Assessing the ability of the antiangiogenic and anticytokine agent thalidomide to modulate radiation-induced lung injury.
OBJECTIVE
Thalidomide has broad anticytokine properties, which might protect normal tissues in patients undergoing chemoradiotherapy. The purpose of this study was to determine the maximal tolerated dose of thalidomide when used in combination with vinorelbine plus thoracic radiotherapy.


METHODS
Eligible patients had inoperable Stage III non-small-cell lung cancer, a Karnofsky Performance Status>or=70, and life expectancy>or=6 months. Patients underwent pretreatment evaluation of lung function. Radiotherapy consisted of 66 Gy in 6.5 weeks. Vinorelbine was administered i.v. (5 mg/m2) 3 times per week just before radiotherapy. Thalidomide was begun at 50 mg, p.o., on day 1 of chemoradiotherapy and continued once daily for 6 months. Side effects were scored using National Cancer Institute Common Toxicity Criteria.


RESULTS
Ten patients were enrolled. Of the first 6 patients, 2 developed major thrombotic events that were believed to be possibly related to thalidomide. The study was suspended and modified to require prophylactic anticoagulation. Of the last 4 patients, 2 developed dose-limiting toxicity attributable to thalidomide; both patients required a dose reduction of thalidomide to <50 mg/day. Because the drug is not available in an oral product providing <50 mg/day, the study was closed.


CONCLUSIONS
The combination of thalidomide concurrently with thoracic radiotherapy and vinorelbine resulted in excessive toxicity.
Anscher
Mitchell S
MS
Department of Radiation Oncology, Duke University Medical Center, Durham, NC 27710, USA. ansch001@notes.duke.edu
Garst
Jennifer
J
Marks
Lawrence B
LB
Larrier
Nicole
N
Dunphy
Frank
F
Herndon
James E
JE
Clough
Robert
R
Marino
Christine
C
Vujaskovic
Zeljko
Z
Zhou
Sumin
S
Dewhirst
Mark W
MW
Shafman
Timothy D
TD
Crawford
Jeffrey
J
D000368:Aged; D000369:Aged, 80 and over; D020533:Angiogenesis Inhibitors / Q000008:administration & dosage / Q000009:adverse effects*; D002289:Carcinoma, Non-Small-Cell Lung / Q000098:blood supply / Q000532:radiotherapy*; D005260:Female; D016222:Fibroblast Growth Factor 2 / Q000037:antagonists & inhibitors; D006801:Humans; D008175:Lung Neoplasms / Q000098:blood supply / Q000532:radiotherapy*; D008297:Male; D020714:Maximum Tolerated Dose; D008875:Middle Aged; D009389:Neovascularization, Pathologic / Q000517:prevention & control; D017564:Radiation Pneumonitis / Q000517:prevention & control*; D011838:Radiation-Sensitizing Agents / Q000008:administration & dosage; D013792:Thalidomide / Q000008:administration & dosage / Q000009:adverse effects*; D013927:Thrombosis / Q000139:chemically induced*; D042461:Vascular Endothelial Growth Factor A / Q000037:antagonists & inhibitors; D014747:Vinblastine / Q000008:administration & dosage / Q000031:analogs & derivatives; D000077235:Vinorelbine
D020533:Angiogenesis Inhibitors; D011838:Radiation-Sensitizing Agents; D042461:Vascular Endothelial Growth Factor A; D016222:Fibroblast Growth Factor 2; D013792:Thalidomide; D014747:Vinblastine; D000077235:Vinorelbine