Radioimmunotherapy for advanced breast cancer using I-131-ChL6 antibody.
BACKGROUND
The biologically active, antiadenocarcinoma monoclonal antibody chimeric L6 (ChL6) was labeled with 131I and administered in cycles to patients with metastatic breast cancer who had failed standard therapy. The therapeutic potential, tumor targeting and maximum tolerated dose of 131I-ChL6 were studied.


METHODS
Ten patients with L6 reactive breast cancer received an imaging dose of 131I-ChL6 followed 24 hours later by a therapy dose of 131I-ChL6 (20-70 mCi/m2). Patients received up to 4 monthly cycles unless they had significant myelosuppression, progression of disease, or a high human anti-mouse antibody titer. In vivo activation of effector cell function, complement levels and cytokine release were studied.


RESULTS
All 10 patients had detectable cancer on the imaging study. In 7 patients with superficial cancer, the radiation dose was 120 to 3700 cGy/cycle; 5-30 times higher than the whole body dose. Therapy resulted in minimal acute or subacute toxicity. Dose limiting toxicities were neutropenia and thrombocytopenia. Six of 10 patients had clinically measurable tumor responses; 5 had responses that lasted more than one month (1.5-5 months). The MTD for 131I-ChL6, given in at least two monthly doses, was 60 mCi/m2.


CONCLUSIONS
Objective clinical responses were seen in five of 10 patients treated with 131I-ChL6. The tumor response in heavily pretreated, advanced breast cancer may be related to the combined effects of targeted radiation and the biological activity of L6/ChL6.
Denardo
S J
SJ
Division of Hematology/Oncology, University of California Davis Medical Center, Sacramento.
O'Grady
L F
LF
Richman
C M
CM
Goldstein
D S
DS
O'Donnell
R T
RT
Denardo
D A
DA
Kroger
L A
LA
Lamborn
K R
KR
Hellström
K E
KE
Hellström
I
I
Denardo
G L
GL
D000230:Adenocarcinoma / Q000532:radiotherapy*; D000328:Adult; D000368:Aged; D000818:Animals; D000911:Antibodies, Monoclonal / Q000009:adverse effects / Q000493:pharmacokinetics / Q000627:therapeutic use*; D001943:Breast Neoplasms / Q000473:pathology / Q000532:radiotherapy*; D005260:Female; D006801:Humans; D007074:Immunoglobulin G; D007457:Iodine Radioisotopes / Q000009:adverse effects / Q000493:pharmacokinetics / Q000627:therapeutic use*; D051379:Mice; D008875:Middle Aged; D009362:Neoplasm Metastasis; D009367:Neoplasm Staging; D016499:Radioimmunotherapy; D011993:Recombinant Fusion Proteins; D014018:Tissue Distribution
D000911:Antibodies, Monoclonal; C106337:ChL6 monoclonal antibody; D007074:Immunoglobulin G; D007457:Iodine Radioisotopes; D011993:Recombinant Fusion Proteins