ORIGINAL ARTICLE

Thymidine phosphorylase expression in tumour cells and tumour response to capecitabine plus docetaxel chemotherapy in non-small cell lung cancer

J-Y Han, E K Hong, S Y Lee, S M Yoon, D H Lee and J S Lee

Research Institute and Hospital, National Cancer Centre, Goyang, Gyeonggi, 809 Madu1-dong, Ilsan-gu, Goyang-si, Gyeonggi-do, 411-769, Korea

Correspondence to:
Correspondence to:
Dr J S Lee
Research Institute and Hospital, National Cancer Centre, Korea, 809 Madu1-dong, Ilsan-gu, Goyang-si, Gyeonggi-do, 411-769, Korea; jslee{at}ncc.re.kr

Background: Thymidine phosphorylase (TP) is the key enzyme for capecitabine activation in tumour cells.

Aims: To examine whether TP expression in tumour cells and stroma is predictive of the tumour response to capecitabine plus docetaxel chemotherapy in patients with advanced non-small cell lung cancer (NSCLC).

Methods: Tumour samples were available from 30 of 39 patients enrolled in a previous phase II study of capecitabine/docetaxel chemotherapy in patients with advanced NSCLC. Stromal and tumour cell TP expression was evaluated by immunohistochemistry using monoclonal antibody PD-ECGF.

Results: High tumour cell TP expression was found in 13 of 30 cases and was negatively associated with stromal TP expression (p = 0.000). High stromal TP expression was found in 16 of 28 cases and was strongly associated with intense macrophage infiltration (p = 0.002), suggesting that macrophages are the major component of TP expression in the stroma. Tumour response to capecitabine/docetaxel was significantly associated with high tumour cell TP expression (p = 0.004) and low stromal TP expression (p = 0.009). Moreover, high tumour cell TP expression was significantly associated with severe hand–foot syndrome, a toxic side effect of capecitabine (p = 0.01). Improved survival was seen for high tumour cell and low stromal TP expression, although results were not significant (p = 0.6 and 0.3, respectively).

Conclusions: In advanced NSCLC, TP expression in tumour cells and stroma is associated with tumour response to capecitabine/docetaxel chemotherapy, and might be a useful predictor of tumour response to capecitabine based chemotherapy. A large scale prospective study is needed to confirm the prognostic significance of TP expression in NSCLC.

Abbreviations: 5-FU, 5-fluorouracil; NSCLC, non-small cell lung cancer; TP, thymidine phosphorylase

Keywords: thymidine phosphorylase; capecitabine; docetaxel; non-small cell lung cancer

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