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  • 1
    ISSN: 1573-7217
    Keywords: aromatase inhibitor ; hormone independent ; liarozole ; metastatic breast cancer ; RAMBA
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract Three phase II studies were conducted to determine the efficacy and tolerability of liarozole fumarate (R85246; liarozole), a retinoic acid metabolism blocking agent (RAMBA) and aromatase inhibitor. Additionally, animal experiments in the MNU-induced rat mammary tumor model and in immature ovariectomized rats were conducted to further elucidate liarozole's mechanisms of action. Patients were postmenopausal with either: ER negative disease in first relapse (Group 1; n = 16); ER positive or unknown disease refractory to tamoxifen (Group 2; n = 16); ER positive, negative or unknown disease resistant or refractory to chemotherapy (Group 3; n = 27). Treatment was liarozole (150–300 mg) twice daily orally until disease progression. Response rates were: 25% in group 1 (95% CI 11.0–52.3%; median duration (MD) 20 months; range 2–36.5); 25% in group 2 (95% CI 11.0–52.3%; MD 6.5 months; range 3.5–38); 11% in group 3 (95% CI 4.2–29.2%; MD 7 months; range 3–8.5). No significant improvement in quality of life scores (FLI-C) was noted. Toxicities observed were predominantly dermatological (skin disorders: 88%; dry mouth/eyes/lips: 69%). Plasma estradiol decreased from mean pre-treatment levels of 72.7 pM (9.1–1839 pM) to below detection (9.2 pM) after 1 month. Liarozole, but not vorozole, partially inhibited estradiol induced uterine hypertrophy and demonstrated dose-dependent anti-tumor effects in the rats, only partially overcome by coadministration of estradiol. The clinical responses observed, together with our preclinical results, confirm liarozole's dual mechanism of action and provide a rationale for further evaluation of RAMBAs in the treatment of breast cancer.
    Type of Medium: Electronic Resource
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  • 2
    Electronic Resource
    Electronic Resource
    Springer
    Quality of life research 9 (2000), S. 1041-1052 
    ISSN: 1573-2649
    Keywords: Cancer ; Proxy ; Quality of life
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract The objective of the study was to determine possible differences in perception of quality of life (QoL) between patients with metastatic breast or prostate cancer, their partners, and the treating physician. Patients with metastatic breast cancer (n = 71), and metastatic prostate cancer (n = 29), a partner, and the physician each completed the same QoL questionnaire indicating how they perceived the patient's QoL. The European organization for research and treatment of cancer (EORTC) QLQ-C30 questionnaire was used to assess patients with breast cancer and the modified prostate cancer specific quality of life instrument (PROSQOLI) for patients with prostate cancer. There was reasonable agreement in mean scores between patients, and physicians or partners, for many domains of QoL; however, there was substantial discordance between scores when considering individual patients. For patients with metastatic breast cancer, physicians systematically underestimated overall QoL (p = 0.0002), social functioning (p = 0.001), and role functioning (p = 0.008), while partners showed better agreement. With prostate cancer physicians tended to underestimate pain, while mean scores for spouses were more concordant. There is substantial variability between ratings of QoL by physicians or partners, as compared to patient ratings. Medical decisions should be based on information about QoL provided by patients using validated methods.
    Type of Medium: Electronic Resource
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