Normal view MARC view ISBD view

Colorectal cancer cells from patients treated with FOLFOX or CAPOX are resistant to oxaliplatin. [Review]

MedStar author(s):

Citation: European Journal of Surgical Oncology. 47(4):738-742, 2021 Apr.PMID: 33004272Institution: Washington Cancer InstituteForm of publication: Journal ArticleMedline article type(s): Journal Article | ReviewSubject headings: *Colorectal Neoplasms/dt [Drug Therapy] | *Drug Resistance, Neoplasm/de [Drug Effects] | *Oxaliplatin/pd [Pharmacology] | *Peritoneal Neoplasms/dt [Drug Therapy] | Antineoplastic Combined Chemotherapy Protocols/tu [Therapeutic Use] | Apoptosis/de [Drug Effects] | Capecitabine/ad [Administration & Dosage] | Colorectal Neoplasms/pa [Pathology] | Colorectal Neoplasms/su [Surgery] | Fluorouracil/pd [Pharmacology] | Fluorouracil/tu [Therapeutic Use] | Humans | Hyperthermic Intraperitoneal Chemotherapy | Irinotecan/pd [Pharmacology] | Leucovorin/tu [Therapeutic Use] | Mitomycin/pd [Pharmacology] | Neoadjuvant Therapy | Organoplatinum Compounds/tu [Therapeutic Use] | Oxaliplatin/ad [Administration & Dosage] | Peritoneal Neoplasms/sc [Secondary] | Primary Cell Culture | Tumor Cells, CulturedYear: 2021 ISSN:

0748-7983

Name of journal: European journal of surgical oncology : the journal of the European Society of Surgical Oncology and the British Association of Surgical OncologyAbstract: 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.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. Copyright (c) 2020. Published by Elsevier Ltd.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).All authors: Evans S, Nagourney AJ, Nagourney RA, Sugarbaker PH, Tran PHOriginally published: European Journal of Surgical Oncology. 2020 Sep 19Fiscal year: FY2021Digital Object Identifier:

https://dx.doi.org/10.1016/j.ejso.2020.09.017

Date added to catalog: 2020-12-29

Holdings ( 1 )
Title notes ( 5 )

Holdings
Item type	Current library	Collection	Call number	Status	Date due	Barcode
Journal Article	MedStar Authors Catalog	Article	33004272	Available		33004272

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.

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. Copyright (c) 2020. Published by Elsevier Ltd.

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).

English