A Phase I-II Study to Determine the Maximum Tolerated Infusion Rate of Rituximab with Special Emphasis on Monitoring the Effect of Rituximab on Cardiac Function

• Published in: Clinical cancer research Vol. 14; no. 23; pp. 7935 - 7939
• Main Authors: SIANO, Marco, LERCH, Erika, GHIELMINI, Michele, NEGRETTI, Laura, ZUCCA, Emanuele, RODRIGUEZ-ABREU, Delvys, OBERSON, Michel, LEONCINI, Leda, MORA, Oreste, SESSA, Cristiana, GALLINO, Augusto
• Format: Journal Article
• Language: English
• Published: Philadelphia, PA American Association for Cancer Research 01.12.2008
• Subjects: Adult; Aged; Antibodies, Monoclonal - administration & dosage; Antibodies, Monoclonal - adverse effects; Antibodies, Monoclonal, Murine-Derived; Antineoplastic agents; Antineoplastic Agents - administration & dosage; Antineoplastic Agents - adverse effects; Biological and medical sciences; Blood Pressure - drug effects; Cardiac; Electrocardiography; Female; Heart - drug effects; Humans; Infusion-rate; Lymphoma, B-Cell - drug therapy; Male; maximum; Maximum Tolerated Dose; Medical sciences; Middle Aged; Natriuretic Peptide, Brain - drug effects; Pharmacology. Drug treatments; Phase I/II; Rituximab; safety; Troponin - drug effects; Antineoplastic agent; Human; Cardiac performance; Rituximab; Monoclonal antibody; Maximum; Treatment; Surveillance; Perfusion; Immunotherapy; Phase II trial; Phase I trial; Monitoring
• ISSN: 1078-0432; 1557-3265
• DOI: 10.1158/1078-0432.CCR-08-1124

Purpose: This phase I infusion rate escalation trial was undertaken to evaluate the maximum applicable infusion rate for rituximab without steroid premedication in patients having received one previous rituximab infusion. Experimental Design: Cohorts of at least three patients were assigned to rituximab with or without concomitant chemotherapy. The initial infusion rate was 200 mg/h in the first cohort, and was increased by 100 mg/h in each subsequent cohort to a maximum of 700 mg/h. In each patient the infusion rate was increased by 100 mg/h every 30 minutes to the total dose (375 mg/m 2 ). In the first six cohorts (21 patients), two well-tolerated rituximab administrations were required; in the 7th cohort (11 patients) one previously well-tolerated rituximab infusion was required. Patients did not receive steroid premedication and were monitored with electrocardiograms (ECG), echocardiograms, Holter ECGs, troponin, and brain natriuretic peptide (BNP). Results: Thirty-two patients were included and 128 cycles were done, 85 at a rate of 700 mg/h. Patients tolerated infusion rates without major side effects. There were no new clinically relevant ECG alterations. Troponin (< 0.1 ng/L) and mean cardiac ejection fraction (65%) remained in the reference range; BNP baseline level increased significantly 24 hours after rituximab administration (from 30.4 to 64.1 ng/L; P < 0.0001). Conclusions: Rituximab can be administered safely at 700 mg/h without steroid premedication in patients having received at least one rituximab dose in the previous 3 months.