A pharmacogenomic study of docetaxel and gemcitabine for the initial treatment of advanced non-small cell lung cancer.
BACKGROUND
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.


METHODS
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.


RESULTS
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).


CONCLUSIONS
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.
Petty
W Jeffrey
WJ
Department of Medicine, Section on Hematology and Oncology, Wake Forest University Health Sciences, Winston-Salem, North Carolina 27157, USA.
Knight
Sommer N
SN
Mosley
Libyadda
L
Lovato
James
J
Capellari
James
J
Tucker
Robert
R
Blackstock
A William
AW
Miller
Mark Steven
MS
Miller
Antonius A
AA
D000328:Adult; D000368:Aged; D000970:Antineoplastic Agents / Q000627:therapeutic use*; D002289:Carcinoma, Non-Small-Cell Lung / Q000188:drug therapy* / Q000235:genetics / Q000473:pathology; D003841:Deoxycytidine / Q000031:analogs & derivatives* / Q000627:therapeutic use; D000077143:Docetaxel; D005260:Female; D006801:Humans; D008175:Lung Neoplasms / Q000188:drug therapy* / Q000235:genetics / Q000473:pathology; D008297:Male; D008875:Middle Aged; D009367:Neoplasm Staging; D010597:Pharmacogenetics; D011110:Polymorphism, Genetic; D043823:Taxoids / Q000627:therapeutic use*; D000093542:Gemcitabine
D000970:Antineoplastic Agents; D043823:Taxoids; D003841:Deoxycytidine; D000077143:Docetaxel; D000093542:Gemcitabine