Nakamura Brad, Senguttuvan Rosemary, Ruel Nora H, Frankel Paul H, Yost Susan E, Cole Sarah, Chang Sue, Jung Alexander, Eng Melissa, Tinsley Raechelle, Stewart Daphne, Wang Edward, Cohen Joshua, Villella Jeannine, Whelan Richard L, Merchea Amit, DePeralta Danielle K, Cristea Mihaela, Wakabayashi Mark T, Raoof Mustafa, Dellinger Thanh Hue
Department of Surgery, City of Hope National Medical Center, Duarte, CA, United States.
Department of Computation and Quantitative Medicine, City of Hope National Medical Center, Duarte, CA, United States.
Front Oncol. 2024 Aug 1;14:1404936. doi: 10.3389/fonc.2024.1404936. eCollection 2024.
Low grade serous ovarian carcinoma (LGSOC) is a rare subtype of ovarian cancer (OC) that is challenging to treat due to its relative chemoresistance. Given that LGSOC patients often recur in the peritoneal cavity, novel intraperitoneal (IP) chemotherapy should be explored. Pressurized intraperitoneal aerosolized chemotherapy (PIPAC) is a method that has demonstrated peritoneal disease control in cancers with peritoneal metastases.
NCT04329494 is a US multicenter phase 1 trial evaluating the safety of PIPAC in recurrent ovarian, uterine, and GI cancers with peritoneal metastases. This analysis describes the outcomes of a sub-cohort of four LGSOC patients treated with IP cisplatin 10.5 mg/m, doxorubicin 2.1 mg/m PIPAC q4-6 weeks. Primary endpoints included dose-limiting toxicities (DLT) and incidence of adverse events (AE). Secondary endpoints were progression free survival (PFS) and treatment response based on radiographic, intraoperative, and pathological findings.
Four patients with LGSOC were enrolled of which three were heavily pretreated. Median prior lines of therapy was 5 (range 2-10). Three patients had extraperitoneal metastases, and two patients had baseline partial small bowel obstructive (SBO) symptoms. Median age of patients was 58 (38-68). PIPAC completion rate (≥2 PIPACs) was 75%. No DLTs or Clavien-Dindo surgical complications occurred. No G4/G5 AEs were observed, and one G3 abdominal pain was reported. One patient had a partial response after 3 cycles of PIPAC and completed an additional 3 cycles with compassionate use amendment. Two patients came off study after 2 cycles due to extraperitoneal progressive disease. One patient came off study after 1 cycle due to toxicity. Median decrease in peritoneal carcinomatosis index between cycles 1 and 2 was 5.0%. Ascites decreased in 2 out of 3 patients who had ≥2 PIPACs. Median PFS was 4.3 months (1.7-21.6), median overall survival was 11.6 months (5.4-30.1), and objective response rate was 25%.
PIPAC with cisplatin/doxorubicin is well tolerated in LGSOC patients without baseline SBO symptoms. IP response was seen in 2 out of 3 patients that completed ≥2 PIPAC cycles. Further study of PIPAC for patients with recurrent disease limited to the IP cavity and with no partial SBO symptoms should be considered.
低级别浆液性卵巢癌（LGSOC）是卵巢癌（OC）的一种罕见亚型，由于其相对的化疗耐药性，治疗具有挑战性。鉴于LGSOC患者常于腹腔复发，应探索新型腹腔内（IP）化疗方法。加压腹腔雾化化疗（PIPAC）是一种已在伴有腹膜转移的癌症中证明可控制腹膜疾病的方法。
NCT04329494是一项美国多中心1期试验，评估PIPAC在伴有腹膜转移的复发性卵巢癌、子宫癌和胃肠道癌症中的安全性。本分析描述了4例接受IP顺铂10.5mg/m²、阿霉素2.1mg/m²，每4 - 6周进行一次PIPAC治疗的LGSOC患者亚组的结果。主要终点包括剂量限制性毒性（DLT）和不良事件（AE）发生率。次要终点是无进展生存期（PFS）以及基于影像学、术中及病理结果的治疗反应。
4例LGSOC患者入组，其中3例接受过大量预处理。既往治疗的中位疗程数为5（范围2 - 10）。3例患者有腹膜外转移，2例患者有基线部分小肠梗阻（SBO）症状。患者的中位年龄为58岁（38 - 68岁）。PIPAC完成率（≥2次PIPAC）为75%。未发生DLT或Clavien - Dindo手术并发症。未观察到4/5级AE，报告了1例3级腹痛。1例患者在3个周期的PIPAC治疗后出现部分缓解，并通过同情用药修正案完成了另外3个周期的治疗。2例患者在2个周期后因腹膜外疾病进展退出研究。1例患者因毒性在1个周期后退出研究。第1周期和第2周期之间腹膜癌指数的中位下降率为5.0%。在进行了≥2次PIPAC治疗的3例患者中，2例腹水减少。中位PFS为4.3个月（1.7 - 21.6），中位总生存期为11.6个月（5.4 - 30.1），客观缓解率为25%。
对于无基线SBO症状的LGSOC患者，顺铂/阿霉素PIPAC耐受性良好。在完成≥2次PIPAC周期的3例患者中，2例出现IP反应。对于疾病复发局限于IP腔且无部分SBO症状的患者，应考虑进一步研究PIPAC。
