Phase I study of oral irinotecan as a single-agent and given sequentially with capecitabine

Laura W. Goff*, Al B Benson III, Patricia M. LoRusso, Antoinette R. Tan, Jordan D. Berlin, Louis J. Denis, Rebecca J. Benner, Donghua Yin, Mace L. Rothenberg

*Corresponding author for this work

Research output: Contribution to journalArticle

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Abstract

Purpose To assess the maximum tolerated dose (MTD) and dose-limiting toxicities (DLT) of orally administered irinotecan in the semi-solid matrix (SSM) formulation, both as a single agent and in sequential combination with capecitabine, in patients with advanced solid tumors. Patients and Methods Forty-three patients were treated with irinotecan given as a single oral daily dose on days 1-5 every three weeks. An additional forty patients were treated with sequential oral irinotecan given daily on days 1-5 followed by capecitabine given orally as a divided dose twice daily on days 6-14 of each three week cycle. Results The MTD of single-agent oral irinotecan was estimated to be 60 mg/m 2/day, and DLT included diarrhea, nausea, and neutropenia. In an initial group of patients with Eastern Cooperative Oncology Group (ECOG) performance status (PS) of 0 to 2, the MTD of sequential oral irinotecan/ capecitabine was estimated to be 40/1600 mg/m 2/day with DLT of delayed diarrhea. In a subsequent group of patients with ECOG PS of 0 or 1, the MTD for the sequential combination was 50/2000 mg/m 2/day. The most common adverse events were fatigue, diarrhea, nausea/vomiting and dehydration. Pharmacokinetic (PK) evaluation showed that oral irinotecan was rapidly absorbed and effectively converted to the active metabolite, SN-38, achieving approximately 50% of the SN-38 systemic exposure resulting from an equivalent IV dose. Conclusions Oral irinotecan can be safely administered as a single agent or in sequential combination with capecitabine. The efficacy of oral irinotecan should be explored further as a potentially convenient alternative to IV chemotherapy.

Original languageEnglish (US)
Pages (from-to)290-298
Number of pages9
JournalInvestigational New Drugs
Volume30
Issue number1
DOIs
StatePublished - Feb 1 2012

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irinotecan
Maximum Tolerated Dose
Diarrhea
Nausea
Capecitabine

Keywords

  • Capecitabine
  • Irinotecan

ASJC Scopus subject areas

  • Oncology
  • Pharmacology
  • Pharmacology (medical)

Cite this

Goff, L. W., Benson III, A. B., LoRusso, P. M., Tan, A. R., Berlin, J. D., Denis, L. J., ... Rothenberg, M. L. (2012). Phase I study of oral irinotecan as a single-agent and given sequentially with capecitabine. Investigational New Drugs, 30(1), 290-298. https://doi.org/10.1007/s10637-010-9528-x
Goff, Laura W. ; Benson III, Al B ; LoRusso, Patricia M. ; Tan, Antoinette R. ; Berlin, Jordan D. ; Denis, Louis J. ; Benner, Rebecca J. ; Yin, Donghua ; Rothenberg, Mace L. / Phase I study of oral irinotecan as a single-agent and given sequentially with capecitabine. In: Investigational New Drugs. 2012 ; Vol. 30, No. 1. pp. 290-298.
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abstract = "Purpose To assess the maximum tolerated dose (MTD) and dose-limiting toxicities (DLT) of orally administered irinotecan in the semi-solid matrix (SSM) formulation, both as a single agent and in sequential combination with capecitabine, in patients with advanced solid tumors. Patients and Methods Forty-three patients were treated with irinotecan given as a single oral daily dose on days 1-5 every three weeks. An additional forty patients were treated with sequential oral irinotecan given daily on days 1-5 followed by capecitabine given orally as a divided dose twice daily on days 6-14 of each three week cycle. Results The MTD of single-agent oral irinotecan was estimated to be 60 mg/m 2/day, and DLT included diarrhea, nausea, and neutropenia. In an initial group of patients with Eastern Cooperative Oncology Group (ECOG) performance status (PS) of 0 to 2, the MTD of sequential oral irinotecan/ capecitabine was estimated to be 40/1600 mg/m 2/day with DLT of delayed diarrhea. In a subsequent group of patients with ECOG PS of 0 or 1, the MTD for the sequential combination was 50/2000 mg/m 2/day. The most common adverse events were fatigue, diarrhea, nausea/vomiting and dehydration. Pharmacokinetic (PK) evaluation showed that oral irinotecan was rapidly absorbed and effectively converted to the active metabolite, SN-38, achieving approximately 50{\%} of the SN-38 systemic exposure resulting from an equivalent IV dose. Conclusions Oral irinotecan can be safely administered as a single agent or in sequential combination with capecitabine. The efficacy of oral irinotecan should be explored further as a potentially convenient alternative to IV chemotherapy.",
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Goff, LW, Benson III, AB, LoRusso, PM, Tan, AR, Berlin, JD, Denis, LJ, Benner, RJ, Yin, D & Rothenberg, ML 2012, 'Phase I study of oral irinotecan as a single-agent and given sequentially with capecitabine', Investigational New Drugs, vol. 30, no. 1, pp. 290-298. https://doi.org/10.1007/s10637-010-9528-x

