ABSTRACT
After cisplatin / 5-fluorouracil chemotherapy for nasopharyngeal carcinoma, an 18-year female patient developed aortobifemoral embolism. Besides chemotherapy, additional risk factors for arterial thromboembolic events were smoking, contraceptive medication and adjuvant antiemetic treatment with dexamethasone. Thrombophilia screening was negative. Thromboembolic complications during or after cisplatin have been reported in a frequency of 17.6 % in lung cancer patients, and in 8.4 % of patients with germ cell tumors. The incidence of arterial thromboembolic events was 9.3 % and 1.7 %, respectively. The pathogenesis of cisplatin induced thromboembolism is thought to be caused by endothelial damage leading to endothelial cell dysfunction, increased von Willebrand factor plasma levels, and hypomagnesaemia.
Subject(s)
Antineoplastic Combined Chemotherapy Protocols/adverse effects , Aortic Diseases/chemically induced , Arterial Occlusive Diseases/chemically induced , Carcinoma/drug therapy , Embolism/chemically induced , Femoral Artery , Ischemia/chemically induced , Nasopharyngeal Neoplasms/drug therapy , Adolescent , Antiemetics/adverse effects , Aortic Diseases/diagnostic imaging , Aortic Diseases/therapy , Arterial Occlusive Diseases/diagnostic imaging , Arterial Occlusive Diseases/therapy , Cisplatin/administration & dosage , Contraceptive Agents, Female/adverse effects , Embolectomy , Embolism/diagnostic imaging , Embolism/therapy , Female , Femoral Artery/diagnostic imaging , Fluorouracil/administration & dosage , Humans , Ischemia/diagnostic imaging , Ischemia/therapy , Risk Factors , Smoking/adverse effects , Tomography, X-Ray Computed , Treatment OutcomeABSTRACT
BACKGROUND: First-line treatment in AML commonly included high cumulative doses of anthracyclines with an increasing risk of cardiotoxicity. Liposomal daunorubicin (L-DNR) is thought to be less cardiotoxic without impairment of efficacy. METHODS: The AML-BFM REZ 97 study included two reinduction blocks with L-DNR (2 x 60 mg/m (2) n = 38, since 2/1999 3 x 60 mg/m (2) n = 31) combined with cytarabine (500 mg/m (2) 4 d). Children who achieved a second blast clearance were allocated to allogeneic stem cell transplantation either from a matched related (MRD) or a matched unrelated donor (MUD). Lack of a donor justified haploidentical SCT in early relapse (1st remission < 1 year) and autologous SCT in late relapse. PATIENTS: Between 1/1997 and 9/2001, 69 children were enrolled in the AML-BFM 97 relapse study. The median duration of first remission was 0.9 years. Forty-one patients had a remission of less than one year, 28 of more than a year. RESULTS: 46 children (67 %) achieved a second remission, defined as clearance of blasts in bone marrow and at least a partial hematological reconstitution. Seventeen of these children are alive (12 of 25 children receiving allogeneic SCT (MFD/MUD); 1 of 8 children after haploidentical SCT; 1 of 4 patients after autologous SCT and 3 of 9 patients treated with chemotherapy only). Further three children without 2nd remission survived after MFD-SCT (n = 2) or chemotherapy (n = 1; follow-up 0.3 to 0.7 years). Duration of first remission remains a significant prognostic factor. The pharmacokinetic investigation showed a high overall AUC of 234.6 mg/l h at a dose of 60 mg/m (2), and a volume of distribution of 1.98 l/m (2), which is much lower in comparison to conventional Daunorubicin. Regarding toxicity, the combination of L-DNR and cytarabine followed by SCT was feasible in experienced centers, however, acute complications like infection or septicemia in aplasia, mucositis and GvHD were common. By contrast, no clinical relevant cardiotoxicity was seen so far, but definitive results in long-term cardiotoxicity await a longer follow-up. In conclusion, L-DNR/cytarabine treatment induced a 2nd remission in most of the children with relapsed or refractory AML. It has to be followed by allogeneic SCT which enables long-term survival.
Subject(s)
Antineoplastic Combined Chemotherapy Protocols/administration & dosage , Cytarabine/administration & dosage , Daunorubicin/administration & dosage , Leukemia, Myeloid, Acute/drug therapy , Adolescent , Antineoplastic Combined Chemotherapy Protocols/adverse effects , Child , Child, Preschool , Cytarabine/adverse effects , Daunorubicin/adverse effects , Dose-Response Relationship, Drug , Female , Follow-Up Studies , Humans , Infant , Leukemia, Myeloid, Acute/mortality , Liposomes , Male , Remission Induction , Stem Cell Transplantation , Survival RateABSTRACT
Stimulated by the public discussion about an antimalignant effect of the supplement drug Recancostat compositum (200 mg glutathione, 40 mg cysteine, 50 mg anthocyanin) the drug was given in high doses to 16 young patients with intensively pretreated and measurable solid tumors for 1-30 weeks. In all patients the disease progressed, and they died 1-48 weeks following the start of the therapy. Side effects were not seen. This observation does not support the claim of an antitumor effect of Recancostat compositum.