In small-cell lung cancer (SCLC), resistance to cancer drugs presents a major problem, limiting the effectiveness of chemotherapy. A better understanding of the molecular biology is essential to improve currently available cytotoxic therapy. In this paper a systematic review of studies evaluating the predictive value of multidrug resistance-associated proteins (MDR1, MRP1, MRP2 and MVP), topoisomerase II and ERCC1 for chemotherapy outcomes is presented.
COBISS.SI-ID: 28546777
Multiple drug resistance limits the efficacy of numerous cytotoxic drugs used in the treatment of small cell lung cancer (SCLC). The drug efflux protein ATP-binding cassette transporter B1 (ABCB1) has an important role in this process, and its gene variability may affect chemotherapy outcomes. The aim of our study was to evaluate the associations between ABCB1 polymorphisms G2677T/A, C3435T, and their haplotype with progression-free survival (PFS) and overall survival (OS) in SCLC patients treated with cisplatin-etoposide or cyclophosphamide-epirubicin-vincristine chemotherapy. Our study reported a possible predictive value of ABCB1 polymorphisms G2677T/A, C3435T, and their haplotype for longer PFS and OS in Caucasian SCLC patients treated with chemotherapy. However, to be implemented into routine clinical practice, ABCB1 polymorphisms require further validation.
COBISS.SI-ID: 29829337
The excision repair cross-complementing 1 (ERCC1) protein is an extensively investigated molecular marker because it may decrease sensitivity to platinum-based chemotherapy. Low ERCC1 expression has been correlated with better treatment efficacy in non-small-cell lung cancer patients treated with platinum-based chemotherapy. However, the data on a prognostic and/or predictive value of ERCC1 in small-cell lung cancer (SCLC) have been scare. Therefore, our group evaluated the impact of ERCC1 expression levels on response to first-line platinum-based chemotherapy and survival in SCLC patients.In our group of 77 SCLC patients, ERCC1 protein expression was not found to correlate with either response rate to platinum-based chemotherapy or survival outcomes.
COBISS.SI-ID: 30115033
In lung cancer patients treated with chemotherapy, renal function is an important parameter to be monitored. Since measurement of renal function with either isotope or creatinine clearance is time consuming and expensive, we evaluated which of the equations: Cockcroft-Gault (CG), Wright, modification of diet in renal disease equation (MDRD), MDRD adjusted for body surface area (BSA) and chronic kidney disease epidemiology collaboration (CKD-EPI) best resembles endogenous creatinine clearance (ECC) and could therefore replace its measurement in clinical practice. METHODS: 218 lung cancer patients, who had their 24-h creatinine secretion in urine measured prior to the start of any chemotherapy, were included. Estimation of renal function was calculated and compared to ECC. RESULTS: There were no major differences in the performance of the tested equations. Mean percentage error of more than 20% and general underestimation was common to all equations. Wright equation performed best although it describes only 43% of ECC variability. Mean measured ECC was 94 mL/min (95% confidence interval [CI]: 90-98 mL/min) and 90 mL/min for Wright equation (95% CI: 87-93 mL/min) (Supp. Fig. 3). MDRD and CKD-EPI equation performed poorest since they do not include any body size descriptor. Large deviations of differences were observed, with a median standard deviation of more than 20% and deviations from ECC exceeding 100%. Wright equation performed best, whereas, despite their leading role in the detection of renal diseases, the MDRD and CKD-EPI equation performed poorest since they do not include any body size descriptor. In the range of ECC(50 mL/(min×1.73 m(2)), the CG equation most often detected a contraindication for cisplatin use. Differences between ECC and calculated values correlated with patients' weight, BSA and body mass index when these were not included in the equation itself. CONCLUSIONS: In evaluating the renal function of lung cancer patients, equations adjusted for body size descriptors should be preferred. Estimated renal function should be interpreted against the characteristics of patient's body size and special attention is needed when these are reaching the extremes.