RESUMO
BACKGROUND: Cisplatin-based chemotherapy is a standard treatment of metastatic urothelial carcinoma (UC), though carboplatin-based chemotherapy is frequently substituted due to improved tolerability. Because comparative effectiveness in clinical outcomes of cisplatin- versus carboplatin-based chemotherapy is lacking, a meta-analysis was carried out. METHODS: PubMed was searched for articles published from 1966 to 2010. Eligible studies included prospective randomized trials evaluating cisplatin- versus carboplatin-based regimens in patients with metastatic UC. Individual patient data were not available and survival data were inconsistently reported. Therefore, the analysis focused on overall response (OR) and complete response (CR) rates. The Mantel-Haenszel method was used for combining trials and calculating pooled risk ratios (RRs). RESULTS: A total of 286 patients with metastatic UC from four randomized trials were included. Cisplatin-based chemotherapy was associated with a significantly higher likelihood of achieving a CR [RR = 3.54; 95% confidence interval (CI) 1.48-8.49; P = 0.005] and OR (RR = 1.34; 95% CI 1.04-1.71; P = 0.02). Survival end points could not be adequately assessed due to inconsistent reporting among trials. CONCLUSIONS: Cisplatin-based, as compared with carboplatin-based, chemotherapy significantly increases the likelihood of both OR and CR in patients with metastatic UC. The impact of improved response proportions on survival end points could not be assessed.
Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Carboplatina/uso terapêutico , Carcinoma de Células de Transição/tratamento farmacológico , Cisplatino/uso terapêutico , Pesquisa Comparativa da Efetividade , Neoplasias Urológicas/tratamento farmacológico , Carcinoma de Células de Transição/secundário , Feminino , Humanos , Masculino , Ensaios Clínicos Controlados Aleatórios como Assunto , Neoplasias Urológicas/secundárioRESUMO
PURPOSE: Taxane based chemotherapy has activity in advanced prostate cancer but previous studies of neoadjuvant docetaxel demonstrated a prostate specific antigen response with no obvious antitumor activity. The efficacy and safety of neoadjuvant albumin-bound paclitaxel (nab-paclitaxel, Abraxane), a novel nanoparticle based formulation, were assessed in patients with high risk, locally advanced prostate cancer. MATERIALS AND METHODS: Eligible patients had locally advanced prostatic adenocarcinoma, clinical stage cT2b or greater, Gleason score 8 or greater, or serum prostate specific antigen 15 ng/ml or greater without metastatic disease. Patients received 2 cycles of 150 mg/m(2) nab-paclitaxel weekly for 3 weeks during each 4-week cycle, followed by radical prostatectomy with bilateral lymphadenectomy. Efficacy assessments included pathological and prostate specific antigen response. RESULTS: A total of 19 patients completed neoadjuvant therapy and 18 underwent radical prostatectomy. Median pretreatment prostate specific antigen was 8.5 ng/ml and median Gleason score was 8. Despite the lack of complete pathological responses 5 of 18 patients (28%) had organ confined disease and 9 of 18 (50%) had specimen confined disease. Post-chemotherapy prostate specific antigen was decreased in 18 of 19 (95%) patients and median decrease was 2.9 ng/ml (35%, p <0.001). An initial prostate specific antigen after radical prostatectomy of 0.02 ng/ml or less was achieved in 17 of 18 (94%) patients. There were no significant perioperative complications. Cytoplasmic vacuolization (focal in 10 and extensive in 7) was evident in all but 1 patient (94%). Ten patients (56%) had grade 3 and 1 had grade 4 neutropenia with no febrile neutropenia. CONCLUSIONS: Neoadjuvant nab-paclitaxel was well tolerated. Similar to our experience with neoadjuvant docetaxel there were no pathological complete responses, although a possible histological antitumor effect was observed.
Assuntos
Adenocarcinoma/tratamento farmacológico , Adenocarcinoma/cirurgia , Albuminas/uso terapêutico , Paclitaxel/uso terapêutico , Prostatectomia , Neoplasias da Próstata/tratamento farmacológico , Neoplasias da Próstata/cirurgia , Idoso , Humanos , Masculino , Pessoa de Meia-Idade , Terapia Neoadjuvante , Fatores de RiscoRESUMO
PURPOSE: TG4010 is a recombinant MVA vector expressing the tumor-associated antigen MUC1 and IL2. We explored the effect two schedules of TG4010 on PSA in men with PSA progression. PATIENTS AND METHODS: A randomized phase II trial was conducted in 40 patients with PSA progression. Patients had PSA doubling times less than 10 months, with no overt evidence of disease. Patients received either weekly subcutaneous injection (sc) of TG4010 10(8) pfu for 6 weeks, then one injection every 3 weeks or sc injection of TG4010 10(8) pfu every 3 weeks. RESULTS: The primary endpoint of a 50% decrease in PSA values from baseline was not observed. Nevertheless, 13 of 40 patients had a more than two fold improvement in PSA doubling time. Ten patients had their PSA stabilized for over 8 months. Therapy was well tolerated. CONCLUSIONS: Although the primary endpoint was not achieved, there is evidence of biologic activity of TG4010 in patients with PSA progression, further investigation in prostate cancer is warranted.
