Fever as the only manifestation of hypersensitivity reactions associated with oxaliplatin in a patient with colorectal cancer Oxaliplatin-induced hypersensitivity reaction

Table 1 Common terminology criteria for adverse events grading of hypersensitivity reactions (version 3.0)[26]

Grade	Hypersensitivity reactions
1	Transient flushing or rash; drug fever < 38°C
2	Rash; flushing; urticaria; dyspnea; drug fever ≥ 38°C
3	Symptomatic bronchospasm, with or without urticaria; parenteral medication(s) indicated; allergy-related edema/angioedema; hypotension
4	Anaphylaxis

Table 2 Incidence of HSR in pivotal studies of oxaliplatin in metastatic and adjuvant treatment of colorectal cancer

Study	Number of patients	Patients with HSR (%)	Patients with Grade 3/4 HSR (%)
Data from first-line[10]	259	12	2
Data from second-line[10]	150	10	< 1
MOSAIC (adjuvant)[2]	1123	10.3	2.9
Siu et al[1] all patients	180	15	2.2
Siu et al[11] adjuvant/ first-line metastatic	88	10.2
Siu et al[11] second-line metastatic	92	19.6

HSR: Hypersensitivity reactions.

Table 3 Characteristics of HSR with different Platinum compounds

	Cisplatinum[12,13]	Carboplatinum[4,15]	Oxaliplatin[5-9]
Incidence	5%-20% ( Increased with radiation)	16%	12% (14), < 1% grade 3-4
Initial onset	-	After 6 cycles( range 2-12)	After 7 cycles ( range 2-25)
Time of onset	Minutes	Minutes-days	Minutes-hours
Symptoms	Variable( fever, anxiety, pruritus, cough, dyspnea, diaphoresis, angioedema, vomiting, bronchospasm, rash and pruritus, and hypotension	Variable (itching ,rash, chest tightness, Blood pressure changes, facial swelling)	Variable (flushing, alterations in heart rate, dyspnea, back pain, fever, pruritis, erythema, nausea, rash)
Can it be re-introduced?	-	Yes, with slowing the infusion rate (6% discontinued)	Yes, with pre-medications, slowing the infusion rate, and/or desensitization

Table 4 Published cases of hypersensitivity associated with oxaliplatin

Reference	Presenting Features	Premedication	Oxaliplatin dose and serial dilution if used	Duration of therapy
Lydia et al[23]	Diaphoresis, hypotension, nausea, abdominal cramping rash, coryza	D1-prednisone 20 mg Po Q6 h × 4 D2 45 min pre chemo ondansterone 8 mg + dexamethasone 20 mg iv 30 min prior diphenylhydramine 50 mg iv + cemetidine 300 mg iv	140 mg on d 2 dilutions from 1:10000 to 1:1	8 h
Thomas et al[5]	Erythematic, flushing	Dexamethasone 20 mg 6 h and 12 h prior 30 min pre infusion: solumedrol 125 mg iv, diphenylhydramine 50 mg iv, cimetidine 50 mg iv	-	2-4 h
Bhargava et al[22]	Palpitation, flushing, hypotension	Dexamethasone starting 24 h prior 30 min before infusion received dexamethasone, diphenylhydramine, hydrocortisone 100 mg iv	1:10000, 1:1000, 1:100, 1:10 each bag infuse over one hour	6-8 h
Meyer et al[7]		dexamethasone-famotidine and diphenylhydramine	90% of total dose 1:1000, 1:100 and 1:10 dilution over 90 min	6 h
Lim et al[24]	Abdominal distension, heat, pruritis	D 1 diphenylhydramine 50 mg QID 30 min prior to infusion metoclopramide 9 mg, morazepam 2 mg, dexamethasone 5 mg iv	Fixed dose infusion over 24 h with dilute solution (0.15 mg/mL)	24 h
Present case	Fever	-	Refused further oxaliplatin therapy	-