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Nimesulide — a New Trigger of Radiation Recall Reaction
364
CLINICAL ONCOLOGY
Once the diagnosis of LCV is made, emphasis should be on the search for a cause and identification of the involved organs. If possible, the underlying cause should be treated or removed, for example, discontinuation of drugs. The prognosis of patients with cutaneous vasculitis depends on the underlying syndrome or the presence of end-organ dysfunction. Patients with disease that primarily affects the skin and/or the joints have a good prognosis. Patients with Wegener granulomatosis, polyarteritis nodosa, Churge Strauss syndrome, or severe necrotising vasculitis have a potentially fatal disease. Treatment with corticosteroids and/or immunosuppressive/cytotoxic agents often saves the patient’s life [3,4]. Only if physicians recognise and report severe reactions to regulatory authorities and manufacturers, can new drugs associated with a risk of such reactions be identified. Physicians should therefore be aware that vinorelbine can cause a non-serious adverse effect that needs discontinuation of therapy.
doi:10.1016/j.clon.2007.02.012
Nimesulide d a New Trigger of Radiation Recall Reaction Sir d Radiation recall reaction is an induced inflammatory reaction in previously irradiated fields, usually by pharmacological agents. Chemotherapeutic agents are the most frequent, but not the only, culprits. Isolated reports have shown that tamoxifen, simvastatin and anti-tuber culosis drugs should also be added to the list [1]. There were three reports describing the role of anti-microbial agents, namely septrin [2], cefazolin [3] and the most recently reported gatifloxacin [4]. We report the first case of nimesulide, a non-steroidal anti-inflammatory drug (NSAID), attributing to radiation recall reaction. A 45-year-old man with biopsy-proven undifferentiated carcinoma of the nasopharynx, clinical stage T2bN2M0, received radical radiotherapy to the faciocervical region concurrently with cisplatin for one cycle (the patient refused further chemotherapy) 2.5 years ago. His past health was unremarkable. Radiotherapy was given in two phases: phase I lateral opposing faciocervical fields with anterior cervical field; and phase II, three-field technique with two lateral opposing faciocervical and one anterior facial field and anterior cervical field after 40 Gy. Shieldings were used for the tongue, eyes and brainstem for all phases. A total dose of 66 Gy was given in conventional fractionation over 45 days. The long-term dermatological toxicity of radiation was minimal with no obvious hyperpigmentation or induration. He was recently prescribed nimesulide, paracetamol and chlorpheniramine for upper respiratory tract symptoms by a general practitioner. Three hours after taking one tablet of nimesulide (without taking any paracetamol or chlorpheniramine), he developed sharply demarcated skin erythema with vesicles matching the shape of the previous radiotherapy portal in the face and neck, especially over the area
D. K. BILKU C. V. BRAMMER
New Cross Hospital, Wolverhampton, West Midlands, UK
References 1 Kouroukis C, Hings I. Respiratory failure following vinorelbine tartarate infusion in a patient with non-small cell lung cancer. Chest 1997;112:846e848. 2 Hohneker JA. A summary of vinorelbine safety data from North American clinical trials. Semin Oncol 1994;21(5 suppl. 10):42e47. 3 Koutkia P, Mylonakis E, Rounds S, Erickson A. Leucocytoclastic vasculitis: an update for the clinician. Scand J Rheumatol 2001; 30(6):315e322. 4 Fiorentino DF. Cutaneous vasculitis. J Am Acad Dermatol 2003; 48(3):311e340. 5 Carlson JA, Ng BT, Chen KR. Cutaneous vasculitis update: diagnostic criteria, classification, epidemiology, etiology, pathogenesis, evaluation and prognosis. Am J Dermatopathol 2005; 27(6):504e528.
of shielding at the tongue and ear (see Figs. 1 and 2). There was no rash over other parts of the body. Nimesulide was stopped immediately on the same day. Apart from dermatitis, mucositis over the nasopharynx was confirmed by endoscopy on the following day. Dermatitis was treated conservatively with 1% hydrocortisone cream three times per day as for other acute skin reactions after radiotherapy. It subsided completely after 4 days. Future use of the offending drug should be avoided but is not absolutely contraindicated. Nimesulide is an NSAID with analgesic and anti-pyretic properties. It is a selective cyclooxygenase-2 inhibitor and is a sulphonanilide analogue [5]. Although banned in the
Fig. 1 e Sharp demarcation of skin erythema consistent with the previous irradiation field portal.
