PMC3861587_01
Chest computed tomography (CT) findings showing evidence of a tumor response. Chest CT images showed a tumor response prior to and after the patient received icotinib. (A) The first appearance of a nodule on August 12, 2010, at four months post-kidney transplant. (B) On February 9, 2011, the nodule remained stable as previously. (C) On October 13, 2011, CT imaging showed a marginal increase in the size of the nodule. (D) On February 15, 2012 (prior to treatment with icotinib), the nodule was pathologically diagnosed as adenocarcinoma. (E) Imaging results on March 12, 2012, following one week of treatment with icotinib. (F) Imaging results on August 7, 2012, following five months of treatment with icotinib. The patient met the Response Evaluation Criteria in Solid Tumors (RECIST) for a partial response. The arrows indicate the tumor site.
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August 2010 showed evidence of a suspicious nodule in the right upper lobe of the lung. A chest computed tomography (CT) scan revealed a 6-mm diameter nodule, with a surrounding cavity and fibrous lesions (Fig. 1). A follow-up chest CT scan subsequent to more than one month of icotinib treatment showed evidence of a further decrease in the size of the pulmonary nodule (Fig. 1), and a partial response (PR) was evaluated according to the Response Evaluation Criteria in Solid Tumors.
Serum tumor markers prior to and following icotinib treatment. Serum (A) carcinoembryonic antigen (CEA) and (B) CA19-9 levels decreased following treatment with icotinib.
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The carcinoembryonic antigen (CEA) levels were 5.7 ng/ml (normal range, 0-5 ng/ml) and the carbohydrate/cancer antigen 19-9 (CA19-9) level was 15.7 U/ml (normal range, 0-37 U/ml) (Fig. 2). By April 30, 2012, the CEA level had decreased to 19.5 ng/ml and the CA19-9 level to 69.4 U/ml (Fig. 2).
Computed tomography (CT) evidence of interstitial pneumonitis. (A) On October 13, 2011, the CT image showed for the first time scattered, patchy shadows in the two lower lobes of the lung. (B) On February 15, 2012, no shadows were detected. (C) CT findings on May 12, 2012, three months after the start of icotinib. (D) CT findings on August 7, 2012, five months after the start of icotinib. (E) CT findings on October 15, 2012, two months after the patient discontinued rapamycin and icotinib. (F) CT findings on November 10, 2012, one month after the patient underwent a segmentectomy. The arrows indicate the site of the interstitial lung disease.
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A chest CT on August 7, 2012, showed bilateral patchy and diffuse interstitial infiltrates, which were signs of interstitial pneumonitis (Fig. 3). A review of the previous chest CT images identified an unnoticed, transient interstitial pneumonitis on October 13, 2011 (Fig. 3).
Plasma concentration of icotinib. Eight time points (0, 0.5, 3, 6, 8, 11, 16 and 24 h post-dose) were selected to determine the plasma concentration of icotinib (125 mg TID) by high-performance liquid chromatography tandem mass spectrometry. The resulting plasma concentration time profile was similar to that in the published phase I trial of icotinib.
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The results (Fig. 4) showed concentrations similar to those reported in the published phase I trial of icotinib, indicating that the interstitial pneumonitis was not due to the increase in icotinib plasma concentration.