Assuntos
Vacinas Anticâncer/uso terapêutico , Glicoproteínas de Membrana/uso terapêutico , Antígeno Prostático Específico/efeitos dos fármacos , Neoplasias da Próstata/tratamento farmacológico , Idoso , Vacinas Anticâncer/administração & dosagem , Vacinas Anticâncer/efeitos adversos , Progressão da Doença , Esquema de Medicação , Humanos , Imunoterapia/métodos , Injeções Subcutâneas , Interleucina-2/imunologia , Masculino , Glicoproteínas de Membrana/administração & dosagem , Glicoproteínas de Membrana/efeitos adversos , Pessoa de Meia-Idade , Mucina-1/imunologia , Antígeno Prostático Específico/sangue , Neoplasias da Próstata/imunologia , Fatores de Tempo , Resultado do TratamentoRESUMO
BACKGROUND: Sorafenib is an orally bioavailable vascular endothelial growth factor receptor (VEGFR) inhibitor with antitumor activity in metastatic renal cell carcinoma (RCC). Sunitinib, also a VEGFR inhibitor, induces biochemical hypothyroidism in 85% of metastatic RCC patients, the majority of whom have signs or symptoms of hypothyroidism. Hence, the incidence of thyroid function test (TFT) abnormalities in patients with metastatic RCC receiving sorafenib was investigated. PATIENTS AND METHODS: Sixty-eight patients with metastatic RCC were treated with sorafenib at the Cleveland Clinic Taussig Cancer Center, and 39 patients had TFTs available. RESULTS: Eight patients (21%) had thyroid dysfunction possibly caused by sorafenib [seven hypothyroidism (18%) and one hyperthyroidism (3%)] and eight additional patients (21%) had findings compatible with nonthyroidal illness. Only two patients had clinical signs and symptoms secondary to thyroid dysfunction and received thyroid hormone replacement. CONCLUSIONS: In summary, clinically significant TFT abnormalities were not common in patients treated with sorafenib, and replacement therapy was rarely indicated. TFTs should be measured before sorafenib therapy in RCC patients and subsequently only if clinically indicated.
Assuntos
Benzenossulfonatos/efeitos adversos , Carcinoma de Células Renais/tratamento farmacológico , Carcinoma de Células Renais/secundário , Hipotireoidismo/induzido quimicamente , Neoplasias Renais/tratamento farmacológico , Neoplasias Renais/patologia , Piridinas/efeitos adversos , Administração Oral , Adulto , Idoso , Idoso de 80 Anos ou mais , Benzenossulfonatos/uso terapêutico , Carcinoma de Células Renais/patologia , Quimioterapia Adjuvante , Estudos de Coortes , Relação Dose-Resposta a Droga , Esquema de Medicação , Feminino , Seguimentos , Humanos , Hipotireoidismo/epidemiologia , Neoplasias Renais/mortalidade , Masculino , Pessoa de Meia-Idade , Metástase Neoplásica , Niacinamida/análogos & derivados , Compostos de Fenilureia , Piridinas/uso terapêutico , Estudos Retrospectivos , Medição de Risco , Sorafenibe , Testes de Função TireóideaRESUMO
We observed major responses in two patients with adenocarcinoma of the lung who had received a combination of interferon (IFN)-beta and IFN-gamma, immediately followed by chemotherapy. To verify these observations, we initiated a prospective randomized phase II-III trial of etoposide and cisplatin, with or without IFN-beta and IFN-gamma, in patients with inoperable non-small cell lung cancer. Thirty-seven patients were randomized to receive either two cycles of chemotherapy or 6 weeks of IFN-beta plus IFN-gamma followed by two cycles of chemotherapy. Chemotherapy consisted of 60 mg of cisplatin/m2 on day 1 and 120 mg of etoposide/m2 on days 4, 6, and 8, repeated every 21 days. Patients who were randomized to the IFN plus chemotherapy arm received 200 micrograms of IFN-gamma and 30 x 10(6) U of IFN-beta three times per week for 6 weeks, followed by two cycles of chemotherapy. Three of 18 (17%) eligible patients in the chemotherapy arm and two of 18 (11%) patients in the combination arm had partial responses. All responses occurred while patients were receiving chemotherapy. Median survival was 190 days for the chemotherapy arm and 246 days in the combined modality arm, as estimated from Kaplan-Meier curves (P = .35). We observed no significant difference in subjective toxic effects between the two arms. We observed more hematologic toxicity during chemotherapy on the combined modality arm (P = .02). We conclude that pretreatment with IFN-beta and IFN-gamma does not enhance the efficacy of etoposide and cisplatin in this disease. Although the combined modality arm is relatively well tolerated, it does result in more chemotherapy-associated toxic effects. This study also exemplifies a hybrid phase II-III trial design, which is useful in allowing phase II results to be quickly incorporated into a phase III trial.
Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Carcinoma Pulmonar de Células não Pequenas/tratamento farmacológico , Neoplasias Pulmonares/tratamento farmacológico , Protocolos de Quimioterapia Combinada Antineoplásica/efeitos adversos , Carcinoma Pulmonar de Células não Pequenas/mortalidade , Carcinoma Pulmonar de Células não Pequenas/secundário , Carcinoma Pulmonar de Células não Pequenas/cirurgia , Cisplatino/administração & dosagem , Cisplatino/efeitos adversos , Esquema de Medicação , Avaliação de Medicamentos , Etoposídeo/administração & dosagem , Etoposídeo/efeitos adversos , Humanos , Interferon Tipo I/administração & dosagem , Interferon gama/administração & dosagem , Neoplasias Pulmonares/mortalidade , Neoplasias Pulmonares/secundário , Neoplasias Pulmonares/cirurgia , Estudos Prospectivos , Ensaios Clínicos Controlados Aleatórios como Assunto/métodosRESUMO
PURPOSE: Phase II trial in metastatic urothelial carcinoma using a novel combination chemotherapy regimen consisting of vinblastine, ifosfamide, and gallium nitrate (VIG). PATIENTS AND METHODS: Twenty-seven patients were entered onto this phase II study. Dosages were vinblastine 0.11 mg/kg days 1 and 2, ifosfamide 1.2 gm/m2 days 1 through 5 (with mesna), and gallium 300 mg/m2 as a 24-hour infusion days 1 through 5, with calcitriol (1,25-dihydroxycholecalciferol) 0.5 microgram/d orally starting 3 days before each course (except the first) and continuing throughout gallium administration, plus recombinant human granulocyte colony-stimulating factor (rhG-CSF) (filgrastim) 5 micrograms/kg/d days 7 through 16. Courses were repeated every 21 days for a maximum of six cycles. RESULTS: The major toxicity was granulocytopenia. Fifteen patients (55.6%) had grade 3 or 4 granulocytopenia, including eight patients with granulocytopenic fevers. Eleven patients had grade 3 or 4 anemia and four had grade 3 or 4 nephrotoxicity, which was reversible. Other grade 3 to 4 toxicities included hypocalcemia (three patients), thrombocytopenia (two), encephalopathy (one), and temporary blindness (one). There was one treatment-related mortality. Toxicity was more severe in patients older than 70 years and those with prior pelvic irradiation, prior cisplatin adjuvant therapy, or prior nephrectomy. We now decrease VIG by 20% in this patient population. Eighteen patients (67%) achieved an objective response, including 11 (41%) who attained a disease-free status (five with VIG alone and six with subsequent surgery). Median duration of remission was 20 weeks, with five patients still in remission at 22+ to 56+ weeks. CONCLUSION: VIG combination chemotherapy is very active in patients with metastatic urothelial carcinoma. Toxicity was significant but manageable.
Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Carcinoma/tratamento farmacológico , Neoplasias da Bexiga Urinária/tratamento farmacológico , Adulto , Idoso , Idoso de 80 Anos ou mais , Agranulocitose/induzido quimicamente , Protocolos de Quimioterapia Combinada Antineoplásica/efeitos adversos , Calcitriol/administração & dosagem , Calcitriol/efeitos adversos , Carcinoma/mortalidade , Carcinoma/secundário , Esquema de Medicação , Feminino , Filgrastim , Gálio/administração & dosagem , Gálio/efeitos adversos , Fator Estimulador de Colônias de Granulócitos/administração & dosagem , Fator Estimulador de Colônias de Granulócitos/efeitos adversos , Humanos , Ifosfamida/administração & dosagem , Ifosfamida/efeitos adversos , Masculino , Pessoa de Meia-Idade , Proteínas Recombinantes/administração & dosagem , Proteínas Recombinantes/efeitos adversos , Neoplasias da Bexiga Urinária/mortalidade , Vimblastina/administração & dosagem , Vimblastina/efeitos adversosRESUMO
PURPOSE: Alkylating agents have modest activity in advanced urothelial carcinoma. Ifosfamide (IFX) is an agent as yet unstudied in advanced urothelial carcinoma. Despite recent advances in the treatment of this disease, there continues to be a need to identify new active agents and their toxicity spectra. Here we report results from the use of IFX in this population. PATIENTS AND METHODS: Ambulatory patients with advanced urothelial carcinoma were treated with IFX 3,750 mg/m2 and mesna 2250 mg/m2 both intravenously (IV) daily for 2 days every 3 weeks. Significant renal and CNS toxicity required a dose change of IFX to 1,500 mg/m2 IV with mesna 750 mg/m2 IV for 5 days every 3 weeks. Doses were modified for hematologic, renal, and CNS toxicity. RESULTS: Of 56 eligible patients entered onto the study, 26 received the 2-day schedule and 30 were treated on the 5-day regimen. All patients had progressive disease following prior systemic chemotherapy. There were five complete responses (CRs) and six partial responses (PRs) for an overall response rate of 20% (exact 95% confidence interval [CI], 10% to 32%). Renal and CNS toxicity was severe before the change in schedule, but manageable after the change. Major identified toxicities were gastrointestinal, myelosuppressive, renal, and CNS. There were four early deaths to which treatment probably contributed, but were multifactorial in etiology. CONCLUSION: IFX has significant activity, but also major toxicity in a heavily cisplatin-pretreated cohort with advanced urothelial carcinoma. A modification of dose and/or schedule from that described should be considered in future trials. Combination regimens using this agent should be explored.
Assuntos
Antineoplásicos Alquilantes/uso terapêutico , Carcinoma de Células de Transição/tratamento farmacológico , Ifosfamida/uso terapêutico , Idoso , Idoso de 80 Anos ou mais , Antineoplásicos Alquilantes/administração & dosagem , Antineoplásicos Alquilantes/efeitos adversos , Esquema de Medicação , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Análise de Sobrevida , Resultado do TratamentoRESUMO
PURPOSE: This multicenter cooperative group phase I/II trial evaluated the toxicity and efficacy of escalated dosages of methotrexate, vinblastine, doxorubicin, and cisplatin (M-VAC) with recombinant human granulocyte colony-stimulating factor (rhG-CSF) in patients with advanced urothelial carcinoma. PATIENTS AND METHODS: From November 1990 through October 1991, 35 patients with advanced urothelial cancer previously untreated with chemotherapy were treated with escalated dosages of M-VAC (M-VACII). In patients with prior pelvic radiotherapy, standard M-VAC (M-VACI) was administered plus rhG-CSF. For other patients, M-VACII dosages were methotrexate 40 mg/m2 (days 1, 15, and 22), vinblastine 4 mg/m2 (days 2, 15, and 22), doxorubicin 40 mg/m2 (day 2), and cisplatin 100 mg/m2 (day 2). In addition, rhG-CSF was administered at a dosage of 300 micrograms subcutaneously on days 4 to 11. Cycles were repeated every 4 weeks. For patients who tolerated the first course of therapy, subsequent escalation by 25% of all drugs was performed. RESULTS: Six complete responses and 15 partial responses were observed (60%; 95% confidence interval, 42% to 76%). The median duration of response was 4.6 months, and the median survival time was 9.4 months (range, 0.5 to 23.5+). Twenty-eight of 35 patients experienced grade 3 or 4 leukopenia, including 14 patients who developed fever associated with neutropenia. Eight (23%) early deaths were observed. CONCLUSION: This regimen (M-VACII) with escalated dosages of M-VAC was associated with significant toxicity and had no apparent benefit over M-VACI therapy with regard to complete response rate or survival. Further evaluation of the dose-intensity of the components of this regimen in this disease is likely to be of limited benefit to patients.
Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica/administração & dosagem , Doenças da Medula Óssea/prevenção & controle , Carcinoma de Células de Transição/tratamento farmacológico , Fator Estimulador de Colônias de Granulócitos/uso terapêutico , Idoso , Protocolos de Quimioterapia Combinada Antineoplásica/efeitos adversos , Doenças da Medula Óssea/induzido quimicamente , Cisplatino/administração & dosagem , Doxorrubicina/administração & dosagem , Esquema de Medicação , Feminino , Humanos , Masculino , Metotrexato/administração & dosagem , Pessoa de Meia-Idade , Estudos Prospectivos , Proteínas Recombinantes/uso terapêutico , Análise de Sobrevida , Resultado do Tratamento , Neoplasias da Bexiga Urinária/tratamento farmacológico , Vimblastina/administração & dosagemRESUMO
PURPOSE: Cisplatin and paclitaxel are active agents in advanced urothelial cancer. A phase II trial of this combination was performed to determine the activity and toxicity of these agents in a multi-institutional setting. PATIENTS AND METHODS: Fifty-two patients with advanced urothelial carcinoma were treated on one day with paclitaxel 175 mg/m(2) over 3 hours followed by cisplatin 75 mg/m(2), both intravenously, every 21 days. Cycles were repeated every 21 days until progression or a maximum of six cycles. RESULTS: Twenty-six patients obtained an objective response, for an overall response rate of 50% (95% confidence interval, 36% to 64%). Four patients achieved complete clinical responses. The median overall survival time for the group was 10.6 months. Toxicity was moderate, with granulocytopenia and neurotoxicity being the most common side effects noted. CONCLUSION: The combination of cisplatin and paclitaxel is active in advanced urothelial cancer. Responses in visceral, nodal, and soft tissues sites were observed. Granulocytopenia without fever and grade 2/3 neurotoxicity were common. The confidence interval of the overall response rate in this study overlaps most of the other reported regimens. The optimal therapy for advanced urothelial cancer remains undefined.
Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Carcinoma de Células de Transição/tratamento farmacológico , Cisplatino/uso terapêutico , Paclitaxel/uso terapêutico , Neoplasias Urológicas/tratamento farmacológico , Adulto , Idoso , Idoso de 80 Anos ou mais , Protocolos de Quimioterapia Combinada Antineoplásica/efeitos adversos , Cisplatino/administração & dosagem , Cisplatino/efeitos adversos , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Paclitaxel/administração & dosagem , Paclitaxel/efeitos adversos , Resultado do Tratamento , UrotélioRESUMO
One thousand four hundred sixty patients with 2,590 patient-years of follow-up were treated on 15 protocols for metastatic breast cancer with dibromodulcitol (mitolactol; DBD)-containing regimens since 1976. Twenty-three patients developed myelodysplastic syndrome (MDS) and/or acute nonlymphocytic leukemia (ANLL). The overall risk of developing MDS or ANLL per person is 1.6%. In patients who had received more than 16,000 mg of DBD the risk per person is 6%, and in the high-dose subsets of patients who received no prior radiation or alkylator therapy, it is 7.9%. The risk per person increases to a maximum by 30 to 36 months (5.3%). The high risk was seen despite a study population of metastatic breast cancer patients with a median survival of 16 months. This analysis strongly suggests that DBD is one of the most potent of the reported leukemogenic-inducing agents. Further use of this drug in both the adjuvant and metastatic situation should be reconsidered.
Assuntos
Neoplasias da Mama/tratamento farmacológico , Leucemia Mieloide Aguda/induzido quimicamente , Mitolactol/efeitos adversos , Síndromes Mielodisplásicas/induzido quimicamente , Adulto , Idoso , Humanos , Leucemia Mieloide Aguda/mortalidade , Pessoa de Meia-Idade , Síndromes Mielodisplásicas/mortalidade , RiscoRESUMO
PURPOSE: To assess the efficacy and toxicity of single-agent paclitaxel as first-line chemotherapy in patients with locally advanced or metastatic transitional-cell carcinoma of the urothelium. PATIENTS AND METHODS: Twenty-six eligible patients were enrolled onto this cooperative group study and treated with paclitaxel at a dosage of 250 mg/m2 by 24-hour continuous infusion every 21 days until progression or patient intolerance. All patients received recombinant human granulocyte colony-stimulating factor (rhG-CSF) at 5 micrograms/kg/d for at least 10 days during each cycle. RESULTS: Eleven of 26 patients (42%; 95% confidence interval [CI], 23% to 63%) demonstrated an objective response, with seven achieving a complete clinical response (CR) (27%; 95% CI, 12% to 48%) and four (15%) a partial response (PR). The median duration of response in the 11 responders is 7+ months (range, 4 to 17), with five responders (four CRs, one PR) remaining progression-free at 5, 6, 10, 12, and 16 months from the start of therapy. The estimated median survival duration for all patients is 8.4 months. Hematologic toxicity consisted of anemia (12% grade 3) and granulocytopenia (4% grade 3, 19% grade 4), with two patients developing granulocytopenic fevers. Nonhematologic toxicity included grade 3 mucositis in 11%, grade 3 neuropathy in 11%, and grade 4 diarrhea in 4%. CONCLUSION: Single-agent paclitaxel at this dosage and schedule is one of the most active single agents in previously untreated patients with advanced urothelial carcinoma, and is well tolerated by this patient population when given with hematopoetic growth factor support.
