Oxaliplatin plus dual inhibition of thymidilate synthase during preoperative pelvic radiotherapy for locally advanced rectal carcinoma: Long-term outcome

Antonio Avallone, Paolo Delrio, Biagio Pecori, Fabiana Tatangelo, Antonella Petrillo, Nigel Scott, Pietro Marone, Luigi Aloi, Claudia Sandomenico, Secondo Lastoria, Vincenzo Rosario Iaffaioli, Dario Scala, Giovanni Iodice, Alfredo Budillon, Pasquale Comella

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Abstract

Purpose: To assess the safety and efficacy of oxaliplatin (OXA) plus dual inhibition of thymidilate synthase during preoperative pelvic radiotherapy (RT) in patients with poor prognosis for rectal carcinoma. Methods and Materials: Sixty-three patients with the following characteristics, a clinical (c) stage T4, cN1-2, or cT3N0 of ≤5 cm from the anal verge and/or with a circumferential resection margin (CRM) of ≤5 mm (by magnetic resonance imaging), received three biweekly courses of chemotherapy with OXA, 100 mg/m 2; raltitrexed (RTX), 2.5 mg/m 2 on day 1, and 5-fluorouracil (5-FU), 900 mg/m 2 (31 patients) or 800 mg/m 2 (32 patients); levo-folinic acid (LFA), 250 mg/m 2 on day 2, during pelvic RT (45 Gy). Pathologic response was defined as complete pathological response (ypCR), major (tumor regression grade(TRG) 2 to 3, with ypCRM-ve and ypN-ve) or minor or no response (TRG4 to -5, or ypCRM+ve, or ypN+ve). Adjuvant 5-FU/LFA regimen was given in cases of cT4, ypN+ve, or ypCRM+ve. Results: Overall, neutropenia (40%) and diarrhea (13%) were the most common grade ≥3 toxicities, and tolerability was better with a 5-FU dose reduction. No significant difference in pathologic response was seen according 5-FU dosage: overall, a ypCR was obtained in 24 (39%) patients, and a major response in 20 (32%) patients. The 5-year probability of freedom from recurrence was 80% (95% confidence interval, 68%-92%); it was 56% for the minor/no response group, while it was around 90% for both the ypCR and the major response group. Conclusions: OXA, RTX, and 5-FU/LFA administered during pelvic RT produced promising early and long-term results in rectal carcinoma patients with poor prognosis. The postoperative treatment strategy applied in our study supports the risk-adapted approach in postoperative management.

Original languageEnglish
Pages (from-to)670-676
Number of pages7
JournalInternational Journal of Radiation Oncology Biology Physics
Volume79
Issue number3
DOIs
Publication statusPublished - Mar 1 2011

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oxaliplatin
radiation therapy
Radiotherapy
cancer
Fluorouracil
Carcinoma
Leucovorin
prognosis
acids
grade
dosage
chemotherapy
Neutropenia
toxicity
magnetic resonance
confidence

Keywords

  • MRI staging
  • Neoadjuvant chemoradiation
  • Oxaliplatin
  • Rectal cancer
  • Thymidilate synthase inhibition

ASJC Scopus subject areas

  • Oncology
  • Radiology Nuclear Medicine and imaging
  • Radiation
  • Cancer Research

Cite this

@article{988a82a00980484f9b84f069ce2ff006,
title = "Oxaliplatin plus dual inhibition of thymidilate synthase during preoperative pelvic radiotherapy for locally advanced rectal carcinoma: Long-term outcome",
abstract = "Purpose: To assess the safety and efficacy of oxaliplatin (OXA) plus dual inhibition of thymidilate synthase during preoperative pelvic radiotherapy (RT) in patients with poor prognosis for rectal carcinoma. Methods and Materials: Sixty-three patients with the following characteristics, a clinical (c) stage T4, cN1-2, or cT3N0 of ≤5 cm from the anal verge and/or with a circumferential resection margin (CRM) of ≤5 mm (by magnetic resonance imaging), received three biweekly courses of chemotherapy with OXA, 100 mg/m 2; raltitrexed (RTX), 2.5 mg/m 2 on day 1, and 5-fluorouracil (5-FU), 900 mg/m 2 (31 patients) or 800 mg/m 2 (32 patients); levo-folinic acid (LFA), 250 mg/m 2 on day 2, during pelvic RT (45 Gy). Pathologic response was defined as complete pathological response (ypCR), major (tumor regression grade(TRG) 2 to 3, with ypCRM-ve and ypN-ve) or minor or no response (TRG4 to -5, or ypCRM+ve, or ypN+ve). Adjuvant 5-FU/LFA regimen was given in cases of cT4, ypN+ve, or ypCRM+ve. Results: Overall, neutropenia (40{\%}) and diarrhea (13{\%}) were the most common grade ≥3 toxicities, and tolerability was better with a 5-FU dose reduction. No significant difference in pathologic response was seen according 5-FU dosage: overall, a ypCR was obtained in 24 (39{\%}) patients, and a major response in 20 (32{\%}) patients. The 5-year probability of freedom from recurrence was 80{\%} (95{\%} confidence interval, 68{\%}-92{\%}); it was 56{\%} for the minor/no response group, while it was around 90{\%} for both the ypCR and the major response group. Conclusions: OXA, RTX, and 5-FU/LFA administered during pelvic RT produced promising early and long-term results in rectal carcinoma patients with poor prognosis. The postoperative treatment strategy applied in our study supports the risk-adapted approach in postoperative management.",
keywords = "MRI staging, Neoadjuvant chemoradiation, Oxaliplatin, Rectal cancer, Thymidilate synthase inhibition",
author = "Antonio Avallone and Paolo Delrio and Biagio Pecori and Fabiana Tatangelo and Antonella Petrillo and Nigel Scott and Pietro Marone and Luigi Aloi and Claudia Sandomenico and Secondo Lastoria and Iaffaioli, {Vincenzo Rosario} and Dario Scala and Giovanni Iodice and Alfredo Budillon and Pasquale Comella",
year = "2011",
month = "3",
day = "1",
doi = "10.1016/j.ijrobp.2009.12.007",
language = "English",
volume = "79",
pages = "670--676",
journal = "International Journal of Radiation Oncology Biology Physics",
issn = "0360-3016",
publisher = "Elsevier Inc.",
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TY - JOUR

