Primary tumor response to preoperative chemoradiation with or without oxaliplatin in locally advanced rectal cancer: Pathologic results of the STAR-01 randomized phase III trial

Carlo Aschele, Luca Cionini, Sara Lonardi, Carmine Pinto, Stefano Cordio, Gerardo Rosati, Salvatore Artale, Angiolo Tagliagambe, Giovanni Ambrosini, Paola Rosetti, Andrea Bonetti, Maria Emanuela Negru, Maria Chiara Tronconi, Gabriele Luppi, Giovanni Silvano, Domenico Cristiano Corsi, Anna Maria Bochicchio, Germana Chiaulon, Maurizio Gallo, Luca Boni

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Abstract

Purpose: To investigate oxaliplatin combined with fluorouracil-based chemoradiotherapy as preoperative treatment for locally advanced rectal cancer. Patients and Methods: Seven hundred forty-seven patients with resectable, locally advanced (cT3-4 and/or cN1-2) adenocarcinoma of the mid-low rectum were randomly assigned to receive pelvic radiation (50.4 Gy in 28 daily fractions) and concomitant infused fluorouracil (225 mg/m2/d) either alone (arm A, n = 379) or combined with oxaliplatin (60 mg/m2 weekly × 6; arm B, n = 368). Overall survival is the primary end point. A protocol-planned analysis of response to preoperative treatment is reported here. Results: Grade 3 to 4 adverse events during preoperative treatment were more frequent with oxaliplatin plus fluorouracil and radiation than with radiation and fluorouracil alone (24% v 8% of treated patients; P <.001). In arm B, 83% of the patients treated with oxaliplatin had five or more weekly administrations. Ninety-one percent, compared with 97% in the control arm, received ≥ 45 Gy (P <.001). Ninety-six percent versus 95% of patients underwent surgery with similar rates of abdominoperineal resections (20% v 18%, arm A v arm B). The rate of pathologic complete responses was 16% in both arms (odds ratio = 0.98; 95% CI, 0.66 to 1.44; P = .904). Twenty-six percent versus 29% of patients had pathologically positive lymph nodes (arm A v arm B; P = .447), 46% versus 44% had tumor infiltration beyond the muscularis propria (P = .701), and 7% versus 4% had positive circumferential resection margins (P = .239). Intra-abdominal metastases were found at surgery in 2.9% versus 0.5% of patients (arm A v arm B; P = .014). Conclusion: Adding oxaliplatin to fluorouracil-based preoperative chemoradiotherapy significantly increases toxicity without affecting primary tumor response. Longer follow-up is needed to assess the impact on efficacy end points.

Original languageEnglish
Pages (from-to)2773-2780
Number of pages8
JournalJournal of Clinical Oncology
Volume29
Issue number20
DOIs
Publication statusPublished - Jul 10 2011

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oxaliplatin
Rectal Neoplasms
Fluorouracil
Neoplasms
Chemoradiotherapy
Radiation
Radiation Dosage
Rectum

ASJC Scopus subject areas

  • Cancer Research
  • Oncology

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Primary tumor response to preoperative chemoradiation with or without oxaliplatin in locally advanced rectal cancer : Pathologic results of the STAR-01 randomized phase III trial. / Aschele, Carlo; Cionini, Luca; Lonardi, Sara; Pinto, Carmine; Cordio, Stefano; Rosati, Gerardo; Artale, Salvatore; Tagliagambe, Angiolo; Ambrosini, Giovanni; Rosetti, Paola; Bonetti, Andrea; Negru, Maria Emanuela; Tronconi, Maria Chiara; Luppi, Gabriele; Silvano, Giovanni; Corsi, Domenico Cristiano; Bochicchio, Anna Maria; Chiaulon, Germana; Gallo, Maurizio; Boni, Luca.

In: Journal of Clinical Oncology, Vol. 29, No. 20, 10.07.2011, p. 2773-2780.

