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Safety and efficacy of chemosaturation in patients with primary and secondary liver tumors

  • Original Article – Clinical Oncology
  • Published:
Journal of Cancer Research and Clinical Oncology Aims and scope Submit manuscript

Abstract

Background

Chemosaturation with percutaneous hepatic perfusion (CS-PHP; hepatic CHEMOSAT® delivery system; Delcath Systems Inc, USA) is a novel medical device, which delivers high doses of melphalan directly to the liver in patients with primary and secondary liver tumors while limiting systemic toxicity through hemofiltration of the hepatic venous blood. The aim of this study was to analyze the safety and efficacy of the second-generation CS-PHP after 54 treatments at Hannover Medical School, Germany.

Methods

Overall response rates (ORR) were assessed according to response evaluation criteria in solid tumors (RECIST1.1). Overall survival (OS), progression-free survival (PFS), and hepatic PFS (hPFS) were analyzed using the Kaplan–Meier estimation.

Results

29 patients were treated with CS-PHP as last-line therapy up to five sessions. 19 patients had unresectable hepatic metastases from solid tumors [ocular melanoma (OM) n = 11; colorectal carcinoma n = 2; pancreatic adenocarcinoma n = 2; periampular carcinoma n = 2; breast and endometrial cancer each n = 1] and 10 patients were diagnosed with hepatocellular or cholangiocarcinoma (HCC/CCA). ORR was 19.2%. Patients with OM had the highest ORR (33.3%). Similar to patients with OM, patients with hepatobiliary tumors had durable disease stabilization (40%). Median OS, PFS, and hPFS were 261, 117, and 135 days, respectively. Tumor volume negatively correlated with OS. Complications and toxicities included thrombocytopenia, cardiovascular events, ulcerous bleeding, and edema.

Conclusion

Second-generation CS-PHP seems to be effective and tolerable. Patient selection based on tumor volume and entity is of importance. Particularly, patients with OM and hepatobiliary tumors represent promising candidates for CS-PHP.

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Abbreviations

AFP:

Alpha-fetoprotein

ALT:

Alanine transaminase

AST:

Aspartate transaminase

BAC:

Best alternative treatment

CCA:

CHOLANGIOCARCINOMA

CI:

Correlation index

CRC:

Colorectal carcinoma

CRP:

c-Reactive protein

CTCAE:

Common Terminology Criteria for adverse Events

CS-PHP:

Chemosaturation percutaneous hepatic perfusion

CT:

Computed tomography

ECG:

Electrocardiogram

ECOG:

Eastern Cooperative Oncology Group

HCC:

Hepatocellular carcinom

OM:

Occular melanoma

ORR:

Overall response rate

PR:

Partial response

PD:

Progressive disease

PS:

Performance status

RECIST:

Response Evaluation Criteria In Solid Tumours

SD:

Stable disease

ULN:

Upper limit of normal

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Author notes

  1. Martha M. Kirstein, Steffen Marquardt, Frank Wacker and Arndt Vogel authors contributed equally.

Authors and Affiliations

  1. Department of Gastroenterology, Hepatology and Endocrinology, Hannover Medical School, Carl-Neuberg-Str. 1, 30625, Hannover, Germany

    Martha M. Kirstein, Nils Jedicke, Silke Marhenke, Michael P. Manns & Arndt Vogel

  2. Institute for Radiology, Hannover Medical School, Hannover, Germany

    Steffen Marquardt & Frank Wacker

  3. Department of Anesthesiology, Hannover Medical School, Hannover, Germany

    Wolfgang Koppert

Authors
  1. Martha M. Kirstein
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  2. Steffen Marquardt
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  3. Nils Jedicke
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  4. Silke Marhenke
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  6. Michael P. Manns
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  7. Frank Wacker
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Corresponding author

Correspondence to Martha M. Kirstein.

Ethics declarations

Financial support

Martha M. Kirstein was supported by the Ellen Schmidt program from Hannover Medical School.

Conflict of interest

Arndt Vogel and Steffen Marquardt have received honoraria from Delcath Systems Inc for AdVisiory Boards and speakers activities. Frank Wacker reports grants and personal fees from Delcath Systems, Inc. during the conduct of the study; grants from Siemens Healthineers, Promedicus Ltd., personal fees from Novartis Pharma GmbH, outside the submitted work.

Ethical approval

All procedures performed in studies involving human participants were in accordance with the ethical standards of the institutional and/or national research committee and with the 1964 Helsinki declaration and its later amendments or comparable ethical standards. Informed consent was not obtained from all patients included in the study due to the retrospective nature of this study in accordance with the institutional research committee.

Electronic supplementary material

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432_2017_2461_MOESM1_ESM.ppt

Supplemental Fig. 1 Laboratory values from day 0 of CS-PHO until day 21. Assessment of hematologic function by hemoglobin (A) and liver injury by CRP (B). Pairwise analyses were performed using the Wilcoxon signed-rank test. *** = p<0.001; **p < 0.01; *p < 0.05 (PPT 111 kb)

432_2017_2461_MOESM2_ESM.doc

Supplemental Table 1 List of treatments prior to first CS-PHP. FUFOX/FOLFOX = 5-fluoropyrimidine and oxaliplatin; XELOX = capecitabine and oxaliplatin; FOLFIRI = 5-fluoropyrimidine and irinotecan (DOC 83 kb)

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Kirstein, M.M., Marquardt, S., Jedicke, N. et al. Safety and efficacy of chemosaturation in patients with primary and secondary liver tumors. J Cancer Res Clin Oncol 143, 2113–2121 (2017). https://doi.org/10.1007/s00432-017-2461-z

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  • DOI: https://doi.org/10.1007/s00432-017-2461-z

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