Pharmacodynamic stimulation of thrombogenesis by angiotensin (1-7) in recurrent ovarian cancer patients receiving gemcitabine and platinum-based chemotherapy.
Cancer Chemother Pharmacol
; 71(4): 965-72, 2013 Apr.
Article
en En
| MEDLINE
| ID: mdl-23370663
ABSTRACT
PURPOSE:
This randomized, double-blind, placebo-controlled Phase 2 study evaluated safety and efficacy of A(1-7) for reduction in Grade 3-4 thrombocytopenia in patients receiving myelosuppressive chemotherapy. Pharmacodynamic activity of A(1-7) in platelet production and retention of scheduled dose intensity were also determined.METHODS:
Thirty-four patients with ovarian, Fallopian tube, or peritoneal carcinoma receiving gemcitabine and carboplatin or cisplatin were evaluated. Patients were randomized to receive study drug subcutaneously at 100 mcg/kg (n = 11), 300 mcg/kg (n = 13), or placebo (n = 10) following chemotherapy for up to six cycles. Hematologic variables were obtained throughout each treatment cycle.RESULTS:
There were no drug-related safety issues. There were no instances of Grade 4 thrombocytopenia in patients who received 100 mcg/kg treatment compared to 6 % of chemotherapy cycles for patients receiving placebo (p = 0.07). The maximal percentage increase in platelet concentration from baseline was higher for patients who received 100 mcg/kg A(1-7) compared to placebo (p = 0.02). This increase was accompanied by a reduction in the nadir absolute neutrophil count (p = 0.04). Relative dose intensity for the combination chemotherapy was higher for patients who received 100 mcg/kg A(1-7) compared to placebo (p = 0.04). There were no differences in outcomes for patients receiving 300 mcg/kg dose compared to placebo.CONCLUSIONS:
A 100 mcg/kg dose of A(1-7) was shown to produce pharmacodynamic effects on peripheral blood platelet counts, preserve planned dose intensity, and reduce Grade 3-4 thrombocytopenia following gemcitabine and platinum chemotherapy. These findings are consistent with A(1-7)-induced stimulation of thrombogenesis in the bone marrow following marrow-toxic chemotherapy.
Texto completo:
1
Colección:
01-internacional
Base de datos:
MEDLINE
Asunto principal:
Neoplasias Ováricas
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Fragmentos de Péptidos
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Trombocitopenia
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Angiotensina I
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Protocolos de Quimioterapia Combinada Antineoplásica
Tipo de estudio:
Clinical_trials
Límite:
Adult
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Aged
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Aged80
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Female
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Humans
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Middle aged
Idioma:
En
Revista:
Cancer Chemother Pharmacol
Año:
2013
Tipo del documento:
Article
País de afiliación:
Estados Unidos