PT  - JOURNAL ARTICLE
AU  - Saleh, Mansoor N.
AU  - Khazaeli, M. B.
AU  - Wheeler, Richard H.
AU  - Bucy, R. Pat
AU  - Liu, Tiepu
AU  - Everson, Michael P.
AU  - Munn, David H.
AU  - Schlom, Jeff
AU  - LoBuglio, Albert F.
TI  - Phase II Trial of Murine Monoclonal Antibody D612 Combined with Recombinant Human Monocyte Colony-stimulating Factor (rhM-CSF) in Patients with Metastatic Gastrointestinal Cancer
DP  - 1995 Oct 01
TA  - Cancer Research
PG  - 4339--4346
VI  - 55
IP  - 19
4099  - http://cancerres.aacrjournals.org/content/55/19/4339.short
4100  - http://cancerres.aacrjournals.org/content/55/19/4339.full
SO  - Cancer Res1995 Oct 01; 55
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.