van der Schelling G P, IJzermans J N, Kok T C, Scheringa M, Marquet R L, Splinter T A, Jeekel J
Department of Surgery, General Hospital Stuivenberg, Antwerp, Belgium.
Eur J Cancer. 1992;28A(6-7):1073-8. doi: 10.1016/0959-8049(92)90460-j.
15 patients with therapy-resistant liver metastases were treated in a phase I study with recombinant tumour necrosis factor (rTNF). rTNF was injected into a liver metastasis by ultrasound guidance, using a 50 micrograms escalating dose schedule (3 patients/dosage) ranging from 100 to 350 micrograms per injection. Influenza-like symptoms such as fever, chills, nausea and vomiting were the main clinical side-effects. 2 patients experienced transient hypotension, probably due to concomitant use of morphine. Other toxicities, as reported after systemic use of rTNF, such as decrease in leucocytes and platelet counts, renal or liver toxicity were not observed. No difference was seen in subpopulations of lymphocytes (CD3+, CD4+, CD8+, CD16+ and CD19+) prior to and after rTNF injection. In 8 patients stable disease occurred in rTNF-treated metastases. The maximal dose used by this route of administration is 350 micrograms per injection. Based on these observations we conclude that the toxicity of rTNF injected into liver metastases by sonographic control is transient and mild. The results suggest that intratumoral administration of rTNF might play a role in local tumour control.
