Phase I study of 131I-chimeric(ch) TNT-1/B monoclonal antibody for the treatment of advanced colon cancer.
OBJECTIVE
The primary aim of this study was to evaluate the biodistribution and toxicity of 131I-chimeric(ch) TNT-1/B monoclonal antibody (MAB), which binds to intracellular antigens of necrotic regions within tumors, in patients with advanced colon or colorectal cancer. The rationale for targeting areas of tumor necrosis is the observation that necrotic lesions are more abundant in cancer lesions than in surrounding tissues.


METHODS
Cohorts of patients with advanced colon or colorectal cancer were administered a one-time 30-60-minute intravenous (i.v.) infusion of 131I-chTNT-1/B at doses ranging from 12.95 to 66.23 MBq/kg (0.35-1.79 mCi/kg).


RESULTS
The dose-limiting toxicity, experienced at 66.23 MBq/kg (1.79 mCi/kg) 131I-chTNT-1/B MAB, was myelosuppression. Two (2) patients at the 66.23-MBq/kg (1.79 mCi/kg) dose level had both grade 3 thrombocytopenia and grade 3 neutropenia that persisted for at least 2 weeks but were reversible. The maximum tolerated dose was 58.09 MBq/kg (1.57 mCi/kg) 131I-chTNT-1/B MAB. Of the 21 patients, one developed a moderate human antichimeric antibody (HACA) response and 6 developed low HACA responses.


CONCLUSIONS
The infusion of 131I-chTNT-1/B MAB was well tolerated, without significant nonhematological toxicity. No patient obtained a complete or partial response, based on tumor cross-product response criteria. Tumor localization was seen in patients with dose levels at, and exceeding, 50.23 MBq/kg (1.36 mCi/kg) 131I-chTNT-1/B MAB.
Street
Hilary Hardy
HH
Department of Radiation Oncology, Stanford University, Stanford, CA 943053, USA.
Goris
Michael L
ML
Fisher
George Albert
GA
Wessels
Barry W
BW
Cho
Cheryl
C
Hernandez
Carmen
C
Zhu
Hongyun June
HJ
Zhang
Yuxia
Y
Nangiana
Jasvinder Singh
JS
Shan
Joseph S
JS
Roberts
Karen
K
Knox
Susan J
SJ
D000328:Adult; D000368:Aged; D000911:Antibodies, Monoclonal / Q000737:chemistry*; D002986:Clinical Trials as Topic; D003110:Colonic Neoplasms / Q000532:radiotherapy*; D015179:Colorectal Neoplasms / Q000532:radiotherapy*; D005260:Female; D006801:Humans; D007457:Iodine Radioisotopes / Q000627:therapeutic use*; D008297:Male; D008875:Middle Aged; D009336:Necrosis; D016499:Radioimmunotherapy / Q000295:instrumentation* / Q000379:methods*; D011874:Radiometry; D011993:Recombinant Fusion Proteins / Q000737:chemistry; D015899:Tomography, Emission-Computed, Single-Photon / Q000379:methods; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism
D000911:Antibodies, Monoclonal; D007457:Iodine Radioisotopes; D011993:Recombinant Fusion Proteins; D014409:Tumor Necrosis Factor-alpha