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Titolo:
A phase II trial of mitomycin C, 5 '-deoxy-5-fluorouridine, etoposide and medroxyprogesterone acetate (McVD-MPA) as a salvage chemotherapy to anthracycline-resistant tumor in relapsed breast cancer and its mechanism(s) of antitumor action
Autore:
Kim, R; Osaki, A; Tanabe, K; Kojima, J; Toge, T;
Indirizzi:
Hiroshima Univ, Res Inst Radiat Biol & Med, Dept Surg Oncol, Minami Ku, Hiroshima 7348553, Japan Hiroshima Univ Hiroshima Japan 7348553 nami Ku, Hiroshima 7348553, Japan
Titolo Testata:
ONCOLOGY REPORTS
fascicolo: 3, volume: 8, anno: 2001,
pagine: 597 - 603
SICI:
1021-335X(200105/06)8:3<597:APITOM>2.0.ZU;2-G
Fonte:
ISI
Lingua:
ENG
Soggetto:
MULTIDRUG-RESISTANCE; THYMIDINE PHOSPHORYLASE; RANDOMIZED TRIAL; GENE-EXPRESSION; PACLITAXEL; APOPTOSIS; CARCINOMA; THERAPY; METHOTREXATE; MITOCHONDRIA;
Keywords:
breast cancer; anthracycline resistance; mitomycin C; VP-16; 5 '-DFUR; medroxyprogesterone acetate;
Tipo documento:
Article
Natura:
Periodico
Settore Disciplinare:
Clinical Medicine
Citazioni:
35
Recensione:
Indirizzi per estratti:
Indirizzo: Kim, R Hiroshima Univ, Res Inst Radiat Biol & Med, Dept Surg Oncol, MinamiKu, 1-2-3 Kasumi, Hiroshima 7348553, Japan Hiroshima Univ 1-2-3 Kasumi Hiroshima Japan 7348553 7348553, Japan
Citazione:
R. Kim et al., "A phase II trial of mitomycin C, 5 '-deoxy-5-fluorouridine, etoposide and medroxyprogesterone acetate (McVD-MPA) as a salvage chemotherapy to anthracycline-resistant tumor in relapsed breast cancer and its mechanism(s) of antitumor action", ONCOL REP, 8(3), 2001, pp. 597-603

Abstract

To assess the therapeutic efficacy in the combination of mitomycin C (MMC), 5'-deoxy-5-fluorouridine (5'-DFUR), etoposide (VP-16) and medroxyprogesterone acetate (MPA) (McVD-MPA) to anthracycline-resistant tumor as a salvagechemotherapy, a phase II trial was conducted in patients with relapsed breast cancer. Fifty-five patients were enrolled in this trial and 54 were assessable, who had all priviously been treated with an anthracycline regimen. The treatment schedule was designed with the intravenous administration ofMMC (6 mg/m(2)) on day 1 followed by peroral administration of VP-16 (75 mg/m(2)) on day 2, 4, 6 and the peroral administration of 5'-DFUR (600 mg/m(2)) and MPA (400 mg/m(2)) on day 1 through 21 in one cycle. The overall tumor response rate was 40.7% (22/54) including 16.6% (9 cases) in complete response and 24.0% (13 cases) in partial response, and the long no change (NC) was observed in 18.5% (10/54) out of 44.4% (24/54) in NC. Of the patientswith primary resistance to anthracycline 30.0% responded to McVD-MPA therapy. Bone and liver metastases responded in 50.0% and 50.0%, whereas soft tissue and lung metastases responded in 36.8% and 35.2%, respectively. The mean time to response and response duration were 2.7 and 15.6 months, respectively. The overall survival of the patient treated with the McVD-MPA was superior to the non-treatment of second line therapy, and the median survivalbetween McVD-MPA and non-treatment was 86 days and 50 days, respectively. The major adverse effect was observed in hematological toxicity (31.7%) such as leukopenia and thrombocytopenia and non-hematological toxicity of gastrointestinal events (31.7%), the toxicity was less than grade 2, and was tolerable during the treatment. In the experiment of MDA-MB-231 breast cancercell line that was overexpressed with P-glycoprotein (P-gp) and multidrug resistance associated protein (MRP), the mechanism(s) by which McVD-MPA induces the antitumor effect to anthracycline-resistant tumor may be explainedat least in part as follows: i) The treatment of MMC suppressed the expression of P-gp and MRP in a dose-and time-dependent manner, connecting the increase of the intracellular concentration of VP-16; ii) The treatment of MMC enhanced the expression of thymidine phosphorylase to increase the production of 5-FU from 5'-DFUR in the antiangiogenic effect of MPA. These results indicate that the combination chemotherapy of the McVD-MPA may be an effective regimen to anthracycline-resistant tumor as a salvage chemotherapy toprolong the survival in the patient with relapsed breast cancer.

ASDD Area Sistemi Dipartimentali e Documentali, Università di Bologna, Catalogo delle riviste ed altri periodici
Documento generato il 10/07/20 alle ore 08:55:02