Journal of Clinical Oncology, Vol 11, 726-737, Copyright © 1993 by American Society of Clinical Oncology
Anti-B4-blocked ricin: a phase I trial of 7-day continuous infusion in patients with B-cell neoplasms
ML Grossbard, JM Lambert, VS Goldmacher, NL Spector, J Kinsella, L Eliseo, F Coral, JA Taylor, WA Blattler and CL Epstein
Division of Tumor Immunology, Dana-Farber Cancer Institute, Boston, MA 02115.
PURPOSE: This phase I trial was undertaken to determine the maximum-
tolerated dose (MTD) and dose-limiting toxicities (DLTs) of the B-cell-
restricted immunotoxin anti-B4-blocked ricin (anti-B4-bR) when it is
administered by 7-day continuous infusion. PATIENTS AND METHODS: Thirty-
four patients with relapsed and refractory B-cell neoplasms (26 non-
Hodgkin's lymphoma [NHL], four chronic lymphocytic leukemia [CLL], four
acute lymphoblastic leukemia [ALL]) received 7-day continuous infusion
anti-B4-bR. Successive cohorts of at least three patients were treated at
doses of 10 to 70 micrograms/kg/d for 7 days with the dose increased by 10
micrograms/kg/d for each cohort. The initial three cohorts of patients (10,
20, and 30 micrograms/kg/d x 7 days) also received a bolus infusion of 20
micrograms/kg before beginning the continuous infusion. RESULTS: The MTD
was reached at 50 micrograms/kg/d x 7 days. The DLTs were National Cancer
Institute Common Toxicity Criteria (NCI CTC) grade IV reversible increases
in AST and ALT, and grade IV decreases in platelet counts. Adverse
reactions included fevers, nausea, headaches, myalgias, hypoalbuminemia,
dyspnea, edema, and capillary leak syndrome. Potentially therapeutic serum
levels of anti- B4-bR could be sustained for 4 days in patients treated at
the MTD. Two complete responses (CRs), three partial responses (PRs), and
11 transient responses (TRs) were observed. CONCLUSION: Anti-B4-bR can be
administered safely by 7-day continuous infusion with tolerable, reversible
toxicities to patients with relapsed B-cell neoplasms. Although occasional
responses were seen, future trials will use anti-B4- bR in patients with
lower tumor burdens to circumvent the obstacle of immunotoxin delivery to
bulk disease.
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|
|
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