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Titolo:
High-dose tamoxifen added to concurrent biochemotherapy with decrescendo interleukin-2 in patients with metastatic melanoma
Autore:
ODay, SJ; Boasberg, PD; Kristedja, TS; Martin, M; Wang, HJ; Fournier, P; Cabot, M; DeGregorio, MW; Gammon, G;
Indirizzi:
St Johns Hlth Ctr, John Wayne Canc Inst, Div Med Oncol, Santa Monica, CA 90404 USA St Johns Hlth Ctr Santa Monica CA USA 90404 l, Santa Monica, CA 90404 USA Univ Calif Davis, Sch Med, Div Hematol & Oncol, Sacramento, CA 95817 USA Univ Calif Davis Sacramento CA USA 95817 Oncol, Sacramento, CA 95817 USA
Titolo Testata:
CANCER
fascicolo: 3, volume: 92, anno: 2001,
pagine: 609 - 619
SICI:
0008-543X(20010801)92:3<609:HTATCB>2.0.ZU;2-P
Fonte:
ISI
Lingua:
ENG
Soggetto:
ADVANCED MALIGNANT-MELANOMA; HUMAN CANCER-CELLS; PHASE-II; INTERFERON-ALPHA; SEQUENTIAL CHEMOIMMUNOTHERAPY; GLYCOSPHINGOLIPID METABOLISM; MULTIDRUG-RESISTANCE; RANDOMIZED TRIAL; DACARBAZINE CVD; BREAST-CANCER;
Keywords:
biochemotherapy; metastatic melanoma; tamoxifen; decrescendo interleukin-2;
Tipo documento:
Article
Natura:
Periodico
Settore Disciplinare:
Clinical Medicine
Life Sciences
Citazioni:
58
Recensione:
Indirizzi per estratti:
Indirizzo: O'Day, SJ St Johns Hlth Ctr, John Wayne Canc Inst, Div Med Oncol, 2001 Santa Monica Blvd,Suite 560W, Santa Monica, CA 90404 USA St Johns Hlth Ctr 2001 Santa Monica Blvd,Suite 560W Santa Monica CA USA 90404
Citazione:
S.J. O'Day et al., "High-dose tamoxifen added to concurrent biochemotherapy with decrescendo interleukin-2 in patients with metastatic melanoma", CANCER, 92(3), 2001, pp. 609-619

Abstract

BACKGROUND. In vitro cell culture data and preclinical models suggest thattamoxifen modulates tumor cell sensitivity to a wide range of therapeutic agents. In the current study, the authors examined whether high-dose tamoxifen (HDT) improved the overall and complete response in patients with metastatic melanoma who were treated with concurrent biochemotherapy. METHODS. Forty-nine patients were treated with a biochemotherapy regimen of dacarbazine, vinblastine, cisplatin, decrescendo interleukin-2, interferon-alpha -2b, and tamoxifen. The study had a 2-step design, beginning with atamoxifen dose escalation from 40 mg to 320 mg (17 subjects) to evaluate safety and tolerability, followed by Phase II accrual of 32 patients to HDT (320 mg) to assess clinical efficacy. Efficacy was compared with a similar modified biochemotherapy regimen with low-dose tamoxifen (LDT). Pharmacokinetic studies were performed to determine in vivo tamoxifen levels. RESULTS. Tamoxifen dose escalation was completed without any reported dose-limiting toxicity. The overall response rate in the HDT group was 50% (95%confidence interval, 33.2%-66.8%), with a complete response rate of 6% anda median survival of 9.5 months. The overall response rate was not improved and the complete response and survival appeared inferior compared with that of patients recently treated with concurrent biochemotherapy and LDT. Serum tamoxifen levels were found to correlate with the dose administered, with a mean of 0.9 muM at the 40-mg dose to 4.6 muM at the 320-mg dose. Ultrafiltered protein-free sera demonstrated low (< 0.01 <mu>M) concentrations of tamoxifen. CONCLUSIONS. The addition of HDT to a regimen of concurrent biochemotherapy did not appear to improve response rates or overall survival, despite reaching the targeted plasma concentration. Unknown drug interactions or high protein binding of tamoxifen may account for the lack of clinical effectiveness. Cancer 2001;92: 609-19. (C) 2001 American Cancer Society.

ASDD Area Sistemi Dipartimentali e Documentali, Università di Bologna, Catalogo delle riviste ed altri periodici
Documento generato il 18/09/20 alle ore 16:39:25