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 language | English |
|---|---|
| Pages (from-to) | 273-279 |
| Number of pages | 7 |
| Journal | Clinical Colorectal Cancer |
| Volume | 7 |
| Issue number | 4 |
| DOIs | |
| Publication status | Published - 2008 |
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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 journal › Article
}
TY - JOUR
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
Y1 - 2008
N2 - 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.
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.
KW - Cutaneous toxicity
KW - Gastrointestinal toxicity
KW - Monoclonal antibodies
KW - Rash
KW - Salvage therapy
UR - http://www.scopus.com/inward/record.url?scp=49149097899&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=49149097899&partnerID=8YFLogxK
U2 - 10.3816/CCC.2008.n.035
DO - 10.3816/CCC.2008.n.035
M3 - Article
VL - 7
SP - 273
EP - 279
JO - Clinical Colorectal Cancer
JF - Clinical Colorectal Cancer
SN - 1533-0028
IS - 4
ER -