RESUMO
BACKGROUND: Abnormal epidermal growth factor receptor expression and pre-clinical data prompted us to investigate the activity of gefitinib, a selective epidermal growth factor receptor tyrosine kinase inhibitor, in hormone-refractory prostate cancer. METHODS: Eighty-two patients were randomly assigned to receive prednisone plus gefitinib (pG; n = 44) or prednisone plus placebo (ppl; n = 38). On progression, patients initially assigned to placebo were offered the possibility to receive gefitinib. Best prostate-specific antigen response was the primary endpoint. RESULTS: At a median follow-up time of 29.0 months (26.0-32.0), 77 patients progressed and 51 died. Prostate-specific antigen response was recorded in 6/38 (15.8%; 95% CI 4.2-27.4) and in 5/44 (11.4%; 95% CI 2.0-20.8) patients in pG and ppl groups, respectively. There was no difference between groups in time to progression (median pG 4.0 months, range 3.5-4.5; median ppl 4.5 months, range 3.5-5.0) and survival (median pG 26.5 months, range 16.0-37.0; median ppl 20.5 months, range 14.0-27.0). Adverse events occurred in 19 patients in each arm and were generally mild. CONCLUSIONS: pG showed a good tolerability profile but only a limited therapeutic activity in hormone-refractory prostate cancer.
Assuntos
Adenocarcinoma/tratamento farmacológico , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Neoplasias Ósseas/tratamento farmacológico , Neoplasias Hormônio-Dependentes/tratamento farmacológico , Neoplasias da Próstata/tratamento farmacológico , Adenocarcinoma/secundário , Idoso , Idoso de 80 Anos ou mais , Neoplasias Ósseas/secundário , Método Duplo-Cego , Gefitinibe , Humanos , Metástase Linfática , Masculino , Pessoa de Meia-Idade , Neoplasias Hormônio-Dependentes/patologia , Placebos , Prednisona/administração & dosagem , Prognóstico , Neoplasias da Próstata/patologia , Quinazolinas/administração & dosagem , Taxa de Sobrevida , Resultado do TratamentoRESUMO
OBJECTIVE: A randomized multicenter (14 centers) trial was conducted in 114 men with prostate cancer to determine whether the antiestrogen tamoxifen ('Nolvadex') 20 mg or the aromatase inhibitor anastrozole ('Arimidex') 1 mg prevent gynecomastia and breast pain during treatment with the non-steroidal antiandrogen bicalutamide ('Casodex') 150 mg, without compromising efficacy, safety, or quality of life. Plasma samples were collected in a subgroup of these patients to investigate whether trough (pre-dose) concentrations of bicalutamide 150 mg are influenced by concomitant administration of tamoxifen 20 mg or anastrozole 1 mg; the results of this pilot study are reported in this article. METHODS: A subpopulation of patients from a randomized placebo-controlled trial evaluating tamoxifen 20 mg and anastrozole 1 mg for the prevention of gynecomastia and breast pain in men receiving bicalutamide 150 mg for early or recurrent prostate cancer were selected on a voluntary basis from three of the trial centers. Plasma samples were collected on days 7, 14, 28, and 84 of therapy and analyzed to determine the plasma concentrations of (R)-bicalutamide and (S)-bicalutamide. In addition, plasma concentrations of tamoxifen, N-desmethyltamoxifen, and anastrozole were determined. RESULTS: A total of 21 patients were selected. There was no significant difference between treatment groups with respect to the trough plasma concentrations of either bicalutamide enantiomer at any point during the study. Plasma concentrations of the enantiomers, and the relative proportion of the (R))- and (S)-enantiomers, were consistent with those reported in previous studies. Plasma concentrations of tamoxifen, N-desmethyltamoxifen, and anastrozole were also similar to those described elsewhere in the literature. CONCLUSIONS: The findings of this pilot study suggest that trough plasma concentrations of bicalutamide enantiomers following administration of bicalutamide 150 mg are not markedly influenced by concomitant administration of tamoxifen 20 mg or anastrozole 1 mg. However, an effect of tamoxifen on bicalutamide pharmacokinetics can not be completely excluded due to the size of this study. Further studies are needed to clarify the effect of tamoxifen on bicalutamide pharmacokinetics and prostate cancer control in bicalutamide-treated patients. 'Arimidex', 'Casodex', and 'Nolvadex' are trademarks of the AstraZeneca group of companies.
