Catalogo Articoli (Spogli Riviste)

OPAC HELP

Titolo:
A PHASE-I STUDY OF BOLUS VERSUS CONTINUOUS-INFUSION OF THE ANTI-CD19 IMMUNOTOXIN, IGG-HD37-DGA, IN PATIENTS WITH B-CELL LYMPHOMA
Autore:
STONE MJ; SAUSVILLE EA; FAY JW; HEADLEE D; COLLINS RH; FIGG WD; STETLERSTEVENSON M; JAIN V; JAFFE ES; SOLOMON D; LUSH RM; SENDEROWICZ A; GHETIE V; SCHINDLER J; UHR JW; VITETTA ES;
Indirizzi:
UNIV TEXAS,SW MED CTR,CTR CANC IMMUNOBIOL,5323 HARRY HINES BLVD DALLAS TX 75235 UNIV TEXAS,SW MED CTR,CTR CANC IMMUNOBIOL DALLAS TX 75235 UNIV TEXAS,SW MED CTR,DEPT MICROBIOL DALLAS TX 75235 BAYLOR UNIV,MED CTR DALLAS TX 00000 CHARLES A SAMMONS CANC CTR DALLAS TX 00000 NCI,PATHOL LAB,CLIN PHARMACOL BRANCH,DEV THERAPEUT PROGRAM BETHESDA MD 20892
Titolo Testata:
Blood
fascicolo: 4, volume: 88, anno: 1996,
pagine: 1188 - 1197
SICI:
0006-4971(1996)88:4<1188:APSOBV>2.0.ZU;2-9
Fonte:
ISI
Lingua:
ENG
Soggetto:
RICIN-A-CHAIN; SEVERE COMBINED IMMUNODEFICIENCY; ANTIVIRAL PROTEIN IMMUNOTOXIN; LARGE-SCALE PREPARATION; MONOCLONAL-ANTIBODIES; ANTI-B4-BLOCKED RICIN; ANTITUMOR-ACTIVITY; INVIVO EFFICACY; TRIAL; MICE;
Tipo documento:
Article
Natura:
Periodico
Settore Disciplinare:
Science Citation Index Expanded
Citazioni:
36
Recensione:
Indirizzi per estratti:
Citazione:
M.J. Stone et al., "A PHASE-I STUDY OF BOLUS VERSUS CONTINUOUS-INFUSION OF THE ANTI-CD19 IMMUNOTOXIN, IGG-HD37-DGA, IN PATIENTS WITH B-CELL LYMPHOMA", Blood, 88(4), 1996, pp. 1188-1197

Abstract

IgG-HD37-SMPT-dgA is a deglycosylated ricin A chain (dgA)containing immunotoxin (IT) prepared by conjugating the monoclonal murine (MoAb) anti-CD19 antibody, HD37, to dgA using the heterobifunctional hindered disulfide linker, l-oxycarbonyl-alpha-methyl-alpha-(2-pyridyldithio) toluene (SMPT). In this report, we have used two regimens for the administration of IgG-HD37-SMPT-dgA to patients with non-Hodgkin's lymphoma(NHL) in two concomitant phase I trials. One trial examined four intermittent bolus infusions administered at 48-hour intervals. The other studied a continuous infusion (CI) administered over the same 8-day period. In the intermittent bofus regimen, the maximum tolerated dose (MTD) was 16 mg/m(2)/8 d and the dose limiting toxicity (DLT) consisted of vascular leak syndrome (VLS), aphasia, and evidence of rhabdomyolysis encountered at 24 mg/m(2)/8 d. Using the Cl regimen, the MTD was defined by VLS at 19.2 mg/m(2)/8 d. At the MTD of both regimens, a noveltoxicity, consisting of acrocyanosis with reversible superficial distal digital skin necrosis in the absence of overt evidence of systemic vasculitis, occurred in 3 patients. Of 23 evaluable patients on the bolus schedule, there was 1 persisting complete response (OR; >40 months) and 1 partial response (PR). Of 9 evaluable patients on the continuous infusion regimen, there was 1 PR. Pharmacokinetic parameters for the bolus regimen at the MTD showed a mean maximum serum concentration (C-max) of 1,209 +/- 430 ng/mL, with a median T(1/2)beta for all courses of 18.2 hours (range, 10.0 to 80.0 hours), a volume of distribution (Vd) of 10.9 L (range, 3.1 to 34.5 L), and a clearance (CL) of 0.45 L/h (range, 0.13 to 2.3 L/h). For the Ci regimen at MTD, the mean C-max was 953 +/- 473 ng/mL, with a median T(1/2)beta for all courses of 22.8 hours (range, 24.1 to 30.6 hours), a Vd of 9.4 L (range, 4.4 to 19.5L), and a CL of 0.32 L/h (range, 0.12 to 0.55 L/h). Twenty-five percent of the patients on the bolus infusion regimen and 30% on the CI regimen made antibody against mouse Ig (HAMA) and/or ricin A chain antibody (HARA). We conclude that this IT can be administered safely and that both regimens achieve comparable peak serum concentrations at the MTD; these concentrations are similar to those achieved previously usingother regimens with IgG-dgA ITs at their respective MTDs. Thus, toxicity is related to tile serum level of the IT and does not differ with different targeting MoAbs. (C) 1996 by The American Society of Hematology.

ASDD Area Sistemi Dipartimentali e Documentali, Università di Bologna, Catalogo delle riviste ed altri periodici
Documento generato il 05/07/20 alle ore 07:28:40