Phase I and II trial on infusional 5-fluorouracil and gefitinib in combination with preoperative radiotherapy in rectal cancer: 10-years median follow-up

Maria Antonietta Gambacorta, Antonino De Paoli, Marco Lupattelli, Giuditta Chiloiro, Angela Pia Solazzo, Brunella Barbaro, Sergio Alfieri, Fabio Maria Vecchio, Jacopo Lenkowicz, Francesco Navarria, Elisa Palazzari, Giulio Bertola, Alessandro Frattegiani, Bruce Minsky, Vincenzo Valentini

Research output: Contribution to journalArticle

Abstract

Purpose: The aim of this study is to evaluate the long term survival of the addition of gefitinib to chemoradiotherapy (CRT) in locally advanced rectal cancer (LARC).

Methods and materials: This previously published multicentre, open-label, phase I-II study, enrolled patients (pts) with LARC to receive CRT with concurrent 5-fluorouracil continuous intravenous infusion and a dose escalation of orally administered gefitinib, followed 6-8 weeks later by surgery. An intra-operative radiotherapy boost of 10 Gy was planned. Adjuvant chemotherapy was administrated in ypN1-2 pts. After a median f/u of >10 years, we analyzed Local Control (LC), Metastasis Free Survival (MFS), Disease Free Survival (DFS), Disease Specific Survival (DSS) and Overall Survival (OS). Predictive endpoints of clinical outcomes were tested by univariate and multivariate analysis. Variables analyzed included: age, gefitinib dose and interruptions, adjuvant CT, surgery type, ypT, ypN, and TRG grade. We have also analyzed late toxicity according to CTCAEv4.

Results: Of the 41 initially enrolled pts, 39 were evaluable (27M, 12F). With a median f/u of 133 months, LC, MFS, DFS, OS and DSS at 5 years were 84%; 71%; 64%; 87% and 92%, respectively. The OS and DSS at 10 years were 61,5% and 76%, respectively. Grade 3-4 late toxicity occurred in 38% of pts: sexual (28,2%) and gastrointestinal toxicities (10,2%).

Conclusion: Long term outcomes and late toxicity were similar to previously reported series. The addition of gefitinib did not improve outcomes in LARC. Gefitinib is not recommended for rectal cancer patients who received 5-FU based preoperative CRT. Further studies may identify if gefitinib is beneficial in selected group of patients.

Original languageEnglish
Pages (from-to)23-28
Number of pages6
JournalClinical and translational radiation oncology
Volume10
DOIs
Publication statusPublished - Mar 2018

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Rectal Neoplasms
Fluorouracil
Radiotherapy
Survival
Chemoradiotherapy
Disease-Free Survival
Neoplasm Metastasis
Adjuvant Chemotherapy
gefitinib
Intravenous Infusions
Multivariate Analysis

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Phase I and II trial on infusional 5-fluorouracil and gefitinib in combination with preoperative radiotherapy in rectal cancer : 10-years median follow-up. / Gambacorta, Maria Antonietta; De Paoli, Antonino; Lupattelli, Marco; Chiloiro, Giuditta; Solazzo, Angela Pia; Barbaro, Brunella; Alfieri, Sergio; Vecchio, Fabio Maria; Lenkowicz, Jacopo; Navarria, Francesco; Palazzari, Elisa; Bertola, Giulio; Frattegiani, Alessandro; Minsky, Bruce; Valentini, Vincenzo.

In: Clinical and translational radiation oncology, Vol. 10, 03.2018, p. 23-28.

Research output: Contribution to journalArticle

Gambacorta, Maria Antonietta ; De Paoli, Antonino ; Lupattelli, Marco ; Chiloiro, Giuditta ; Solazzo, Angela Pia ; Barbaro, Brunella ; Alfieri, Sergio ; Vecchio, Fabio Maria ; Lenkowicz, Jacopo ; Navarria, Francesco ; Palazzari, Elisa ; Bertola, Giulio ; Frattegiani, Alessandro ; Minsky, Bruce ; Valentini, Vincenzo. / Phase I and II trial on infusional 5-fluorouracil and gefitinib in combination with preoperative radiotherapy in rectal cancer : 10-years median follow-up. In: Clinical and translational radiation oncology. 2018 ; Vol. 10. pp. 23-28.
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abstract = "Purpose: The aim of this study is to evaluate the long term survival of the addition of gefitinib to chemoradiotherapy (CRT) in locally advanced rectal cancer (LARC).Methods and materials: This previously published multicentre, open-label, phase I-II study, enrolled patients (pts) with LARC to receive CRT with concurrent 5-fluorouracil continuous intravenous infusion and a dose escalation of orally administered gefitinib, followed 6-8 weeks later by surgery. An intra-operative radiotherapy boost of 10 Gy was planned. Adjuvant chemotherapy was administrated in ypN1-2 pts. After a median f/u of >10 years, we analyzed Local Control (LC), Metastasis Free Survival (MFS), Disease Free Survival (DFS), Disease Specific Survival (DSS) and Overall Survival (OS). Predictive endpoints of clinical outcomes were tested by univariate and multivariate analysis. Variables analyzed included: age, gefitinib dose and interruptions, adjuvant CT, surgery type, ypT, ypN, and TRG grade. We have also analyzed late toxicity according to CTCAEv4.Results: Of the 41 initially enrolled pts, 39 were evaluable (27M, 12F). With a median f/u of 133 months, LC, MFS, DFS, OS and DSS at 5 years were 84{\%}; 71{\%}; 64{\%}; 87{\%} and 92{\%}, respectively. The OS and DSS at 10 years were 61,5{\%} and 76{\%}, respectively. Grade 3-4 late toxicity occurred in 38{\%} of pts: sexual (28,2{\%}) and gastrointestinal toxicities (10,2{\%}).Conclusion: Long term outcomes and late toxicity were similar to previously reported series. The addition of gefitinib did not improve outcomes in LARC. Gefitinib is not recommended for rectal cancer patients who received 5-FU based preoperative CRT. Further studies may identify if gefitinib is beneficial in selected group of patients.",
author = "Gambacorta, {Maria Antonietta} and {De Paoli}, Antonino and Marco Lupattelli and Giuditta Chiloiro and Solazzo, {Angela Pia} and Brunella Barbaro and Sergio Alfieri and Vecchio, {Fabio Maria} and Jacopo Lenkowicz and Francesco Navarria and Elisa Palazzari and Giulio Bertola and Alessandro Frattegiani and Bruce Minsky and Vincenzo Valentini",
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TY - JOUR

