melphalan and Tachycardia

Severe systemic toxicity and hemodynamic changes after isolated limb perfusion (ILP) with tumor necrosis factor-alpha (TNF-alpha) and melphalan, with or without interferon-gamma, have been reported in several series. We studied whether these side effects could be precluded by preventing leakage from the isolated circuit into the systemic circulation.. Clinical and pharmacokinetic data for 20 consecutive patients with recurrent melanoma of the limbs who were treated by ILP with TNF-alpha (3-4 mg) and melphalan, with or without interferon-gamma, were studied. Leakage rates and TNF-alpha levels were determined during and after ILP and were correlated with systemic toxicity and hemodynamic changes.. Only two patients experienced leaks (2% and 13%) during ILP. For 18 patients without leakage, the mean peak systemic TNF-alpha level was 2.8 ng/ml at 10 minutes after ILP. After leakage, the peak systemic TNF-alpha levels were 31.9 and 88.3 ng/ml at 5 minutes. Toxicity was mild and consisted mainly of fever (n = 17) and nausea/vomiting (n = 19) during the first day after ILP. Some patients developed tachycardia (n = 6), hypotension (n = 3; responding immediately to fluid challenge), a decrease in the WBC count (n = 3; grade I) or thrombocyte count (n = 11; grade I/II, no hemorrhage or therapeutic intervention), or hepatotoxicity [cytolysis (n = 15; 14 grade I/II and 1 grade IV) or hyperbilirubinemia (n = 7; grade I/II, all resolving spontaneously)]. Patients with tachycardia or hepatotoxicity exhibited significantly higher TNF-alpha levels after ILP, compared with other patients.. Systemic toxicity after ILP with TNF-alpha is minimal and does not differ from that after ILP with melphalan alone when leakage is adequately controlled.

Topics: Adult; Aged; Aged, 80 and over; Antineoplastic Agents, Alkylating; Chemotherapy, Cancer, Regional Perfusion; Extremities; Female; Humans; Hypotension; Interferon-gamma; Leukopenia; Male; Melanoma; Melphalan; Middle Aged; Neoplasm Recurrence, Local; Tachycardia; Thrombocytopenia; Tumor Necrosis Factor-alpha

Isolated limb perfusion is the treatment of stage III melanoma with in-transit metastasis. This technique allows the administration of cytostatics at an effective concentration and temperature, which could not be administered systemically because of their toxicity. The toxicity due to leakage of the chemotherapy agent from the limb into the systemic circulation is the most serious short-term complication, and is manifested by a systemic inflammatory response syndrome in the immediate post-intervention period. Early detection of this complication and its peri-operative management requires a multidisciplinary approach, in which the anaesthesiologist plays a key role. A case of isolated lower limb perfusion is reported in which the procedure had to be interrupted due to the passage of tumour necrosis factor into the systemic circulation, with severe intra-operative haemodynamic repercussions.

Topics: Acid-Base Imbalance; Aged; Antineoplastic Combined Chemotherapy Protocols; Bicarbonates; Calcium; Chemotherapy, Cancer, Regional Perfusion; Epinephrine; Extravasation of Diagnostic and Therapeutic Materials; Female; Humans; Hyperthermia, Induced; Hypotension; Intraoperative Complications; Leg; Lymph Node Excision; Lymphatic Metastasis; Melanoma; Melphalan; Methylene Blue; Norepinephrine; Skin Neoplasms; Tachycardia; Tumor Necrosis Factor-alpha

Topics: Adult; Antineoplastic Agents; Bone Marrow; Burns; Creatine Kinase; Electroencephalography; Etoposide; Female; Humans; Hyperthermia, Induced; L-Lactate Dehydrogenase; Male; Melanoma; Melphalan; Middle Aged; Neoplasm Metastasis; Neoplasms; Peripheral Nervous System Diseases; Remission, Spontaneous; Tachycardia

Topics: Adolescent; Adult; Aged; Anemia; Cardiomyopathies; Chemotherapy, Cancer, Regional Perfusion; Child; Cyclophosphamide; Electrocardiography; Humans; Leg; Leukopenia; Melphalan; Middle Aged; Neoplasms; Tachycardia; Thiotepa; Vascular Diseases