Chemotherapy treatment led by pharmacogenomics characteristics in the elderly patient with nsclc: phase II clinical trial

Lung cancer is the most common cancer worldwide contributing nearly 13% of the total number of new cases diagnosed in 2008. Nearly 80% of lung tumors diagnosed are non-small cell lung cancer (NSCLC) [1]. The standard chemotherapy in patients with NSCLC is the association of a platinum derivative with a second chemotherapeutic registered for this disease [2]. In patients over 70, which presents a profile of comorbidities such as not to allow the use of a cisplatin-based chemotherapy in high doses (> 70 mg/m2), the standard treatment is reduced to a single drug currently registered for this pathology without platinum derivatives [3]. Some phase II studies, however, have shown a benefit from the use of platinum derivatives in modified doses or different non-platinum-containing doublets chemotherapy in selected patients [4]. On the basis of these considerations, at the Medical Oncology Unit of Molinette Hospital of Turin, a phase II clinical protocol entitled “trattamento chemioterapico guidato da caratteristiche di farmacogenomica nel paziente anziano affetto da NSCLC” has been developed [5]. The primary objectives of this study, that will involve 43 patients, will be the evaluation of the response and toxicity rates of treatment in patients treated with a therapeutic regimen individualized on the basis of histological and pharmacogenomics criteria. Therefore, in order to achieve the targets, the study protocol involves administering, to elderly patients or unsuitable for the high-dose cisplatinum, a first-line customized chemotherapy. Eligible patients will then be divided into 4 different therapeutic subgroups which will lead the administration of the following chemotherapeutic doublets: docetaxel + gemcitabine, cisplatin + gemcitabine, carboplatin + pemetrexed, pemetrexed + oral vinorelbina. Regarding the association between oral vinorelbine and pemetrexed and, in particular, in order to assess any alteration in the pharmacokinetics of pemetrexed when coadministered with oral vinorelbine, the study has also involved the Department of Scienza e Tecnologia del Farmaco of University of Turin (DSTF). At the DTS the HPLC method for the pharmacokinetic study for Pemetrexed and oral Vinorelbine have been developed. As regards the development of the HPLC method an UV detector has been used for both pemetrexed and vinorelbine. In particular the developed pemetrexed extraction technique has shown, in the simulations with standardized samples of plasma, a recovery of about 80% of the active principle. Taking into account the high plasma protein binding of pemetrexed [6] this can be considered an excellent result. Regarding the vinorelbina, a constant control of the pH conditions (during both the extraction from plasma and the analysis by HPLC) has shown a recovery from plasma during the simulations around 90%. The described methods will permit to evaluate the concentration of the two molecules in the plasma of patients after 2, 4 and 18 hours after administration. Presently the study protocol has been approved and in a short time the enrollments will start.