RESUMEN
Objective: Nanosomal docetaxel lipid suspension (NDLS) is a novel formulation developed to overcome toxicity issues caused by excipients (polysorbate 80 and ethanol) present in commercially available docetaxel formulation. We conducted a prospective, observational study to compare the outcomes of nanosomal docetaxel lipid suspension (NDLS)-based versus conventional docetaxel-based chemotherapy in primary operable breast cancer. Methods: Sixty adult women with newly diagnosed stage IIb-III breast cancer were included. Patients received NDLS-based (n=30) or docetaxel-based (n=30) chemotherapy. Patients received (1) four cycles of preoperative doxorubicin and cyclophosphamide (AC) followed by four cycles of NDLS or docetaxel (T) and surgery (neoadjuvant ACâNDLS [n=9], or neoadjuvant ACâT [n=10]), or (2) four cycles of preoperative AC followed by surgery and postoperative NDLS or T (neoadjuvant ACâadjuvant NDLS [n=14], or neoadjuvant ACâadjuvant T [n=15]), or (3) surgery followed by postoperative ACâNDLS or T (adjuvant ACâNDLS [n=7], or adjuvant ACâT [n=5]) regimens. The study outcomes were pathological complete response (pCR) rates, clinical overall response rates (ORR), disease-free survival (DFS), overall survival (OS), and adverse event (AE) profile. Results: For neoadjuvant ACâT (n=10) vs neoadjuvant ACâNDLS (n=9), the pCR rates were 100% each, and the ORR were 100% vs 88.9% (p=1.0). All patients were alive at 6 months, and the median OS was not reached. Three patients had progressive disease (T: n=2, NDLS: n=1) with a DFS of 12 weeks in all three patients. Grade 3 infusion-related reactions were seen in five patients (16.7%) in T vs none in NDLS arms. Conclusion: NDLS-based neo/adjuvant chemotherapy was efficacious in the treatment of primary operable breast cancer and showed comparable pCR, ORR, DFS and OS rates versus conventional docetaxel. NDLS was better tolerated than conventional docetaxel.
RESUMEN
INTRODUCTION: Chemotherapy is the standard and recommended treatment for lung cancer apart from surgery and radiotherapy. Chemotherapy is administered as mono-agents or as combination therapy. In this study, we examined the role of MDR1 C3435T polymorphisms in lung cancer patients undergoing chemotherapy. METHODS AND RESULTS: We genotyped 126 cases with lung cancer and 111 healthy controls, using the polymerase chain reaction-restriction fragment length polymorphism method (PCR-RFLP). Frequencies of MDR1 C3435C, C3435T and T3435T genotypes were 61, 16 and 23 % in lung cancer patients and 86, 9 and 5 % in the controls, respectively. The T3435T genotypes had a 5.23-fold increased risk for lung cancer. (OR 5.23; 95 % CI 2.082-13.146; p = 0.0004). Patients with TT genotypes were more frequent in stage IV and were significantly associated with the disease (p = 0.05). Habitual smoker lung cancer patients were 50 % CC genotypes whereas TT genotypes were 34 %. The non-smokers had 46 % CC genotypes and 23 % TT genotypes. Furthermore, we collected tissue biopsy samples for expression analysis from 20 patients (for controls we used the non-cancerous region of the same tissue). The present study showed mRNA expression of MDR1 was up-regulated in 80 % of the cancer group in comparison with the control group (p = 0.0002). We also correlated the association between MDR1 genotypes with different combinations of chemotherapy. The combinations and genotype distributions in the group receiving paclitaxel + cisplatin were as follows: CC (67 %), CT (24 %) and TT (9 %) genotypes, respectively, and the group receiving carboplatin + gemcitabine CC (46 %), CT (19 %) and TT (35 %) genotypes, respectively. We found that MDR1 (rs1045642) C3435T polymorphism and gene expression was significantly associated with the clinical outcome in lung carcinoma patients. CONCLUSION: In conclusion, it is suggested that MDR1 TT genotypes had higher risk for the development of lung cancer. Also, this polymorphism could be used as a genetic marker for predicting the clinical outcome of lung cancer patients.