TY - JOUR
T1 - First-line palliative systemic therapy alternated with oxaliplatin-based pressurized intraperitoneal aerosol chemotherapy for unresectable colorectal peritoneal metastases
T2 - A single-arm phase II trial (CRC-PIPAC-II)
AU - Rauwerdink, Paulien
AU - van de Vlasakker, Vincent C.J.
AU - Wassenaar, Emma C.E.
AU - Rovers, Koen P.
AU - Los, Maartje
AU - Herbschleb, Karin H.
AU - Creemers, Geert Jan M.
AU - Thijs, Annemarie M.J.
AU - Raicu, Mihaela G.
AU - Huysentruyt, Clément J.R.
AU - van der Hoeven, Erik J.R.J.
AU - Nederend, Joost
AU - Peeters, Rifka Y.M.
AU - Deenen, Maarten J.
AU - Elias, Sjoerd G.
AU - Fijneman, Remond J.A.
AU - Constantinides, Alexander
AU - Kranenburg, Onno
AU - Burger, Pim W.A.
AU - Nienhuijs, Simon W.
AU - Wiezer, René J.
AU - Lurvink, Robin J.
AU - de Hingh, Ignace H.J.T.
AU - Boerma, Djamila
N1 - Funding Information:
This work was supported by the St. Antonius Research Foundation and Innovation Foundation [no grant numbers \u2013 to D.B.]; and the Catharina Research Foundation [no grant number \u2013 to I.H.J.T.H.]. The funders had no role in the study design, data collection, data analysis, data interpretation or writing of the report.IHJTH received research grants unrelated to the submitted work from QP&S, RanD Biotech and Hoffman-La Roche. All remaining authors have declared no conflicts of interest.This work was supported by the St. Antonius Research Foundation and Innovation Foundation [no grant numbers \u2013 to D.B.]; and the Catharina Research Foundation [no grant number \u2013 to I.H.J.T.H.]. The authors thank all patients for participation in this study.
Publisher Copyright:
© 2024 Elsevier Ltd, BASO ~ The Association for Cancer Surgery, and the European Society of Surgical Oncology
PY - 2024/9/1
Y1 - 2024/9/1
N2 - Background: Palliative systemic therapy alternated with electrostatic precipitation oxaliplatin-based pressurized intraperitoneal aerosol chemotherapy (ePIPAC) has never been prospectively investigated in patients with unresectable colorectal peritoneal metastases (CPM). The CRC-PIPAC-II study aimed to assess safety, feasibility and efficacy of such bidirectional therapy. Methods: This two-center, single-arm, phase II trial enrolled chemotherapy-naïve patients to undergo three treatment cycles, consisting of systemic therapy (CAPOX, FOLFOX, FOLFIRI, or FOLFOXIRI, all with bevacizumab) and oxaliplatin-based ePIPAC (92 mg/m2) with intravenous leucovorin (20 mg/m2) and 5-fluorouracil (400 mg/m2). Primary outcome were major treatment-related adverse events. Secondary outcomes included minor events, tumor response, progression-free survival (PFS) and overall survival (OS). Results: Twenty patients completed 52 treatment cycles. Fifteen major events occurred in 7 patients (35 %): 5 events (33 %) related to systemic therapy; 5 (33 %) related to ePIPAC; and 5 (33 %) were biochemical events. No treatment-related deaths occurred. All patients experienced minor events, mostly abdominal pain, nausea and peripheral sensory neuropathy. After treatment, radiological, pathological, cytological, and biochemical response was observed in 0 %, 88 %, 38 %, and 31 % of patients respectively. Curative surgery was achieved in one patient. Median PFS was 10.0 months (95 % confidence interval [CI] 8.0–13.0) and median OS was 17.5 months (95 % CI 13.0–not reached). Conclusions: Combining palliative systemic therapy with oxaliplatin-based ePIPAC in patients with unresectable CPM was feasible and showed an acceptable safety profile. Treatment-induced response and survival are promising, yet further research is required to determine the additional value of ePIPAC to systemic therapy.
AB - Background: Palliative systemic therapy alternated with electrostatic precipitation oxaliplatin-based pressurized intraperitoneal aerosol chemotherapy (ePIPAC) has never been prospectively investigated in patients with unresectable colorectal peritoneal metastases (CPM). The CRC-PIPAC-II study aimed to assess safety, feasibility and efficacy of such bidirectional therapy. Methods: This two-center, single-arm, phase II trial enrolled chemotherapy-naïve patients to undergo three treatment cycles, consisting of systemic therapy (CAPOX, FOLFOX, FOLFIRI, or FOLFOXIRI, all with bevacizumab) and oxaliplatin-based ePIPAC (92 mg/m2) with intravenous leucovorin (20 mg/m2) and 5-fluorouracil (400 mg/m2). Primary outcome were major treatment-related adverse events. Secondary outcomes included minor events, tumor response, progression-free survival (PFS) and overall survival (OS). Results: Twenty patients completed 52 treatment cycles. Fifteen major events occurred in 7 patients (35 %): 5 events (33 %) related to systemic therapy; 5 (33 %) related to ePIPAC; and 5 (33 %) were biochemical events. No treatment-related deaths occurred. All patients experienced minor events, mostly abdominal pain, nausea and peripheral sensory neuropathy. After treatment, radiological, pathological, cytological, and biochemical response was observed in 0 %, 88 %, 38 %, and 31 % of patients respectively. Curative surgery was achieved in one patient. Median PFS was 10.0 months (95 % confidence interval [CI] 8.0–13.0) and median OS was 17.5 months (95 % CI 13.0–not reached). Conclusions: Combining palliative systemic therapy with oxaliplatin-based ePIPAC in patients with unresectable CPM was feasible and showed an acceptable safety profile. Treatment-induced response and survival are promising, yet further research is required to determine the additional value of ePIPAC to systemic therapy.
KW - Bevacizumab
KW - Bidirectional therapy
KW - Colorectal peritoneal metastases
KW - Electrostatic PIPAC
KW - First-line systemic therapy
KW - Oxaliplatin
U2 - 10.1016/j.ejso.2024.108487
DO - 10.1016/j.ejso.2024.108487
M3 - Article
SN - 0748-7983
VL - 50
JO - European Journal of Surgical Oncology
JF - European Journal of Surgical Oncology
IS - 9
M1 - 108487
ER -