LETTERS
365
reaction by nimesulide may be related to its peculiar mechanism causing skin toxicity. Prompt identification and discontinuation of the offending agent is crucial to the treatment of radiation recall reaction. Although well recognised and rare, its cause remains unknown. We should remain open-minded in finding the culprit of reaction recall reaction once diagnosed, as a wider range of pharmacological agents could be responsible. A. W. Y. NG F. C. S. WONG S. Y. TUNG S. K. O
Tuen Mun Hospital, Hong Kong, China
References Fig. 2 e Previous treatment planning for nasopharyngeal carcinoma of this patient.
USA and many European countries due to established lifethreatening hepatotoxicities, it is still available in more than 50 countries worldwide, including France, Portugal, Greece, Switzerland, Brazil and many Asian countries. Other well-documented adverse skin reactions include rash, urticaria, angioedema and necrotising fasciitis. As NSAIDs are one of the choices for treatment of radiation recall reaction, the mechanism of causing radiation recall
doi:10.1016/j.clon.2007.02.011
Radiotherapy Plus Cetuximab is Safe in a Head and Neck Cancer Patient on Immunosuppressants for Liver Transplant Sir d We report the case of a 56-year-old man with T1N1M0 squamous cell carcinoma (SCC) of the right pyriform fossa. He presented with a 6-week history of painless right neck swelling. He had been diagnosed in 1989 with transitional cell carcinoma of the bladder and treated with neoadjuvant MVAC chemotherapy, cystectomy and neobladder formation. In 2005, he underwent orthotopic liver transplantation for decompensated alcoholic liver cirrhosis. He was put on the immunosuppressants mycophenylate 1 g twice a day, tacrolimus 2 mg twice a day and prednisolone 2.5 mg once a day. His past history included a heavy alcohol intake before the liver transplant. He was a heavy smoker, with a 30e40 pack year history. The clinical examination revealed a 2 cm lymph node on the right neck at level 2. Fine needle aspiration cytology showed metastatic SCC. Panendoscopy revealed a pedunculated polyp in the right pyriform fossa, which was removed. The histopathology was invasive moderately differentiated keratinising SCC. Positron emission tomography/computed tomography showed the primary lesion in the right pyriform fossa and the right cervical lymph node (maximum standardized uptake value 11.5).
1 Azria D, Magne N, Zouhair A, et al. Radiation recall: a well recognized but neglected phenomenon. Cancer Treat Rev 2005; 31:555e570. 2 Lesile MD, Williams DS, Patel P. A localized hypersensitivity reaction to cotrimoxazole in a previously irradiation field simulating a recall phenomenon. Br J Radiol 1990;63(752):661. 3 Garza LA, Yoo EK, Junkins-hopkins JM, VanVoorhees AS. Photo recall effect in association with cefazolin. Cutis 2004;73:79e85. 4 Kang SK. Radiation recall reaction after antimicrobial therapy. N Engl J Med 2006;354(6):622. 5 Thawani V, Sontakke S, Gharpure K, Pimpalkhute S. Nimesulide: the current controversy. Indian J Pharmacol 2003;35:121e122.
He was referred for radical radiotherapy. As he was on immunosuppressants, cisplatin was not used. Cetuximab has been found to improve locoregional control and survival when added to radiotherapy for head and neck cancers [1]. As cetuximab is not known to cause significant myelosuppression or liver toxicity [2], the patient was offered this combination treatment. Radiotherapy was delivered with the concomitant boost technique to the primary tumour and upper neck (70 Gy/40 fractions/42 days), matched to the lower anterior neck (50 Gy/25 fractions/35 days), to the ICRU reference points. Cetuximab was given 1 week before radiotherapy as a 400 mg/m2 loading dose, followed by 250 mg/m2 weekly during radiotherapy [1]. His baseline blood counts were as follows: leucocytes 7.5 109/l, haemoglobin 14.3 g/dl, platelets 53 109/l. His liver function test showed elevated enzymes: alkaline phosphatase 247 U/l (40e150), aspartate aminotransferase 163 U/l (5e34), alanine aminotransferase 125 U/l (0e55), gamma-glutamyl transferase 1003 U/l (12e64). A viral screen was negative for infection with cytomegalovirus, EpsteineBarr virus, Herpes simplex, Varicella zoster, hepatitis A, B and C. The thrombocytopaenia was thought to be due to mycophenylate, which was discontinued. The treatment was commenced without any major side-effects. The liver enzymes remained elevated but stable. A liver biopsy revealed steatohepatitis, believed to be due to alcohol consumption. Triple-phase computed tomography
CLINICAL ONCOLOGY
Once the diagnosis of LCV is made, emphasis should be on the search for a cause and identification of the involved organs. If possible, the underlying cause should be treated or removed, for example, discontinuation of drugs. The prognosis of patients with cutaneous vasculitis depends on the underlying syndrome or the presence of end-organ dysfunction. Patients with disease that primarily affects the skin and/or the joints have a good prognosis. Patients with Wegener granulomatosis, polyarteritis nodosa, Churge Strauss syndrome, or severe necrotising vasculitis have a potentially fatal disease. Treatment with corticosteroids and/or immunosuppressive/cytotoxic agents often saves the patient’s life [3,4]. Only if physicians recognise and report severe reactions to regulatory authorities and manufacturers, can new drugs associated with a risk of such reactions be identified. Physicians should therefore be aware that vinorelbine can cause a non-serious adverse effect that needs discontinuation of therapy.
