Dataset Information

Phase II Trial of Adjuvant Dendritic Cell Vaccine in Combination with Celecoxib, Interferon-?, and Rintatolimod in Patients Undergoing Cytoreductive Surgery and Hyperthermic Intraperitoneal Chemotherapy for Peritoneal Metastases.

ABSTRACT:

Background

Peritoneal metastases portend poor prognosis in the setting of standard chemotherapy. Cytoreductive surgery and hyperthermic intraperitoneal chemotherapy (CRS/HIPEC) improves outcomes, but relapse is common. We report a phase II trial evaluating the safety and efficacy of adjuvant ?DC1 vaccination with chemokine modulation (CKM) after CRS/HIPEC.

Methods

Patients undergoing CRS/HIPEC for appendiceal cancer, colorectal cancer, or peritoneal mesothelioma were enrolled. In addition to standard adjuvant chemotherapy, patients received intranodal and intradermal injections of autologous tumor-loaded ?DC1 vaccine. After each vaccine booster, patients received CKM over 4 days, consisting of celecoxib, interferon (IFN)-?, and rintatolimod.

Results

Forty-six patients underwent CRS/HIPEC followed by ?DC1 treatment, including 24 appendiceal primaries, 20 colorectal, and 2 mesotheliomas. DC maturation was successful, with 97% expressing HLA-DR and CD86. Tumor cell recovery from peritoneal tumors was challenging, resulting in only 17% of patients receiving the target dose of ?DC1. The ?DC1 and CKM regimen was well tolerated. CKM successfully modulated serum inflammatory cytokine and chemokine levels. Median progression-free survival (PFS) for appendiceal primaries was 50.4, 34.2, and 8.9 months for grade 1, 2, and 3 tumors, respectively, while median PFS for colorectal cancer was 20.5 and 8.9 months for moderately and poorly differentiated tumors, respectively.

Conclusions

Adjuvant autologous tumor antigen-loaded ?DC1 vaccine and CKM is well tolerated. The mucinous nature of peritoneal metastases limits the feasibility of obtaining adequate autologous tumor cells. The improvement in median PFS did not meet our predefined thresholds, leading us to conclude that ?DC1 vaccination is not appropriate for patients undergoing CRS/HIPEC for peritoneal metastases.

SUBMITTER: Ramanathan R

PROVIDER: S-EPMC7784622 | biostudies-literature | 2021 Jan

REPOSITORIES: biostudies-literature

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Publications

Phase II Trial of Adjuvant Dendritic Cell Vaccine in Combination with Celecoxib, Interferon-α, and Rintatolimod in Patients Undergoing Cytoreductive Surgery and Hyperthermic Intraperitoneal Chemotherapy for Peritoneal Metastases.

Ramanathan Rajesh R Choudry Haroon H Jones Heather H Girgis Mark M Gooding William W Kalinski Pawel P Bartlett David L DL

Annals of surgical oncology 20210105 8

<h4>Background</h4>Peritoneal metastases portend poor prognosis in the setting of standard chemotherapy. Cytoreductive surgery and hyperthermic intraperitoneal chemotherapy (CRS/HIPEC) improves outcomes, but relapse is common. We report a phase II trial evaluating the safety and efficacy of adjuvant αDC1 vaccination with chemokine modulation (CKM) after CRS/HIPEC.<h4>Methods</h4>Patients undergoing CRS/HIPEC for appendiceal cancer, colorectal cancer, or peritoneal mesothelioma were enrolled. In ...[more]

PMID: 33400000

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