A phase II study of cetuximab/irinotecan in patients with heavily pretreated metastatic colorectal cancer

Predictive value of early specific toxicities

Teresa Gamucci, Fabrizio Nelli, Giovanni Cianci, Giulia Grassi, Luca Moscetti, Isabella Sperduti, Massimo Zeuli, Enrico Cortesi, Giuliana D'Auria, Camillo Francesco Pollera

Research output: Contribution to journalArticle

10 Citations (Scopus)

Abstract

Background: This study was designed to evaluate the predictive value of early specific toxicities on efficacy of weekly irinotecan/cetuximab administered as salvage therapy in patients with metastatic colorectal cancer (CRC) refractory to oxaliplatin and irinotecan. Patients and Methods: Seventy patients received a regimen composed of weekly irinotecan 125 mg/m2 as a 1-hour intravenous infusion and cetuximab 400 mg/m2 infused over 2 hours as the initial dose and 250 mg/m2 infused over 1 hour for subsequent administrations. A single treatment cycle was composed of 4 weekly irinotecan infusions followed by 2 weeks of rest. The predictive value of adverse events (AEs) attributable to cetuximab (rash) and major toxicities attributable to irinotecan (gastrointestinal [G1] and hematologic) were observed after the first cycle of treatment and, therefore, correlated to activity and efficacy of cetuximab and weekly irinotecan. Results: Sixty-six of 70 patients received ≥ 1 cycle of chemotherapy and were therefore evaluable for response. Overall, toxicity observed was generally mild and manageable. According to an intent-to-treat analysis, a partial response was exhibited in 15.7% of patients, with a median progression-free survival (PFS) and median overall survival time of 4 months and 9 months, respectively. As expected, PFS (P = .01) and median survival (P = .04) correlated strongly with the presence and severity of the rash. Surprisingly, the presence of at least moderate hematologic and G1 toxicity was associated with improved PFS (P = .03). Conclusion: Our data suggest that irinotecan-induced AEs might predict a better outcome in advanced CRC. This finding would identify a different subset of patients - those likely to benefit from a renewed sensitivity to irinotecan induced by cetuximab.

Original languageEnglish
Pages (from-to)273-279
Number of pages7
JournalClinical Colorectal Cancer
Volume7
Issue number4
DOIs
Publication statusPublished - 2008

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irinotecan
Colorectal Neoplasms
Disease-Free Survival
oxaliplatin
Exanthema
Salvage Therapy
Survival
Cetuximab
Intravenous Infusions

Keywords

  • Cutaneous toxicity
  • Gastrointestinal toxicity
  • Monoclonal antibodies
  • Rash
  • Salvage therapy

ASJC Scopus subject areas

  • Oncology

Cite this

A phase II study of cetuximab/irinotecan in patients with heavily pretreated metastatic colorectal cancer : Predictive value of early specific toxicities. / Gamucci, Teresa; Nelli, Fabrizio; Cianci, Giovanni; Grassi, Giulia; Moscetti, Luca; Sperduti, Isabella; Zeuli, Massimo; Cortesi, Enrico; D'Auria, Giuliana; Pollera, Camillo Francesco.

In: Clinical Colorectal Cancer, Vol. 7, No. 4, 2008, p. 273-279.

