Table 5.

Suggested Management of Fever, Which Is Commonly Seen in Patients Receiving Dabrafenib

	Recommended Evaluations	Recommended Treatment
Uncomplicated first occurrence	Evaluate patient for signs and symptoms of infection and  consider imaging/testing as appropriate	Hold drug until fever resolves
	Routine laboratory testing should include:	Encourage oral hydration
	• CBC with differential	Give antipyretic until fever resolves:
	• Blood cultures	• Acetaminophen every 6 h
	• Renal function testing	• Consider alternating acetaminophen and ibuprofen (ibuprofen should be used cautiously owing to possible renal insufficiency)
		• Consider a short trial of oral corticosteroids
		Resume drug at same dose when fever is resolved
		Consider fever prophylaxis:
		• Acetaminophen and/or ibuprofen are reasonable for prophylaxis, but they may not be as effective as prednisone
		• Prednisone (e.g., 10–20 mg daily); titrate down each week over 2–4 weeks
Uncomplicated second or subsequent occurrence	Evaluate patient for signs and symptoms of infection and  consider imaging/testing as appropriate	Hold drug until fever resolves
	Routine laboratory testing should include:	Encourage oral hydration
	• CBC with differential	Give antipyretic until fever resolves:
	• Blood cultures	• Acetaminophen every 6 h
	• Renal function testing	• Consider alternating acetaminophen and ibuprofen (ibuprofen should be used cautiously owing to possible renal insufficiency)
		• Consider oral corticosteroids
		If uncomplicated fever recurs in spite of fever prophylaxis:
		• If acetaminophen or ibuprofen was used for prophylaxis, switch to prednisone
		• If prednisone was used as prophylaxis, use a higher dose of prednisone; once fever resolves, restart at the same dose
		• If uncomplicated fever recurs in spite of a higher dose of steroid-based prophylaxis (e.g., 40 mg daily), reduce dabrafenib dose to the next lowest dose (e.g., from 150 mg to 100 mg)
Complicated first occurrence	Patient should be evaluated immediately by a physician to  determine the severity of symptoms	Hold drug until fever resolves
	Evaluate patient for signs and symptoms of infection and  consider imaging/testing as appropriate	Encourage oral hydration or provide IV hydration
	Acute/severe issues (e.g., hypotension, arrhythmia) should  be managed aggressively and require hospitalization	Give antipyretic until fever resolves (see guidelines for uncomplicated fever):
	Routine laboratory testing should include:	• Oral steroids are recommended; a higher dose may be necessary (e.g., prednisone at 20–40 mg depending on the severity of the event); titrate steroids down over a period of 2 wk
	• CBC with differential	Consider pyrexia prophylaxis; titrate steroids down slowly (e.g., over 2–4 wk)
	• Blood cultures	Once fever resolves, reduce dabrafenib dose to the next lowest dose (e.g.,  from 150 mg to 100 mg)
	• Renal function testing	In patients who experience severe symptoms (e.g., hypotension, arrhythmia),  consider discontinuing dabrafenib permanently
Complicated second occurrence	Repeat evaluations described above for complicated first occurrence	If severe symptoms recur in spite of dose reduction and pyrexia prophylaxis, consider discontinuing dabrafenib permanently

Note: Adverse events are defined using the Common Terminology Criteria for Adverse Events (CTCAE), v5.0, US Department of Health and Human Services, National Institutes of Health, National Cancer Institute; 27 November 2017. Available at: https://ctep.cancer.gov/protocolDevelopment/electronic_applications/ctc.htm.

Definitions: uncomplicated: temperature <104°F with no hypotension, dehydration, dizziness, arrhythmia, rigor, or grade 3–related symptoms; complicated: temperature ≥104°F with hypotension, dehydration, dizziness, arrhythmia, rigor, and/or grade 3–related symptoms.

Abbreviation: CBC, complete blood count.

[Reprinted with permission from Copyright Clearance Center: Springer, Hormones & Cancer, Cabanillas ME, Patel A, Danysh BP, Dadu R, Kopetz S, Falchook G. BRAF inhibitors: experience in thyroid cancer and general review of toxicity. Horm Cancer 2015;6:21–36.]