Opioid receptor receiving at least one prior chemotherapy regimen. In this study, 66 NSCLC patients were enrolled to receive weekly infusions of cetuximab until disease progression or treatment intolerance. The RR was 4.5%, the median PFS was 2.3 months and the median OS was 8.9 months. Sunitinib malate is an oral, multitargeted TKI with antiangiogenic and antitumour activities. In a phase II clinical trial, 63 patients were assigned to receive sunitinib after platinum based chemotherapy failure. Results were promising showing overall RR of 11.1%, median PFS of 12.0 weeks and median OS 23.4 weeks. The 1 year survival rate was 20.2% and the treatment was well tolerated. One more phase II study evaluated sunitinib malate at a continuous oral dose of 37.5 mg/day. Forty seven NSCLC patients who had received of one or two previous chemotherapy regimens were evaluated. The RR was 2.1% whereas the disease remained stable in 19.1% of cases. The median PFS was 12.3 weeks, median IkB signaling OS was 38.1 weeks and toxicity was tolerable. One more oral multi kinase inhibitor that targets the Raf/MEK/ERK pathway, sorafenib, was evaluated in a phase II clinical trial.
A number of 52 previously treated patients with JAK signaling pathway relapsed or refractory advanced NSCLC received 400 mg bid of sorafenib continuously. Fifty nine percent of patients presented with SD. The median PFS was 11.9 weeks and the median OS was 29.3 weeks with acceptable toxicity. Furthermore, a randomised, double blind, placebo controlled phase II study evaluated the role of sorafenib in third line and beyond in NSCLC. This study used a randomized discontinuation design in order to enrich for patients with slowly growing disease who are theoretically more likely to benefit from sorafenib. Preliminary results suggest sorafenib prolongs PFS in heavily pre treated patients, while toxicity is mild with symptoms including rash, hand foot syndrome, fatigue, INR abnormalities and hemoptysis. AZD6244 is a selective MEK prasugrel inhibitor that was recently studied by Hainsworth et al. in second and third line settings. AZD6244 showed clinical activity but its advantage over pemetrexed is yet to be proven. The authors suggested it be further studied taking the status of BRAF or RAS mutation into account. Several agents that inhibit mTOR kinase, an important mediator of tumour growth and proliferation, are currently studied in clinical trials.
Everolimus was evaluated in a phase II trial comparing prolong patients who failed 2 lines of chemotherapy, one platinum based to those who failed second line chemotherapy combined with an EGFR antagonist. Eighty five patients were enrolled in this study. The median PFS was 2.6 months in arm 1 and 2.7 months in arm 2, while toxicity was moderate. Enzastaurin, an oral serine/threonine kinase inhibitor, represents one more agent under evaluation for recurrent NSCLC. In a phase II study, 55 patients who had previously failed one or two systemic regimens received 500 mg/day of enzastaurin. Median OS was 8.4 months and median PFS was 1.8 months. Toxicity was mild. Vascular endothelial growth factor is the dominant growth factor controlling angiogenesis. Tumour cells, like normal cells, require a blood supply with subsequent access to several nutrients in order to grow and survive.