RESUMO
BACKGROUND: Questions about optimal sequencing of systemic therapy in metastatic castration-resistant prostate cancer (mCRPC) and whether cross-resistance occurs between different drugs remain largely unanswered. Previous studies have produced conflicting data on the activity of docetaxel in patients who did not attain a prostate-specific antigen (PSA) response to abiraterone acetate (abiraterone). We investigated whether the biochemical response to abiraterone is associated with efficacy of subsequent docetaxel therapy. METHODS: mCRPC patients treated with docetaxel after abiraterone were retrospectively identified at three Canadian institutions. Patients who had also received docetaxel prior to abiraterone were termed "docetaxel-experienced," while those not treated with docetaxel prior to abiraterone were termed "docetaxel-naïve." Treatment outcomes on docetaxel were stratified by prior response to abiraterone and compared using χ(2) -square test for confirmed PSA response rate (≥ 50% decline from baseline maintained for ≥ 3 weeks) and the log-rank method for progression-free survival (PFS) and overall survival (OS). RESULTS: Eighty-six patients were treated with abiraterone, of whom 49 were docetaxel-experienced and 37 were docetaxel-naïve. Prior PSA response to abiraterone was no decline, <50% decline and ≥ 50% decline in 37%, 26%, and 37% of patients respectively. The overall PSA response rate to docetaxel was 34.9%, median PFS was 4.0 months and median OS was 11.66 months. Notably, no differences were seen in confirmed PSA response rates (38% vs. 36% vs. 31%, P = 0.86), median PFS (4.04 months vs. 3.94 months vs. 4.24 months, P = 0.43) and median OS (11.86 months vs. 15.38 months vs. 11.00 months, P = 0.56) on docetaxel for patients with no PSA decline, <50% decline and ≥ 50% decline on abiraterone respectively. Importantly, PSA response rates to docetaxel were comparable in the docetaxel-experienced and docetaxel-naïve cohorts and were not linked to prior response to abiraterone in either group. CONCLUSION: Activity of docetaxel was not associated with the biochemical response to prior abiraterone therapy. These data suggest that prior response to abiraterone should not influence decisions on subsequent use of docetaxel in mCRPC.
Assuntos
Androstenóis/uso terapêutico , Antineoplásicos/uso terapêutico , Inibidores das Enzimas do Citocromo P-450/uso terapêutico , Neoplasias de Próstata Resistentes à Castração/tratamento farmacológico , Taxoides/uso terapêutico , Idoso , Idoso de 80 Anos ou mais , Androstenos , Canadá , Intervalo Livre de Doença , Docetaxel , Humanos , Masculino , Pessoa de Meia-Idade , Antígeno Prostático Específico/sangue , Estudos Retrospectivos , Análise de Sobrevida , Resultado do TratamentoRESUMO
BACKGROUND: The activity of enzalutamide after prior treatment with both abiraterone acetate (abiraterone) and docetaxel has been examined in several retrospective studies. However, limited data are available on the efficacy of enzalutamide following abiraterone in chemotherapy-naive patients with metastatic castration-resistant prostate cancer (mCRPC). OBJECTIVE: To compare the activity of enzalutamide after abiraterone in docetaxel-experienced and docetaxel-naive mCRPC patients. DESIGN, SETTING, AND PARTICIPANTS: The British Columbia Cancer Agency Cancer Registry was searched for mCRPC patients who received enzalutamide after prior abiraterone. Clinicopathologic characteristics, confirmed prostate-specific antigen (PSA) response rates (PSA decline ≥ 50% confirmed ≥ 3 wk later), and survival data were collected. OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS: Outcomes on enzalutamide were compared between docetaxel-experienced and docetaxel-naive patients using chi-square for PSA response and log-rank test for time to PSA progression and overall survival (OS). Univariate analysis was performed to identify variables associated with confirmed PSA response on enzalutamide, using either chi-square for categorical variables or logistic regression for continuous variables. RESULTS AND LIMITATIONS: A total of 115 patients received enzalutamide after abiraterone: 68 had received prior docetaxel and 47 were docetaxel naive. Median time on enzalutamide was 4.1 mo. Confirmed PSA response rates (22% vs 26%; p=0.8), median time to radiologic/clinical progression (4.6 mo vs 6.6 mo; p=0.6), and median OS (10.6 mo vs 8.6 mo; p=0.2) did not differ significantly between docetaxel-experienced and docetaxel-naive patients. No clinical variables (including prior response to abiraterone) were found to associate significantly with confirmed PSA response to enzalutamide. CONCLUSIONS: Antitumour activity of enzalutamide following abiraterone was limited in mCRPC patients irrespective of prior docetaxel use. Identifying clinical and molecular factors predictive of response to enzalutamide remains a high priority for future research. PATIENT SUMMARY: We looked at the effectiveness of enzalutamide after abiraterone acetate for treatment of advanced prostate cancer. We found that patients who had received docetaxel chemotherapy before abiraterone gained similar benefit from enzalutamide compared with patients who had not received docetaxel. These results suggest that earlier treatment with docetaxel does not have a large impact on the activity of enzalutamide after abiraterone.
Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Neoplasias Ósseas/tratamento farmacológico , Neoplasias de Próstata Resistentes à Castração/tratamento farmacológico , Acetato de Abiraterona , Idoso , Idoso de 80 Anos ou mais , Androstenos/administração & dosagem , Benzamidas , Neoplasias Ósseas/secundário , Progressão da Doença , Docetaxel , Humanos , Metástase Linfática , Masculino , Pessoa de Meia-Idade , Nitrilas , Feniltioidantoína/administração & dosagem , Feniltioidantoína/análogos & derivados , Antígeno Prostático Específico/sangue , Neoplasias de Próstata Resistentes à Castração/sangue , Neoplasias de Próstata Resistentes à Castração/patologia , Taxa de Sobrevida , Taxoides/administração & dosagemRESUMO
INTRODUCTION: BLP25 liposome vaccine (L-BLP25) is an innovative therapeutic cancer vaccine designed to induce an immune response resulting in elimination of tumor cells expressing the MUC1 antigen, which is overexpressed in non-small-cell lung cancer (NSCLC). Manufacturing modifications have produced subtle changes to the lipid A acyl chain composition of L-BLP25. This open-label phase II study was conducted to evaluate the safety of the new formulation in patients with unresectable stage IIIA/IIIB NSCLC. PATIENTS AND METHODS: Twenty-two patients received L-BLP25 1000 µg every week for 8 weeks plus best supportive care. Maintenance vaccinations were given every 6 weeks, commencing at week 13, until disease progression. RESULTS: Median treatment duration was 9.9 months (range, 1-30 months), 9 patients remain on treatment, and 8 have received treatment for > 2 years. Fifteen patients (68%) had adverse events considered to be related to L-BLP25: these were all grade 1/2, except for 1 grade 3 event (pneumonia). The most common adverse events were injection-site reactions (bruising [23%], erythema [18%], pain [14%], fatigue [18%], and influenza-like illness [14%]). After a median follow-up of 26.7 months, the 1-year survival rate was 82% (95% CI, 66%-98%), and the 2-year survival rate was 64% (95% CI, 44%-84%). CONCLUSION: The results suggest that the new formulation of L-BLP25 has a safety profile similar to the original formulation and is safe to use in the phase III clinical development program.
Assuntos
Vacinas Anticâncer/efeitos adversos , Carcinoma Pulmonar de Células não Pequenas/terapia , Neoplasias Pulmonares/terapia , Glicoproteínas de Membrana/efeitos adversos , Idoso , Vacinas Anticâncer/administração & dosagem , Carcinoma Pulmonar de Células não Pequenas/imunologia , Carcinoma Pulmonar de Células não Pequenas/patologia , Progressão da Doença , Feminino , Seguimentos , Humanos , Lipossomos , Neoplasias Pulmonares/imunologia , Neoplasias Pulmonares/patologia , Masculino , Glicoproteínas de Membrana/administração & dosagem , Pessoa de Meia-Idade , Mucina-1/imunologia , Taxa de Sobrevida , Fatores de TempoRESUMO
OBJECTIVE: Efficacious regimens are needed for the treatment of metastatic bladder cancer. The aim of this study was to determine the toxicity and phase II dose of a triplet regimen of cisplatin, gemcitabine, and weekly docetaxel for patients with advanced transitional cell carcinoma. METHODS: Thirteen patients were enrolled to the study: 3 to dose level 1 (cisplatin 70 mg/m2 on day 1; gemcitabine 1000 mg/m2, day 1 and 8; and docetaxel 30 mg/m2, day 1 and 8, every 21 days), and 10 to dose level -1 (cisplatin 70 mg/m2 on day 1; gemcitabine 800 mg/m2, day 1 and 8; and docetaxel 30 mg/m2, day 1 and 8, every 21 days). RESULTS: Grade 3-4 hematologic toxicities included neutropenia (40%) and thrombocytopenia (20%). Grade 3 nonhematologic toxicity was restricted to diarrhea. There were 2 early deaths: 1 from a suspected pulmonary embolism and another from sepsis. In 11 patients who received > or =2 cycles the response rate was 73%. CONCLUSIONS: The recommended phase II dose of this triplet regimen in advanced transitional cell carcinoma is cisplatin 70 mg/m2 on day 1; gemcitabine 800 mg/m2 day 1 and 8; and docetaxel 30 mg/m2 day 1 and 8, repeated every 21 days. The preliminary objective response rate was high in this cohort of patients.