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Effect of droloxifene treatment in metastatic breast cancer on tumor markers
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c-031 DROLOXIFENE: EFFICACY AN0 ENDOCRINE EFFECTS IN TREATMENT OF METASTATIC BREAST CANCER Rreitbech, G.P, MijbueV., Eastert G., Kreienberg R., Huber H.J.*, Steab H.J.* Univereitfitsfrsuenkliniken 6650 Homburg und 6500 Mainz, lKlinge Pharms GmbH 8000 MUnchen; F.A.G. Since October 1985 14 patients have been treated in phase I/II droloxifene studies, six of them had evsluable disease and were assessed for response according to UICC criteria. We recorded in one ceee complete remission of lung metastsses holding on now for ten months, one patient had partial remission of bone metestases since three months, three ere in stable disease from two to nine months +, having bone, lung and soft tissue metsstases. One patient progressed with lung metsstases after two months and died. We observed no eevere side effects besides one case with hypercalcemia and bone metestases. Parallel determination of endocrine parameters such ss LH, FSH, PAL, progesterone, testosterone, estrsdiol, fT3, fT4 and TSH were not affected under treatment; there seemed to be an increase of SHBG, which up to now is not statistically significant. Standard laboratory parameters also were not affected. As anticipated from phase I single dose studies, droloxifene wes absorbed very fast from the gastrointestinal tract. A steady state wee reached after approximately three to five days of treatment. The substance nor metabolites did not accumulate in the organism. Major metsbolites were N-desmethyl-droloxifeneend the corresponding glucuranides.
c-032 EFFECT OF DROLOXIFENE TREATMENT IN METASTATIC BREAST CANCER ON TUMOH MARKERS MGbus V., Ereitbsch G.P., Kreienberg Ft.,Eestert G., Staab H.J.+ Universittitsfrauenkliniken 6500 Main und 6650 Hanburg, *Klinge Pherma GmbH BOO0 Miinchen;F.R.G. In combined phase I/II studies with the new antiestrogen droloxifene in patients with metsstatic breast cancer tumor markers euch ae CEA, CA 15-3, CA 19-9 and CA 125 have been continuously determined. At first, patients have been controlled in short intervals of 24 hours for one week, thereafter in weekly intervals up to day 28. Further followup wee performed monthly. 14 patients entered the studies, in eight of them tuner associated antigens (TAA) were evalusble up to day 28. Five patients had elevated CA 15-3 at treatment onset. Surprisingly three of those five patients with initially elevated TAA levels showed intermittent increase of tumor marker concentrations up to the twentyfold of the starting point, returning to lower concentrations again. Tumor marker time couree resembled treatment induced spikes seen under chemotherapeutic regimens.
c-033
EFFECTS OF TAI%JXIFENON PDDLACTIN RRSPONSE TO VALPROATE AND DOPABINE INPUSION IN BREAST CANCER PATIRNTS. Vegh I., Stalldecker G., Pigni J., Levy C. Endocrinology Dept. J.M.Ramos Mejia Hospital . Buenos Aires. Argentina. Ye studied 2 drugs whose systemic administration inhibit prolactin (Prl) secretion,a)Dopamine (direct receptor agonist)inPusion,O.O04ug/kg/min. and b)S. Valproate &- aminobutyric acid mimetic) 400 mg/p.o. in breast cancer pts. before and during tamoxifen (TAB) treatment.Previously we observed a partial resistance of Prl to dopamine Lnfusion and S. valproate i= pre and postmenopausal pts. as compared to the response of normal controls.The % (Mean - SEM) of Max. inhibition by Dopamine at 160': Before TAM (II=13) :+ 5.6 z 10.5 % vs+ premenopausal p(O.005. During TAM(n = 6) :-30.3 + 7.9 % < Before TAM (n = 7) :+12.4 2 12.1 % vs. menopausal p(0.0025. For S.Valproate at 180': During TAB(n : 6) :-30.3 2 5.1 % < we observed similar behavior in these pts. These findings in pts. treated with TAB are similar to controls without a familary history'for this disease. Conclusion : we observed changes on Prl response to dopamine infusion and Se Valproate vhen estrogen receptor is blocked by TAM.
