Hyperthermic antiblastic perfusion with TNFalpha and melphalan in stage III limb melanoma patients: A phase I - II SITILO study.

Abstract

Hyperthermic antiblastic perfusion (HAP) has been proven to be an effective treatment of loco-regional spreading limb melanoma. The mean complete response (CR) rate obtained is 54%, with an objective responses (OR) rate ranging between 70% and 100%. Recently, Tumor Necrosis Factor (TNFalpha) has been employed at high dosages (3-4 mg) in association to Melphalan and hyperthermia. This trimodality combination increased the percentage of CR (70%-90%), but systemic toxicity was also reported due to high TNF doses. A phase I - II study was undertaken in order to assess the MTD of TNFalpha in association to true hyperthermia (41.5 degrees C) and Melphalan. Twenty patients affected with stages IIIA (9 patients), IIIAB (10 patients), and IV (1 patient) were enrolled in this study. The trimodality treatment did not increase the local and systemic toxicity. CR was observed in 70% of the patients, PR in 20% with on OR rate of 90%. These figures are overlapping those obtained with high TNF dosages. No correlation was observed between tumor responses and TNF doses. Taking into account that 70% of our patients have been treated with TNF dosages between 0.5 mg on 1.6 mg, we conclude that 1 mg is the best dosage to be applied during HAP. Patients with bulky tumor are the best candidate to TNF perfusion, because no differences have been observed in terms of CR in patients with low tumor burden treated with TNF-Melphalan-hyperthermia or Melphalan-hyperthermia.

• Authors: F Di Filippo, C R Rossi, R Garinei, M Anzà, F Cavaliere, C Botti, P Perri, S Di Filippo, P Di Angelo, F Principi, L Laurenzi
• Journal: Journal of experimental & clinical cancer research : CR (J Exp Clin Cancer Res) Vol. 22 Issue 4 Suppl Pg. 97-101 (Dec 2003) ISSN: 0392-9078 [Print] England
• PMID: 16767914 (Publication Type: Clinical Trial, Phase I, Clinical Trial, Phase II, Journal Article, Multicenter Study)

Chemical References

• Tumor Necrosis Factor-alpha
• Melphalan

Topics

• Adult
• Aged
• Antineoplastic Combined Chemotherapy Protocols (administration & dosage, adverse effects)
• Chemotherapy, Cancer, Regional Perfusion (adverse effects)
• Combined Modality Therapy
• Dose-Response Relationship, Drug
• Extremities (pathology)
• Female
• Humans
• Hyperthermia, Induced (adverse effects)
• Male
• Maximum Tolerated Dose
• Melanoma (drug therapy, mortality)
• Melphalan (administration & dosage, adverse effects)
• Middle Aged
• Survival Analysis
• Tumor Necrosis Factor-alpha (administration & dosage, adverse effects)