A Pharmacogenomic Study of Docetaxel and Gemcitabine for the Initial Treatment of Advanced Non-Small Cell Lung Cancer

School of Medicine, Wake Forest University, Winston-Salem, North Carolina, United States
Journal of thoracic oncology: official publication of the International Association for the Study of Lung Cancer (Impact Factor: 5.28). 04/2007; 2(3):197-202. DOI: 10.1097/JTO.0b013e318031cd89
Source: PubMed


Pharmacogenomic profiling is an attractive strategy for individualizing chemotherapy. Several genetic polymorphisms predict the survival of patients with non-small cell lung cancer treated with platinum-based chemotherapy. This phase II clinical trial was performed using a non-platinum-based chemotherapy doublet. The impact of previously identified polymorphisms on clinical outcomes was assessed.
Patients with advanced non-small cell lung cancer who had not received previous chemotherapy were treated with docetaxel 40 mg/m2 on days 1 and 8 and gemcitabine 800 mg/m2 days 1 and 8 every 21 days until disease progression or unacceptable toxicity. A pretreatment blood sample was obtained, and genomic DNA was analyzed for polymorphisms in DNA repair and metabolic genes.
Forty-nine patients were enrolled and evaluated for response and survival. The overall radiographic response rate was 38%, and the median survival was 8.6 months. Nonhematologic toxicity was generally mild. Two treatment related deaths occurred: one due to neutropenic sepsis during the first cycle and one due to pulmonary edema after 12 cycles of treatment. Polymorphisms in XPD, XRCC1, and XRCC3 did not significantly predict survival, but trends similar to those reported for platinum-based chemotherapy were observed. The wild-type XPD genotype was associated with prolonged survival and a significantly higher risk of grade 4 neutropenia (p = 0.02).
This regimen of docetaxel and gemcitabine is well tolerated and active for the treatment of advanced non-small cell lung cancer. The impact of XPD polymorphisms on hematologic toxicity is similar to what has been reported for platinum-based chemotherapy.

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    • "Association between tumor expression level of SLC29A1 [Kim, 1999; Myers et al., 2006], ERCC1 [Bepler et al., 2006], and DCK [Mey et al., 2006; Shi et al., 2004] and clinical outcomes in patients treated with gemcitabine has been reported. Genetic variations in CDA [Gilbert et al., 2006; Sugiyama et al., 2007; Yonemori et al., 2005], DCTD [Gilbert et al., 2006], ERCC2 (XPD) [Camps et al., 2003; Petty et al., 2007], and XRCC3 [de las Penas et al., 2006] genes were implicated to have association or trend with response, toxicity, or survival in gemcitabine-treated patients. SNPs in RECQL, RAD54L, XRCC1, and ATM were investigated in patients treated with gemcitabine and were found to have significant effects on overall survival [Li et al., 2006]. "
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