RESUMO
PURPOSE: Interferons have shown a definite activity in the intravesical treatment of residual papillary bladder cancer or carcinoma in situ (CIS). The purpose of the present study was to investigate the efficacy of interferon alfa-2b (IFN) as prophylactic treatment of superficial bladder cancer. PATIENTS AND METHODS: Two hundred eighty-seven patients with primary pTa G2, pT1 G1 to G2 superficial bladder cancer, following complete transurethral resection (TUR), were randomly allocated to receive intravesical treatment, either with IFN (50 x 10(6) IU) or mitomycin (MIT-C; 40 mg). Drugs were instilled on a weekly basis for a total of 8 weeks. RESULTS: MIT-C was superior to IFN treatment with respect to time to recurrence, relative recurrence rate, recurrence rate per 100 patients per month, and recurrence tumor rate per 100 patients per month. This difference was particularly evident in patients with pTa G2 tumors. After multivariate analysis, the number of primary tumors and tumor grade were the best predictors of recurrence, while allocated treatment had only a moderate effect. Intravesical treatment was well tolerated in both arms. However, more local toxicity was experienced by patients treated with MIT-C. On the other hand, fever occurred significantly more frequently in patients treated with IFN. CONCLUSION: IFN was less effective, although locally better tolerated, than MIT-C as prophylactic treatment of primary superficial bladder cancer.
Assuntos
Carcinoma in Situ/tratamento farmacológico , Carcinoma Papilar/tratamento farmacológico , Interferon-alfa/uso terapêutico , Mitomicina/uso terapêutico , Recidiva Local de Neoplasia/prevenção & controle , Neoplasias da Bexiga Urinária/prevenção & controle , Administração Intravesical , Adulto , Idoso , Idoso de 80 Anos ou mais , Carcinoma in Situ/patologia , Carcinoma Papilar/patologia , Cistoscopia , Esquema de Medicação , Feminino , Humanos , Interferon alfa-2 , Interferon-alfa/administração & dosagem , Interferon-alfa/efeitos adversos , Masculino , Pessoa de Meia-Idade , Mitomicina/administração & dosagem , Mitomicina/efeitos adversos , Proteínas Recombinantes , Estatística como Assunto , Resultado do Tratamento , Neoplasias da Bexiga Urinária/patologiaRESUMO
Retinoids have shown a potential activity in preventing tumor recurrence in superficial bladder cancer. We assessed the activity of the synthetic retinoid fenretinide in superficial bladder cancer using DNA flow cytometry and conventional cytology as surrogate biomarkers. A total of 99 subjects with resected superficial bladder cancer (pTa, pT1) were randomized to either fenretinide (200 mg day p.o. for 24 months) or no intervention. Cystoscopy and bladder washing for DNA flow cytometry end points (proportion of DNA aneuploid histograms, hyperdiploid fraction, and percentage of apoptotic cells) and proportion of abnormal cytological examinations were repeated every 4 months for up to 36 months. The primary study end point was the proportion of DNA aneuploid histograms after 12 months. This figure was 48.9% in the fenretinide arm and 41.9% in the control arm (odds ratio, 1.16; 95% confidence interval, 0.44-3.07). There was no difference in any other response biomarker between the two groups up to 36 months, nor was any biomarker able to predict recurrence risk. Recurrence-free survival was comparable between the arms (27 events in the fenretinide arm versus 21 in the control arm; P = 0.36). Twelve subjects in the fenretinide arm complained of diminished dark adaptability, and nine subjects in the fenretinide arm versus one control subject had mild dermatological alterations. We conclude that fenretinide showed a lack of effect on the DNA content distribution and the morphology of urothelial cells obtained in serial bladder washings. Recurrence-free survival was comparable between groups. Because our data are hampered by the lack of predictivity of the selected biomarkers, additional studies are necessary to assess the activity of fenretinide in preventing bladder cancer.