c-031 DROLOXIFENE: EFFICACY AN0 ENDOCRINE EFFECTS IN TREATMENT OF METASTATIC BREAST CANCER Rreitbech, G.P, MijbueV., Eastert G., Kreienberg R., Huber H.J.*, Steab H.J.* Univereitfitsfrsuenkliniken 6650 Homburg und 6500 Mainz, lKlinge Pharms GmbH 8000 MUnchen; F.A.G. Since October 1985 14 patients have been treated in phase I/II droloxifene studies, six of them had evsluable disease and were assessed for response according to UICC criteria. We recorded in one ceee complete remission of lung metastsses holding on now for ten months, one patient had partial remission of bone metestases since three months, three ere in stable disease from two to nine months +, having bone, lung and soft tissue metsstases. One patient progressed with lung metsstases after two months and died. We observed no eevere side effects besides one case with hypercalcemia and bone metestases. Parallel determination of endocrine parameters such ss LH, FSH, PAL, progesterone, testosterone, estrsdiol, fT3, fT4 and TSH were not affected under treatment; there seemed to be an increase of SHBG, which up to now is not statistically significant. Standard laboratory parameters also were not affected. As anticipated from phase I single dose studies, droloxifene wes absorbed very fast from the gastrointestinal tract. A steady state wee reached after approximately three to five days of treatment. The substance nor metabolites did not accumulate in the organism. Major metsbolites were N-desmethyl-droloxifeneend the corresponding glucuranides.
c-032 EFFECT OF DROLOXIFENE TREATMENT IN METASTATIC BREAST CANCER ON TUMOH MARKERS MGbus V., Ereitbsch G.P., Kreienberg Ft.,Eestert G., Staab H.J.+ Universittitsfrauenkliniken 6500 Main und 6650 Hanburg, *Klinge Pherma GmbH BOO0 Miinchen;F.R.G. In combined phase I/II studies with the new antiestrogen droloxifene in patients with metsstatic breast cancer tumor markers euch ae CEA, CA 15-3, CA 19-9 and CA 125 have been continuously determined. At first, patients have been controlled in short intervals of 24 hours for one week, thereafter in weekly intervals up to day 28. Further followup wee performed monthly. 14 patients entered the studies, in eight of them tuner associated antigens (TAA) were evalusble up to day 28. Five patients had elevated CA 15-3 at treatment onset. Surprisingly three of those five patients with initially elevated TAA levels showed intermittent increase of tumor marker concentrations up to the twentyfold of the starting point, returning to lower concentrations again. Tumor marker time couree resembled treatment induced spikes seen under chemotherapeutic regimens.
c-033
EFFECTS OF TAI%JXIFENON PDDLACTIN RRSPONSE TO VALPROATE AND DOPABINE INPUSION IN BREAST CANCER PATIRNTS. Vegh I., Stalldecker G., Pigni J., Levy C. Endocrinology Dept. J.M.Ramos Mejia Hospital . Buenos Aires. Argentina. Ye studied 2 drugs whose systemic administration inhibit prolactin (Prl) secretion,a)Dopamine (direct receptor agonist)inPusion,O.O04ug/kg/min. and b)S. Valproate &- aminobutyric acid mimetic) 400 mg/p.o. in breast cancer pts. before and during tamoxifen (TAB) treatment.Previously we observed a partial resistance of Prl to dopamine Lnfusion and S. valproate i= pre and postmenopausal pts. as compared to the response of normal controls.The % (Mean - SEM) of Max. inhibition by Dopamine at 160': Before TAM (II=13) :+ 5.6 z 10.5 % vs+ premenopausal p(O.005. During TAM(n = 6) :-30.3 + 7.9 % < Before TAM (n = 7) :+12.4 2 12.1 % vs. menopausal p(0.0025. For S.Valproate at 180': During TAB(n : 6) :-30.3 2 5.1 % < we observed similar behavior in these pts. These findings in pts. treated with TAB are similar to controls without a familary history'for this disease. Conclusion : we observed changes on Prl response to dopamine infusion and Se Valproate vhen estrogen receptor is blocked by TAM.