Background: Several Asian studies demonstrated feasibility of front-line administration of gefitinib for the treatment of non-small cell lung carcinomas (NSCLCs) harboring intragenic epidermal growth factor receptor (EGFR) mutations. The experience of the use of this EGFR tyrosine kinase inhibitor (TKI) in non-Asian subjects remains limited. Patients and Methods: The study included lung adenocarcinoma (AC) patients treated at the N.N. Petrov Institute of Oncology (Russia). Results: DNA analysis of 192 consecutive AC revealed 38 (20%) TKI-sensitizing mutations. Presence of the exon 19 deletion (del19) or L858R was strongly correlated with nonsmoking status (smokers: 8/98 (8%); non-smokers: 30/94 (32%); p = 0.00004). The efficacy of first-line gefitinib therapy was evaluated in 25 patients with EGFR-mutated advanced AC. Twelve (48%) cases demonstrated tumor response (1 (4%) complete response, 11 (44%) partial responses; 10/17 (59%) patients with del19 mutation vs. 2/8 (25%) cases with L858R substitution, p = 0.11). The remaining 13 (52%) patients experienced disease stabilization. Median progression-free survival was 8.0 months. Grade 3 toxicity was the maximal adverse event, being observed only in 4 (16%) cases. Conclusion: Gefitinib may be considered as an upfront treatment option for EGFR-mutated NSCLC.

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Ovarian carcinomas (OC) arising in BRCA1 and BRCA2 mutation carriers demonstrate pronounced sensitivity to platinum-based therapy due to deficiency of double-strand break DNA repair. However, the choice of subsequent treatment lines for this category of women remains complicated. We considered mitomycin C for heavily pretreated hereditary OC patients, based on multiple evidence for BRCA-specific activity of this drug. Twelve patients carrying BRCA1 germ-line mutation were included in the study. All women had a history of surgical intervention followed by adjuvant platinum-based therapy; three patients also received platinating agents prior the operation. The number of preceding treatment lines for metastatic disease was one for three patients, two for four patients, three for two patients, four for two patients and six for one woman. Administration of mitomycin C (10 mg/m2, every 4 weeks) resulted in one complete response (duration 36 weeks), two partial responses (duration 36 and 48 weeks) and six instances of disease stabilization (duration 12, 16, 20, 24, 24 and 24 weeks). In addition, three patients with the stable disease showed a decline of CA-125 level. We conclude that mitomycin C may deserve further evaluation in clinical trials involving BRCA1/2-related cancers.