The role of intraperitoneal chemotherapy in the surgical management of pancreatic ductal adenocarcinoma: a systematic review

Brind’Amour, Alexandre; Webb, Mitchell; Parapini, Marina; Sidéris, Lucas; Segedi, Maja; Chung, Stephen W.; Chartier-Plante, Stephanie; Dubé, Pierre; Scudamore, Charles H.; Kim, Peter T. W.

doi:10.1007/s10585-021-10074-2

Cited by 9 publications

(5 citation statements)

References 46 publications

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“…Based on these limited data, the treatment was concluded to be well tolerated and potentially suited for short-term disease control, whereas adjuvant HIPEC in resectable PDAC was discouraged. 38 Although significant oncological effectiveness of HIPEC in PDAC may emerge as doubtful, such comprehensive conclusions based on very limited and preliminary evidence may likewise be questioned. Since HIPEC is influenced by a multitude of factors, 39 , 40 preclinical research and modeling appears pivotal as a guide for the future.…”

Section: Discussionmentioning

confidence: 99%

A Prospective, Phase I/II, Open-Label Pilot Trial to Assess the Safety of Hyperthermic Intraperitoneal Chemotherapy After Oncological Resection of Pancreatic Adenocarcinoma

Yurttas

Horvath

Fischer³

et al. 2021

Ann Surg Oncol

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Background Pancreatic ductal adenocarcinoma (PDAC) is a common fatal disease with unfavorable prognosis, even after oncological resection. To improve survival, adding hyperthermic intraperitoneal chemotherapy (HIPEC) has been suggested. Whether HIPEC entails disproportional short-term mortality is unknown and a prospectively determined adverse events profile is lacking. Since both pancreatic resection and HIPEC may relevantly influence morbidity and mortality, this uncontrolled single-arm, open-label, phase I/II pilot trial was designed to assess the 30-day mortality rate, treatment feasibility, and adverse events connected with HIPEC after oncological pancreatic surgery. Methods This trial recruited patients scheduled for PDAC resection. A sample size of 16 patients receiving study interventions was estimated to establish a predefined margin of treatment-associated short-term mortality with a power of > 80%. Patients achieving complete macroscopic resection received HIPEC with gemcitabine administered at 1000 mg/m2 body surface area heated to 42 °C for 1 hour. Results Within 30 days after intervention, no patient died or experienced any adverse events higher than grade 3 that were related to HIPEC. Furthermore, treatment-related adverse events were prospectively documented and categorized as expected or unexpected. This trial supports that the actual mortality rate after PDAC resection and HIPEC is below 10%. HIPEC treatment proved feasible in 89% of patients allocated to intervention. Pancreatic fistulas, as key complications after pancreas surgery, occurred in 3/13 patients under risk. Conclusion Combined pancreas resection and gemcitabine HIPEC proved feasible and safe, with acceptable morbidity and mortality. Based on these results, further clinical evaluation can be justified. Registration Number NCT02863471 (http://www.clinicaltrials.gov).

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Section: Discussionmentioning

confidence: 99%

A Prospective, Phase I/II, Open-Label Pilot Trial to Assess the Safety of Hyperthermic Intraperitoneal Chemotherapy After Oncological Resection of Pancreatic Adenocarcinoma

Yurttas

Horvath

Fischer³

et al. 2021

Ann Surg Oncol

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“…Until the multimodal management of primary and local regional disease improves, CRS/HIPEC has a limited role in the management of PM for these primary tumors. It may be considered in clinical settings when certain conditions are met, such as patients with low disease burden who have demonstrated a durable response to systemic therapy 21‐24 …”

Section: Overviewmentioning

confidence: 99%

The contemporary management of peritoneal metastasis: A journey from the cold past of treatment futility to a warm present and a bright future

