PHASE-I TRIAL OF A 90-MINUTE INFUSION OF THE FUSION TOXIN DAB486IL-2 IN HEMATOLOGICAL CANCERS

Citation
Cf. Lemaistre et al., PHASE-I TRIAL OF A 90-MINUTE INFUSION OF THE FUSION TOXIN DAB486IL-2 IN HEMATOLOGICAL CANCERS, Cancer research, 53(17), 1993, pp. 3930-3934
Citations number
20
Categorie Soggetti
Oncology
Journal title
ISSN journal
00085472
Volume
53
Issue
17
Year of publication
1993
Pages
3930 - 3934
Database
ISI
SICI code
0008-5472(1993)53:17<3930:PTOA9I>2.0.ZU;2-P
Abstract
DAB486IL-2, a recombinant fusion toxin in which the native receptor bi nding domain of diphtheria toxin has been replaced with interleukin-2 (IL-2), has displayed significant activity in patients with chemothera py refractory hematological cancers. To further investigate the safety and antitumor effect of this agent, we conducted a single arm, dose e scalation study of a 90-min infusion of DAB486IL-2 daily for 5 days. P atients with cancers of a histology previously reported to express the p55 component of the IL-2 receptor and who could not receive potentia lly more effective therapy were eligible for enrollment. Fifteen men a nd 8 women with a median age of 49 years were given a total of 51 cour ses of DAB486IL-2. The maximum tolerated dose was 0.3 mg/kg/day define d by renal insufficiency associated with hemolysis and thrombocytopeni a. The clearance of DAB486IL-2 from serum fit a one-compartment model with a half-life of 11.5 +/- 4.3 (SD) min at the 0.2-mg/kg dose. Two p atients sustained a partial response and 4 patients had tumor reductio n not qualifying for an objective response. No tumors that were negati ve for expression of the p55 subunit of the receptor responded to DAB4 86IL-2 treatment. Reduction in size occurred in 2 tumors in which p55 expression was unknown and 4 patients with tumors that were known to b e p55 positive. Dosing determined by specific activity rather than mas s also appeared to be an important determinant of response. This study suggests that the presence of p55 expression on tumor cells is necess ary, but alone may not be sufficient to achieve a tumor response. The correlation of additional variables such as specific activity of DAB48 6IL-2 and tumor expression of the p75 subunit of the IL-2 receptor and receptor function will also require further study.