T1 - Phase I and II trial on infusional 5-fluorouracil and gefitinib in combination with preoperative radiotherapy in rectal cancer

T2 - 10-years median follow-up

AU - Gambacorta, Maria Antonietta

AU - De Paoli, Antonino

AU - Lupattelli, Marco

AU - Chiloiro, Giuditta

AU - Solazzo, Angela Pia

AU - Barbaro, Brunella

AU - Alfieri, Sergio

AU - Vecchio, Fabio Maria

AU - Lenkowicz, Jacopo

AU - Navarria, Francesco

AU - Palazzari, Elisa

AU - Bertola, Giulio

AU - Frattegiani, Alessandro

AU - Minsky, Bruce

AU - Valentini, Vincenzo

PY - 2018/3

Y1 - 2018/3

N2 - Purpose: The aim of this study is to evaluate the long term survival of the addition of gefitinib to chemoradiotherapy (CRT) in locally advanced rectal cancer (LARC).Methods and materials: This previously published multicentre, open-label, phase I-II study, enrolled patients (pts) with LARC to receive CRT with concurrent 5-fluorouracil continuous intravenous infusion and a dose escalation of orally administered gefitinib, followed 6-8 weeks later by surgery. An intra-operative radiotherapy boost of 10 Gy was planned. Adjuvant chemotherapy was administrated in ypN1-2 pts. After a median f/u of >10 years, we analyzed Local Control (LC), Metastasis Free Survival (MFS), Disease Free Survival (DFS), Disease Specific Survival (DSS) and Overall Survival (OS). Predictive endpoints of clinical outcomes were tested by univariate and multivariate analysis. Variables analyzed included: age, gefitinib dose and interruptions, adjuvant CT, surgery type, ypT, ypN, and TRG grade. We have also analyzed late toxicity according to CTCAEv4.Results: Of the 41 initially enrolled pts, 39 were evaluable (27M, 12F). With a median f/u of 133 months, LC, MFS, DFS, OS and DSS at 5 years were 84%; 71%; 64%; 87% and 92%, respectively. The OS and DSS at 10 years were 61,5% and 76%, respectively. Grade 3-4 late toxicity occurred in 38% of pts: sexual (28,2%) and gastrointestinal toxicities (10,2%).Conclusion: Long term outcomes and late toxicity were similar to previously reported series. The addition of gefitinib did not improve outcomes in LARC. Gefitinib is not recommended for rectal cancer patients who received 5-FU based preoperative CRT. Further studies may identify if gefitinib is beneficial in selected group of patients.

AB - Purpose: The aim of this study is to evaluate the long term survival of the addition of gefitinib to chemoradiotherapy (CRT) in locally advanced rectal cancer (LARC).Methods and materials: This previously published multicentre, open-label, phase I-II study, enrolled patients (pts) with LARC to receive CRT with concurrent 5-fluorouracil continuous intravenous infusion and a dose escalation of orally administered gefitinib, followed 6-8 weeks later by surgery. An intra-operative radiotherapy boost of 10 Gy was planned. Adjuvant chemotherapy was administrated in ypN1-2 pts. After a median f/u of >10 years, we analyzed Local Control (LC), Metastasis Free Survival (MFS), Disease Free Survival (DFS), Disease Specific Survival (DSS) and Overall Survival (OS). Predictive endpoints of clinical outcomes were tested by univariate and multivariate analysis. Variables analyzed included: age, gefitinib dose and interruptions, adjuvant CT, surgery type, ypT, ypN, and TRG grade. We have also analyzed late toxicity according to CTCAEv4.Results: Of the 41 initially enrolled pts, 39 were evaluable (27M, 12F). With a median f/u of 133 months, LC, MFS, DFS, OS and DSS at 5 years were 84%; 71%; 64%; 87% and 92%, respectively. The OS and DSS at 10 years were 61,5% and 76%, respectively. Grade 3-4 late toxicity occurred in 38% of pts: sexual (28,2%) and gastrointestinal toxicities (10,2%).Conclusion: Long term outcomes and late toxicity were similar to previously reported series. The addition of gefitinib did not improve outcomes in LARC. Gefitinib is not recommended for rectal cancer patients who received 5-FU based preoperative CRT. Further studies may identify if gefitinib is beneficial in selected group of patients.

U2 - 10.1016/j.ctro.2018.02.003

DO - 10.1016/j.ctro.2018.02.003

M3 - Article

C2 - 29928702

VL - 10

SP - 23

EP - 28

JO - Clinical and translational radiation oncology

JF - Clinical and translational radiation oncology

SN - 2405-6308

ER -