/66, 33.33%). DHRs were mild-moderate, severe and life-threatening in 60.72%, 28.57% and 10.71% of cases, respectively. The success rate of RDD protocols, defined as the rate of complete administration of full target dose with no breakthrough reactions, was 81.82% (n = 54/66). Success rate was lower for carboplatin compared to other drugs (65.22% vs 90.7%; = .017678). The RDD protocol used in our institution was found to be safe, with a meaningful success rate. However, further research is needed to better understand the underlying mechanisms of DHRs and to enhance effectiveness, particularly for patients experiencing DHRs to platinum compounds. This study was approved by the ethics committee of Verona and Rovigo (Italy) with approval number 15476 on 10/03/2023 and it was registered with the Register of Observational Studies of the Italian Medicines Agency (AIFA) (available since 31 January 2023), with ID n. 109, on 28/02/2023 (https://www.aifa.gov.it/en/registro-studi-osservazionali).
抗肿瘤药物（ADs）可诱发药物过敏反应（DHRs）。快速药物脱敏（RDD）方案是减轻复发性DHRs的重要选择，从而能够以治疗剂量安全使用ADs。这项回顾性研究的目的是评估在我们机构实施的RDD方案的有效性。“DESARCh”研究是一项回顾性观察性研究，纳入了2011年1月至2022年12月期间在意大利维罗纳内格拉尔迪瓦尔波利切拉的IRCCS圣心医院唐卡拉布里亚分院接受RDD方案的连续患者。RDD方案包括一个五步方案，使用5种不同浓度的药物，分别为1:1、1:10、1:100、1:1000和1:10000稀释度，每种浓度在1小时内静脉输注，浓度从最稀释形式逐渐增加到最浓缩形式，之前有30分钟的预处理方案。共对患有卵巢癌（64%；n = 16/25）、乳腺癌（12%；n = 3/25）、子宫内膜癌（8%；n = 2/25）、宫颈癌（8%；n = 2/25）、子宫癌（4%；n = 1/25）和输卵管癌（4%；n = 1/25）的25名女性患者实施了66次RDD方案。36%（n = 9/25）的患者有特应性/过敏史。患者因对卡铂（n = 23/66，34.85%）、紫杉醇（n = 18/66，27.27%）、聚乙二醇脂质体阿霉素（n = 3/66，4.55%）和曲妥珠单抗（n = 22/66，33.33%）发生DHRs而接受RDD方案。DHRs分别在60.72%、28.57%和10.71%的病例中为轻度 - 中度、重度和危及生命。RDD方案的成功率定义为完全给予全目标剂量且无突破性反应的比例，为81.82%（n = 54/66）。与其他药物相比，卡铂的成功率较低（65.22%对90.7%；P = 0.017678）。我们机构使用的RDD方案被发现是安全的，成功率较高。然而，需要进一步研究以更好地理解DHRs的潜在机制并提高有效性,特别是对于对铂类化合物发生DHRs的患者。本研究于2023年3月10日获得维罗纳和罗维戈（意大利）伦理委员会批准，批准号为15476，并于2023年2月28日在意大利药品管理局（AIFA）的观察性研究登记处注册（自2023年1月31日起可用），ID号为109（https://www.aifa.gov.it/en /registro-studi-osservazionali）。