Assuntos
Antineoplásicos/uso terapêutico , Biomarcadores Tumorais/análise , DNA de Neoplasias/genética , Fenretinida/uso terapêutico , Neoplasias da Bexiga Urinária/tratamento farmacológico , Neoplasias da Bexiga Urinária/genética , Idoso , Antineoplásicos/efeitos adversos , DNA de Neoplasias/análise , Intervalo Livre de Doença , Feminino , Fenretinida/efeitos adversos , Citometria de Fluxo , Humanos , Masculino , Pessoa de Meia-Idade , Recidiva Local de Neoplasia , Resultado do Tratamento , Bexiga Urinária/patologiaRESUMO
PURPOSE: The aim of this Phase II study was to determine a bladder-sparing treatment in patients with invasive bladder cancer, allowing a better quality of life. Objectives were to test toxicity and disease-free and overall survival of patients given an alternated chemo-radiotherapy definitive treatment. METHODS AND MATERIALS: Seventy-six patients with bladder cancer Stage T1G3 through T4 N0 M0 were entered in the same chemotherapy regimen (Cisplatin 20 mg/mq and 5-Fluorouracil 200 mg/mq daily for 5 days) alternated with different radiotherapy scheduling, the first 18 patients received two cycles of 20 Gy/10 fractions/12 days each; the second group of 58 patients received two cycles of 25 Gy/10 fractions/12 days each (the last 21 patients received Methotrexate 40 mg/mq instead of 5-Fluorouracil). RESULTS: A clinical complete response was observed in 57 patients (81%), partial response in 7 patients (10%), and a nonresponse in 6 patients (9%). At a median follow-up of 45 months, 33 patients (47%) were alive and free of tumor. The 6-year overall survival and progression-free survival was 42% and 40%, respectively. Systemic side effects were mild, while a moderate or severe local toxicity was observed in 14 patients and 13 patients (about 20%), respectively. CONCLUSION: Our conservative combination treatment allowed bladder-sparing in a high rate of patients and resulted in a survival comparable to that reported after radical cystectomy.
Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Neoplasias da Bexiga Urinária/tratamento farmacológico , Neoplasias da Bexiga Urinária/radioterapia , Adulto , Idoso , Vacina BCG/uso terapêutico , Quimioterapia Adjuvante , Cisplatino/administração & dosagem , Cistectomia , Intervalo Livre de Doença , Feminino , Fluoruracila/administração & dosagem , Humanos , Masculino , Pessoa de Meia-Idade , Metástase Neoplásica , Recidiva Local de Neoplasia/terapia , Seleção de Pacientes , Indução de Remissão , Terapia de Salvação , Neoplasias da Bexiga Urinária/cirurgiaRESUMO
A group of 73 patients with advanced renal cell carcinoma, treated in different phase II trials with interferon alpha and/or interleukin-2, have been evaluated to identify potential baseline prognostic factors predicting their survival. The eligibility criteria were very similar across studies and included ECOG performance status < or = 2, measurable or evaluable disease and no CNS metastases. The overall response rate was 8%. The overall survival was 33% at 2 years and 18% at 1 year. In the univariate analysis three prognostic factors were correlated with disease outcome: ECOG performance status (0 versus > or = 1), time from diagnosis to treatment (< or = 12 months versus > 12 months) and number of metastatic sites (1 versus > or = 2). Multivariate analysis identified ECOG performance status and number of metastatic sites as important prognostic factors for survival. The true impact on patient survival of the selection of patients rather than the treatment itself should be evaluated in controlled trials.
Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Carcinoma de Células Renais/terapia , Interferon-alfa/uso terapêutico , Interleucina-2/uso terapêutico , Neoplasias Renais/terapia , Adulto , Idoso , Feminino , Humanos , Interferon-alfa/administração & dosagem , Interleucina-2/administração & dosagem , Masculino , Pessoa de Meia-Idade , Valor Preditivo dos Testes , Prognóstico , Estudos RetrospectivosRESUMO
A total of 12 patients with completely resected, recurrent papillary tumors of the bladder were entered into a dose-finding study using intravesical idarubicin, a new anthracycline agent that has been shown in vitro to be more active than doxorubicin or daunorubicin, its parental compound. Patients were scheduled to receive eight weekly instillations with the following dose levels: 6.5, 12.5, and 20 mg, all of them diluted in 50 ml saline. Each dose level was initially studied in 3 patients. Dose escalation in the individual patients was not allowed so as to avoid undue toxicity and to evaluate the cumulative toxicity induced by each dose level. Overall, 4 patients were withdrawn due to severe local toxicity (chemocystitis) after a median of 2 instillations (range 1-3) and 3 more patients refused to continue treatment due to mild to moderate toxicity after a median of 4 instillations (range 2-4). Both the patients treated with 20 mg idarubicin and 2 of the 6 patients treated with 12.5 mg were withdrawn due to local toxicity. In contrast, no systemic toxicity was encountered at any dose level. We conclude that doses ranging from 6.5 to 12.5 mg and concentrations varying between 0.125 and 0.250 mg/ml are more appropriate for phase II studies, implying repeated instillations. At these doses and concentrations, however, it is unlikely that idarubicin might be more active than doxorubicin or epirubicin, whereas it might be more toxic.
Assuntos
Antibióticos Antineoplásicos/uso terapêutico , Idarubicina/uso terapêutico , Recidiva Local de Neoplasia/tratamento farmacológico , Neoplasias da Bexiga Urinária/tratamento farmacológico , Administração Intravesical , Idoso , Antibióticos Antineoplásicos/administração & dosagem , Antibióticos Antineoplásicos/efeitos adversos , Cistite/induzido quimicamente , Relação Dose-Resposta a Droga , Feminino , Humanos , Idarubicina/administração & dosagem , Idarubicina/efeitos adversos , MasculinoRESUMO
Urinary tract infections in 32 patients were treated with 250 mg of ciprofloxacin twice daily for seven to eight days. Clinical and laboratory examinations were performed before and after treatment. The infections were eradicated in 30 of the 32 patients. Ciprofloxacin was well tolerated by all patients.
Assuntos
Infecções Bacterianas/tratamento farmacológico , Ciprofloxacina/uso terapêutico , Infecções Urinárias/tratamento farmacológico , Adolescente , Adulto , Idoso , Criança , Ciprofloxacina/efeitos adversos , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Infecções Urinárias/microbiologiaRESUMO
Thirteen patients with progressive metastatic renal cell carcinoma were treated with circadian continuous Fluorodeoxyuridine (FUDR) infusions. The drug was delivered according to the variable rate infusion of Hrushesky protocol. All patients had previously received and failed systemic treatment and presented more than one metastatic site. The toxicity was low, however, no objective responses were observed. Despite previous reports of activity of FUDR in metastatic renal cancer, we suggest that the present regimen cannot be recommended in poor prognosis metastatic renal cancer.
RESUMO
Sixteen patients with metastatic renal cell carcinoma were treated with a combination of low-dose subcutaneous interleukin-2 (IL-2) and recombinant interferon (IFN)-alpha. One treatment course included 6 weeks of treatment followed by a 2-week rest. Patients received therapy as outpatients. All patients were assessable for toxicity and response assessment. Nine patients experienced severe toxicities resulting in dosage modification. The major treatment-limiting side effects were gastrointestinal, cutaneous, fever and flu-like symptoms. One patient (6%) had partial remission and six patients (37.5%) had disease stabilization. Overall median survival was 8 months. In our study IL-2 and IFN-alpha showed a low activity and a quite high toxicity. It seems that the prognostic factors per se rather than treatment options might impact the treatment results in advanced renal cancer patients.
Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Carcinoma de Células Renais/tratamento farmacológico , Neoplasias Renais/tratamento farmacológico , Adulto , Idoso , Protocolos de Quimioterapia Combinada Antineoplásica/efeitos adversos , Relação Dose-Resposta a Droga , Feminino , Humanos , Injeções Subcutâneas , Interferon Tipo I/administração & dosagem , Interleucina-2/administração & dosagem , Masculino , Pessoa de Meia-Idade , Prognóstico , Proteínas RecombinantesRESUMO
Twenty consecutive metastatic renal cell carcinoma patients were treated with a combination of recombinant alpha-2a interferon (18 X 10(6) U three times weekly) and vinblastine (0.1 mg/kg every 3 weeks). Two patients (10% response rate; 95% confidence limits 1.23-31.7%) achieved partial response and 11 (55%) stable disease. Toxicity was significant but always acceptable: most frequently, patients complained of fever and flu-like symptoms (18 of 19 patients), fatigue (18 of 19 patients), worsening in performance status (15 of 19 patients), and anorexia (15 of 19). The combination of recombinant alpha-2a interferon and vinblastine is active in renal cell carcinoma.
Assuntos
Carcinoma de Células Renais/terapia , Interferon gama/uso terapêutico , Neoplasias Renais/terapia , Vimblastina/uso terapêutico , Adulto , Idoso , Esquema de Medicação , Avaliação de Medicamentos , Sinergismo Farmacológico , Quimioterapia Combinada , Feminino , Humanos , Interferon gama/administração & dosagem , Interferon gama/efeitos adversos , Masculino , Pessoa de Meia-Idade , Metástase Neoplásica , Prognóstico , Proteínas Recombinantes/administração & dosagem , Proteínas Recombinantes/efeitos adversos , Proteínas Recombinantes/uso terapêutico , Indução de Remissão , Vimblastina/administração & dosagemRESUMO
Thirty-two patients with infiltrating bladder cancer were treated with transurethral resection followed by one course of alternating chemoradiotherapy before radical cystectomy (group A, 20 patients) or two courses as definitive procedure (group B, 12 patients). One course consisted of: cisplatin 20 mg/m2 i.v. and 5-fluorouracil 200 mg/m2 i.v. for 5 consecutive days, the first and the fourth weeks; radiotherapy 20 Gy in 10 fractions in the second and third weeks. At the seventh week the same integrated therapy was restarted in group B. All 32 patients were evaluable for toxicity after the first course: no grade IV toxicity was observed. Significant increase in hematological toxicity was observed in 12 patients who received the second course of chemoradiotherapy: two patients had grade IV toxicity, and five patients had grade III. Fifteen patients of group A underwent radical cystectomy: 40% had a pathological (p) complete response (CR) and 13.3% a partial response Five patients in group A did not receive either the second course of therapy or cystectomy because of age (three patients), vascular obliteration (one patient) and enteritis (one patient). Actuarial disease-free survival in group A is 78% at 21 months. All patients of group B obtained clinical (c) CR and all but one have no evidence of disease at a median follow-up of 10 months (range 6-13). The high pCR and cCR obtained in patients of group A and group B, respectively, appears promising. A longer follow-up and a larger number of patients is required to determine the role of this integrated treatment.
