Document Type

Article

Department

Haematology and Oncology, East Africa

Abstract

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 ug/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 mono- cytosis (peak absolute monocyte count, 1444 ±394/mm3) and thrombocytopenia (nadir count, 78 ±10/nim '). Monocyte surface marker analysis revealed a high baseline expression of CD Id ' cells in our patient popu lation 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 (3S.8 ±2 versus 27 ±2.9 h; P < 0.05). Eleven of fourteen patients developed low-moderate levels of anti-D612 antibody. Despite the ob served 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.

Comments

This work was published before the author joined Aga Khan University.

Publication (Name of Journal)

Cancer research

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