Foster

Zhang

Rehman

et al. 2022

CA A Cancer J Clinicians

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Peritoneal metastasis (PM) is often regarded as a less frequent pattern of spread; however, collectively across all spectra of primary tumors, the consequences of PM impact a large population of patients annually. Unlike other modes of metastasis, symptoms at presentation or during the treatment course are common, representing an additional challenge in the management of PM. Early efforts with chemotherapy and incomplete surgical interventions transiently improved symptoms, but durable symptom control and survival extension were rare, which established a perspective of treatment futility for PM through most of the 20th century. Notably, the continued development of better systemic therapy combinations, optimization of cytoreductive surgery (CRS), and rigorous investigation of combining regional therapy-specifically hyperthermic intraperitoneal chemotherapy-with CRS, have resulted in more effective multimodal treatment options for patients with PM. In this article, the authors provide a comprehensive review of the data establishing the contemporary approach for tumors with a high frequency of PM, including appendix, colorectal, mesothelioma, and gastric cancers. The authors also explore the emerging role of adding hyperthermic intraperitoneal chemotherapy to the well established paradigm of CRS and systemic therapy for advanced ovarian cancer, as well as the recent clinical trials identifying the efficacy of poly(adenosine diphosphate ribose) polymerase maintenance therapy. Finally, recent data are included that explore the role of precision medicine technology in PM management that, in the future, may help further improve patient selection, identify the best systemic therapy regimens, detect actionable mutations, and identify new targets for drug development.

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“…250 (160–295) B. 55 (45–95) C. 20 [ 18 – 23 ] (vs. A-B p < 0.01) – – – Emoto et al [ 68 ] A. Control (n = 6) B. Blanc hydrogel (n = 6) C. Free CDDP 1 mg/kg (n = 6) D. Hydrogel-CDDP 1 mg/kg (n = 6) n.a A.…”

Section: Outcome Measuresmentioning

confidence: 99%

“…Unfortunately, due to strict contra-indications, only 10–25% of patients with PM of colorectal origin are eligible for CRS and HIPEC [ 15 , 16 ]. For PM of non-colorectal gastro-intestinal origins such as gastric or pancreatic adenocarcinoma, CRS and HIPEC are considered experimental because of limited available evidence and poor survival [ 17 , 18 ]. For those patients not eligible for CRS and HIPEC, pressurized intraperitoneal aerosol chemotherapy (PIPAC) is a new palliative treatment option that is considered safe.…”

Section: Introductionmentioning

confidence: 99%

Intraperitoneal drug delivery systems releasing cytostatic agents to target gastro-intestinal peritoneal metastases in laboratory animals: a systematic review

Wintjens

Simkens

Fransen³

et al. 2022

Clin Exp Metastasis

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For peritoneal metastases (PM), there are few curative treatment options, and they are only available for a select patient group. Recently, new therapies have been developed to deliver intraperitoneal chemotherapy for a prolonged period, suitable for a larger patient group. These drug delivery systems (DDSs) seem promising in the experimental setting. Many types of DDSs have been explored in a variety of animal models, using different cytostatics. This review aimed to provide an overview of animal studies using DDSs containing cytostatics for the treatment of gastro-intestinal PM and identify the most promising therapeutic combinations. The review was conducted following the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines and Systematic Review Center for Laboratory Animal Experimentation (SYRCLE) guidelines. The 35 studies included revealed similar results: using a cytostatic-loaded DDS to treat PM resulted in a higher median survival time (MST) and a lower intraperitoneal tumor load compared to no treatment or treatment with a ‘free’ cytostatic or an unloaded DDS. In 65% of the studies, the MST was significantly longer and in 24% the tumor load was significantly lower in the animals treated with cytostatic-loaded DDS. The large variety of experimental setups made it impossible to identify the most promising DDS-cytostatic combination. In most studies, the risk of bias was unclear due to poor reporting. Future studies should focus more on improving the clinical relevance of the experiments, standardizing the experimental study setup, and improving their methodological quality and reporting.

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The role of intraperitoneal chemotherapy in the surgical management of pancreatic ductal adenocarcinoma: a systematic review

Cited by 9 publications

References 46 publications

A Prospective, Phase I/II, Open-Label Pilot Trial to Assess the Safety of Hyperthermic Intraperitoneal Chemotherapy After Oncological Resection of Pancreatic Adenocarcinoma

A Prospective, Phase I/II, Open-Label Pilot Trial to Assess the Safety of Hyperthermic Intraperitoneal Chemotherapy After Oncological Resection of Pancreatic Adenocarcinoma

The contemporary management of peritoneal metastasis: A journey from the cold past of treatment futility to a warm present and a bright future

Intraperitoneal drug delivery systems releasing cytostatic agents to target gastro-intestinal peritoneal metastases in laboratory animals: a systematic review

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