Research output: Contribution to journalArticle

Aschele, C, Cionini, L, Lonardi, S, Pinto, C, Cordio, S, Rosati, G, Artale, S, Tagliagambe, A, Ambrosini, G, Rosetti, P, Bonetti, A, Negru, ME, Tronconi, MC, Luppi, G, Silvano, G, Corsi, DC, Bochicchio, AM, Chiaulon, G, Gallo, M & Boni, L 2011, 'Primary tumor response to preoperative chemoradiation with or without oxaliplatin in locally advanced rectal cancer: Pathologic results of the STAR-01 randomized phase III trial', Journal of Clinical Oncology, vol. 29, no. 20, pp. 2773-2780. https://doi.org/10.1200/JCO.2010.34.4911
Aschele, Carlo ; Cionini, Luca ; Lonardi, Sara ; Pinto, Carmine ; Cordio, Stefano ; Rosati, Gerardo ; Artale, Salvatore ; Tagliagambe, Angiolo ; Ambrosini, Giovanni ; Rosetti, Paola ; Bonetti, Andrea ; Negru, Maria Emanuela ; Tronconi, Maria Chiara ; Luppi, Gabriele ; Silvano, Giovanni ; Corsi, Domenico Cristiano ; Bochicchio, Anna Maria ; Chiaulon, Germana ; Gallo, Maurizio ; Boni, Luca. / Primary tumor response to preoperative chemoradiation with or without oxaliplatin in locally advanced rectal cancer : Pathologic results of the STAR-01 randomized phase III trial. In: Journal of Clinical Oncology. 2011 ; Vol. 29, No. 20. pp. 2773-2780.
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abstract = "Purpose: To investigate oxaliplatin combined with fluorouracil-based chemoradiotherapy as preoperative treatment for locally advanced rectal cancer. Patients and Methods: Seven hundred forty-seven patients with resectable, locally advanced (cT3-4 and/or cN1-2) adenocarcinoma of the mid-low rectum were randomly assigned to receive pelvic radiation (50.4 Gy in 28 daily fractions) and concomitant infused fluorouracil (225 mg/m2/d) either alone (arm A, n = 379) or combined with oxaliplatin (60 mg/m2 weekly × 6; arm B, n = 368). Overall survival is the primary end point. A protocol-planned analysis of response to preoperative treatment is reported here. Results: Grade 3 to 4 adverse events during preoperative treatment were more frequent with oxaliplatin plus fluorouracil and radiation than with radiation and fluorouracil alone (24{\%} v 8{\%} of treated patients; P <.001). In arm B, 83{\%} of the patients treated with oxaliplatin had five or more weekly administrations. Ninety-one percent, compared with 97{\%} in the control arm, received ≥ 45 Gy (P <.001). Ninety-six percent versus 95{\%} of patients underwent surgery with similar rates of abdominoperineal resections (20{\%} v 18{\%}, arm A v arm B). The rate of pathologic complete responses was 16{\%} in both arms (odds ratio = 0.98; 95{\%} CI, 0.66 to 1.44; P = .904). Twenty-six percent versus 29{\%} of patients had pathologically positive lymph nodes (arm A v arm B; P = .447), 46{\%} versus 44{\%} had tumor infiltration beyond the muscularis propria (P = .701), and 7{\%} versus 4{\%} had positive circumferential resection margins (P = .239). Intra-abdominal metastases were found at surgery in 2.9{\%} versus 0.5{\%} of patients (arm A v arm B; P = .014). Conclusion: Adding oxaliplatin to fluorouracil-based preoperative chemoradiotherapy significantly increases toxicity without affecting primary tumor response. Longer follow-up is needed to assess the impact on efficacy end points.",
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T1 - Primary tumor response to preoperative chemoradiation with or without oxaliplatin in locally advanced rectal cancer