Assuntos
Antagonistas de Androgênios/uso terapêutico , Anilidas/uso terapêutico , Antineoplásicos Hormonais/uso terapêutico , Inibidores da Aromatase/uso terapêutico , Ginecomastia/prevenção & controle , Nitrilas/uso terapêutico , Neoplasias da Próstata/tratamento farmacológico , Tamoxifeno/uso terapêutico , Triazóis/uso terapêutico , Idoso , Idoso de 80 Anos ou mais , Anastrozol , Antagonistas de Androgênios/sangue , Antagonistas de Androgênios/farmacocinética , Anilidas/sangue , Anilidas/farmacocinética , Antineoplásicos Hormonais/administração & dosagem , Antineoplásicos Hormonais/sangue , Inibidores da Aromatase/administração & dosagem , Inibidores da Aromatase/sangue , Cromatografia Líquida de Alta Pressão , Método Duplo-Cego , Interações Medicamentosas , Humanos , Masculino , Pessoa de Meia-Idade , Nitrilas/administração & dosagem , Nitrilas/sangue , Dor/prevenção & controle , Neoplasias da Próstata/complicações , Neoplasias da Próstata/cirurgia , Tamoxifeno/administração & dosagem , Tamoxifeno/sangue , Compostos de Tosil , Triazóis/administração & dosagem , Triazóis/sangueRESUMO
Background. The aim of this paper was to evaluate the activity and tolerability of docetaxel (D) and bevacizumab (Bev) in patients with metastatic castrate-resistant prostate cancer (CRPC) previously exposed to D. Methods. Treatment consisted of D 30 mg/m(2) i.v. for four consecutive weekly administrations followed by a 2-week rest interval, in addition to Bev 5 mg/kg i.v. every 2 weeks. Results. Forty-three patients were enrolled: a PSA response was observed in 27 patients (62.7%, 95% CI: 0.41 to 0.91), and a palliative response was achieved in 31 patients (72.1%, 95%CI: 0.48 to 1.02). After a median followup of 11.3 months, only five patients had died. The regimen was generally well tolerated. Conclusion. Weekly D + biweekly Bev seems to be an effective and well-tolerated treatment option for patients with metastatic CRPC previously exposed to D-based chemotherapy.
RESUMO
OBJECTIVES: To evaluate the efficacy and safety of a new regimen that combines weekly docetaxel and weekly epirubicin for the treatment of advanced hormone-refractory prostate cancer. METHODS: Docetaxel 30 mg/m2 and epirubicin 30 mg/m2 were intravenously administered on a weekly basis, for a maximum of 24 cycles. The therapy was discontinued after the first 12 cycles in the patients who responded or had stable disease and was resumed as soon as any signs of progression were noted. RESULTS: Of the 38 evaluable patients, 26 achieved a confirmed greater than 50% decrease in prostate-specific antigen level (68.4%, 95% confidence interval [CI] 51.2% to 82.0%). The median response duration was 8.8 months (95% CI 6.2 to 11.8), and the median time to progression was 7.4 months (95% CI 5.6 to 9.6). Pain was rapidly reduced in 24 (72.7%, 95% CI 54.2 to 86.7) of the 33 patients who were symptomatic at baseline. Of the 38 patients, 21 resumed therapy after the planned interruption; of these, 3 had a prostate-specific antigen response (14.2%) and 12 had stable disease (57.1%). The regimen was well tolerated. Grade 3 neutropenia occurred in 15.7% of the patients, grade 3 anemia in 13.1%, and grade 3 thrombocytopenia in 7.8%. CONCLUSIONS: The results of this study have suggested the feasibility and tolerability of the combination of weekly docetaxel and weekly epirubicin, which led to a rapid and long-lasting decrease in prostate-specific antigen levels and a palliative response in patients with advanced hormone-refractory prostate cancer.
Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica/administração & dosagem , Neoplasias da Próstata/tratamento farmacológico , Idoso , Antagonistas de Androgênios/uso terapêutico , Antineoplásicos/administração & dosagem , Progressão da Doença , Docetaxel , Esquema de Medicação , Epirubicina/administração & dosagem , Hormônio Liberador de Gonadotropina/agonistas , Humanos , Masculino , Pessoa de Meia-Idade , Neoplasias da Próstata/patologia , Taxoides/administração & dosagem , Falha de TratamentoRESUMO
OBJECTIVE: To evaluate the activity and tolerability of weekly high-dose calcitriol and docetaxel in patients with metastatic hormone-refractory prostate cancer (HRPC) previously exposed to docetaxel, as patients who progress after docetaxel treatment might be considered for second-line chemotherapy, but with no standard salvage therapy available we hypothesised that high-dose calcitriol might restore sensitivity to chemotherapy. PATIENTS AND METHODS: The study comprised 26 patients who had progressed after first-line treatment with docetaxel-based chemotherapy had failed. Treatment cycles consisted of calcitriol (32 microg orally as 0.5 microg tablets) on day 1 and docetaxel (30 mg/m(2) intravenous) on day 2, administered for six consecutive weeks followed by a 2-week rest interval for a maximum of 24 cycles. RESULTS: There was a response in prostate-specific antigen (PSA) level in eight patients (31%); seven (27%) had a stable PSA level for >/= 12 weeks. The median time to PSA progression was 4.2 months and the median survival was 9.3 months. The regimen was generally well tolerated; there was grade 2 hypercalcaemia, probably related to calcitriol, in one patient after six treatment cycles. CONCLUSION: Weekly high-dose calcitriol and docetaxel seems to be an effective and well-tolerated treatment option for patients with metastatic HRPC previously exposed to docetaxel-based chemotherapy.
Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Neoplasias da Próstata/tratamento farmacológico , Idoso , Calcitriol/administração & dosagem , Progressão da Doença , Docetaxel , Esquema de Medicação , Resistencia a Medicamentos Antineoplásicos/efeitos dos fármacos , Humanos , Masculino , Pessoa de Meia-Idade , Metástase Neoplásica , Antígeno Prostático Específico/sangue , Taxoides/administração & dosagem , Resultado do TratamentoRESUMO
The aim of this study was to evaluate the activity and toxicity of capecitabine as third-line treatment in patients with advanced renal cell carcinoma for whom immunotherapy had failed. Twenty-one patients with metastatic clear renal cell carcinoma were enrolled. Capecitabine was administered orally twice daily at a dosage of 2500 mg/m(2) for 14 days, followed by 7 days of rest. The median number of administered cycles was five (1-13). One patient (4.8%) achieved a remission after eight treatment cycles. Stable disease was observed in nine patients (42.8%), whereas 11 progressed (52.4%). The estimated median time to progression was 3.6 months (confidence interval: 1.4 to 5.2). The estimated median overall survival was 7.2 months (confidence interval: 4.6 to 8.8). The regimen was well tolerated and no unexpected toxic effects were observed. Capecitabine as third-line treatment showed a favourable toxicity profile, but exhibited low activity in patients with advanced renal cell carcinoma after failing immunotherapy.
