A platinum salt (oxaliplatin or cisplatin) is widely used to enhance chemoradation (CRT) response. The potential of cisplatin in neoadjuvant CRT for locally advanced rectal cancer (LARC) has not been fully investigated. Consecutive patients with histologically confirmed LARC were treated with standard pelvic radiotherapy and concurrent cisplatin plus capecitabine (CisCape CRT). Surgery and eight cycles of adjuvant FOLFOX4 were offered to all patients after CRT. Common biochemical variables and key germline genetic polymorphisms were analyzed as predictors of pathological complete response (pCR). Fifty-one patients were enrolled. pCR (regression AJCC grade 0) was documented in 7 patients (14%), nearly complete response (AJCC grade 1) in 10 pts. There was a strong association between disease-free survival and AJCC grade (p 0.0047). Grade 3-4 toxicities (mainly diarrhea) was observed in 41% of patients. Among all analyzed variables, baseline hemoglobin (Hb) was significantly associated with AJCC grade 0-1 response (p 0.027). As for the pharmacogenetic analysis, XRCC1 rs25487 polymorphism was significantly associated with AJCC grade 0-1, Odds Ratio 25.8, p 0.049. AJCC grade 0-1 response rate for patients with high Hb and/or XRCC1 rs25487 G/G genotype was as high as 57%. Baseline Hb and XRCC1 polymorphisms are valuable selection criteria for the CisCape CRT regimen, given its otherwise meaningful toxicity.

Formica, V., Benassi, M., Del Vecchio Blanco, G., Doldo, E., Martano, L., Portarena, I., et al. (2018). Hemoglobin level and XRCC1 polymorphisms to select patients with locally advanced rectal cancer candidate for neoadjuvant chemoradiotherapy with concurrent capecitabine and a platinum salt. MEDICAL ONCOLOGY, 35(6), 83 [10.1007/s12032-018-1141-4].

Hemoglobin level and XRCC1 polymorphisms to select patients with locally advanced rectal cancer candidate for neoadjuvant chemoradiotherapy with concurrent capecitabine and a platinum salt

Formica, Vincenzo;Doldo, Elena;Rossi, Piero;Anselmo, Alessandro;Sileri, Pierpaolo;Sica, Giuseppe;Orlandi, Augusto;Santoni, Riccardo;Roselli, Mario
2018-05-02

Abstract

A platinum salt (oxaliplatin or cisplatin) is widely used to enhance chemoradation (CRT) response. The potential of cisplatin in neoadjuvant CRT for locally advanced rectal cancer (LARC) has not been fully investigated. Consecutive patients with histologically confirmed LARC were treated with standard pelvic radiotherapy and concurrent cisplatin plus capecitabine (CisCape CRT). Surgery and eight cycles of adjuvant FOLFOX4 were offered to all patients after CRT. Common biochemical variables and key germline genetic polymorphisms were analyzed as predictors of pathological complete response (pCR). Fifty-one patients were enrolled. pCR (regression AJCC grade 0) was documented in 7 patients (14%), nearly complete response (AJCC grade 1) in 10 pts. There was a strong association between disease-free survival and AJCC grade (p 0.0047). Grade 3-4 toxicities (mainly diarrhea) was observed in 41% of patients. Among all analyzed variables, baseline hemoglobin (Hb) was significantly associated with AJCC grade 0-1 response (p 0.027). As for the pharmacogenetic analysis, XRCC1 rs25487 polymorphism was significantly associated with AJCC grade 0-1, Odds Ratio 25.8, p 0.049. AJCC grade 0-1 response rate for patients with high Hb and/or XRCC1 rs25487 G/G genotype was as high as 57%. Baseline Hb and XRCC1 polymorphisms are valuable selection criteria for the CisCape CRT regimen, given its otherwise meaningful toxicity.
2-mag-2018
Pubblicato
Rilevanza internazionale
Articolo
Esperti anonimi
Settore MED/18 - CHIRURGIA GENERALE
English
Cisplatin
Locally advanced rectal cancer
Neoadjuvant chemoradiotherapy
XRCC1
Adult
Aged
Antineoplastic Combined Chemotherapy Protocols
Capecitabine
Chemoradiotherapy, Adjuvant
Cisplatin
Female
Fluorouracil
Hemoglobins
Humans
Leucovorin
Male
Middle Aged
Neoadjuvant Therapy
Organoplatinum Compounds
Polymorphism, Genetic
Predictive Value of Tests
Rectal Neoplasms
X-ray Repair Cross Complementing Protein 1
Formica, V., Benassi, M., Del Vecchio Blanco, G., Doldo, E., Martano, L., Portarena, I., et al. (2018). Hemoglobin level and XRCC1 polymorphisms to select patients with locally advanced rectal cancer candidate for neoadjuvant chemoradiotherapy with concurrent capecitabine and a platinum salt. MEDICAL ONCOLOGY, 35(6), 83 [10.1007/s12032-018-1141-4].
Formica, V; Benassi, M; Del Vecchio Blanco, G; Doldo, E; Martano, L; Portarena, I; Nardecchia, A; Lucchetti, J; Morelli, C; Giudice, E; Rossi, P; Anselmo, A; Sileri, P; Sica, G; Orlandi, A; Santoni, R; Roselli, M
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Utilizza questo identificativo per citare o creare un link a questo documento: https://hdl.handle.net/2108/261212
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