T1 - Oxaliplatin plus dual inhibition of thymidilate synthase during preoperative pelvic radiotherapy for locally advanced rectal carcinoma

T2 - Long-term outcome

AU - Avallone, Antonio

AU - Delrio, Paolo

AU - Pecori, Biagio

AU - Tatangelo, Fabiana

AU - Petrillo, Antonella

AU - Scott, Nigel

AU - Marone, Pietro

AU - Aloi, Luigi

AU - Sandomenico, Claudia

AU - Lastoria, Secondo

AU - Iaffaioli, Vincenzo Rosario

AU - Scala, Dario

AU - Iodice, Giovanni

AU - Budillon, Alfredo

AU - Comella, Pasquale

PY - 2011/3/1

Y1 - 2011/3/1

N2 - Purpose: To assess the safety and efficacy of oxaliplatin (OXA) plus dual inhibition of thymidilate synthase during preoperative pelvic radiotherapy (RT) in patients with poor prognosis for rectal carcinoma. Methods and Materials: Sixty-three patients with the following characteristics, a clinical (c) stage T4, cN1-2, or cT3N0 of ≤5 cm from the anal verge and/or with a circumferential resection margin (CRM) of ≤5 mm (by magnetic resonance imaging), received three biweekly courses of chemotherapy with OXA, 100 mg/m 2; raltitrexed (RTX), 2.5 mg/m 2 on day 1, and 5-fluorouracil (5-FU), 900 mg/m 2 (31 patients) or 800 mg/m 2 (32 patients); levo-folinic acid (LFA), 250 mg/m 2 on day 2, during pelvic RT (45 Gy). Pathologic response was defined as complete pathological response (ypCR), major (tumor regression grade(TRG) 2 to 3, with ypCRM-ve and ypN-ve) or minor or no response (TRG4 to -5, or ypCRM+ve, or ypN+ve). Adjuvant 5-FU/LFA regimen was given in cases of cT4, ypN+ve, or ypCRM+ve. Results: Overall, neutropenia (40%) and diarrhea (13%) were the most common grade ≥3 toxicities, and tolerability was better with a 5-FU dose reduction. No significant difference in pathologic response was seen according 5-FU dosage: overall, a ypCR was obtained in 24 (39%) patients, and a major response in 20 (32%) patients. The 5-year probability of freedom from recurrence was 80% (95% confidence interval, 68%-92%); it was 56% for the minor/no response group, while it was around 90% for both the ypCR and the major response group. Conclusions: OXA, RTX, and 5-FU/LFA administered during pelvic RT produced promising early and long-term results in rectal carcinoma patients with poor prognosis. The postoperative treatment strategy applied in our study supports the risk-adapted approach in postoperative management.

AB - Purpose: To assess the safety and efficacy of oxaliplatin (OXA) plus dual inhibition of thymidilate synthase during preoperative pelvic radiotherapy (RT) in patients with poor prognosis for rectal carcinoma. Methods and Materials: Sixty-three patients with the following characteristics, a clinical (c) stage T4, cN1-2, or cT3N0 of ≤5 cm from the anal verge and/or with a circumferential resection margin (CRM) of ≤5 mm (by magnetic resonance imaging), received three biweekly courses of chemotherapy with OXA, 100 mg/m 2; raltitrexed (RTX), 2.5 mg/m 2 on day 1, and 5-fluorouracil (5-FU), 900 mg/m 2 (31 patients) or 800 mg/m 2 (32 patients); levo-folinic acid (LFA), 250 mg/m 2 on day 2, during pelvic RT (45 Gy). Pathologic response was defined as complete pathological response (ypCR), major (tumor regression grade(TRG) 2 to 3, with ypCRM-ve and ypN-ve) or minor or no response (TRG4 to -5, or ypCRM+ve, or ypN+ve). Adjuvant 5-FU/LFA regimen was given in cases of cT4, ypN+ve, or ypCRM+ve. Results: Overall, neutropenia (40%) and diarrhea (13%) were the most common grade ≥3 toxicities, and tolerability was better with a 5-FU dose reduction. No significant difference in pathologic response was seen according 5-FU dosage: overall, a ypCR was obtained in 24 (39%) patients, and a major response in 20 (32%) patients. The 5-year probability of freedom from recurrence was 80% (95% confidence interval, 68%-92%); it was 56% for the minor/no response group, while it was around 90% for both the ypCR and the major response group. Conclusions: OXA, RTX, and 5-FU/LFA administered during pelvic RT produced promising early and long-term results in rectal carcinoma patients with poor prognosis. The postoperative treatment strategy applied in our study supports the risk-adapted approach in postoperative management.

KW - MRI staging

KW - Neoadjuvant chemoradiation

KW - Oxaliplatin

KW - Rectal cancer

KW - Thymidilate synthase inhibition

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U2 - 10.1016/j.ijrobp.2009.12.007

DO - 10.1016/j.ijrobp.2009.12.007

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VL - 79

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EP - 676

JO - International Journal of Radiation Oncology Biology Physics

JF - International Journal of Radiation Oncology Biology Physics

SN - 0360-3016

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