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Apatinib was administered until consent withdrawal, disease progression, unacceptable toxicity after two dose of reductions, or toxicity requiring cumulative dose interruption of more than 14 days or twice in an initiating treatment cycle happened.
Drop-off in the APD group was attributable to inability to sustain temporary pharmacological withdrawal, disease severity, (making it too demanding to lie still in the SPECT camera) refusal, or death.
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Some patients did not complete the study due to withdrawal, progressive disease, or death.
The primary reason for study withdrawal was disease progression, accounting for 66% of patients on both schedules (Table 2).
Five patients with treatment-emergent AEs withdrew from the study although, in one of these, the primary reason for withdrawal was disease progression.
Treatments were administered until progression, intolerance, or patient withdrawal, with disease progression assessed via CT scan according to RECIST criteria every 8 weeks.
The reason for treatment withdrawal was disease progression in 29 % of the FOLFOX/bevacizumab and CapeOX/bevacizumab groups combined and adverse events in 32%%.
Therefore, a more rational approach to drug discontinuation might involve tapering a single drug therapy at a time with careful monitoring for symptoms of withdrawal and disease exacerbation.
Patients who came off study for withdrawal, progressive disease or death were considered treatment failures for the primary analysis, but a supportive analysis was performed excluding these patients.
However, upon rapamycin withdrawal, most disease symptoms reappear, and hamartomas and lung function declined supporting the need to identify alternative targets for therapies.
There was no therapeutic effect in other solid tumours treated, although three out of six patients were nonevaluable due to withdrawal or disease progression.
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