Phase I study of oral irinotecan as a single-agent and given sequentially with capecitabine. / Goff, Laura W.; Benson III, Al B; LoRusso, Patricia M.; Tan, Antoinette R.; Berlin, Jordan D.; Denis, Louis J.; Benner, Rebecca J.; Yin, Donghua; Rothenberg, Mace L.

In: Investigational New Drugs, Vol. 30, No. 1, 01.02.2012, p. 290-298.

Research output: Contribution to journalArticle

TY - JOUR

T1 - Phase I study of oral irinotecan as a single-agent and given sequentially with capecitabine

AU - Goff, Laura W.

AU - Benson III, Al B

AU - LoRusso, Patricia M.

AU - Tan, Antoinette R.

AU - Berlin, Jordan D.

AU - Denis, Louis J.

AU - Benner, Rebecca J.

AU - Yin, Donghua

AU - Rothenberg, Mace L.

PY - 2012/2/1

Y1 - 2012/2/1

N2 - Purpose To assess the maximum tolerated dose (MTD) and dose-limiting toxicities (DLT) of orally administered irinotecan in the semi-solid matrix (SSM) formulation, both as a single agent and in sequential combination with capecitabine, in patients with advanced solid tumors. Patients and Methods Forty-three patients were treated with irinotecan given as a single oral daily dose on days 1-5 every three weeks. An additional forty patients were treated with sequential oral irinotecan given daily on days 1-5 followed by capecitabine given orally as a divided dose twice daily on days 6-14 of each three week cycle. Results The MTD of single-agent oral irinotecan was estimated to be 60 mg/m 2/day, and DLT included diarrhea, nausea, and neutropenia. In an initial group of patients with Eastern Cooperative Oncology Group (ECOG) performance status (PS) of 0 to 2, the MTD of sequential oral irinotecan/ capecitabine was estimated to be 40/1600 mg/m 2/day with DLT of delayed diarrhea. In a subsequent group of patients with ECOG PS of 0 or 1, the MTD for the sequential combination was 50/2000 mg/m 2/day. The most common adverse events were fatigue, diarrhea, nausea/vomiting and dehydration. Pharmacokinetic (PK) evaluation showed that oral irinotecan was rapidly absorbed and effectively converted to the active metabolite, SN-38, achieving approximately 50% of the SN-38 systemic exposure resulting from an equivalent IV dose. Conclusions Oral irinotecan can be safely administered as a single agent or in sequential combination with capecitabine. The efficacy of oral irinotecan should be explored further as a potentially convenient alternative to IV chemotherapy.

AB - Purpose To assess the maximum tolerated dose (MTD) and dose-limiting toxicities (DLT) of orally administered irinotecan in the semi-solid matrix (SSM) formulation, both as a single agent and in sequential combination with capecitabine, in patients with advanced solid tumors. Patients and Methods Forty-three patients were treated with irinotecan given as a single oral daily dose on days 1-5 every three weeks. An additional forty patients were treated with sequential oral irinotecan given daily on days 1-5 followed by capecitabine given orally as a divided dose twice daily on days 6-14 of each three week cycle. Results The MTD of single-agent oral irinotecan was estimated to be 60 mg/m 2/day, and DLT included diarrhea, nausea, and neutropenia. In an initial group of patients with Eastern Cooperative Oncology Group (ECOG) performance status (PS) of 0 to 2, the MTD of sequential oral irinotecan/ capecitabine was estimated to be 40/1600 mg/m 2/day with DLT of delayed diarrhea. In a subsequent group of patients with ECOG PS of 0 or 1, the MTD for the sequential combination was 50/2000 mg/m 2/day. The most common adverse events were fatigue, diarrhea, nausea/vomiting and dehydration. Pharmacokinetic (PK) evaluation showed that oral irinotecan was rapidly absorbed and effectively converted to the active metabolite, SN-38, achieving approximately 50% of the SN-38 systemic exposure resulting from an equivalent IV dose. Conclusions Oral irinotecan can be safely administered as a single agent or in sequential combination with capecitabine. The efficacy of oral irinotecan should be explored further as a potentially convenient alternative to IV chemotherapy.

KW - Capecitabine

KW - Irinotecan

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U2 - 10.1007/s10637-010-9528-x

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