Increased toxicity with gefitinib, capecitabine, and radiation therapy in pancreatic and rectal cancer

Phase I trial results

Brian G. Czito, Christopher G. Willett, Johanna C. Bendell, Michael A. Morse, Douglas Tyler, Nishan H. Fernando, Christopher R. Mantyh, Gerard C. Blobe, Wanda Honeycutt, Daohai Yu, Bryan M. Clary, Theodore N. Pappas, Kirk A. Ludwig, Herbert I. Hurwitz

Research output: Contribution to journalArticle

118 Citations (Scopus)

Abstract

Purpose: Overexpression of epidermal growth factor receptor (EGFR) has been associated with aggressive tumor phenotypes, chemotherapy, and radiation resistance, as well as poor survival in preclinical and clinical models. The EGFR inhibitor gefitinib potentiates chemotherapy and radiation tumor cytotoxicity in preclinical models, including pancreatic and colorectal cancer. We initiated two phase I trials assessing the combination of gefitinib, capecitabine, and radiation in patients with localized pancreatic and rectal cancer. Patients and Methods: Patients with pathologically confirmed adenocarcinoma of the pancreas and rectum were eligible. Pretreatment staging included computed tomography, endoscopic ultrasound, and surgical evaluation. Patients received 50.4 Gy of external-beam radiation therapy to the tumor in 28 fractions. Capecitabine and gefitinib were administered throughout the radiation course. Following completion, patients were restaged and considered for resection. Primary end points included determination of dose-limiting toxicity (DLT) and a phase II dose; secondary end points included determination of non-DLTs and preliminary radiographic and pathologic response rates. Results: Ten patients were entered in the pancreatic study and six in the rectal study. DLT was seen in six of 10 patients in the pancreatic study and two of six patients in the rectal study. The primary DLT in both studies was diarrhea. Two patients developed arterial thrombi. Conclusion: The combination of gefitinib, capecitabine, and radiation in pancreatic and rectal cancer patients resulted in significant toxicity. A recommended phase II dose was not determined in either of our studies. Further investigation with this combination should be approached with caution.

Original languageEnglish (US)
Pages (from-to)656-662
Number of pages7
JournalJournal of Clinical Oncology
Volume24
Issue number4
DOIs
StatePublished - Feb 1 2006
Externally publishedYes

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Rectal Neoplasms
Pancreatic Neoplasms
Radiotherapy
Radiation
Endpoint Determination
Epidermal Growth Factor Receptor
Capecitabine
gefitinib
Drug Therapy
Neoplasms
Rectum
Pancreas
Colorectal Neoplasms
Diarrhea
Adenocarcinoma
Thrombosis
Tomography
Phenotype
Survival

ASJC Scopus subject areas

  • Cancer Research
  • Oncology

Cite this

Increased toxicity with gefitinib, capecitabine, and radiation therapy in pancreatic and rectal cancer : Phase I trial results. / Czito, Brian G.; Willett, Christopher G.; Bendell, Johanna C.; Morse, Michael A.; Tyler, Douglas; Fernando, Nishan H.; Mantyh, Christopher R.; Blobe, Gerard C.; Honeycutt, Wanda; Yu, Daohai; Clary, Bryan M.; Pappas, Theodore N.; Ludwig, Kirk A.; Hurwitz, Herbert I.

In: Journal of Clinical Oncology, Vol. 24, No. 4, 01.02.2006, p. 656-662.

Research output: Contribution to journalArticle

Czito, BG, Willett, CG, Bendell, JC, Morse, MA, Tyler, D, Fernando, NH, Mantyh, CR, Blobe, GC, Honeycutt, W, Yu, D, Clary, BM, Pappas, TN, Ludwig, KA & Hurwitz, HI 2006, 'Increased toxicity with gefitinib, capecitabine, and radiation therapy in pancreatic and rectal cancer: Phase I trial results', Journal of Clinical Oncology, vol. 24, no. 4, pp. 656-662. https://doi.org/10.1200/JCO.2005.04.1749
Czito, Brian G. ; Willett, Christopher G. ; Bendell, Johanna C. ; Morse, Michael A. ; Tyler, Douglas ; Fernando, Nishan H. ; Mantyh, Christopher R. ; Blobe, Gerard C. ; Honeycutt, Wanda ; Yu, Daohai ; Clary, Bryan M. ; Pappas, Theodore N. ; Ludwig, Kirk A. ; Hurwitz, Herbert I. / Increased toxicity with gefitinib, capecitabine, and radiation therapy in pancreatic and rectal cancer : Phase I trial results. In: Journal of Clinical Oncology. 2006 ; Vol. 24, No. 4. pp. 656-662.
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T1 - Increased toxicity with gefitinib, capecitabine, and radiation therapy in pancreatic and rectal cancer