Assuntos
Antimetabólitos Antineoplásicos/uso terapêutico , Carcinoma de Células Renais/tratamento farmacológico , Desoxicitidina/análogos & derivados , Fluoruracila/análogos & derivados , Neoplasias Renais/tratamento farmacológico , Administração Oral , Idoso , Antimetabólitos Antineoplásicos/administração & dosagem , Antimetabólitos Antineoplásicos/efeitos adversos , Capecitabina , Carcinoma de Células Renais/patologia , Desoxicitidina/administração & dosagem , Desoxicitidina/efeitos adversos , Desoxicitidina/uso terapêutico , Progressão da Doença , Relação Dose-Resposta a Droga , Feminino , Fluoruracila/administração & dosagem , Fluoruracila/efeitos adversos , Fluoruracila/uso terapêutico , Humanos , Imunoterapia , Neoplasias Renais/patologia , Masculino , Pessoa de Meia-Idade , Metástase Neoplásica , Pró-Fármacos , Indução de Remissão , Taxa de Sobrevida , Falha de TratamentoRESUMO
OBJECTIVES: To investigate the prognostic value of some conventional bone markers and a number of other factors in terms of the survival of patients with hormone-resistant prostate cancer and bone metastases treated with chemotherapy. METHODS: The data of 141 patients were analyzed to verify the influence of the following factors on survival: bone-alkaline phosphatase, type I collagen propeptide, the carboxyterminal telopeptide of type I collagen, the urinary calcium/creatinine ratio, patient age, Karnofsky performance status, pathologic grade, duration of response to primary hormonal therapy, prostate-specific antigen, hemoglobin, lactate dehydrogenase, and extent of bone disease. RESULTS: When all the variables were simultaneously analyzed using the multivariate proportional hazard model, only Karnofsky performance status (P <0.005) and duration of response to primary hormonal therapy (P <0.0001) remained statistically significant. CONCLUSIONS: The results of this study suggest that bone-alkaline phosphatase, type I collagen propeptide, the carboxyterminal telopeptide of type I collagen, and the urinary calcium/creatinine ratio are not prognostic of survival in patients with hormone-resistant prostate cancer and bone metastases treated with chemotherapy.
Assuntos
Adenocarcinoma/secundário , Fosfatase Alcalina/sangue , Biomarcadores Tumorais/sangue , Neoplasias Ósseas/secundário , Colágeno/sangue , Peptídeos/sangue , Fosfopeptídeos/sangue , Pró-Colágeno/sangue , Neoplasias da Próstata/sangue , Adenocarcinoma/sangue , Adenocarcinoma/tratamento farmacológico , Adenocarcinoma/mortalidade , Idoso , Antagonistas de Androgênios/farmacologia , Antagonistas de Androgênios/uso terapêutico , Antineoplásicos Hormonais/farmacologia , Antineoplásicos Hormonais/uso terapêutico , Neoplasias Ósseas/sangue , Neoplasias Ósseas/tratamento farmacológico , Neoplasias Ósseas/mortalidade , Cálcio/urina , Colágeno Tipo I , Creatinina/urina , Resistencia a Medicamentos Antineoplásicos , Seguimentos , Humanos , Itália/epidemiologia , Avaliação de Estado de Karnofsky , Tábuas de Vida , Masculino , Pessoa de Meia-Idade , Modelos de Riscos Proporcionais , Neoplasias da Próstata/tratamento farmacológico , Neoplasias da Próstata/mortalidade , Análise de Sobrevida , Fatores de TempoRESUMO
OBJECTIVE: The aim of this study was to evaluate the activity and tolerability of docetaxel in patients with hormone-resistant prostate cancer previously exposed to chemotherapy. METHODS: We enrolled 27 patients with hormone-resistant prostatic cancer that had progressed during first-line chemotherapy. The primary end-point was palliative response defined as a 2-point reduction in the 6-point present pain intensity scale, and an improvement in Karnofsky performance status of one 10-point category. The treatment consisted of weekly docetaxel 25 mg/m(2) body surface area administered by means of a 1-hour intravenous infusion with corticosteroid premedication. RESULTS: The primary criterion of palliative response was met in 13 patients (48%) after eight treatment cycles; its median duration was 6 months (range 1-8). Mean global quality of life improved in 8 and 10 patients after respectively four and eight treatment cycles. After a median follow-up of 8 months, 21 patients had died: the median survival was 9+ months (range 2-18). Weekly docetaxel was very well tolerated: grade 3 neutropenia occurred in 1 patient and grade 3 anemia in 2. CONCLUSIONS: Weekly low-dose docetaxel is an effective and well-tolerated treatment for patients with hormone-resistant prostate cancer previously exposed to chemotherapy.