Annals of Oncology Advance Access originally published online on February 23, 2006
Annals of Oncology 2006 17(8):1334; doi:10.1093/annonc/mdl022
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© 2006 European Society for Medical Oncology
letter to the editor |
Successful recovery after accidental overdose of cyclophosphamide
Accidental overdose of chemotherapy is an infrequent situation. However, under certain circumstances an error can lead to the administration of chemotherapy in high doses with fatal consequences. We describe the clinical course of a 42-year-old Arab man who received an overdose of chemotherapy including a very high dose of cyclophosphamide.
The patient was receiving chemotherapy in another institution, consisting of alternating courses of ifosfamide, vincristine, actynomicin D, carboplatin, epirubicin and etoposide, according to the CEVAIE protocol (Table 1) [1
]. He was diagnosed with embryonal rhabdomyosarcoma with meningeal extension, and had received the first three courses of treatment before transferring to our hospital.
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At admission, blood-cell counts and biochemical profile were normal. A translation error of the protocol led to the administration of cyclophosphamide instead of ifosfamide, giving the following total doses of drugs (1.8 m2 body surface area): vincristine 2 mg, actynomicin D 2.7 mg and cyclophosphamide 5400 mg daily for 3 consecutive days (total dose 16200 mg) with mesna uroprotection. After moderate emesis for the first 3 days his general condition worsened and at day +8, a blood count showed leukocytes 0.023 x 109/l, absolute neutrophil count (ANC) 0.0018 x 109/l, hemoglobin 9.8 g/dl and platelets 5.3 x 109/l. Severe mucositis and fever developed, and total parenteral nutrition (TPN), broad spectrum antibiotics and granulocyte colony stimulating factors were started. In the following days, respiratory distress led to oxygen therapy and a chest radiograph showed bilateral alveolar and interstitial pulmonary infiltrates. After 5 days, antifungal therapy with caspofungin was commenced. An echocardiography revealed moderate to severe left-ventricular dysfunction, with slight pericardial and moderate bilateral pleural effusions. Neither renal failure nor hemorrhagic cystitis developed. By day +16 ANC was superior to 0.5 x109/l, and platelets levels of greater than 25 000 and 50 000 x 109/l were observed at days +21 and +25, respectively. During all this time the patient received transfusion support with 8 units of red blood cells and 60 units of platelets in total. Moderate and reversible liver damage was detected at day +26, with normal values of bilirubin and an increase of liver enzymes of five to 10 times the normal range. Fever disappeared at day +28 and TPN was stopped at day +30. Control chest radiograph showed partial resolution of the pulmonary infiltrates and the patient recovered normal oxygenation. At day +32, echocardiography showed a normal left ventricular ejection fraction of 50% and complete resolution of the pericardial and pleural effusions. The patient is now receiving radiation therapy over the residual spinal tumour.
This clinical case highlights the need for a careful prescription of cytostatic drugs when treating cancer patients [2, 3]. Cyclophosphamide is administered in a wide range of doses, generally between 500 and 750 mg/m2 in combination therapy for breast cancer and lymphomas. High-dose chemotherapy with autologous hematopoietic stem-cell rescue protocols usually employs doses of 4000–8000 mg/m2. Fulminant cardiac toxicity is associated with high-dose cyclophosphamide at 60 mg/kg for 4 days [4]. Our patient received a total dose of 16 200 mg, which is more than 77 mg/kg for 3 days. Fortunately his cardiac dysfunction was reversible and he did not experienced hemorrhagic cystitis despite severe and prolonged thrombocytopenia.
Servicio de Oncología Médica, Hospital Universitario de Gran Canaria Dr. Negrín, Las Palmas de Gran Canaria, Spain
* (E-mail: dagubuj{at}gobiernodecanarias.org)
References
1. Modritz D, Ladenstein R, Potschger U et al. Treatment for soft tissue sarcoma in childhood and adolescence. Austrian results within the CWS 96 study. Wien Klin Wochenschr 2005; 117: 196–209.[CrossRef][Web of Science][Medline]
2. Fischer DS, Alfano S, Knobf MT et al. Improving the cancer chemotherapy use process. J Clin Oncol 1996; 14: 3148–3155.[Abstract]
3. Aguirrezabal Arredondo A, Alvarez Lavin M, Yurrebasco Ibarreche MJ et al. Detecting errors in chemotherapy prescription. Farm Hosp 2003; 27: 219–223.[Medline]
4. Colvin OM. Pharmacology of cancer chemotherapy. Antitumor alkylating agents. In DeVita Vt Jr, Hellman S, Rosenberg SA (eds): Cancer: Principles and Practice of Oncology, 6th edition. Philadelphia, PA: Lippincott Williams & Wilkins 2001; 363–376.
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