Isolated lung perfusion with melphalan for resectable lung metastases: a phase I clinical trial.
BACKGROUND
Current 5-year survival after complete resection of pulmonary metastases is 20% to 40%, and many patients develop intrathoracic recurrences. Isolated lung perfusion is an experimental technique to deliver high-dose chemotherapy to the lung without systemic exposure. A phase I trial of isolated lung perfusion with melphalan (MN) combined with pulmonary metastasectomy for resectable lung metastases was conducted to define the dose-limiting toxicity and maximum tolerated dose.


METHODS
From May 2001 to August 2003, 16 patients underwent isolated lung perfusion with MN, followed by surgical resection of lung metastases. Patients were treated with increasing MN doses (15, 30, 45, and 60 mg). For each dose level, normothermia (37 degrees C) and hyperthermia (42 degrees C) were evaluated (n = 3 per level). Serum samples were obtained during the procedure. Pulmonary, hematologic, and nonhematologic toxicities were recorded. The primary tumor was colorectal in 7 patients, renal in 5, sarcoma in 3, and salivary gland in 1. Isolated lung perfusion was performed unilaterally in 11 patients, and staged bilaterally in 5.


RESULTS
In total, 21 procedures of isolated lung perfusion with complete metastasectomy were performed without technical difficulties. Operative mortality was 0%, and no systemic toxicity was encountered. Grade 3 pulmonary toxicity developed at a dose of 60 mg of MN at 37 degrees C in 2 of 3 patients at this dose, terminating the trial.


CONCLUSIONS
Isolated lung perfusion with MN combined with pulmonary metastasectomy is feasible. Dose-limiting toxicity occurred at a dose of 60 mg of MN at 37 degrees C, and the maximum tolerated dose was set at 45 mg of MN at 42 degrees C.
Hendriks
Jeroen M H
JM
Department of Thoracic and Vascular Surgery, University Hospital Antwerp, Edegem, Belgium.
Grootenboers
Marco J J H
MJ
Schramel
Franz M N H
FM
van Boven
Wim J
WJ
Stockman
Bernard
B
Seldenrijk
Cornelis A
CA
ten Broecke
Pieter
P
Knibbe
Catherijne A J
CA
Slee
Peter
P
De Bruijn
Ernst
E
Vlaeminck
Renate
R
Heeren
Jos
J
Vermorken
Jan B
JB
van Putte
Bart
B
Romijn
Sander
S
Van Marck
Eric
E
Van Schil
Paul E Y
PE
D000328:Adult; D000368:Aged; D018906:Antineoplastic Agents, Alkylating / Q000008:administration & dosage* / Q000009:adverse effects; D010478:Chemotherapy, Cancer, Regional Perfusion; D015179:Colorectal Neoplasms / Q000473:pathology; D003131:Combined Modality Therapy; D005260:Female; D006801:Humans; D007680:Kidney Neoplasms / Q000473:pathology; D008175:Lung Neoplasms / Q000188:drug therapy* / Q000556:secondary* / Q000601:surgery; D008297:Male; D008558:Melphalan / Q000008:administration & dosage* / Q000009:adverse effects; D008875:Middle Aged; D013510:Pulmonary Surgical Procedures; D012468:Salivary Gland Neoplasms / Q000473:pathology; D012509:Sarcoma / Q000556:secondary
D018906:Antineoplastic Agents, Alkylating; D008558:Melphalan