Feasibility and pharmacokinetic study of a chimeric anti-CD20 monoclonal antibody (IDEC-C2B8, rituximab) in relapsed B-cell lymphoma. The IDEC-C2B8 Study Group.
BACKGROUND
In clinical trials in the USA, IDEC-C2B8 (a mouse-human chimeric anti-CD20 monoclonal antibody) has demonstrated high response rates with only mild toxic effects in relapsed B-cell lymphoma at a dose of four weekly 375 mg/m2 infusions. The aim of the present trial was to determine whether or not this dose is practically applicable to Japanese patients with relapsed B-cell lymphoma with respect to safety, pharmacokinetics and efficacy.


METHODS
Patients with relapsed CD20+ B-cell lymphoma received intravenous infusions of IDEC-C2B8 once a week for four weeks. A total of 12 patients (four at 250 mg/m2 and eight at 375 mg/m2) were enrolled.


RESULTS
All 11 eligible patients treated with either dose level tolerated IDEC-C2B8 well. Commonly observed adverse drug reactions were grades 1 or 2 non-hematologic toxicities during the infusion, consisting mostly of flu-like symptoms and skin reactions. All of the observed hematologic toxicities were of grade 3 or less, and transient. A rapid and sustained B-cell decrease in peripheral blood was observed, but no infectious episodes were encountered. Human anti-mouse and anti-chimeric antibodies were not detected. Of the 11 eligible patients (eight with follicular, two with diffuse large-cell and one with mantle cell lymphoma), two showed a complete response and five showed a partial response, and all of the seven responders had lymphoma with follicular histology. A pharmacokinetic analysis showed that the elimination half-life (T1/2) of IDEC-C2B8 was 445 +/- 361 hours, and that the serum antibody levels increased in parallel with the course of infusions, and in most patients was still measurable at three months.


CONCLUSIONS
The dose of four weekly 375 mg/m2 infusions of IDEC-C2B8 is safe and effective in Japanese patients with relapsed B-cell lymphoma. Further studies evaluating IDEC-C2B8 are warranted.
Tobinai
K
K
Department of Medical Oncology, National Cancer Center Hospital, Tokyo. ktobinai@gan2.ncc.go.jp
Kobayashi
Y
Y
Narabayashi
M
M
Ogura
M
M
Kagami
Y
Y
Morishima
Y
Y
Ohtsu
T
T
Igarashi
T
T
Sasaki
Y
Y
Kinoshita
T
T
Murate
T
T
D000328:Adult; D000368:Aged; D000818:Animals; D000911:Antibodies, Monoclonal / Q000493:pharmacokinetics / Q000627:therapeutic use*; D058846:Antibodies, Monoclonal, Murine-Derived; D018951:Antigens, CD20 / Q000627:therapeutic use*; D000970:Antineoplastic Agents / Q000493:pharmacokinetics / Q000627:therapeutic use*; D004305:Dose-Response Relationship, Drug; D004334:Drug Administration Schedule; D005240:Feasibility Studies; D005260:Female; D006801:Humans; D007262:Infusions, Intravenous; D016393:Lymphoma, B-Cell / Q000628:therapy*; D008297:Male; D051379:Mice; D008875:Middle Aged; D011993:Recombinant Fusion Proteins / Q000627:therapeutic use; D000069283:Rituximab; D016896:Treatment Outcome
D000911:Antibodies, Monoclonal; D058846:Antibodies, Monoclonal, Murine-Derived; D018951:Antigens, CD20; D000970:Antineoplastic Agents; D011993:Recombinant Fusion Proteins; D000069283:Rituximab