TY - JOUR
T1 - Isolated limb perfusion with tumour necrosis factor-α and melphalan with or without interferon-γ for the treatment of in-transit melanoma metastases
T2 - A multicentre randomized phase II study
AU - Liénard, D.
AU - Eggermont, A. M.M.
AU - Schraffordt Knoops, H.
AU - Kroon, B.
AU - Towse, G.
AU - Hiemstra, S.
AU - Schmitz, P.
AU - Clarke, J.
AU - Steinmann, G.
AU - Rosenkaimer, F.
AU - Lejeune, F. J.
PY - 1999
Y1 - 1999
N2 - This open, multicentre, randomized phase II trial was conducted to determine the effect of isolated limb perfusion (ILP) with tumour necrosis factor-α (TNFα) in combination with melphalan with or without interferon-γ (IFNγ) in patients with in-transit metastases of melanoma of the limbs (MD Anderson stage IIIa or IIIAB, AJCC stage III). The 64 patients included were randomized to receive either a two- drug regimen consisting of TNFα and melphalan (TM-ILP) or a three-drug regimen consisting of TNFα, melphalan and INFγ (TIM-ILP). Patients randomized to receive IFNγ were pretreated for 2 days before the ILP with once daily 0.2 mg IFNγ subcutaneously and also received the same amount of IFNγ during ILP. A total of 47 complete responses (73%) were reported, 22 (69%) of which occurred in the TM-ILP group and 25 (78%) in the TIM-ILP group; the difference was not significant. The 14 partial responses (22%) were split evenly between the treatment groups. In the TM-ILP group, two cases of stable disease and one case of progressive disease were reported. The overall response rate (complete plus partial responses) was 100% in the TIM-ILP group and 91% in the TM-ILP group, yielding an overall response of 95% for this study. In the historical control data, where 103 patients had received melphalan alone (M-ILP), there were 54 records of complete responses (52%) and 80 of complete or partial responses (78%). The median survival time estimated by the Kaplan-Meier method was 819 days for the TM-ILP group, > 705 days for the TIM-ILP group and 873 days for the combined study population; estimates for time to local progression or recurrence were 327 days, in excess of 498 days and 405 days, respectively. The corresponding figure for the historical controls was 338 days. These data suggest that TNFα associated with melphalan may be superior to melphalan alone for ILP.
AB - This open, multicentre, randomized phase II trial was conducted to determine the effect of isolated limb perfusion (ILP) with tumour necrosis factor-α (TNFα) in combination with melphalan with or without interferon-γ (IFNγ) in patients with in-transit metastases of melanoma of the limbs (MD Anderson stage IIIa or IIIAB, AJCC stage III). The 64 patients included were randomized to receive either a two- drug regimen consisting of TNFα and melphalan (TM-ILP) or a three-drug regimen consisting of TNFα, melphalan and INFγ (TIM-ILP). Patients randomized to receive IFNγ were pretreated for 2 days before the ILP with once daily 0.2 mg IFNγ subcutaneously and also received the same amount of IFNγ during ILP. A total of 47 complete responses (73%) were reported, 22 (69%) of which occurred in the TM-ILP group and 25 (78%) in the TIM-ILP group; the difference was not significant. The 14 partial responses (22%) were split evenly between the treatment groups. In the TM-ILP group, two cases of stable disease and one case of progressive disease were reported. The overall response rate (complete plus partial responses) was 100% in the TIM-ILP group and 91% in the TM-ILP group, yielding an overall response of 95% for this study. In the historical control data, where 103 patients had received melphalan alone (M-ILP), there were 54 records of complete responses (52%) and 80 of complete or partial responses (78%). The median survival time estimated by the Kaplan-Meier method was 819 days for the TM-ILP group, > 705 days for the TIM-ILP group and 873 days for the combined study population; estimates for time to local progression or recurrence were 327 days, in excess of 498 days and 405 days, respectively. The corresponding figure for the historical controls was 338 days. These data suggest that TNFα associated with melphalan may be superior to melphalan alone for ILP.
UR - http://www.scopus.com/inward/record.url?scp=0032695429&partnerID=8YFLogxK
U2 - 10.1097/00008390-199910000-00009
DO - 10.1097/00008390-199910000-00009
M3 - Article
AN - SCOPUS:0032695429
SN - 0960-8931
VL - 9
SP - 491
EP - 502
JO - Melanoma Research
JF - Melanoma Research
IS - 5
ER -