Abstract
Background
Numerous studies have suggested benefit for heated intraperitoneal chemotherapy (HIPEC)
in the treatment of peritoneal metastases from colon cancer. However, the PRODIGE
7 trial that randomized 265 colon cancer patients to surgery plus HIPEC vs. surgery
alone after neoadjuvant chemotherapy (NACT) did not confirm benefit. These data were
published as an abstract and not as a peer-reviewed manuscript. One concern is that
prior drug exposure may select for drug resistance and blunt HIPEC efficacy.
Methods
A database query identified colon cancer specimens evaluated for chemotherapy sensitivity
by ex-vivo analysis of programmed cell death (EVA/PCD), a primary culture platform
that examines drug-induced cell death (apoptotic & non-apoptotic) by morphologic,
metabolic and histologic endpoints.
Results
Of 87 fresh colon cancer specimens, 54 (62%) were untreated and 33 (38%) had received
prior folinic acid, 5-fluorouracil, oxaliplatin (FOLFOX) or capecitabine and oxaliplatin
(CAPOX). In an apoptosis assay, the lethal concentration of 50% (LC50) in untreated
patients was significantly lower than in patients treated by FOLFOX (p = 0.002). Then
to approximate PRODIGE 7, treated patients were separated by having received oxaliplatin
treatment less than or greater than 2 months before EVA/PCD analysis. The degree of
resistance increasing significantly for patients who received treatment less than
2 months prior to EVA/PCD (p < 0.002). Activity for mitomycin and irinotecan was not
significantly different for untreated vs. treated patients, but 5-FU was more resistant
(P = 0.048).
Conclusions
The failure of PRODIGE 7 to improve survival with surgery plus HIPEC following NACT
may reflect diminished oxaliplatin cytotoxicity in patients whose residual disease
has been selected for oxaliplatin and 5-FU resistance.
Keywords
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Article info
Publication history
Published online: September 19, 2020
Accepted:
September 17,
2020
Identification
Copyright
© 2020 Elsevier Ltd, BASO ~ The Association for Cancer Surgery, and the European Society of Surgical Oncology. All rights reserved.