Assuntos
Carcinoma de Células de Transição/tratamento farmacológico , Paclitaxel/uso terapêutico , Neoplasias da Bexiga Urinária/tratamento farmacológico , Adulto , Idoso , Idoso de 80 Anos ou mais , Agranulocitose/induzido quimicamente , Anemia/induzido quimicamente , Carcinoma de Células de Transição/mortalidade , Carcinoma de Células de Transição/secundário , Feminino , Filgrastim , Fator Estimulador de Colônias de Granulócitos/uso terapêutico , Humanos , Infusões Intravenosas , Masculino , Pessoa de Meia-Idade , Paclitaxel/administração & dosagem , Paclitaxel/efeitos adversos , Proteínas Recombinantes/uso terapêutico , Trombocitopenia/induzido quimicamente , Neoplasias da Bexiga Urinária/mortalidade , Neoplasias da Bexiga Urinária/patologiaRESUMO
BACKGROUND: The primary objective of this study was to compare the effects of pomegranate juice on PSA doubling times (PSADT) in subjects with rising PSA levels after primary therapy for prostate cancer. METHODS: Double-blind, placebo-controlled multi-institutional study, evaluated the effects of pomegranate liquid extract on serum PSA levels. The primary end point of this study was change in serum PSADT. Additional secondary and exploratory objectives were to evaluate the safety of pomegranate juice and to determine the interaction of manganese superoxide dismutase (MnSOD) AA genotype and pomegranate treatment on PSADT. RESULTS: One-hundred eighty-three eligible subjects were randomly assigned to the active and placebo groups with a ratio of 2:1 (extract N=102; placebo N=64; juice N=17). The majority of adverse events were of moderate or mild grade. Median PSADT increased from 11.1 months at baseline to 15.6 months in the placebo group (P<0.001) compared with an increase from 12.9 months at baseline to 14.5 months in the extract group (P=0.13) and an increase from 12.7 at baseline to 20.3 in the juice group (P=0.004). However, none of these changes were statistically significant between the three groups (P>0.05). Placebo AA patients experienced a 1.8 month change in median PSADT from 10.9 months at baseline to 12.7 months (P=0.22), while extract patients experienced a 12 month change in median PSADT from 13.6 at baseline to 25.6 months (P=0.03). CONCLUSIONS: Compared with placebo, pomegranate extract did not significantly prolong PSADT in prostate cancer patients with rising PSA after primary therapy. A significant prolongation in PSADT was observed in both the treatment and placebo arms. Men with the MnSOD AA genotype may represent a group that is more sensitive to the antiproliferative effects of pomegranate on PSADT; however, this finding requires prospective hypothesis testing and validation.
Assuntos
Antineoplásicos Fitogênicos/uso terapêutico , Lythraceae/química , Extratos Vegetais/uso terapêutico , Antígeno Prostático Específico/sangue , Neoplasias da Próstata/sangue , Neoplasias da Próstata/tratamento farmacológico , Idoso , Antineoplásicos Fitogênicos/administração & dosagem , Antineoplásicos Fitogênicos/efeitos adversos , Terapia Combinada , Progressão da Doença , Humanos , Masculino , Adesão à Medicação , Pessoa de Meia-Idade , Gradação de Tumores , Estadiamento de Neoplasias , Extratos Vegetais/administração & dosagem , Extratos Vegetais/efeitos adversos , Polimorfismo de Nucleotídeo Único , Neoplasias da Próstata/genética , Neoplasias da Próstata/patologia , Superóxido Dismutase/genética , Resultado do TratamentoRESUMO
Patients with locally advanced prostate cancer present a significant therapeutic dilemma. Despite aggressive local therapies, including radical prostatectomy (RP), these patients are at high risk for biochemical failure. Several research groups have recently demonstrated the feasibility of hormonal and chemohormonal therapy before RP, but limited published data are available regarding the usefulness of chemotherapy without hormonal therapy in the neoadjuvant setting. At Cleveland Clinic Foundation, a phase II trial was initiated to evaluate a 6-week course of docetaxel, 40 mg/m(2) intravenously every 7 days, followed by RP in patients with locally advanced prostate cancer. RP was to be performed within 3 weeks of completion of neoadjuvant chemotherapy. The primary endpoint of this study is pathologic complete response. Preliminary toxicity data suggest that weekly docetaxel is well tolerated and does not increase the risk of perioperative or post operative complications. Reductions in prostate-specific antigen levels were noted in seven of 10 patients who completed the 6-week course of neoadjuvant docetaxel. The neoadjuvant use of investigational cancer therapies may allow for relatively rapid assessment of their antitumor activity.
