TY - JOUR
T1 - Oxaliplatin retreatment in metastatic colorectal cancer
T2 - Systematic review and future research opportunities
AU - Mauri, Gianluca
AU - Gori, Viviana
AU - Bonazzina, Erica
AU - Amatu, Alessio
AU - Tosi, Federica
AU - Bencardino, Katia
AU - Ruggieri, Lorenzo
AU - Patelli, Giorgio
AU - Arena, Sabrina
AU - Bardelli, Alberto
AU - Siena, Salvatore
AU - Sartore-Bianchi, Andrea
N1 - Copyright © 2020 Elsevier Ltd. All rights reserved.
PY - 2020/12
Y1 - 2020/12
N2 - BACKGROUND: Oxaliplatin represents a main component of cytotoxic treatment regimens in colorectal cancer (CRC). Given its efficacy, oxaliplatin is frequently re-administered in the context of the continuum of care in metastatic CRC (mCRC). However, efficacy and tolerability of this therapeutic strategy has not been comprehensively assessed.METHODS: We performed a systematic review of the literature on September 19th 2020, according to PRISMA criteria 2009. The research was performed on PubMed, ASCO Meeting Library, ESMO library and ClinicalTrials.gov for citations or ongoing trials.RESULTS: 64 records were retrieved and 13 included in the systematic review: 8 full-text articles, 4 abstracts and 1 ongoing clinical trial. According to readministration timing, studies were classified as rechallenge/reintroduction (n = 8) or stop & go/intermittent therapeutic strategies (n = 4). The studies presented wide heterogeneity in terms of efficacy (Response Rate 6-31%; Disease Control Rate 39-79%; median Progression-Free Survival 3.1-7 months). Those patients who received retreatment after prior adjuvant oxaliplatin or exploiting a stop-&-go strategy appeared to achieve better outcomes. However, no formal comparisons on treatment outcomes were feasible. The most frequent grade 3 or higher adverse events were hematologic toxicities (5-27%), peripheral neuropathy (5-14%) and hypersensitivity reactions (5-20%).CONCLUSIONS: Retreatment with oxaliplatin for mCRC is practiced based on scarce and heterogeneous data indicating efficacy and manageable toxicity. The best strategy to exploit this approach remains to be defined, and the most promising research avenue to improve therapeutic index of oxaliplatin is represented by selection of responder patients whose tumors harbor molecular defects in the DNA damage repair pathway.
AB - BACKGROUND: Oxaliplatin represents a main component of cytotoxic treatment regimens in colorectal cancer (CRC). Given its efficacy, oxaliplatin is frequently re-administered in the context of the continuum of care in metastatic CRC (mCRC). However, efficacy and tolerability of this therapeutic strategy has not been comprehensively assessed.METHODS: We performed a systematic review of the literature on September 19th 2020, according to PRISMA criteria 2009. The research was performed on PubMed, ASCO Meeting Library, ESMO library and ClinicalTrials.gov for citations or ongoing trials.RESULTS: 64 records were retrieved and 13 included in the systematic review: 8 full-text articles, 4 abstracts and 1 ongoing clinical trial. According to readministration timing, studies were classified as rechallenge/reintroduction (n = 8) or stop & go/intermittent therapeutic strategies (n = 4). The studies presented wide heterogeneity in terms of efficacy (Response Rate 6-31%; Disease Control Rate 39-79%; median Progression-Free Survival 3.1-7 months). Those patients who received retreatment after prior adjuvant oxaliplatin or exploiting a stop-&-go strategy appeared to achieve better outcomes. However, no formal comparisons on treatment outcomes were feasible. The most frequent grade 3 or higher adverse events were hematologic toxicities (5-27%), peripheral neuropathy (5-14%) and hypersensitivity reactions (5-20%).CONCLUSIONS: Retreatment with oxaliplatin for mCRC is practiced based on scarce and heterogeneous data indicating efficacy and manageable toxicity. The best strategy to exploit this approach remains to be defined, and the most promising research avenue to improve therapeutic index of oxaliplatin is represented by selection of responder patients whose tumors harbor molecular defects in the DNA damage repair pathway.
KW - Antineoplastic Agents/adverse effects
KW - Colorectal Neoplasms/drug therapy
KW - Humans
KW - Oxaliplatin/adverse effects
KW - Peripheral Nervous System Diseases/chemically induced
KW - Retreatment
KW - Treatment Outcome
U2 - 10.1016/j.ctrv.2020.102112
DO - 10.1016/j.ctrv.2020.102112
M3 - Article
C2 - 33091698
VL - 91
SP - 102112
JO - Cancer Treat. Rev.
JF - Cancer Treat. Rev.
SN - 0305-7372
ER -