Patient participation in cancer clinical trials: A pilot test of lay navigation.

BACKGROUND: Clinical trials (CT) represent an important treatment option for cancer patients. Unfortunately, patients face challenges to enrolling in CTs, such as logistical barriers, poor CT understanding and complex clinical regimens. Patient navigation is a strategy that may help to improve the delivery of CT education and support services. We examined the feasibility and initial effect of one navigation strategy, use of lay navigators. METHODS: A lay CT navigation intervention was evaluated in a prospective cohort study among 40 lung and esophageal cancer patients. The intervention was delivered by a trained lay navigator who viewed a 17-minute CT educational video with each patient, assessed and answered their questions about CT participation and addressed reported barriers to care and trial participation. RESULTS: During this 12-month pilot project, 85% (95% CI: 72%-93%) of patients eligible for a therapeutic CT consented to participate in the CT navigation intervention. Among navigated patients, CT understanding improved between pre- and post-test (means 3.54 and 4.40, respectively; p-value 0.004), and 95% (95% CI: 82%-98%) of navigated patients consented to participate in a CT. Navigated patients reported being satisfied with patient navigation services and CT participation. CONCLUSIONS: In this formative single-arm pilot project, initial evidence was found for the potential effect of a lay navigation intervention on CT understanding and enrollment. A randomized controlled trial is needed to examine the efficacy of the intervention for improving CT education and enrollment.

Inhibition of sphingosine kinase 2 downregulates the expression of c-Myc and Mcl-1 and induces apoptosis in multiple myeloma.

Sphingolipid metabolism is being increasingly recognized as a key pathway in regulating cancer cell survival and proliferation. However, very little is known about its role in multiple myeloma (MM). We investigated the potential of targeting sphingosine kinase 2 (SK2) for the treatment of MM. We found that SK2 was overexpressed in MM cell lines and in primary human bone marrow (BM) CD1381 myeloma cells. Inhibition of SK2 by SK2- specific short hairpin RNA or ABC294640 (a SK2 specific inhibitor) effectively inhibited myeloma cell proliferation and induced caspase 3­mediated apoptosis. ABC294640 inhibited primary human CD1381 myeloma cells with the same efficacy as with MM cell lines. ABC294640 effectively induced apoptosis of myeloma cells, even in the presence of BM stromal cells. Furthermore, we found that ABC294640 downregulated the expression of pS6 and directed c-Myc and myeloid cell leukemia 1 (Mcl-1) for proteasome degradation. In addition, ABC294640 increased Noxa gene transcription and protein expression. ABC294640, per se, did not affect the expression of B-cell lymphoma 2 (Bcl-2), but acted synergistically with ABT-737 (a Bcl-2 inhibitor) in inducing myeloma cell death. ABC294640 suppressed myeloma tumor growth in vivo in mouse myeloma xenograft models. Our data demonstrated that SK2 provides a novel therapeutic target for the treatment of MM.This trial was registered at www.clinicaltrials.gov as #NCT01410981.