Pivotal study of iodine-131-labeled chimeric tumor necrosis treatment radioimmunotherapy in patients with advanced lung cancer.
OBJECTIVE
Tumor necrosis treatment (TNT) uses degenerating tumor cells and necrotic regions of tumors as targets for radioimmunotherapy. Previous studies in animal tumor models and clinical trials have demonstrated that when linked to the therapeutic radionuclide iodine-131, recombinant chimeric TNT antibody ((131)I-chTNT) can deliver therapeutic doses to tumors regardless of the location or type of malignancy. Therapeutic efficacy and toxicity of (131)I-chTNT in advanced lung cancer patients were studied in this pivotal registration trial.


METHODS
Patients with advanced lung cancer were treated with systemic or intratumoral injection of (131)I-chTNT in eight oncology centers in China. The objective response rate (ORR) was assessed as the primary end point.


RESULTS
All 107 patients who were entered onto the study and completed therapy had experienced treatment failure after prior radiotherapy or chemotherapy a mean of three times. The results showed an ORR of 34.6% (complete response, 3.7%; partial response, 30.8%; no change, 55.1%; and progressive disease, 10.3%) in all patients and 33% in 97 non-small-cell lung cancer patients. A biodistribution study demonstrated excellent localization of the radioactivity in tumors in both systemically and intratumorally injected patients. The most obvious adverse side effect was mild and reversible bone marrow suppression.


CONCLUSIONS
Radioimmunotherapy with (131)I-chTNT was well tolerated and can be used systemically or locally to treat refractory tumors of the lung.
Chen
Shaoliang
S
Zhongshan Hospital and Tumor Hospital, Fudan University, Shanghai, China.
Yu
Like
L
Jiang
Changying
C
Zhao
Yan
Y
Sun
Da
D
Li
Shenyu
S
Liao
Guoqing
G
Chen
Yangchun
Y
Fu
Qing
Q
Tao
Qun
Q
Ye
Dan
D
Hu
Peisheng
P
Khawli
Leslie A
LA
Taylor
Clive R
CR
Epstein
Alan L
AL
Ju
Dian Wen
DW
D000328:Adult; D000368:Aged; D000912:Antibodies, Neoplasm; D002289:Carcinoma, Non-Small-Cell Lung / Q000000981:diagnostic imaging / Q000473:pathology / Q000532:radiotherapy*; D005260:Female; D006801:Humans; D000922:Immunotoxins / Q000008:administration & dosage; D007457:Iodine Radioisotopes / Q000008:administration & dosage* / Q000633:toxicity; D008175:Lung Neoplasms / Q000000981:diagnostic imaging / Q000473:pathology / Q000532:radiotherapy*; D008297:Male; D008875:Middle Aged; D009336:Necrosis; D049268:Positron-Emission Tomography; D016499:Radioimmunotherapy / Q000009:adverse effects / Q000379:methods*; D014018:Tissue Distribution
D000912:Antibodies, Neoplasm; D000922:Immunotoxins; D007457:Iodine Radioisotopes