Gianluca Mauri1, Viviana Gori1, Erica Bonazzina2, Alessio Amatu2, Federica Tosi2, Katia Bencardino2, Lorenzo Ruggieri1, Giorgio Patelli1, Sabrina Arena3, Alberto Bardelli3, Salvatore Siena1, Andrea Sartore-Bianchi4. 1. Niguarda Cancer Center, Grande Ospedale Metropolitano Niguarda, Milano, Italy; Dipartimento di Oncologia ed Emato-Oncologia, Università degli Studi di Milano, Milano, Italy. 2. Niguarda Cancer Center, Grande Ospedale Metropolitano Niguarda, Milano, Italy. 3. Candiolo Cancer Institute, FPO - IRCCS, Candiolo, Torino, Italy; Department of Oncology, University of Torino, Candiolo, Torino, Italy. 4. Niguarda Cancer Center, Grande Ospedale Metropolitano Niguarda, Milano, Italy; Dipartimento di Oncologia ed Emato-Oncologia, Università degli Studi di Milano, Milano, Italy. Electronic address: andrea.sartorebianchi@unimi.it.
Abstract
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.
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.
Authors: Francesca Pia Caruso; Mario Rosario D'Andrea; Luigi Coppola; Matteo Landriscina; Valentina Condelli; Luigi Cerulo; Guido Giordano; Almudena Porras; Massimo Pancione Journal: Cancer Cell Int Date: 2022-08-11 Impact factor: 6.429