Assuntos
Carcinoma/terapia , Neoplasias da Bexiga Urinária/terapia , Adjuvantes Farmacêuticos/administração & dosagem , Adjuvantes Farmacêuticos/efeitos adversos , Adjuvantes Farmacêuticos/uso terapêutico , Idoso , Carcinoma/tratamento farmacológico , Carcinoma/radioterapia , Carcinoma/cirurgia , Cisplatino/administração & dosagem , Cisplatino/efeitos adversos , Cisplatino/uso terapêutico , Terapia Combinada , Esquema de Medicação , Quimioterapia Combinada , Feminino , Fluoruracila/administração & dosagem , Fluoruracila/efeitos adversos , Fluoruracila/uso terapêutico , Seguimentos , Humanos , Masculino , Pessoa de Meia-Idade , Dosagem Radioterapêutica , Indução de Remissão , Neoplasias da Bexiga Urinária/tratamento farmacológico , Neoplasias da Bexiga Urinária/radioterapia , Neoplasias da Bexiga Urinária/cirurgiaAssuntos
DNA de Neoplasias/análise , Fenretinida/uso terapêutico , Neoplasias da Bexiga Urinária/tratamento farmacológico , Adulto , Idoso , Idoso de 80 Anos ou mais , Adaptação à Escuridão/efeitos dos fármacos , Estudos de Viabilidade , Feminino , Fenretinida/efeitos adversos , Citometria de Fluxo , Humanos , Masculino , Pessoa de Meia-Idade , Projetos Piloto , Neoplasias da Bexiga Urinária/patologiaAssuntos
Carcinoma de Células Renais/tratamento farmacológico , Neoplasias Renais/tratamento farmacológico , Vimblastina/análogos & derivados , Adulto , Idoso , Antineoplásicos/uso terapêutico , Avaliação de Medicamentos , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Vimblastina/uso terapêutico , VinorelbinaAssuntos
DNA de Neoplasias/análise , Fenretinida/uso terapêutico , Citometria de Fluxo , Neoplasias da Bexiga Urinária/tratamento farmacológico , Neoplasias da Bexiga Urinária/patologia , Adulto , Idoso , Idoso de 80 Anos ou mais , Aneuploidia , Diploide , Estudos de Viabilidade , Feminino , Fenretinida/efeitos adversos , Seguimentos , Humanos , Masculino , Pessoa de Meia-Idade , Recidiva Local de Neoplasia , Projetos Piloto , Neoplasias da Bexiga Urinária/genéticaRESUMO
Objectives. The treatment of aggressive superficial TCC of the bladder remains controversial. In fact, although still classified as 'superficial', it has been shown that the biological characteristics of T1G3 bladder tumors are the same as those of the muscle-invasive group (T2 and above). Even with close monitoring and intensive intravesical therapy, the reported risk of muscle invasion in these patients is 53% and 1/3 die from this disease in the long-term. The aim of this study is to determine whether the timing of radical cystectomy affects the survival of patients with aggressive superficial bladder tumor. Methods. We consider 74 patients who underwent radical cystectomy between November 1994 and October 2006 before a diagnosis of T1G3 bladder tumor. These patients were divided in 2 subgroups: group A (n=27, 25 M and 2 F) who underwent immediate radical cystectomy, and group B (n=47, 40 M and 7 F) who underwent other conservative treatments before radical cystectomy. Results. The two subgroups were similar concerning age (66.29±8.37 yrs vs 66.87±8.6 yrs, respectively, p NS) and the timing of follow-up (respectively 77±45 vs 60±35 mths, p NS). Moreover, the progression-free survival was significantly higher in subgroup A (53.73±48.54 vs 31.94±35.19 mths, log-rank p<0.05) as well as the overall survival (59.73±45.37 vs 36.45±33.96 mths respectively, log-rank p<0.05). Comparing the histological examinations, the two subgroups were significantly different concerning the T stage (superficial tumors 14/27 vs 16/47, respectively, p<0.05; invasive tumors 13/27 vs 31/47, respectively, p<0.00005) and the lymphonodal dissemination (2N+/27 vs 11N+/47, respectively, p<0.0005). . Delaying radical cystectomy for aggressive superficial bladder tumors leads to a worse progression-free survival; the overall survival is likely to be due also to an early lymphonodal dissemination, which occurs extending the timing between diagnosis and radical treatment.
RESUMO
The authors report a case of successful extraction of renal cell carcinoma thrombus extending into the inferior vena cava and right atrium in a 36-year-old female patient using extracorporeal circulation, profound hypothermia and cardiac arrest.
