Perceived patient burden and acceptability of whole body MRI for staging lung and colorectal cancer; comparison with standard staging investigations.

OBJECTIVE: To evaluate perceived patient burden and acceptability of whole body MRI (WB-MRI) compared to standard staging investigations, and identify predictors of reduced tolerance. METHODS: Patients recruited to multicentre trials comparing WB-MRI with standard staging scans for lung and colorectal cancer were invited to complete two questionnaires: a baseline questionnaire at recruitment, measuring demographics, comorbidities, and distress; and a follow-up questionnaire after staging, measuring recovery time, comparative acceptability/satisfaction between WB-MRI and CT (colorectal cancer) and PET-CT (lung cancer), and perceived scan burden (scored 1, low; 7, high).  Results: 115 patients (median age 66.3 years; 67 males) completed follow up and 103 baseline questionnaires. 69 (63.9%) reported "immediate" recovery from WB-MRI and 73 (65.2%) judged it "very acceptable". Perceived WB-MRI burden was greater than for CT (p < 0.001) and PET-CT (p < 0.001). High distress and comorbidities were associated with greater WB-MRI burden in adjusted analyses, with deprivation only approaching significance (adjusted regression ß = 0.223, p = 0.025; ß = 0.191, p = 0.048; ß = -0.186, p = 0.059 respectively). Age (p = 0.535), gender (p = 0.389), ethnicity (p = 0.081) and cancer type (p = 0.201) were not predictive of WB-MRI burden. CONCLUSION:  WB-MRI is marginally less acceptable and more burdensome than standard scans, particularly for patients with pre-existing distress and comorbidities.  Advances in knowledge: This research shows that WB-MRI scan burden, although low, is higher than for current staging modalities among patients with suspected colorectal or lung cancer. Psychological and physical comorbidities adversely impact on patient experience of WB-MRI. Patients with high distress or comorbid illness may need additional support to undergo a WB-MRI.

A phase 1b study of Selumetinib in combination with Cisplatin and Gemcitabine in advanced or metastatic biliary tract cancer: the ABC-04 study.

BACKGROUND: Combined treatment with cisplatin and gemcitabine (CisGem) is the standard of care for patients with advanced biliary tract cancer (ABC). Selumetinib (AZD6244, ARRY-142886) potently and selectively inhibits MEK1/2, an intracellular kinase and has shown activity in ABC. The objective of the ABC-04 trial was to establish the recommended dose of selumetinib in combination with CisGem in patients with ABC. METHODS: Eligible patients were ≥ 18 years, had histologically or cytologically-confirmed unresectable recurrent or metastatic biliary tract, gallbladder or ampullary carcinoma, WHO performance status 0-2, and adequate major organ function. Patients may have had prior surgery, radiotherapy or adjuvant chemotherapy, but no prior CisGem and no prior chemotherapy for locally advanced or metastatic disease. Patients received cisplatin 25 mg/m(2) plus gemcitabine 1000 mg/m(2) intravenously on days 1 and 8 of a 21-day cycle. Selumetinib capsules were taken daily. Patients received up to 8 cycles of CisGem and could receive selumetinib until disease progression. A dose de-escalation scheme was used to determine the recommended dose of selumetinib. The first dose level was 75 mg bd. Patients were recruited in cohorts of 3 and assessed for dose limiting toxicity (DLT) during the first cycle of treatment. RESULTS: Thirteen patients were recruited, of whom 12 were evaluable for DLT (1 did not start treatment). All evaluable patients received the starting dose of selumetinib 75 mg bd and one patient experienced a DLT (cardiac chest pain). The median number of days selumetinib was taken (adjusted for the number of days of dose interruptions) was 171.5 (IQR: 75.5 to 344). Two patients remained on treatment at 14 and 19 months post registration. There were 3 temporary and 1 permanent interruptions of selumetinib in cycle 1. Eight patients were evaluable for objective response (RECIST v1.1): 3 had a partial response and 5 stable disease. The median PFS was 6.4 months (IQR 5.2 to 13.7). Toxicities related to selumetinib were mostly related to oedema and rash, grade 1-2 and manageable. Pharmacokinetic analysis showed that the AUC(0-t), AUC(0-∞) and Cmax of selumetinib increased by 12, 11 and 30 % respectively when it was administered with CisGem, while Cmax for the N-desmethyl metabolite of selumetinib decreased by 40 %. There was no evidence that the time of Cmax for selumetinib or N-desmethyl metabolite of selumetinib were different when selumetinib was administered alone or with CisGem. CONCLUSION: The recommended dose of selumetinib when combined with CisGem was 75 mg bd. Translational studies are underway to identify biomarkers that may predict outcome (ClinicalTrials.gov identifier: NCT01242605 July 6(th) 2010).