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Clinical Trial
. 2008 Oct;3(10):1112-8.
doi: 10.1097/JTO.0b013e3181874936.

Clinical efficacy and predictive molecular markers of neoadjuvant gemcitabine and pemetrexed in resectable non-small cell lung cancer

Gerold Bepler  1 , K Eric Sommers, Alan Cantor, Xueli Li, Anupama Sharma, Charles Williams, Alberto Chiappori, Eric Haura, Scott Antonia, Tawee Tanvetyanon, George Simon, Coleman Obasaju, Lary A Robinson
Affiliations
Clinical Trial

Clinical efficacy and predictive molecular markers of neoadjuvant gemcitabine and pemetrexed in resectable non-small cell lung cancer

Gerold Bepler et al. J Thorac Oncol. 2008 Oct.

Abstract

Background: A trial of neoadjuvant gemcitabine and pemetrexed (GP) chemotherapy in patients with resectable non-small cell lung cancer was conducted. The goal was to achieve a disease response rate of 50% and to determine if the expression levels of genes associated with GP metabolism are predictive of response.

Methods: Patients had staging with a computed tomography scan, whole body F-18 fluorodeoxyglucose positron emission tomography, and mediastinoscopy. Four biweekly cycles of GP were given. Patients were restaged, and those with resectable stage IB-III disease had thoracotomy. Fresh frozen tumor specimens were collected before and after chemotherapy and the mRNA levels of 14 target genes determined by real-time reverse transcription polymerase chain reaction.

Results: Fifty-two patients started therapy. The radiographic disease response rate was 35% (95% confidence interval 21.7-49.6%), and the progression rate was 6%. Forty-six patients had a thoracotomy. The complete tumor resection rate was 77% (40/52). There were no perioperative deaths or deaths related to chemotherapy. Tumor response to chemotherapy was inversely correlated with the level of expression of RRM1 (p < 0.001; regulatory subunit of ribonucleotide reductase) and TS (p = 0.006; thymidylate synthase); i.e., the reduction in tumor size was greater in those with low levels of expression.

Conclusions: Neoadjuvant GP is well tolerated and produces an objective response rate of 35%. Tumoral RRM1 and TS mRNA levels are predictive of disease response and should be considered as parameters for treatment selection in future trials with this regimen.

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Figures

Figure 1
Figure 1
Water fall blots of radiographic disease response and mRNA gene expression.
Figure 2
Figure 2
Kaplan-Meier overall and disease-free survival estimates. The black curve denotes OS and the red curve DFS. Tick marks indicate censored cases.
Figure 3
Figure 3
Pre- and post-treatment mRNA levels of the genes RRM1 and TS in 10 patients.
See this image and copyright information in PMC

References

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