Assuntos
Antineoplásicos Fitogênicos/uso terapêutico , Paclitaxel/análogos & derivados , Paclitaxel/uso terapêutico , Neoplasias da Próstata/tratamento farmacológico , Taxoides , Idoso , Docetaxel , Humanos , Masculino , Pessoa de Meia-Idade , Terapia Neoadjuvante , Prostatectomia , Neoplasias da Próstata/cirurgiaRESUMO
Paraneoplastic erythrocytosis in patients with Wilms' tumors is exceedingly rare, with only three reported cases in the literature. We report a case of a young man with Wilms' tumor with a significant erythrocytosis but a normal serum erythropoietin level and a tumor that elaborated erythropoietin.
Assuntos
Eritropoetina/biossíntese , Neoplasias Renais/complicações , Síndromes Paraneoplásicas/etiologia , Policitemia/etiologia , Tumor de Wilms/complicações , Adulto , Humanos , Neoplasias Renais/sangue , Masculino , Síndromes Paraneoplásicas/sangue , Policitemia/sangue , Tumor de Wilms/sangueRESUMO
OBJECTIVES: Metastatic prostate cancer remains a disease with no effective therapy. We treated 13 patients with hormone-refractory metastatic prostate cancer with 5-fluorouracil (5-FU) and alpha-2b interferon. Our objectives were to determine the response rate and toxicity of recombinant alpha interferon and 5-FU in patients with hormone-refractory metastatic prostate cancer. METHODS: Patients with progressive hormone-refractory metastatic prostate cancer with adequate hematologic and renal function underwent baseline bone scans, computed tomographic (CT) scans of abdomen and pelvis, and measurement of prostate-specific antigen (PSA). Therapy consisted of a 5-day loading course of 5-FU at 500 mg/m2 with alpha-2b interferon 9 million units subcutaneously 3 times weekly followed by weekly 5-FU and alpha interferon 3 times per week. RESULTS: When PSA was used as a response parameter with modified National Prostatic Cancer Project (NPCP) criteria, no objective responses were seen. Using NPCP criteria alone, 5 patients had stable disease. Post-therapy PSA values increased from baseline in 8 of 11 patients (2% to 72%) and declined in 3 patients (3% to 16%). Frequent dosage modifications were required with the dose intensity of 5-FU and alpha interferon of 57% and 58%, respectively. Toxicity was significant, with 31% of patients having grade 3 to 4 mucositis and 46% grade 3 to 4 fatique. CONCLUSIONS: 5-FU and alpha interferon, when administered at the dosage and schedule utilized in this study, have no clinically significant activity and are associated with unacceptable toxicity in patients with metastatic prostate cancer. The role of PSA as an indicator of response remains unclear.
Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Fluoruracila/uso terapêutico , Interferon-alfa/uso terapêutico , Neoplasias da Próstata/tratamento farmacológico , Idoso , Idoso de 80 Anos ou mais , Protocolos de Quimioterapia Combinada Antineoplásica/efeitos adversos , Neoplasias Ósseas/tratamento farmacológico , Neoplasias Ósseas/secundário , Esquema de Medicação , Resistência a Medicamentos , Fluoruracila/efeitos adversos , Hormônio Liberador de Gonadotropina/uso terapêutico , Hormônios/uso terapêutico , Humanos , Interferon alfa-2 , Interferon-alfa/efeitos adversos , Neoplasias Pulmonares/tratamento farmacológico , Neoplasias Pulmonares/secundário , Metástase Linfática , Masculino , Pessoa de Meia-Idade , Antígeno Prostático Específico/análise , Neoplasias da Próstata/patologia , Proteínas Recombinantes , Resultado do TratamentoRESUMO
OBJECTIVE: To identify a factor or factors that could predict response of muscle invasive transitional cell carcinoma of the bladder to neoadjuvant cisplatin, methotrexate, and vinblastine chemotherapy. METHODS: DNA ploidy analysis and immunohistochemical staining for p-glycoprotein (the product of the multidrug resistance gene, MDR-1) were performed on bladder biopsies obtained prior to chemotherapy. Radical cystectomy specimens were utilized for complete pathologic staging. RESULTS: Tissue was available for DNA ploidy analysis in 25 patients. Ten patients had complete responses to neoadjuvant chemotherapy and 15 patients did not respond. Nineteen patients had aneuploid tumors, of which 7 (37%) were complete responders. Six patients had diploid tumors, of which 3 (50%) were complete responders. This difference was not statistically significant. Tissue was available for immunostaining in 15 patients. Seven of 9 patients (78%) who did not respond to chemotherapy stained positively for p-glycoprotein, whereas 5 of 6 patients (83%) who had complete responses stained positively. This difference was not statistically significant. CONCLUSIONS: Neither DNA ploidy nor p-glycoprotein expression appears to predict successfully those patients likely to respond to neoadjuvant cisplatin, methotrexate, and vinblastine chemotherapy in the treatment of invasive bladder cancer.
Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Carcinoma de Células de Transição/tratamento farmacológico , Proteínas de Transporte/biossíntese , Glicoproteínas de Membrana/biossíntese , Proteínas de Neoplasias/biossíntese , Neoplasias da Bexiga Urinária/tratamento farmacológico , Membro 1 da Subfamília B de Cassetes de Ligação de ATP , Idoso , Idoso de 80 Anos ou mais , Carcinoma de Células de Transição/metabolismo , Carcinoma de Células de Transição/mortalidade , Carcinoma de Células de Transição/patologia , Proteínas de Transporte/genética , Quimioterapia Adjuvante , Cisplatino/administração & dosagem , DNA de Neoplasias/análise , Feminino , Humanos , Masculino , Glicoproteínas de Membrana/genética , Metotrexato/administração & dosagem , Pessoa de Meia-Idade , Invasividade Neoplásica , Proteínas de Neoplasias/genética , Ploidias , Valor Preditivo dos Testes , Indução de Remissão , Taxa de Sobrevida , Neoplasias da Bexiga Urinária/metabolismo , Neoplasias da Bexiga Urinária/mortalidade , Neoplasias da Bexiga Urinária/patologia , Vimblastina/administração & dosagemRESUMO
The utility of surgical resection of solitary metastatic sites in renal cell carcinoma remains controversial. Additionally, the small literature detailing the role of surgical management suggests that patients who have surgical resection of metachronous metastases have a better outcome than those presenting synchronously. We reviewed the medical records of all patients with metastatic renal cell carcinoma who underwent nephrectomy at the University of Iowa Hospitals and Clinics between 1980 and 1993. Patients who had undergone surgical resection of metastatic disease, either at presentation or subsequent to their nephrectomy, were identified. Clinical parameters, time to treatment failure, and survival was evaluated. Eighteen patients underwent surgical resection of metastases, 7 were synchronous to their nephrectomy, and 11 developed metachronous metastases. Resected lesions in both groups included metastases to lung, bone, liver, brain, and soft tissue. The median survival of all patients from time of resection to death or last follow-up was 5.7 years (range, 2 days to 10.7+ years). Two patients remain alive, both with recurrent disease at 5.3 and 10.7 years. Mean time from nephrectomy to death was 2.69 years for the synchronous group and 5.97 years for the metachronous group (p = 0.0599). The role of surgical resection in metastatic renal cell carcinoma remains unproven. The survival of this population is significantly longer than that typical for the disease. In our experience there is no difference in time to treatment failure or survival between synchronous and metachronous resection of metastatic disease.
RESUMO
The management of prostate and bladder cancer in the elderly will increasingly require clinicians to judge the impact on comorbidity and toxicity of the proposed therapy in order to make sound management decisions. As PSA-based screening has rapidly increased, physicians are increasingly challenged to decide the upper age limits for such screening and therapy. Bladder cancer management in the elderly differs little from that offered to the younger patient and the new therapeutic developments may improve the risk-to-benefit ratio of treating advanced disease. It is clear that as the US population ages, management of prostate and bladder cancer will become an increasingly common dilemma for the urologic practitioner.
Assuntos
Neoplasias da Próstata/cirurgia , Neoplasias da Bexiga Urinária/terapia , Fatores Etários , Idoso , Humanos , Masculino , Pessoa de Meia-Idade , Prostatectomia/métodosRESUMO
Patients with regionally advanced bladder cancer not considered candidates for definitive surgical intervention underwent continuous antegrade infusion of doxorubicin by percutaneous nephrostomy tube. Doxorubicin was administered for 7 consecutive days at a rate designed to achieve target urinary concentrations (range 5-80 micrograms/ml). Urine and serum concentrations of doxorubicin were monitored daily. Toxicity was assessed by serial renal scans, antegrade nephrostograms, blood counts, and serum chemistries. Patients were restaged after three cycles of therapy. In all, 23 cycles, constituting 156 days of therapy, were administered to 10 patients. Target urinary drug levels were achieved during all cycles. Total doxorubicin dose ranged from 125 to 2,500 mg. No systemic (neutropenia or myocardial dysfunction) or regional toxicity (extravasation, sepsis, stricture) was noted. Five of 10 patients tolerated the planned three treatment cycles. Poor performance status (PS, Eastern Cooperative Oncology Group: ECOG 3) strongly correlated with treatment intolerance and early death from disease. After three cycles of therapy, 2 of 5 evaluable patients had stable disease, I had radiographic partial response (PR) with a biopsy demonstrating extensive tumor necrosis, I had no identifiable tumor at the time of restaging transurethral resection of bladder tumor (TURBT), and a final patient with upper and lower tract carcinoma in situ (CIS) was cytologically staged NED. (no evidence of disease). These findings demonstrate the feasibility and low toxicity of this approach.