Tailoring heated intraperitoneal mitomycin C for peritoneal metastases originating from colorectal carcinoma: a translational approach to improve survival

Kwakman, R.; Cuba, Erienne M. V. de; Winter, Johan P. de; Hingh, Ignace H. J. T. de; Diemen, Pien M. Delis-van; Tijssen, Marianne; Rooimans, Martin A.; Krijgsman, Oscar; Carvalho, Beatriz; Peters, Godefridus J.; Bonjer, H. Jaap; Meijer, Gerrit A.; Velde, Elisabeth A. te

doi:10.1038/bjc.2015.18

Cited by 15 publications

(13 citation statements)

References 46 publications

(62 reference statements)

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“…A recent investigation demonstrated the utility of PDT for the treatment of micrometastatic ovarian cancer in vivo , using a photoimmunoconjugate composed of BPD and cetuximab and light-diffusing fiber tips for the complete irradiation of the abdominal cavity, achieving significantly reduced micrometastatic tumor burdens [ 49 ]. Intraperitoneal chemotherapy yields promising clinical outcomes for peritoneal carcinomatosis of various cancers [ 50 – 53 ]. The current investigation represents a preclinical model of peritoneal metastases of pancreatic cancer in which the combination of PDT with OxPt shows promise as a clinically feasible strategy to reduce metastatic burdens and prevent peritoneal carcinomatosis following surgery.…”

Section: Discussionmentioning

confidence: 99%

Neoadjuvant photodynamic therapy augments immediate and prolonged oxaliplatin efficacy in metastatic pancreatic cancer organoids

et al. 2018

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Effective treatment of advanced metastatic disease remains the primary challenge in the management of inoperable pancreatic cancer. Current therapies such as oxaliplatin (OxPt)-based chemotherapy regimens (FOLFIRINOX) provide modest short-term survival improvements, yet with significant toxicity. Photodynamic therapy (PDT), a light-activated cancer therapy, demonstrated clinical promise for pancreatic cancer treatment and enhances conventional chemotherapies with non-overlapping toxicities. This study investigates the capacity of neoadjuvant PDT using a clinically-approved photosensitizer, benzoporphyrin derivative (BPD, verteporfin), to enhance OxPt efficacy in metastatic pancreatic cancer. Treatment effects were evaluated in organotypic three-dimensional (3D) cultures, clinically representative models that bridge the gap between conventional cell cultures and in vivo models. The temporally-spaced, multiparametric analyses demonstrated a superior efficacy for combined PDT+OxPt compared to each monotherapy alone, which was recapitulated on different organotypic pancreatic cancer cultures. The therapeutic benefit of neoadjuvant PDT to OxPt chemotherapy materialized in a time-dependent manner, reducing residual viable tissue and tumor viability in a manner not achievable with OxPt or PDT alone. These findings emphasize the need for intelligent combination therapies and relevant models to evaluate the temporal kinetics of interactions between mechanistically-distinct treatments and highlight the promise of PDT as a neoadjuvant treatment for disseminated pancreatic cancer.

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Section: Discussionmentioning

confidence: 99%

Neoadjuvant photodynamic therapy augments immediate and prolonged oxaliplatin efficacy in metastatic pancreatic cancer organoids

et al. 2018

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“…A recent paper found low Bloom syndrome protein (BLM) expression to be associated with high MMC sensitivity in CRC cell lines. Low BLM expression was thereby related to improved survival in CRC patients with PM [ 69 ]. Since identification of sensitivity and resistance mechanisms could lead to mechanism-based therapies and further stratification of HIPEC patients, i.e.…”

Section: Discussionmentioning

confidence: 99%

Versican and vascular endothelial growth factor expression levels in peritoneal metastases from colorectal cancer are associated with survival after cytoreductive surgery and hyperthermic intraperitoneal chemotherapy

