BackgroundThe purpose of this study was to evaluate the safety and efficacy of nimotuzumab in combination with chemotherapy (docetaxel and carboplatin) versus chemotherapy alone in patients with stage IIIB/IV non-small-cell lung cancer.MethodsThis multicenter, open-label, Phase II study randomized 110 patients to receive nimotuzumab plus chemotherapy (nimotuzumab group) or chemotherapy alone (control group), and comprised concomitant, maintenance, and follow-up phases. Nimotuzumab 200 mg was administered once weekly for 13 weeks during the first two phases with four cycles of chemotherapy and docetaxel 75 mg/m2 and carboplatin (area under the curve 5 mg/mL*min) every 3 weeks for a maximum of four cycles during the concomitant phase. The primary endpoint was objective response rate (sum of complete response and partial response). Secondary endpoints, ie, overall survival and progression-free survival, were estimated using the Kaplan–Meier method. Efficacy was evaluated on the intent-to-treat and efficacy-evaluable sets. Safety was assessed from adverse event and serious adverse event data.ResultsThe objective response rate was significantly higher in the nimotuzumab group than in the control group in the intent-to-treat population (54% versus 34.5%; P=0.04). A complete response and partial response were achieved in 3.6% and 50% of patients, respectively, in the nimotuzumab group, and in 4% and 30.9% of patients, respectively, in the control group. No significant differences in median progression-free survival and overall survival were observed. Safety profiles were comparable between the two groups.ConclusionNimotuzumab plus chemotherapy significantly improved the objective response rate as compared with chemotherapy alone. The combination was safe and well tolerated in patients with stage IIIB/IV non-small-cell lung cancer.

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Gallbladder cancer (GBC) is more prevalent than other cancers in North India. The asymptomatic nature of the disease is a problem in the diagnosis and treatment. Analysis of oncogenes or tumor suppressor genes could be of importance in this regard. KRAS is the most frequently mutated member and is said to be one of the most activated oncogenes. The present study was aimed to determine the role of intragenic variants in the KRAS gene, in the progression of GBC in the eastern part of India. Sixty gallbladder carcinoma subjects (13 men and 47 women) with histologically proven diagnosis and 90 individuals (14 men and 76 women) who have no diagnosed cancer were included in the present study. All single-nucleotide polymorphisms present in exons 1 and 2 were analyzed by polymerase chain reaction followed by sequencing. We could not find the most frequently reported mutations at codons 12, 13, and 61 of the KRAS gene that occur in human malignancies. However, in this study, we detected one novel polymorphism at codon 25 (CAG>CAT; Gln25His) in exon 1 of the KRAS gene in both germline and tissue DNA. Multivariable logistic regression analysis with adjustment for age and sex revealed that the Gln25His variant of the KRAS gene was significantly associated with GBC. In silico analysis has validated the KRAS p.Q25H polymorphism as a disease-causing variant. Further, screening of the DNA samples in a cohort of ancestral tribal populations from various parts of the country without information on the phenotype, however, revealed the presence of the previously reported codon 12 and 25 polymorphisms, thereby indicating that the novel variant is population specific in the region.