Assuntos
Carcinoma de Células Renais/cirurgia , Cardiopatias/cirurgia , Trombose/cirurgia , Adulto , Carcinoma de Células Renais/diagnóstico por imagem , Ponte Cardiopulmonar , Feminino , Parada Cardíaca Induzida , Átrios do Coração/diagnóstico por imagem , Cardiopatias/diagnóstico por imagem , Humanos , Neoplasias Renais/diagnóstico por imagem , Neoplasias Renais/patologia , Invasividade Neoplásica , Radiografia , Trombose/diagnóstico por imagem , Veia Cava Inferior/diagnóstico por imagemRESUMO
BACKGROUND: A Phase II study with carboplatin, methotrexate, and vinblastine (CAMV) was conducted with patients who had advanced urothelial cancer to investigate the activity and toxicity of carboplatin when used in combination chemotherapy. METHODS: Thirty-six patients with advanced urothelial cancer were treated with carboplatin 300 mg/m2 (day 1), methotrexate 40 mg/m2 (days 1 and 8) and vinblastine 4 mg/m2 (days 1 and 8) every 4 weeks. Characteristics of the patients were as follows: men:women, 32:4; median age, 65 years (range, 42-76 years); and median Eastern Cooperative Oncology Group performance status, 0 (range, 0-2). Thirty-six patients were evaluable for toxicity and 33 for response. RESULTS: Objective responses (OR) were achieved in 13 patients: 2 were complete responses (CR) (6%) and 11 were partial responses (33.4%). Median duration of OR was 7 months (range, 3-27 months). Median duration of CR was 10 months (range, 4-27 months), and median survival time for patients achieving complete response was 30.5 months (range, 28-33 months). Patients with a pretreatment creatinine clearance greater than or equal to 50 ml/minute showed a higher response rate: 48% OR and 10% CR. Toxicity was evaluated (World Health Organization criteria) on 164 cycles and was generally mild. CONCLUSION: CAMV is an active and safe regimen in patients with advanced urothelial cancer, even in those with impaired renal function. It is recommended that future studies with this regimen be performed with pharmacokinetic modulation of carboplatin to improve the drug's tolerability and therapeutic activity.
Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Carboplatina/administração & dosagem , Carcinoma de Células de Transição/tratamento farmacológico , Metotrexato/administração & dosagem , Neoplasias da Bexiga Urinária/tratamento farmacológico , Vimblastina/administração & dosagem , Adulto , Idoso , Protocolos de Quimioterapia Combinada Antineoplásica/administração & dosagem , Protocolos de Quimioterapia Combinada Antineoplásica/efeitos adversos , Carboplatina/efeitos adversos , Carcinoma de Células Escamosas/tratamento farmacológico , Carcinoma de Células Escamosas/patologia , Carcinoma de Células Escamosas/secundário , Carcinoma de Células de Transição/patologia , Carcinoma de Células de Transição/secundário , Creatinina/urina , Feminino , Seguimentos , Humanos , Neoplasias Renais/tratamento farmacológico , Neoplasias Renais/patologia , Pelve Renal/patologia , Masculino , Metotrexato/efeitos adversos , Pessoa de Meia-Idade , Estadiamento de Neoplasias , Indução de Remissão , Neoplasias da Bexiga Urinária/patologia , Vimblastina/efeitos adversosRESUMO
PURPOSE: In order to select patients properly for a bladder preservation program, this retrospective study aimed to evaluate the predictive role of pretreatment- and treatment-related factors in a group of patients with invasive bladder cancer treated with alternating chemoradiotherapy at a single institution. METHODS AND MATERIALS: From 1986 to 1994, 72 patients with invasive bladder cancer, stages T1 poorly differentiated or T2-4M0 refusing surgery or not eligible for surgery, were treated with alternating chemoradiotherapy. Each patient had a pretreatment cystoscopy with an attempted complete transurethral resection of the bladder tumor (TURB). The treatment schedule consisted of chemotherapy (cisplatin, 5-fluorouracil, or methotrexate) alternated with radiotherapy. Over the years, the treatment schedule was modified with