Sluiter

Cuba

Kwakman

et al. 2016

Clin Exp Metastasis

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Cytoreductive surgery (CRS) and hyperthermic intraperitoneal chemotherapy (HIPEC) can increase survival of colorectal cancer (CRC) patients with peritoneal metastases (PM). This treatment is associated with high morbidity and mortality rates. Therefore, improvement of patient selection is necessary. Assuming that the clinical phenotype is dictated by biological mechanisms, biomarkers could play a crucial role in this process. Since it is unknown whether and to what extent angiogenesis influences the course of disease in patients with PM, we investigated the expression of two angiogenesis-related markers and their relation to overall survival (OS) in CRC patients after CRS and HIPEC. Clinicopathological data and tissue samples were collected from 65 CRC patients with isolated metastases to the peritoneum that underwent CRS and HIPEC. Whole tissue specimens from PM were evaluated for versican (VCAN) expression, VEGF expression and microvessel density (MVD) by immunohistochemistry. The relation between these markers and OS was assessed using univariate and multivariate analysis. Associations between VEGF expression, VCAN expression, MVD and clinicopathological data were tested. High stromal VCAN expression was associated with high MVD (p = 0.001), better resection outcome (p = 0.003) and high T-stage (p = 0.027). High epithelial VCAN expression was associated with MVD (p = 0.007) and a more complete resection (p < 0.001). In multivariate analysis, simplified peritoneal cancer index (p = 0.001), VEGF expression levels (p = 0.012), age (p = 0.030), epithelial VCAN expression levels (p = 0.042) and lymph node status (p = 0.053) were associated with OS. Concluding, VCAN and VEGF were associated with survival in CRC patients with PM after CRS and HIPEC. Independent validation in a well-defined patient cohort is required to confirm the putative prognostic role of these candidate biomarkers.Electronic supplementary materialThe online version of this article (doi:10.1007/s10585-016-9779-9) contains supplementary material, which is available to authorized users.

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“…Hence, drug choice depending on in vitro drug sensitivity testing may result in improved clinical outcome after HIPEC. Recently, low expression of Bloom syndrome protein in colorectal cancer cell lines was associated with high sensitivity to heated intraperitoneally administered mitomycin C and in peritoneal metastases of colorectal cancer patients with improved survival [115]. To date, however, there are no prospective studies demonstrating an improved clinical outcome from drug selection relying on in vitro drug sensitivity testing.…”

Section: Patient-tailored Drug Choicementioning

confidence: 99%

Pharmacological principles of intraperitoneal and bidirectional chemotherapy

Bree

Michelakis

Stamatiou

et al. 2017

Pleura and Peritoneum

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Intraperitoneal chemotherapy is associated with a significant pharmacokinetic and pharmacodynamic benefit and can, alone or in combination with systemic chemotherapy (bidirectional chemotherapy), be used for treating primary and secondary peritoneal surface malignancies. Due to the peritoneal-plasma barrier, high intraperitoneal drug concentration can be achieved by intraperitoneal chemotherapy, whereas systemic concentration remains low. Bidirectional chemotherapy may provide in addition adequate drug concentrations from the side of the subperitoneal space to the peritoneal tumour nodules. Major pharmacological problems of intraperitoneal chemotherapy are limited tissue penetration and poor homogeneity of drug distribution to the entire seroperitoneal surface. Significant pharmacological determinants of intraperitoneal chemotherapy are choice of drug, drug dosage, solution volume, carrier solution, intra-abdominal pressure, temperature, duration, mode of administration, extent of peritonectomy and interindividual variability. Drugs most commonly applied for intraperitoneal chemotherapy include mitomycin C, cisplatin, carboplatin, oxaliplatin, irinotecan, 5-fluoruracil, gemcitabine, paclitaxel, docetaxel, doxorubicin, premetrexed and melphalan. The drugs and their doses that are used vary widely among centres. While the adequate drug choice for intraperitoneal and bidirectional chemotherapy is essential, randomized clinical trials to determine the most optimal drug or drug combination are lacking, and only eight retrospective comparative clinical studies are available. Further clinical pharmacological studies are required to determine the most effective drug regimen for intraperitoneal and bidirectional chemotherapy in various indications. In the future, reliable drug sensitivity testing and genetic profiling of peritoneal metastases will be needed for enabling patient-specific therapy.

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Tailoring heated intraperitoneal mitomycin C for peritoneal metastases originating from colorectal carcinoma: a translational approach to improve survival

Cited by 15 publications

References 46 publications

Neoadjuvant photodynamic therapy augments immediate and prolonged oxaliplatin efficacy in metastatic pancreatic cancer organoids

Neoadjuvant photodynamic therapy augments immediate and prolonged oxaliplatin efficacy in metastatic pancreatic cancer organoids

Versican and vascular endothelial growth factor expression levels in peritoneal metastases from colorectal cancer are associated with survival after cytoreductive surgery and hyperthermic intraperitoneal chemotherapy

Pharmacological principles of intraperitoneal and bidirectional chemotherapy

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