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Am J Clin Oncol. 2009 Apr;32(2):115-21. doi: 10.1097/COC.0b013e318180baa3.

Results of a phase I trial of 12 patients with locally advanced pancreatic carcinoma combining gefitinib, paclitaxel, and 3-dimensional conformal radiation: report of toxicity and evaluation of circulating K-ras as a potential biomarker of response to therapy.

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  • 1Department of Radiation Oncology, University of Colorado Denver Health Sciences Center, Aurora, CO, USA.

Abstract

OBJECTIVE:

To evaluate the toxicity of daily gefitinib, an epidermal growth factor receptor-tyrosine kinase inhibitor, with concurrent chemoradiation (CRT) in patients with locally advanced pancreatic adenocarcinoma and prospectively evaluate plasma k-ras as a potential marker of response to gefitinib and CRT.

METHODS:

Eleven of 12 eligible patients enrolled received a 7-day induction of gefitinib (250 mg PO) followed by daily gefitinib with concurrent CRT. Patients received 50.4 Gy/28 fractions of external beam radiation with weekly paclitaxel (40 mg/m IV) followed by maintenance on gefitinib. Plasma k-ras codon 12 mutations were detected using a two-stage restriction fragment length polymorphism-polymerase chain reaction assay on patients' plasma both before and after therapy. Mutations were confirmed by direct sequencing.

RESULTS:

Common adverse events included grade 1 skin rash (63%), grade 1 to 2 gastrointestinal symptoms including anorexia, nausea, vomiting, and diarrhea occurred in 63% of patients, grade 3 nausea occurred in 45% of patients. Three patients did not complete therapy, only one was possibly associated with study drug. K-ras mutations were detected in the pre-gefitinib plasma of 5/11 patients and in the matched tumor tissue of 3/4 patients. In patients where k-ras mutations were undetectable post-treatment, survival times were favorable.

CONCLUSIONS:

Combination of daily gefitinib with concurrent CRT in this locally advanced pancreatic cancer population was reasonably tolerated. Rapid changes in serum k-ras may provide critical information as to the efficacy of a novel agent and assist in tailoring treatment for cancers of the pancreas.

PMID:
19307945
[PubMed - indexed for MEDLINE]
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