doi:10.1016/j.clon.2007.02.012
Nimesulide d a New Trigger of Radiation Recall Reaction Sir d Radiation recall reaction is an induced inflammatory reaction in previously irradiated fields, usually by pharmacological agents. Chemotherapeutic agents are the most frequent, but not the only, culprits. Isolated reports have shown that tamoxifen, simvastatin and anti-tuber culosis drugs should also be added to the list [1]. There were three reports describing the role of anti-microbial agents, namely septrin [2], cefazolin [3] and the most recently reported gatifloxacin [4]. We report the first case of nimesulide, a non-steroidal anti-inflammatory drug (NSAID), attributing to radiation recall reaction. A 45-year-old man with biopsy-proven undifferentiated carcinoma of the nasopharynx, clinical stage T2bN2M0, received radical radiotherapy to the faciocervical region concurrently with cisplatin for one cycle (the patient refused further chemotherapy) 2.5 years ago. His past health was unremarkable. Radiotherapy was given in two phases: phase I lateral opposing faciocervical fields with anterior cervical field; and phase II, three-field technique with two lateral opposing faciocervical and one anterior facial field and anterior cervical field after 40 Gy. Shieldings were used for the tongue, eyes and brainstem for all phases. A total dose of 66 Gy was given in conventional fractionation over 45 days. The long-term dermatological toxicity of radiation was minimal with no obvious hyperpigmentation or induration. He was recently prescribed nimesulide, paracetamol and chlorpheniramine for upper respiratory tract symptoms by a general practitioner. Three hours after taking one tablet of nimesulide (without taking any paracetamol or chlorpheniramine), he developed sharply demarcated skin erythema with vesicles matching the shape of the previous radiotherapy portal in the face and neck, especially over the area
D. K. BILKU C. V. BRAMMER
New Cross Hospital, Wolverhampton, West Midlands, UK
References 1 Kouroukis C, Hings I. Respiratory failure following vinorelbine tartarate infusion in a patient with non-small cell lung cancer. Chest 1997;112:846e848. 2 Hohneker JA. A summary of vinorelbine safety data from North American clinical trials. Semin Oncol 1994;21(5 suppl. 10):42e47. 3 Koutkia P, Mylonakis E, Rounds S, Erickson A. Leucocytoclastic vasculitis: an update for the clinician. Scand J Rheumatol 2001; 30(6):315e322. 4 Fiorentino DF. Cutaneous vasculitis. J Am Acad Dermatol 2003; 48(3):311e340. 5 Carlson JA, Ng BT, Chen KR. Cutaneous vasculitis update: diagnostic criteria, classification, epidemiology, etiology, pathogenesis, evaluation and prognosis. Am J Dermatopathol 2005; 27(6):504e528.
of shielding at the tongue and ear (see Figs. 1 and 2). There was no rash over other parts of the body. Nimesulide was stopped immediately on the same day. Apart from dermatitis, mucositis over the nasopharynx was confirmed by endoscopy on the following day. Dermatitis was treated conservatively with 1% hydrocortisone cream three times per day as for other acute skin reactions after radiotherapy. It subsided completely after 4 days. Future use of the offending drug should be avoided but is not absolutely contraindicated. Nimesulide is an NSAID with analgesic and anti-pyretic properties. It is a selective cyclooxygenase-2 inhibitor and is a sulphonanilide analogue [5]. Although banned in the
Fig. 1 e Sharp demarcation of skin erythema consistent with the previous irradiation field portal.
