Selective use of sorafenib in the treatment of thyroid cancer

Figures & data

Table 1 Summary of the efficacy of sorafenib in patients with thyroid cancer reported by clinical trials

Study	N	Type	CB (PR + SD) (%)	PR (%)	SD (%)	PD (%)	Median PFS (months)
Gupta-Abramson et al^Citation56	30	27 DTC, 1 MTC, 2 ATC	77	23.3	53.3	7	18
Kloos et al^Citation57	41	PTC	56	15	41	44	15
Hoftijzer et al^Citation59	31	DTC	59	25	34	22	14.5
Cabanillas et al^Citation60,Citation76	13	DTC	80	20	60	20	19
Lam et al^Citation64	21	MTC	95.2	9.5	85.7	4.8	17.9
Keefe et al^Citation61	55	47 DTC, 3 MTC, 5 ATC	85 (DTC)	38 (DTC)	47 (DTC)	15 (DTC)	23.4
Ahmed et al^Citation65	34	19 DTC, 15 MTC		18 (DTC), 25 (MTC)	–	–	–
Marotta et al^Citation62	17	DTC	71	30	41	18	9
Schneider et al^Citation63	31	DTC	73	31	42	27	18
Capdevila et al^Citation66	34	16 DTC, 15 MTC, 3 ATC	69 (DTC), 87 (MTC)	19 (DTC), 47 (MTC)	50 (DTC), 40 (MTC)	25 (DTC), 7 (MTC)	13.3 (DTC), 10.5 (MTC)
Brose et al^Citation47,Citation86	207	DTC	54.1	12.2	41.8	45.9	10.8
Pitoia^Citation73	8	DTC	75	12.5	62.5	25	14–24

Abbreviations: CB, clinical benefit; PR, partial response; SD, stable disease >6 months; PD, progressive disease; PFS, progression-free survival; DTC, differentiated thyroid cancer; MTC, medullary thyroid cancer; ATC, anaplastic thyroid cancer; PTC, papillary thyroid cancer.

Table 2 Adverse effects of sorafenib, fatal events, dose reductions, interruptions, and withdrawals reported in each trial

Study	All grades AEs	Grades 3–4 AEs	Fatal eventsa (%)	Dose reductions (%)	Interruptions (%)	Withdrawals (%)
Gupta-Abramson et al^Citation56	HFS 93%, diarrhea 80%, rash 80%	Hypertension 13%, HFS, rash, weight loss 10%	3	47	63	20
Kloos et al^Citation57	HFS, diarrhea, weight loss	Fatigue (16%), hand or foot pain (12%), arthralgia (11%)	43	52	DNS	25
Hoftijzer et al^Citation59	HFS 66%, weight loss 56%, diarrhea 50%	HFS 18%, hypertension 15%, weight loss 9%	0	56	DNS	18.7
Lam et al^Citation64	HFS 90%, diarrhea 81%, alopecia 76%	HFS 14%, diarrhea, hypertension 10%	DNS	DNS	DNS	DNS
Ahmed et al^Citation65	Dermatology (other) 88%, HFS 79%, diarrhea 77%	HFS 44%	6	82	DNS	6
Marotta et al^Citation62	HFS 88%, increased TSH 76%, fatigue 71%	DNS	30	100	100	12
Schneider et al^Citation63	HFS 71%, weight loss 58%, rash 55%	HFS 22%, weight loss, hypertension 16%	3	58	DNS	23
Capdevila et al^Citation66	HFS, diarrhea 62%, fatigue 56%	HFS 23%, diarrhea, fatigue 15%	3	35	DNS	0
Brose et al^Citation47,Citation86	HFS 73.6%, diarrhea 68.6%, alopecia 67.1%	HFS 20.3%, hypertension 9.7%, hypocalcaemia 9.2%	6	66.2	64.3	18.8
Pitoia^Citation73	Diarrhea 37%, fatigue 37%	Heart failure 12%	12	50	DNS	12

Note:

a Fatal events of all causes.

Abbreviations: AE, adverse effect; HFS, hand–foot syndrome; TSH, thyroid-stimulating hormone; DNS, data not shown.

Table 3 Common Terminology Criteria for Adverse Events

	Grade 1	Grade 2	Grade 3	Grade 4
HFS	Minimal skin changes or dermatitis (eg, erythema, edema, or hyperkeratosis) without pain	Skin changes (eg, peeling, blisters, bleeding, edema, or hyperkeratosis) with pain; limiting instrumental ADLa	Severe skin changes (eg, peeling, blisters, bleeding, edema, or hyperkeratosis) with pain; limiting self-care ADLb
Fatigue	Relieved by rest	Not relieved by rest; limiting instrumental ADLa	Not relieved by rest, limiting self-care ADLb
Hypertension	SBP 120–139 mmHg or DBP 80–89 mmHg	SBP 140–159 mmHg or DBP 90–99 mmHg	SBP ≥160 mmHg or DBP ≥100 mmHg	Life-threatening consequences (malignant hypertension, transient or permanent neurologic deficit, hypertensive crisis)
Anemia	Hgb <LLN–10.0 g/dL	Hgb <10.0–8.0 g/dL	Hgb <8.0 g/dL	Life-threateningconsequences
Thrombocytopenia	<LLN–75,000/mm^3	<75,000–50,000/mm^3	<50,000–25,000/mm^3	<25,000/mm^3
Leukopenia	<LLN–3,000/mm^3	<3,000–2,000/mm^3	<2,000–1,000/mm^3	<1,000/mm^3

Notes:

a Instrumental ADL: preparing meals, shopping for groceries or clothes, using the telephone, managing money, etc.

b Self-care ADL: bathing, dressing and undressing, feeding self, using the toilet, taking medications, and not bedridden. Data from US Dept of Health and Human Services, National Institutes of Health, National Cancer Institute.⁸¹

Abbreviations: HFS, hand–foot syndrome; ADL, activities of daily living; SBP, systolic blood pressure; DBP, diastolic blood pressure; Hgb, hemoglobin value; LLN, low limit of normal.

Figure 1 Management recommendations for hand–foot skin reaction.

Notes: Dose level 0: 800 mg, dose level –1: 600 mg, dose level –2: 400 mg, dose level –3: 200 mg. Data from Brose et al.⁸⁶

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