T2 - Phase I trial results

AU - Czito, Brian G.

AU - Willett, Christopher G.

AU - Bendell, Johanna C.

AU - Morse, Michael A.

AU - Tyler, Douglas

AU - Fernando, Nishan H.

AU - Mantyh, Christopher R.

AU - Blobe, Gerard C.

AU - Honeycutt, Wanda

AU - Yu, Daohai

AU - Clary, Bryan M.

AU - Pappas, Theodore N.

AU - Ludwig, Kirk A.

AU - Hurwitz, Herbert I.

PY - 2006/2/1

Y1 - 2006/2/1

N2 - Purpose: Overexpression of epidermal growth factor receptor (EGFR) has been associated with aggressive tumor phenotypes, chemotherapy, and radiation resistance, as well as poor survival in preclinical and clinical models. The EGFR inhibitor gefitinib potentiates chemotherapy and radiation tumor cytotoxicity in preclinical models, including pancreatic and colorectal cancer. We initiated two phase I trials assessing the combination of gefitinib, capecitabine, and radiation in patients with localized pancreatic and rectal cancer. Patients and Methods: Patients with pathologically confirmed adenocarcinoma of the pancreas and rectum were eligible. Pretreatment staging included computed tomography, endoscopic ultrasound, and surgical evaluation. Patients received 50.4 Gy of external-beam radiation therapy to the tumor in 28 fractions. Capecitabine and gefitinib were administered throughout the radiation course. Following completion, patients were restaged and considered for resection. Primary end points included determination of dose-limiting toxicity (DLT) and a phase II dose; secondary end points included determination of non-DLTs and preliminary radiographic and pathologic response rates. Results: Ten patients were entered in the pancreatic study and six in the rectal study. DLT was seen in six of 10 patients in the pancreatic study and two of six patients in the rectal study. The primary DLT in both studies was diarrhea. Two patients developed arterial thrombi. Conclusion: The combination of gefitinib, capecitabine, and radiation in pancreatic and rectal cancer patients resulted in significant toxicity. A recommended phase II dose was not determined in either of our studies. Further investigation with this combination should be approached with caution.

AB - Purpose: Overexpression of epidermal growth factor receptor (EGFR) has been associated with aggressive tumor phenotypes, chemotherapy, and radiation resistance, as well as poor survival in preclinical and clinical models. The EGFR inhibitor gefitinib potentiates chemotherapy and radiation tumor cytotoxicity in preclinical models, including pancreatic and colorectal cancer. We initiated two phase I trials assessing the combination of gefitinib, capecitabine, and radiation in patients with localized pancreatic and rectal cancer. Patients and Methods: Patients with pathologically confirmed adenocarcinoma of the pancreas and rectum were eligible. Pretreatment staging included computed tomography, endoscopic ultrasound, and surgical evaluation. Patients received 50.4 Gy of external-beam radiation therapy to the tumor in 28 fractions. Capecitabine and gefitinib were administered throughout the radiation course. Following completion, patients were restaged and considered for resection. Primary end points included determination of dose-limiting toxicity (DLT) and a phase II dose; secondary end points included determination of non-DLTs and preliminary radiographic and pathologic response rates. Results: Ten patients were entered in the pancreatic study and six in the rectal study. DLT was seen in six of 10 patients in the pancreatic study and two of six patients in the rectal study. The primary DLT in both studies was diarrhea. Two patients developed arterial thrombi. Conclusion: The combination of gefitinib, capecitabine, and radiation in pancreatic and rectal cancer patients resulted in significant toxicity. A recommended phase II dose was not determined in either of our studies. Further investigation with this combination should be approached with caution.

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