Oral AZD6244 showed clinical activity as second- or third-line therapy for patients with advanced NSCLC. In an unselected NSCLC population, there is no suggestion that AZD6244 monotherapy offers any advantage over standard treatment with pemetrexed. Based on preclinical data and recent clinical observations, further development of AZD6244 in NSCLC should focus on BRAF or RAS mutation-positive patients and/or AZD6244-based combination regimens.

Summary. Limited data are available concerning treatment and outcome of primary lymphoma of the breast (PLB), especially after CHOP (cyclophosphamide, hydroxydoxorubicin, vincristine, prednisone) chemotherapy. We retrospectively reviewed 20 consecutive cases of localized PLB seen at our institution over a 20 year period. All PLB were of B-cell origin: treatment was CHOP or a CHOP-like regimen in all patients. Sixteen of the 20 patients achieved complete remission (CR) and two achieved partial remission (. 75% tumour regression). Two patients had progressive disease on therapy. With a median follow-up of 54 months, six patients relapsed after 8±66 months. Two of the relapses involved the central nervous system (CNS) (isolated in one case, associated with other sites of relapse in the other). The two patients who achieved partial remission also had progression in the CNS, 4 and 8 months after the end of CHOP chemotherapy. All four patients have died as a result of their disease 3, 6, 10 and 13 months after CNS relapse. Of the 16 centroblastic diffuse large B-cell lymphoma (DLCL), three had CNS disease at relapse. We also observed three (15%) controlateral breast relapses. Thirteen of the initial 20 patients are alive in CR, six patients have died as a result of their lymphoma and one of unrelated disease. In conclusion, we observed a high incidence of CNS relapse in this group of localized extranodal lymphoma, strongly suggesting that CNS prophylaxis should be associated with systemic chemotherapy in localized PLB.

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Objective. This study assessed the efficacy of lenvatinib, a multitargeted tyrosine kinase inhibitor, as secondline therapy in patients with unresectable endometrial cancer. The primary end point was the objective response rate (ORR) as assessed by independent radiologic review (IRR). Secondary end points included median progression-free survival (PFS), overall survival (OS), and clinical benefit rate. Exploratory end points examined the association of baseline levels of plasma biomarkers (50 circulating cytokine and/or angiogenic factors measured by immunoassays) with efficacy outcomes. Methods. An international, open-label, single-arm, multicenter, phase 2 trial was conducted. Eligible patients had histologically confirmed unresectable endometrial cancer that relapsed after 1 prior systemic platinumbased chemotherapy. Patients received once-daily oral lenvatinib 24 mg in a 28-day dosing cycle. Results. There were 133 patients in the study. By IRR, 19 patients had a confirmed objective response for an ORR of 14.3% (95% CI: 8.8-21.4). Durable stable disease (≥23 weeks) was observed in 31 patients (23.3%) and the clinical benefit rate was 37.6% (95% CI: 29.3-46.4). Median PFS was 5.6 months (95% CI: 3.7-6.3), and median OS was 10.6 months (95% CI: 8.9-14.9). The most common (any grade) treatment-related adverse events were fatigue/asthenia (48%), hypertension (49%), nausea/vomiting (32%), decreased appetite (32%), and diarrhea (31%). Lower baseline levels of angiopoietin-2 were associated with longer PFS, OS, and a higher ORR. Conclusions. Patients with recurrent endometrial cancer treated with second-line lenvatinib experienced modest antitumor activity and treatment was generally well tolerated, with a safety profile consistent with previous studies.

There was no improvement in efficacy with talactoferrin alfa in patients with advanced NSCLC whose disease had failed two or more previous regimens.

Among mechanisms potentially involved in resistance to alkylating agents and anthracyclines, the glutathione system has been extensively studied in vitro. We analyzed by immunohistochemistry the relation between glutathione stransferase p (GST-p) expression in tumor cells and outcome in 69 cases of diffuse large B-cell NHL (DLBCL). GST-p expression was considered as low when o50% of tumor cells were stained and high when X50% tumor cells were stained. Median follow-up was 58 months. GST-p expression was correlated with the probability of achieving complete remission (CR). Patients with high GST-p expression had a worse 5-year freedom from progression (FFP). High GST-p expression was associated with a trend for lower survival. In the group of patients with International Prognostic Index (IPI) 0-1, low GST-p expression was associated with a CR rate of 88%, a 5-year FFP of 76720% and a 5-year survival of 78716% compared to 36, 14716 and 40732%, respectively, in patients with a high GST-p expression (P ¼ 0.002, Po10 À5 and P ¼ 0.01, respectively). No correlation was found between GST-p expression and lactico deshydrogenase serum level, age, Ann Arbor stage, performance status, and IPI index. Both GST-p expression and the IPI index correlated with FFP. After incorporating IPI and GST-p expression in a multivariate analysis for FFP, GST-p expression remained the only prognostic factor (P ¼ 0.003). Our findings suggest that GST-p expression had strong prognostic significance in DLBCL, which appears to be independent of other prognostic parameters in those disorders.

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