BackgroundThe rising incidence of cancer and increasing number of cancer survivors place competing demands on specialist oncology clinics. This has led to a need to consider collaborative care between primary and secondary care for the long-term post-treatment care of cancer survivors.ObjectiveTo explore the views of breast and colorectal cancer survivors, their oncologist and GP about GPs taking a more active role in long-term cancer follow-up care.MethodsSemi-structured interviews using a thematic analysis framework. Respondents were asked their views on the specialist hospital-based model for cancer follow-up care and their views on their GP taking a greater or leading role in follow-up care. Researcher triangulation was used to refine the coding framework and emergent themes; source triangulation and participant validation were used to increase credibility.ResultsFifty-six interviews were conducted (22 patients, 16 oncologists, 18 GPs). Respondents highlighted the importance of GPs needing specialist cancer knowledge; the need for GPs to have an interest in and time for cancer follow-up care; the GPs role in providing psychosocial care; and the reassurance that was provided from a specialist overseeing care. A staged, shared care team arrangement with both GPs and specialists flexibly providing continuing care was found to be acceptable for most.ConclusionCollaborative care of cancer survivors may lessen the load on specialist oncology clinics. The findings suggest that building this model will require early and ongoing shared care processes.
Combined CBT/GET improves fatigue and functional outcomes for a subset of patients with post-cancer fatigue. Further studies to improve the response rate and the magnitude of the benefit are warranted.
Purpose: Dabrafenib is a selective, potent ATP-competitive inhibitor of the BRAFV600-mutant kinase that has demonstrated efficacy in clinical trials. We report the rationale for dose selection in the first-inhuman study of dabrafenib, including pharmacokinetics, tissue pharmacodynamics, 2[18F]fluoro-2-deoxy-D-glucose-positron emission tomography (FDG-PET) pharmacodynamics, and dose-response relationship.Experimental Design: Dabrafenib was administered orally once, twice (BID), or three times daily (TID). Selected dose cohorts were expanded to collect adequate data on safety, pharmacokinetics, or pharmacodynamics. A recommended phase II dose (RP2D) was chosen based on safety, pharmacokinetic, pharmacodynamic, and response data.Results: One hundred and eighty-four patients were enrolled and treated with doses ranging from 12 mg once daily to 300 mg BID in 10 cohorts. Pharmacokinetic assessment of dabrafenib demonstrated a lessthan-dose-proportional increase in exposure after repeat dosing above 150 mg BID. Similar to parent drug concentrations, exposure for all metabolites demonstrated less-than-dose-proportional increases. Predicted target inhibition of pERK (>80%) was achieved at 150 mg BID, with a similar magnitude of inhibition at higher doses in BRAFV600 mutation melanoma biopsy samples. Although there was large variability between patients, FDG uptake decreased with higher daily doses in patients with BRAFV600 mutationpositive melanoma. A favorable activity and tolerability profile was demonstrated at 150 mg BID. There was no improvement with TID dosing compared with BID dosing, based on FDG-PET and tumor response analyses in patients with melanoma.Conclusion: The RP2D of dabrafenib was determined to be 150 mg BID after considering multiple factors, including pharmacokinetics, tissue pharmacodynamics, FDG-PET pharmacodynamics, and the dose-response relationship. A maximum tolerated dose for dabrafenib was not determined. Clin Cancer Res; 20(17); 4449-58. Ó2014 AACR.
Albendazole was well tolerated on the schedule tested in this trial. The results of this study suggest that the recommended dose for further study is 1,200 mg twice daily for 14 days in a 21-day cycle.
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