Table 1 Case reports of hypersensitivity reactions to folinic acid
References | Age (years), sex | Type of cancer and uneventful treatment | Chemotherapy regimen with folinic acid reaction | Clinical events and number of chemotherapy cycles before FA discontinuation | Diagnosis of HSR to FA |
|---|---|---|---|---|---|
Benchalal et al. [9] | 80, M | Stage III colon adenocarcinoma 6 cycles of 5-FU and FA | 1st cycle of FOLFIRI | 1. Rash 2. Rash, hypotension (R/adrenaline) | No more reactions after FA withdrawal |
Vermeulen et al. 1st case [6] | 57, M | Metastatic rectal cancer Palliative treatment with 5-FU and FA | 1st cycle of 5-FU and FA | 1. Urticaria, difficulty breathing | 3 months later: SPT + for FA SPT—for folic acid IDT + for FA (200 μg/mL) |
Vermeulen et al. 2nd case [6] | 59, M | Metastatic colon cancer following a colectomy FOLFOX | 1st and 2nd infusion of FOLFOX | 1. Urticaria | SPT—for FA IDT + for FA (2 mg/mL) Successful oral desensitization (increased FA doses orally to a dose of 375 mg) |
Prabu et al. [20] | 16, M | Stage III T-cell lymphoblastic lymphoma MTX and FA | 2nd cycle of MTX and FA | 1. Chills, rash, fever 2. Rash, vomiting, dizziness, hypotension (R/dopamine) | No argument for sepsis High serum IgE levels of 711 IU/ml (normal: 0.0–158 IU/ml) No more reactions after FA withdrawal |
Katirtzoglou et al. [3] | 67, F | Stage IV KRAS wild-type colon cancer 18 cycles of FOLFOX6 plus cetuximab | 19th cycle of FOLFOX-6 plus cetuximab | 1. Facial flushing, dyspnea, cough, hypertension (R/hydrocortisone) 2. Flushing, diarrhea 3. Flushing, dyspnea, hypotension (R/epinephrine, salbutamol) | No more reactions after FA withdrawal (after 3 reactions requiring hydrocortisone or epinephrine) |
Damaske et al. [21] | 53, M | Stage IV KRAS mutation colon cancer 12 cycles of FOLFOX6 plus bevacizumab 12 cycles of FOLFIRI-bevacizumab 12 cycles of FOLFOX6-bevacizumab | 13th cycle of FOLFOX-6 plus bevacizumab | 1. Flushing, rash, pruritus 2. Urticaria 3. Headache, facial flushing, generalized pain 4. Pruritus, dyspnea, back pain, generalized discomfort, headache (epinephrine) 5. Hypertension (227/114), facial flushing, headache, severe lower back pain (no epinephrine) | No more reactions after FA withdrawal (after 7 more cycles with discontinuation of 5-FU or oxaliplatin) |
Ureña-Tavera et al. 1st case [7] | 65, M | Stage IV gastric adenocarcinoma – | 1st cycle of FOLFOX | 1. Facial erythema, urticaria 2. Urticaria | SPT—for FA IDT—for FA (100 μg/mL) DPT + (urticaria) Normal tryptase levels after DPT |
Ureña-Tavera et al. 2nd case [7] | 66, F | Stage IV colon adenocarcinoma 17 cycles of FOLFOX | 18th cycle of FOLFOX | 1. Genital and scalp itching, rhinoconjunctivitis, general malaise 2. Urticaria, rhinoconjunctivitis | SPT—for FA IDT—for FA (100 μg/mL) DPT + (urticaria, rhinoconjunctivitis) Normal tryptase levels after DPT |
Ureña-Tavera et al. 3rd case [7] | 52, F | Stage IV rectal adenocarcinoma 18 cycles of FOLFOX | 19th cycle of FOLFOX | 1. Intense chills 2. Chills, back pain, hypertension, fever | SPT—for FA IDT—for FA (100 μg/mL) DPT + (chills, back pain, hypertension, fever) Normal tryptase levels after DPT |
Ureña-Tavera et al. 4th case [7] | 73, M | Stage IV colon adenocarcinoma - | 1st cycle of FOLFIRI | 1. Facial erythema, urticaria, eyelid angioedema 2. Urticaria, eyelid angioedema | SPT—for FA IDT—for FA (100 μg/mL) DPT + (urticaria, eyelid angioedema) Normal tryptase level after DPT |
Ureña-Tavera et al. 5th case [7] | 80, F | Stage IV colon adenocarcinoma 10 cycles of FOLFOX 7 cycles of FOLFIRI | 8th cycle of FOLFIRI | 1. Dyspnea, chest pain, desaturation, facial erythema 2. Chills, chest pain, facial erythema | SPT—for FA IDT—for FA (100 μg/mL) DPT + (chills, chest pain, facial erythema) |
Florit-Sureda et al. [4] | 56, M | Stage III sigmoid KRAS wild-type colon cancer 12 cycles of FOLFOX4 FOLFIRI not tolerated 9 cycles of FOLFOX6 | 10th cycle of FOLFOX6 | 1. Facial erythema, edema, pruritus, abdominal pain 2. Facial erythema, pruritus, dyspnea 3. Facial erythema, pruritus, dyspnea | No more reactions after FA withdrawal (after 3 more cycles) |
This report - case 1 | 72, M | Stage IV colon KRAS wild-type adenocarcinoma FOLFOX-panitumumab Capecitabine-irinotecan-bevacizumab FOLFIRI-bevacizumab FOLFOX-panitumumab | 4th cycle of FOLFOX | 1. Lower back muscle pain 2. Chills and facial oedema at home 3. Facial and chest erythema with chills (despite premedication) 4. Diffuse erythema with labial oedema (no adrenaline) | Elevated tryptase levels (16 μg/L; reference value, < 14 μg/L) SPT—for FA IDT + for FA (2.5 μg/mL) SPT and DPT (> 4 mg)—for Folavit |
This report - case 2 | 45, F | Stage IV caecal adenocarcinoma 12 cycles of FOLFOX | > 10th cycle of FOLFOX 1st cycle of FOLFIRI-bevacizumab | 1. Lower back muscle pain, chills 2. Lower back muscle pain, chills (during FA administration without oxaliplatin) 3. Chills, cyanosis without desaturation, tachycardia during FA administration | Normal tryptase levels Persistent symptoms despite oxaliplatin discontinuation Normal tryptase levels SPT—for FA IDT—for FA (2.5 mg/mL) No more reactions after FA withdrawal |