RT Journal Article
SR Electronic
T1 Phase II Trial of Murine Monoclonal Antibody D612 Combined with Recombinant Human Monocyte Colony-stimulating Factor (rhM-CSF) in Patients with Metastatic Gastrointestinal Cancer
JF Cancer Research
JO Cancer Res
FD American Association for Cancer Research
SP 4339
OP 4346
VO 55
IS 19
A1 Saleh, Mansoor N.
A1 Khazaeli, M. B.
A1 Wheeler, Richard H.
A1 Bucy, R. Pat
A1 Liu, Tiepu
A1 Everson, Michael P.
A1 Munn, David H.
A1 Schlom, Jeff
A1 LoBuglio, Albert F.
YR 1995
UL http://cancerres.aacrjournals.org/content/55/19/4339.abstract
AB In a Phase II study, 14 patients with metastatic gastrointestinal cancer received the mAb D612 (40 mg/m2, days 4, 7, and 11) in combination with recombinant human monocyte colony-stimulating factor [(rhM-CSF) 80 µg/kg/days 1–14]. The combined treatment was well tolerated and resulted in characteristic biological activity associated with each of the agents. Thus, 10 of 14 patients experienced D612-associated secretory diarrhea, which responded to the prostaglandin inhibitor Indomethacin in 5 of 7 patients. rhM-CSF therapy was associated with peripheral monocytosis (peak absolute monocyte count, 1444 ± 394/mm3) and thrombocytopenia (nadir count, 78 ± 10/mm3). Monocyte surface marker analysis revealed a high baseline expression of CD16+ cells in our patient population with an additional increase with rhM-CSF therapy. We observed a correlation between the degree of thrombocytopenia and the pretreatment CD16+ monocyte count. Of the plasma cytokines assayed, serum Neopterin demonstrated the most consistent increase during rhM-CSF therapy. There was a significant difference in the half-life of the first and last dose of D612 (35.8 ± 2 versus 27 ± 2.9 h; P < 0.05). Eleven of fourteen patients developed low-moderate levels of anti-D612 antibody. Despite the observed biological activity of both rhM-CSF and D612 and the previously described in vitro synergy, no clinical antitumor responses were observed in this Phase II study. ©1995 American Association for Cancer Research.