Phase 1 trial study of 131I-labeled chimeric 81C6 monoclonal antibody for the treatment of patients with non-Hodgkin lymphoma.
We report a phase 1 study of pharmacokinetics, dosimetry, toxicity, and response of (131)I anti-tenascin chimeric 81C6 for the treatment of lymphoma. Nine patients received a dosimetric dose of 370 MBq (10 mCi). Three patients received an administered activity of 1480 MBq (40 mCi), and 2 developed hematologic toxicity that required stem cell infusion. Six patients received an administered activity of 1110 MBq (30 mCi), and 2 developed toxicity that required stem cell infusion. The clearance of whole-body activity was monoexponential with a mean effective half-life of 110 hours (range, 90-136 hours) and a mean effective whole-body residence time of 159 hours (range, 130-196 hours). There was rapid uptake within the viscera; however, tumor uptake was slower. Activity in normal viscera decreased proportional to the whole body; however, tumor sites presented a slow clearance (T(1/2), 86-191 hours). The mean absorbed dose to whole-body was 67 cGy (range, 51-89 hours), whereas the dose to tumor sites was 963 cGy (range, 363-1517 cGy). Despite lack of a "blocking" antibody, 1 of 9 patients attained a complete remission and 1 a partial remission. These data demonstrate this radiopharmaceutical to be an encouraging agent for the treatment of lymphoma particularly if methods to protect the normal viscera are developed.
Rizzieri
David A
DA
Department of Medicine, Duke University Medical Center, Durham, NC 27710, USA. rizzi003@mc.duke.edu
Akabani
Gamal
G
Zalutsky
Michael R
MR
Coleman
R Edward
RE
Metzler
Scott D
SD
Bowsher
James E
JE
Toaso
Bonnie
B
Anderson
Elizabeth
E
Lagoo
Anand
A
Clayton
Steve
S
Pegram
Charles N
CN
Moore
Joseph O
JO
Gockerman
Jon P
JP
DeCastro
Carlos
C
Gasparetto
Cristina
C
Chao
Nelson J
NJ
Bigner
Darell D
DD
D000818:Animals; D000911:Antibodies, Monoclonal / Q000493:pharmacokinetics / Q000633:toxicity*; D001692:Biological Transport; D001706:Biopsy; D001853:Bone Marrow / Q000473:pathology; D005260:Female; D006801:Humans; D000922:Immunotoxins / Q000493:pharmacokinetics / Q000633:toxicity; D007457:Iodine Radioisotopes / Q000493:pharmacokinetics / Q000633:toxicity*; D008198:Lymph Nodes / Q000473:pathology; D008228:Lymphoma, Non-Hodgkin / Q000473:pathology / Q000532:radiotherapy*; D008297:Male; D051379:Mice; D018579:Patient Selection; D019063:Tenascin / Q000032:analysis; D014018:Tissue Distribution; D014057:Tomography, X-Ray Computed
D000911:Antibodies, Monoclonal; D000922:Immunotoxins; D007457:Iodine Radioisotopes; D019063:Tenascin