Research output: Contribution to journalArticle

Gamucci, T, Nelli, F, Cianci, G, Grassi, G, Moscetti, L, Sperduti, I, Zeuli, M, Cortesi, E, D'Auria, G & Pollera, CF 2008, 'A phase II study of cetuximab/irinotecan in patients with heavily pretreated metastatic colorectal cancer: Predictive value of early specific toxicities', Clinical Colorectal Cancer, vol. 7, no. 4, pp. 273-279. https://doi.org/10.3816/CCC.2008.n.035
Gamucci, Teresa ; Nelli, Fabrizio ; Cianci, Giovanni ; Grassi, Giulia ; Moscetti, Luca ; Sperduti, Isabella ; Zeuli, Massimo ; Cortesi, Enrico ; D'Auria, Giuliana ; Pollera, Camillo Francesco. / A phase II study of cetuximab/irinotecan in patients with heavily pretreated metastatic colorectal cancer : Predictive value of early specific toxicities. In: Clinical Colorectal Cancer. 2008 ; Vol. 7, No. 4. pp. 273-279.
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abstract = "Background: This study was designed to evaluate the predictive value of early specific toxicities on efficacy of weekly irinotecan/cetuximab administered as salvage therapy in patients with metastatic colorectal cancer (CRC) refractory to oxaliplatin and irinotecan. Patients and Methods: Seventy patients received a regimen composed of weekly irinotecan 125 mg/m2 as a 1-hour intravenous infusion and cetuximab 400 mg/m2 infused over 2 hours as the initial dose and 250 mg/m2 infused over 1 hour for subsequent administrations. A single treatment cycle was composed of 4 weekly irinotecan infusions followed by 2 weeks of rest. The predictive value of adverse events (AEs) attributable to cetuximab (rash) and major toxicities attributable to irinotecan (gastrointestinal [G1] and hematologic) were observed after the first cycle of treatment and, therefore, correlated to activity and efficacy of cetuximab and weekly irinotecan. Results: Sixty-six of 70 patients received ≥ 1 cycle of chemotherapy and were therefore evaluable for response. Overall, toxicity observed was generally mild and manageable. According to an intent-to-treat analysis, a partial response was exhibited in 15.7{\%} of patients, with a median progression-free survival (PFS) and median overall survival time of 4 months and 9 months, respectively. As expected, PFS (P = .01) and median survival (P = .04) correlated strongly with the presence and severity of the rash. Surprisingly, the presence of at least moderate hematologic and G1 toxicity was associated with improved PFS (P = .03). Conclusion: Our data suggest that irinotecan-induced AEs might predict a better outcome in advanced CRC. This finding would identify a different subset of patients - those likely to benefit from a renewed sensitivity to irinotecan induced by cetuximab.",
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T1 - A phase II study of cetuximab/irinotecan in patients with heavily pretreated metastatic colorectal cancer

T2 - Predictive value of early specific toxicities

AU - Gamucci, Teresa

AU - Nelli, Fabrizio

AU - Cianci, Giovanni

AU - Grassi, Giulia

AU - Moscetti, Luca

AU - Sperduti, Isabella

AU - Zeuli, Massimo

AU - Cortesi, Enrico

AU - D'Auria, Giuliana

AU - Pollera, Camillo Francesco

PY - 2008

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AB - Background: This study was designed to evaluate the predictive value of early specific toxicities on efficacy of weekly irinotecan/cetuximab administered as salvage therapy in patients with metastatic colorectal cancer (CRC) refractory to oxaliplatin and irinotecan. Patients and Methods: Seventy patients received a regimen composed of weekly irinotecan 125 mg/m2 as a 1-hour intravenous infusion and cetuximab 400 mg/m2 infused over 2 hours as the initial dose and 250 mg/m2 infused over 1 hour for subsequent administrations. A single treatment cycle was composed of 4 weekly irinotecan infusions followed by 2 weeks of rest. The predictive value of adverse events (AEs) attributable to cetuximab (rash) and major toxicities attributable to irinotecan (gastrointestinal [G1] and hematologic) were observed after the first cycle of treatment and, therefore, correlated to activity and efficacy of cetuximab and weekly irinotecan. Results: Sixty-six of 70 patients received ≥ 1 cycle of chemotherapy and were therefore evaluable for response. Overall, toxicity observed was generally mild and manageable. According to an intent-to-treat analysis, a partial response was exhibited in 15.7% of patients, with a median progression-free survival (PFS) and median overall survival time of 4 months and 9 months, respectively. As expected, PFS (P = .01) and median survival (P = .04) correlated strongly with the presence and severity of the rash. Surprisingly, the presence of at least moderate hematologic and G1 toxicity was associated with improved PFS (P = .03). Conclusion: Our data suggest that irinotecan-induced AEs might predict a better outcome in advanced CRC. This finding would identify a different subset of patients - those likely to benefit from a renewed sensitivity to irinotecan induced by cetuximab.

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KW - Gastrointestinal toxicity

KW - Monoclonal antibodies

KW - Rash

KW - Salvage therapy

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