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The global sensitivity analysis also confirmed the importance of the redox cycle between SQ . and H 2 Q ( R 4 ), showing that the reverse rate constant, k m4 (SQ . reformation), was the second most sensitive (main interactions) with respect to model OCR and therefore ROS production, suggesting auto-oxidation is an essential part of the doxorubicin redox mechanism

Nausea, vomiting, diarrhea, and constipation occur in 25-50% of patients during dose escalation, typically subsiding within 2-4 weeks

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