respect to the total number of chemotherapy cycles, the type of chemotherapy drugs, the dose per fraction and total dose of radiation therapy, and the presence of a planned treatment gap at midtreatment. Treatments were aligned in order of their received average relative dose intensities of both chemotherapy (ARDICT) and radiotherapy (RDIRT). RESULTS: Twenty-two patients (76%) developed infiltrative bladder recurrences for an estimated 5-year pelvic control rate of 68% +/- 6%; 5-year actuarial survival with intact bladder is 40% +/- 6%. Obstructive uropathy at diagnosis, residual disease after TURB, and ARDICT value equal or below the median were independent predictive factors for pelvic failure, with hazard ratios of 2.87 (95% confidence interval [CI], 1.16-7.04), 8.13 (95% CI, 2.74-24.1), and 3.36 (95% CI, 1.29-8.74), respectively. A more detailed model including interactions among these factors showed that the negative prognostic effect of obstructive uropathy at diagnosis was not modified by ARDICT or TURB resection; on the contrary, the risk of local failure for patients with incomplete TURB was markedly affected by different levels of ARDICT. Also, a trend toward a better local outcome was observed for patients with RDIRT above the median. Hydronephrosis and incomplete TURB were also independent predictors of distant metastases and overall survival, but no effect was found for ARDICT on these endpoints. DISCUSSION: As a result of this analysis we believe that (1) patients with obstructive uropathy should not be offered a bladder-sparing approach, (2) gross total TURB of the primary tumor should be maximized, (3) prompt surgery should be considered for patients with incomplete TURB who are not compliant with the combined-modality treatment, and (4) the intrinsic value of dose intensity of both chemotherapy and radiotherapy should be confirmed in a prospective, controlled study.
Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Neoplasias da Bexiga Urinária/tratamento farmacológico , Neoplasias da Bexiga Urinária/radioterapia , Adulto , Idoso , Cisplatino/administração & dosagem , Terapia Combinada , Relação Dose-Resposta a Droga , Relação Dose-Resposta à Radiação , Esquema de Medicação , Feminino , Fluoruracila/administração & dosagem , Humanos , Masculino , Metotrexato/administração & dosagem , Pessoa de Meia-Idade , Neoplasias Pélvicas/secundário , Valor Preditivo dos Testes , Modelos de Riscos Proporcionais , Estudos Retrospectivos , Resultado do TratamentoRESUMO
The ability of the synthetic retinoid N-(4-hydroxyphenyl)retinamide (4-HPR) to affect the outcome of previously resected superficial bladder cancer was investigated in a pilot study using DNA content flow cytometry and conventional cytology as intermediate endpoints. Twelve patients were treated with oral 4-HPR (200 mg daily) and compared with 17 non-randomized, untreated controls. The median interval between transurethral resection and 4-HPR administration was 5.5 months (range 0-36). The median follow-up period was 12 months (range 3-31) in the 4-HPR group and 9 months (range 2-22) in the control group. The proportion of patients with DNA aneuploid stemlines in bladder-washed cells decreased from 7/12 (58%) to 5/11 (45%) in the 4-HPR group, but increased from 7/17 (41%) to 10/17 (59%) in the control group. In patients with stable diploid profiles, mean (+/- SE) S-phase and G2+M-phase fractions decreased in the course of retinoid treatment from basal levels of 15.2 +/- 4.1% to 7.5 +/- 3.3% and 10.3 +/- 2.2% to 5.2 +/- 0.4%, respectively. The same parameters in the control group changed from basal levels of 14.6 +/- 3.4% to 12.4 +/- 2.7% and 9.8 +/- 1.6% to 12.6 +/- 1.6%, respectively. Positive or suspicious cytologic examinations were present in 3/12 (25%) treated cases prior to 4-HPR administration and all subsequently reverted to normal. The same parameter in the control group increased from 4/17 (24%) to 6/17 (35%) during follow-up. Impaired adaptation to darkness was recorded in 4 patients, and transient dermatologic alterations were observed in one-third of the patients, requiring dose reduction in one case.(ABSTRACT TRUNCATED AT 250 WORDS)
