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Titolo:
Phase I dose-finding and pharmacokinetic trial of irinotecan hydrochloride(CPT-11) using a once-every-three-week dosing schedule for patients with advanced solid tumor malignancy
Autore:
Pitot, HC; Goldberg, RM; Reid, JM; Sloan, JA; Skaff, PA; Erlichman, C; Rubin, J; Burch, PA; Adjei, AA; Alberts, SA; Schaaf, LJ; Elfring, G; Miller, LL;
Indirizzi:
Mayo Clin, Ctr Canc, Div Med Oncol, Rochester, MN 55905 USA Mayo Clin Rochester MN USA 55905 , Div Med Oncol, Rochester, MN 55905 USA Mayo Clin, Div Oncol Res, Rochester, MN 55905 USA Mayo Clin Rochester MN USA 55905 , Div Oncol Res, Rochester, MN 55905 USA Mayo Clin, Biostat Sect, Rochester, MN 55905 USA Mayo Clin Rochester MN USA 55905 n, Biostat Sect, Rochester, MN 55905 USA Pharmacia & Upjohn Co, Peapack, NJ 07977 USA Pharmacia & Upjohn Co Peapack NJ USA 07977 john Co, Peapack, NJ 07977 USA
Titolo Testata:
CLINICAL CANCER RESEARCH
fascicolo: 6, volume: 6, anno: 2000,
pagine: 2236 - 2244
SICI:
1078-0432(200006)6:6<2236:PIDAPT>2.0.ZU;2-Y
Fonte:
ISI
Lingua:
ENG
Soggetto:
METASTATIC COLORECTAL-CANCER; ACTIVE METABOLITE SN-38; FLUOROURACIL FAILURE; RANDOMIZED TRIAL; CAMPTOTHECIN; GLUCURONIDATION; INFUSION;
Tipo documento:
Article
Natura:
Periodico
Settore Disciplinare:
Clinical Medicine
Citazioni:
33
Recensione:
Indirizzi per estratti:
Indirizzo: Pitot, HC Mayo Clin, Ctr Canc, Div Med Oncol, 200 1st St SW, Rochester, MN55905 USA Mayo Clin 200 1st St SW Rochester MN USA 55905 ter, MN 55905 USA
Citazione:
H.C. Pitot et al., "Phase I dose-finding and pharmacokinetic trial of irinotecan hydrochloride(CPT-11) using a once-every-three-week dosing schedule for patients with advanced solid tumor malignancy", CLIN CANC R, 6(6), 2000, pp. 2236-2244

Abstract

A Phase I study was performed to determine the maximum tolerated dose (MTD), toxicities, and pharmacokinetic profile of irinotecan (CPT-11) and its active metabolites when given on a once-every-3-week schedule, Thirty-four patients with advanced refractory solid malignancies were treated with CPT-11 (240-340 mg/m(2)) administered as a 90-min i.v. infusion every 3 weeks. Patients were divided into two groups: those with and those without prior abdominal/pelvic (AP) radiotherapy. Gastrointestinal toxicity (nausea, vomiting, and diarrhea) and hematological toxicity (leukopenia and neutropenia) were dose-limiting side effects. Other common toxicities included anorexia;ia, asthenia, and acute cholinergic symptoms (abdominal cramps, diaphoresis,and lacrimation). For patients with no prior AP radiation therapy, the MTDwas determined to be 320 md/m(2), whereas those with prior AP radiation therapy had a MTD of 290 md/m(2). Dose-proportional increases in the mean area under the concentration-time curves for CPT-11, SN-38, and SN-38G were not observed over the narrow dose range studied. Mean values of terminal phase half-life, clearance, terminal phase volume of distribution, and steady-state volume of distribution for CPT-II were 12.4 +/- 1.8 h, 13.0 +/- 3.8 liters/h/m(2), 234 +/- 83 liters/m(2), and 123 +/- 38 liters/m(2), respectively. The pharmacodynamic analyses indicated the strongest correlation to be between SN-38 area under the concentration-time curves and neutropenia (rho= 0.60; P = 0.001). A total of five responses (one complete response and four partial responses) were observed in the cohort of 32 patients with previously treated metastatic colorectal carcinoma. In conclusion, gastrointestinal toxicity and hematological toxicity were the dose limiting toxicities of CPT-11 when administered as a 90-min infusion every 3 weeks. In this trial, the recommended Phase II starting dose for patients,vith no prior AP radiation therapy was found to be 320 mg/m(2); for patients with prior AP radiation, the recommended Phase II starting dose was 290 mg/m(2). This once-every-3-week schedule has been incorporated into a Phase I trial of CPT-11 combined with 5-fluorouracil and leucovorin.

ASDD Area Sistemi Dipartimentali e Documentali, Università di Bologna, Catalogo delle riviste ed altri periodici
Documento generato il 07/07/20 alle ore 12:42:12