LETTERS
365
reaction by nimesulide may be related to its peculiar mechanism causing skin toxicity. Prompt identification and discontinuation of the offending agent is crucial to the treatment of radiation recall reaction. Although well recognised and rare, its cause remains unknown. We should remain open-minded in finding the culprit of reaction recall reaction once diagnosed, as a wider range of pharmacological agents could be responsible. A. W. Y. NG F. C. S. WONG S. Y. TUNG S. K. O
Tuen Mun Hospital, Hong Kong, China
References Fig. 2 e Previous treatment planning for nasopharyngeal carcinoma of this patient.
USA and many European countries due to established lifethreatening hepatotoxicities, it is still available in more than 50 countries worldwide, including France, Portugal, Greece, Switzerland, Brazil and many Asian countries. Other well-documented adverse skin reactions include rash, urticaria, angioedema and necrotising fasciitis. As NSAIDs are one of the choices for treatment of radiation recall reaction, the mechanism of causing radiation recall
doi:10.1016/j.clon.2007.02.011
Radiotherapy Plus Cetuximab is Safe in a Head and Neck Cancer Patient on Immunosuppressants for Liver Transplant Sir d We report the case of a 56-year-old man with T1N1M0 squamous cell carcinoma (SCC) of the right pyriform fossa. He presented with a 6-week history of painless right neck swelling. He had been diagnosed in 1989 with transitional cell carcinoma of the bladder and treated with neoadjuvant MVAC chemotherapy, cystectomy and neobladder formation. In 2005, he underwent orthotopic liver transplantation for decompensated alcoholic liver cirrhosis. He was put on the immunosuppressants mycophenylate 1 g twice a day, tacrolimus 2 mg twice a day and prednisolone 2.5 mg once a day. His past history included a heavy alcohol intake before the liver transplant. He was a heavy smoker, with a 30e40 pack year history. The clinical examination revealed a 2 cm lymph node on the right neck at level 2. Fine needle aspiration cytology showed metastatic SCC. Panendoscopy revealed a pedunculated polyp in the right pyriform fossa, which was removed. The histopathology was invasive moderately differentiated keratinising SCC. Positron emission tomography/computed tomography showed the primary lesion in the right pyriform fossa and the right cervical lymph node (maximum standardized uptake value 11.5).
1 Azria D, Magne N, Zouhair A, et al. Radiation recall: a well recognized but neglected phenomenon. Cancer Treat Rev 2005; 31:555e570. 2 Lesile MD, Williams DS, Patel P. A localized hypersensitivity reaction to cotrimoxazole in a previously irradiation field simulating a recall phenomenon. Br J Radiol 1990;63(752):661. 3 Garza LA, Yoo EK, Junkins-hopkins JM, VanVoorhees AS. Photo recall effect in association with cefazolin. Cutis 2004;73:79e85. 4 Kang SK. Radiation recall reaction after antimicrobial therapy. N Engl J Med 2006;354(6):622. 5 Thawani V, Sontakke S, Gharpure K, Pimpalkhute S. Nimesulide: the current controversy. Indian J Pharmacol 2003;35:121e122.
He was referred for radical radiotherapy. As he was on immunosuppressants, cisplatin was not used. Cetuximab has been found to improve locoregional control and survival when added to radiotherapy for head and neck cancers [1]. As cetuximab is not known to cause significant myelosuppression or liver toxicity [2], the patient was offered this combination treatment. Radiotherapy was delivered with the concomitant boost technique to the primary tumour and upper neck (70 Gy/40 fractions/42 days), matched to the lower anterior neck (50 Gy/25 fractions/35 days), to the ICRU reference points. Cetuximab was given 1 week before radiotherapy as a 400 mg/m2 loading dose, followed by 250 mg/m2 weekly during radiotherapy [1]. His baseline blood counts were as follows: leucocytes 7.5 109/l, haemoglobin 14.3 g/dl, platelets 53 109/l. His liver function test showed elevated enzymes: alkaline phosphatase 247 U/l (40e150), aspartate aminotransferase 163 U/l (5e34), alanine aminotransferase 125 U/l (0e55), gamma-glutamyl transferase 1003 U/l (12e64). A viral screen was negative for infection with cytomegalovirus, EpsteineBarr virus, Herpes simplex, Varicella zoster, hepatitis A, B and C. The thrombocytopaenia was thought to be due to mycophenylate, which was discontinued. The treatment was commenced without any major side-effects. The liver enzymes remained elevated but stable. A liver biopsy revealed steatohepatitis, believed to be due to alcohol consumption. Triple-phase computed tomography