Assuntos
DNA de Neoplasias/análise , Fenretinida/uso terapêutico , Neoplasias da Bexiga Urinária/tratamento farmacológico , Adulto , Idoso , Idoso de 80 Anos ou mais , Feminino , Citometria de Fluxo , Humanos , Masculino , Pessoa de Meia-Idade , Invasividade Neoplásica , Projetos Piloto , Ploidias , Neoplasias da Bexiga Urinária/genética , Neoplasias da Bexiga Urinária/patologiaRESUMO
Bladder-washing-derived lymphocytes (BWDL) from 67 patients with bladder cancer were studied. The large majority of samples contained a pure population of T lymphocytes, whereas B and NK cells were absent. A comparative analysis of bladder lymphocytes and peripheral blood lymphocytes (PBL), collected in parallel, showed that BWDL significantly differed from PBL. In vitro cultures of bladder lymphocytes were attempted on 21 samples but in vitro expansion was only possible on six patients treated with bacillus Calmette-Guérin (BCG). This finding indicates that BWDL are characterized by a severe proliferative defect. Nevertheless, the addition of BCG on bladder lymphocytes expanded in vitro enhanced their proliferation, suggesting that this population is sensitized against BCG antigen(s). The analysis of T cell receptor restriction patterns showed that bladder lymphocytes from patients under BCG treatment were oligoclonal. A possible explanation for the efficiency of the immune response and good clinical outcome in patients treated with BCG could be found in the high homology between some BCG antigens and human heat-shock proteins, which are overexpressed in transformed cells.
Assuntos
Linfócitos/fisiologia , Neoplasias da Bexiga Urinária/patologia , Adulto , Idoso , Idoso de 80 Anos ou mais , Vacina BCG/farmacologia , Células Cultivadas , Epitopos , Humanos , Ativação Linfocitária , Subpopulações de Linfócitos , Linfócitos/efeitos dos fármacos , Linfócitos/imunologia , Pessoa de Meia-Idade , Fenótipo , Neoplasias da Bexiga Urinária/terapiaRESUMO
Although conventional cytology represents the most widely performed cytometric analysis of bladder cancer cells, DNA flow cytometry has, over the past decade, been increasingly used to evaluate cell proliferation and DNA ploidy in cells from bladder washings. We have investigated whether DNA flow cytometry and conventional cytology of epithelial cells obtained from bladder washings provide reliable surrogate endpoint biomarkers in clinical chemoprevention trials. We used cytometric and clinical data from a chemoprevention trial of the synthetic retinoid Fenretinide on 99 patients with superficial bladder cancer. A total of 642 bladder washing specimens obtained from the patients at 4 month intervals was analyzed. Intra-individual agreement and correlation of flow cytometric DNA ploidy (diploid vs. aneuploid), DNA Index, Hyper-Diploid-Fraction (proportion of cells with DNA content higher than 2C), and conventional cytologic examination, as assessed by kappa statistics and Spearman's correlation test, were poor from baseline through 24 months. Moreover, no correlation was found between DNA ploidy and cytology at each time point. The same results were obtained when the analyses were stratified by treatment group. In addition, the association between the results of bladder washing (by either DNA flow cytometry or cytology) and concomitant tumor recurrence was significant only for abnormal cytology, while neither biomarker was predictive of tumor recurrence at the subsequent visit. During the time of this study only four patients progressed to muscle-invasive bladder cancer, indicating the "low-risk" features of the patient population. We conclude that DNA flow cytometry and conventional cytology on epithelial cells obtained from bladder washings do not appear to provide suitable surrogate endpoint biomarkers during the early stages of bladder carcinogenesis.