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Titolo:
PHASE-I STUDY OF THE DUOCARMYCIN SEMISYNTHETIC DERIVATIVE KW-2189 GIVEN DAILY FOR 5 DAYS EVERY 6 WEEKS
Autore:
ALBERTS SR; ERLICHMAN C; REID JM; SLOAN JA; AMES MM; RICHARDSON RL; GOLDBERG RM;
Indirizzi:
MAYO CLIN,DIV MED ONCOL ROCHESTER MN 55905 MAYO CLIN,DIV DEV ONCOL RES ROCHESTER MN 55905 MAYO CLIN,CTR CANC,STAT UNIT ROCHESTER MN 55905
Titolo Testata:
Clinical cancer research
fascicolo: 9, volume: 4, anno: 1998,
pagine: 2111 - 2117
SICI:
1078-0432(1998)4:9<2111:PSOTDS>2.0.ZU;2-U
Fonte:
ISI
Lingua:
ENG
Soggetto:
DNA STRAND BREAKS; ANTITUMOR ANTIBIOTICS; CARBOXYL ESTERASE; STREPTOMYCES SP; CC-1065; AGENT; CELLS; ADOZELESIN; CARZELESIN; ACTIVATION;
Tipo documento:
Article
Natura:
Periodico
Settore Disciplinare:
Science Citation Index Expanded
Citazioni:
27
Recensione:
Indirizzi per estratti:
Citazione:
S.R. Alberts et al., "PHASE-I STUDY OF THE DUOCARMYCIN SEMISYNTHETIC DERIVATIVE KW-2189 GIVEN DAILY FOR 5 DAYS EVERY 6 WEEKS", Clinical cancer research, 4(9), 1998, pp. 2111-2117

Abstract

The duocarmycins represent a new group of antitumor antibiotics produced by Streptomyces that bind to the minor groove of DNA. KW-2189 is awater-soluble semisynthetic derivative of duocarmycin B-2, with significant activity in murine and human tumor models. We conducted a PhaseI trial of KW-2189 in patients who had solid tumors that were refractory to standard chemotherapy or for whom no more effective therapy existed. KW-2189 was administered as a rapid i.v. bolus daily for 5 days every 6 weeks. Twenty-two patients were enrolled and received a total of 31 cycles of KW-2189, Leukopenia, neutropenia, and thrombocytopeniawere the dose-limiting toxicities, with nadirs occurring at medians of 36, 38, and 29 days, respectively, at the 0.04 mg/m(2)/day dose level. Nonhematological toxicities were mild, although one patient developed grade 3 fatigue, Four patients had stable disease over two to four cycles of treatment and shelved no cumulative toxicity. The mean t(1/2), plasma clearance, and steady-state volume of distribution were 13.5min, 1,287 ml/min/m(2), and 10,638 ml/m(2), respectively, Pharmacokinetics were similar on days 1 and 5, with no drug accumulation in plasma. The active metabolite DU-86 was not consistently found in patient plasma. For Phase II trials, when the 5 days every 6 weeks schedule wasused, 0.04 mg/m(2)/day KW-2189 appears to be the maximal tolerated dose, especially for patients who have received prior chemotherapy, At this dose level, the drug was well tolerated, and the toxicities were acceptable.

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Documento generato il 10/07/20 alle ore 14:51:24