T2 - Pathologic results of the STAR-01 randomized phase III trial

AU - Aschele, Carlo

AU - Cionini, Luca

AU - Lonardi, Sara

AU - Pinto, Carmine

AU - Cordio, Stefano

AU - Rosati, Gerardo

AU - Artale, Salvatore

AU - Tagliagambe, Angiolo

AU - Ambrosini, Giovanni

AU - Rosetti, Paola

AU - Bonetti, Andrea

AU - Negru, Maria Emanuela

AU - Tronconi, Maria Chiara

AU - Luppi, Gabriele

AU - Silvano, Giovanni

AU - Corsi, Domenico Cristiano

AU - Bochicchio, Anna Maria

AU - Chiaulon, Germana

AU - Gallo, Maurizio

AU - Boni, Luca

PY - 2011/7/10

Y1 - 2011/7/10

N2 - Purpose: To investigate oxaliplatin combined with fluorouracil-based chemoradiotherapy as preoperative treatment for locally advanced rectal cancer. Patients and Methods: Seven hundred forty-seven patients with resectable, locally advanced (cT3-4 and/or cN1-2) adenocarcinoma of the mid-low rectum were randomly assigned to receive pelvic radiation (50.4 Gy in 28 daily fractions) and concomitant infused fluorouracil (225 mg/m2/d) either alone (arm A, n = 379) or combined with oxaliplatin (60 mg/m2 weekly × 6; arm B, n = 368). Overall survival is the primary end point. A protocol-planned analysis of response to preoperative treatment is reported here. Results: Grade 3 to 4 adverse events during preoperative treatment were more frequent with oxaliplatin plus fluorouracil and radiation than with radiation and fluorouracil alone (24% v 8% of treated patients; P <.001). In arm B, 83% of the patients treated with oxaliplatin had five or more weekly administrations. Ninety-one percent, compared with 97% in the control arm, received ≥ 45 Gy (P <.001). Ninety-six percent versus 95% of patients underwent surgery with similar rates of abdominoperineal resections (20% v 18%, arm A v arm B). The rate of pathologic complete responses was 16% in both arms (odds ratio = 0.98; 95% CI, 0.66 to 1.44; P = .904). Twenty-six percent versus 29% of patients had pathologically positive lymph nodes (arm A v arm B; P = .447), 46% versus 44% had tumor infiltration beyond the muscularis propria (P = .701), and 7% versus 4% had positive circumferential resection margins (P = .239). Intra-abdominal metastases were found at surgery in 2.9% versus 0.5% of patients (arm A v arm B; P = .014). Conclusion: Adding oxaliplatin to fluorouracil-based preoperative chemoradiotherapy significantly increases toxicity without affecting primary tumor response. Longer follow-up is needed to assess the impact on efficacy end points.

AB - Purpose: To investigate oxaliplatin combined with fluorouracil-based chemoradiotherapy as preoperative treatment for locally advanced rectal cancer. Patients and Methods: Seven hundred forty-seven patients with resectable, locally advanced (cT3-4 and/or cN1-2) adenocarcinoma of the mid-low rectum were randomly assigned to receive pelvic radiation (50.4 Gy in 28 daily fractions) and concomitant infused fluorouracil (225 mg/m2/d) either alone (arm A, n = 379) or combined with oxaliplatin (60 mg/m2 weekly × 6; arm B, n = 368). Overall survival is the primary end point. A protocol-planned analysis of response to preoperative treatment is reported here. Results: Grade 3 to 4 adverse events during preoperative treatment were more frequent with oxaliplatin plus fluorouracil and radiation than with radiation and fluorouracil alone (24% v 8% of treated patients; P <.001). In arm B, 83% of the patients treated with oxaliplatin had five or more weekly administrations. Ninety-one percent, compared with 97% in the control arm, received ≥ 45 Gy (P <.001). Ninety-six percent versus 95% of patients underwent surgery with similar rates of abdominoperineal resections (20% v 18%, arm A v arm B). The rate of pathologic complete responses was 16% in both arms (odds ratio = 0.98; 95% CI, 0.66 to 1.44; P = .904). Twenty-six percent versus 29% of patients had pathologically positive lymph nodes (arm A v arm B; P = .447), 46% versus 44% had tumor infiltration beyond the muscularis propria (P = .701), and 7% versus 4% had positive circumferential resection margins (P = .239). Intra-abdominal metastases were found at surgery in 2.9% versus 0.5% of patients (arm A v arm B; P = .014). Conclusion: Adding oxaliplatin to fluorouracil-based preoperative chemoradiotherapy significantly increases toxicity without affecting primary tumor response. Longer follow-up is needed to assess the impact on efficacy end points.

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