TY - JOUR
T1 - Pressurized intraperitoneal aerosolized chemotherapy (PIPAC) experience in patients with recurrent low grade serous ovarian carcinoma (LGSOC)
T2 - sub-cohort report of phase 1 clinical trial
AU - Nakamura, Brad
AU - Senguttuvan, Rosemary
AU - Ruel, Nora H.
AU - Frankel, Paul H.
AU - Yost, Susan E.
AU - Cole, Sarah
AU - Chang, Sue
AU - Jung, Alexander
AU - Eng, Melissa
AU - Tinsley, Raechelle
AU - Stewart, Daphne
AU - Wang, Edward
AU - Cohen, Joshua
AU - Villella, Jeannine
AU - Whelan, Richard L.
AU - Merchea, Amit
AU - DePeralta, Danielle K.
AU - Cristea, Mihaela
AU - Wakabayashi, Mark T.
AU - Raoof, Mustafa
AU - Dellinger, Thanh Hue
N1 - Publisher Copyright:
Copyright © 2024 Nakamura, Senguttuvan, Ruel, Frankel, Yost, Cole, Chang, Jung, Eng, Tinsley, Stewart, Wang, Cohen, Villella, Whelan, Merchea, DePeralta, Cristea, Wakabayashi, Raoof and Dellinger.
PY - 2024
Y1 - 2024
N2 - Introduction: 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. Methods: 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/m2, doxorubicin 2.1 mg/m2 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. Results: 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%. Conclusion: 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.
AB - Introduction: 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. Methods: 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/m2, doxorubicin 2.1 mg/m2 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. Results: 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%. Conclusion: 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.
KW - LGSOC
KW - PIPAC
KW - low-grade serous ovarian carcinoma
KW - pressurized intraperitoneal aerosolized chemotherapy
KW - recurrent
UR - http://www.scopus.com/inward/record.url?scp=85201390089&partnerID=8YFLogxK
U2 - 10.3389/fonc.2024.1404936
DO - 10.3389/fonc.2024.1404936
M3 - Article
AN - SCOPUS:85201390089
SN - 2234-943X
VL - 14
JO - Frontiers in Oncology
JF - Frontiers in Oncology
M1 - 1404936
ER -