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There's a possible eye irritation, a possible halo effect--patients sometimes report seeing things with a ring of light around them--but that's usually dealt with by a dose reduction.
The low dose CT simulator divides raw data pixel values (y) by a dose reduction quotient q which results in new simulated raw data pixel values y/ q.
In the OLE, all patients initially received CZP 400 mg Q2W + MTX for ≥6 months, followed by a dose reduction to 200 mg Q2W, the approved maintenance dose of CZP.
Grade 2 or worse nonhaematological toxicities led to cessation of 5FU treatment until resolution of toxicity followed by a dose reduction of 5FU except for PPE developing for the first time after 10 weeks of therapy, where treatment was initially recommended at the original starting dose.
Sunitinib-related adverse events are frequently managed by a dose reduction from 50 mg oral daily to 37.5 or 25 mg (Sutent SmPC), suggesting that lower doses of sunitinib are better tolerated than the recommended dose, which would presumably also reduce adverse event management costs.
For the c.1905+1G>A variant, we agree with previous reports suggesting that the severity of side effects will be reduced by a dose reduction of 50 60% before the start of therapy (Deenen et al, 2011; Yang et al, 2011; van Kuilenburg et al, 2012), while patients carrying the other variant DPYD genotypes may benefit from a lesser dose reduction of 25%.
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On the other hand, most patients recovered from the toxicity induced by CEP with a dose reduction and a week's delay of therapy.
Initially, myelosuppression was the major toxicity; potentiation of cyclophosphamide-induced leukopenia by SR2508 required a dose reduction of cyclophosphamide to 750 mg m-2 at SR2508 doses above 7.2 g m-2.
Based on these findings, the protocol was amended after the first 14 patients had been entered, and a procedure on dose reduction related to liver toxicity was included: grade 3 4 transaminitis still present at day 21 but reversible by day 28 required a dose reduction to 1.2 mg m−2, with a subsequent dose reduction to 1 mg m−2 permitted if necessary.
If research showed that appropriate diagnosis were achievable with CT images that contain relatively higher noise levels, this would mean that dose reduction would be feasible; for example, allowing image noise to increase by a factor of 2 would imply that a dose reduction by a factor of 4 would be achieved.
To compare the GP collimator with the high-resolution collimator, a second acquisition was made for both collimators with a total acquisition time of 16 min. The initial analysis of BSGI scans of the 13 patients showed that a dose reduction by a factor of 3 would not have reduced the number of observable hotspots in each of the acquired views.
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Justyna Jupowicz-Kozak
CEO of Professional Science Editing for Scientists @ prosciediting.com