Valutazione bio-endocrinologica del trattamento con triptorelina +/- 4-idrossiandrostenedione in pazienti in premenopausa con carcinoma mammario metastatico
Nel settembre 1993 é stato avviato uno studio sul tumore mammario metastatico in pazienti in premenopausa.
Lo studio (Protocollo 93/4) aveva l’obiettivo di valutare il blocco estrogenico completo indotto dall’associazione GnRH e inibitore dell’aromatasi (4-OHA, formestane) in confronto al solo GnRH in pazienti in premenopausa con carcinoma mammario avanzato.
Sono state arruolate 21 pazienti.
Lo studio ha dimostrato che dopo 4 settimane di trattamento, l’associazione era in grado di ridurre significativamente il profilo estrogenico con un modesto effetto sui livelli di SHBG. Ulteriori analisi condotte successivamente per valutare gli effetti dell’associazione sui marcatori del metabolismo osseo, hanno dimostrato un aumento solamente nei marcatori dell’attività osteoblastica.
Centri partecipanti : Istituto Nazionale Tumori, MILANO
Ospedale S. Gennaro, NAPOLI
- Premenopausal breast cancer patients treated with a gonadotropin-releasing hormone analog alone or in combination with an aromatase inhibitor: a comparative endocrine study.
(Celio L, Martinetti A, Ferrari L, Buzzoni R, Mariani L, Miceli R, Seregni E, Procopio G, Cassata A, Bombardieri E, Bajetta E).
Anticancer Res. 1999 May-Jun;19(3B):2261-8.
The combination of a GnRH analogue and an aromatase inhibitor can induce a complete estrogen blockade in premenopausal breast cancer patients.MATERIAL AND METHODS:
Twenty-one premenopausal women with advanced breast cancer were randomised to receive the GnRH analog triptorelin (3.75 mg i.m. monthly; n = 10) alone or in combination with the aromatase inhibitor formestane (4-OHA, 500 mg i.m. fortnightly; n = 11) to compare the effect of both treatments on the patients’ estrogenic milieu. Therefore, serum estrogen, gonadotropin and sex hormone-binding globulin (SHBG) levels were investigated before the start of treatment and subsequently over a three-month period.RESULTS:
There was a significant between-group difference in estrogen suppression during therapy. In comparison with baseline values, after four weeks of treatment the estradiol levels decreased by an average of 86.9% (95% CI, 70.5-94.2%) in the group treated with triptorelin alone and by 97.3% (95% CI, 94.1-98.8%; P = 0.0422) in the combination group; the respective figures for estrone were 48.5% (95% CI, 27.5-63.5%) and 70.4% (95% CI, 52.3-81.6%; P = 0.0007) and for estrone sulfate 56.7% (95% CI, 40-68.8%) and 80.5% (95% CI, 69.4-87.6%; P = 0.0055). No difference was observed between the groups in terms of gonadotropin suppression; both treatment modalities led to a slight but delayed decrease in SHBG levels. Three of the patients treated with triptorelin alone experienced tumor regression compared with four patients in the combination group. No appreciable side effects of the combination therapy were observed.
The treatment of premenopausal patients with triptorelin plus 4-OHA is feasible and leads to a much greater inhibition of main circulating estrogens than treatment with the analog alone. Since the combination of a GnRH analog and an aromatase inhibitor might potentially enhance the anti-tumor efficacy of the analog alone owing to more favorable endocrine effects, such a therapeutic approach deserves more extensive evaluation in the clinical setting.
PMID: 10472341 [PubMed – indexed for MEDLINE]
Download articolo: Anticancer Res. 1999
- The luteinising hormone-releasing hormone analogue triptorelin with or without the aromatase inhibitor formestane in premenopausal breast cancer: effects on bone metabolism markers.
(Martinetti A, Ferrari L, Celio L, Mariani L, Miceli R, Zilembo N, Di Bartolomeo M, Toffolatti L, Pozzi P, Seregni E, Bombardieri E, Bajetta E).
J Steroid Biochem Mol Biol. 2000 Dec 1;75(1):65-73.
the combination of a luteinising hormone-releasing hormone (LH-RH) analogue and an aromatase inhibitor (AI) induces greater oestrogen suppression than the analogue alone in premenopausal breast cancer. However, very few data on the biological effects of such a combination are currently available.AIM OF THE STUDY:
the short-term effects of treatment with the LH-RH analogue triptorelin alone or in association with the AI formestane on bone metabolism were investigated in premenopausal breast cancer. Circulating levels of the bone formation markers carboxy-terminal and amino-terminal propeptides of type I procollagen (PICP and PINP) and the bone resorption marker cross-linked carboxy-terminal telopeptide of type I collagen (ICTP) were assessed. In addition, serum levels of insulin-like growth factor (IGF)-I, IGF binding protein (IGFBP)-3 and interleukin 6 (IL-6) were evaluated.PATIENTS AND METHODS:
twenty-one patients with advanced breast cancer were randomly given triptorelin monthly alone (n=10, arm A) or in combination with formestane fortnightly (n=11, arm B). Blood samples were collected over a 3-month period.
serum PICP and PINP levels increased significantly over time (P=0.0065 and 0.0197 in arm A and B, respectively); no change in ICTP levels was observed. A rise in IGF-I and IGFBP-3 levels was seen in each treatment group, but only the increase in IGF-I was significant (P=0.0138, always). The on-treatment levels of the bone turnover markers and IGF-system components were inversely correlated with serum oestrogens. Neither treatment modalities significantly affected serum IL-6 levels over time. No difference in the behaviour of any of the assessed biomarkers was observed between patients with or without skeletal metastases.
it is worth noting that complete oestrogen depletion, at least in our case series, seems to increase only osteoblastic activity markers. The observed modifications appear to be related to oestrogen depletion per se rather than the degree of oestrogen suppression or the different therapeutic regimen administered.
PMID: 11179910 [PubMed – indexed for MEDLINE]
Download articolo: J. Steroid Biochem. 2000