RESUMO
Prostate cancer is the most frequent cancer amongst men. Until recently, only two therapeutic options, initial androgen-deprivation therapy in patients without castration-resistant prostate cancer, with addition of docetaxel when the disease becomes castration-resistant, were considered as standard. In the last years, new drugs (abiraterone, enzalutamide, Ra-223, Sipuleucel) have been developed for prostate cancer treatment with important advantages in safety and efficacy. Results from the recent Chaarted study, in patients that received docetaxel for the hormone sensitive disease, have contributed to change the initial treatment approach in metastatic prostate cancer, in order to adapt the best sequence for each patient. Those results have been supported by the Stampede trial. Stampede survival data showed not only a benefit in overall survival of adding docetaxel initially, but also a prolonged time to first skeletal related event. Now it is discussed in which setting the available drugs should be administered. This review article summarizes the treatment options for patients treated with docetaxel initially for hormone sensitive prostate cancer after developing progressive disease, and offers an algorithm proposal for treatment.
Assuntos
Neoplasias da Próstata/tratamento farmacológico , Antineoplásicos/uso terapêutico , Terapia de Reposição Hormonal , Humanos , Imunoterapia , Masculino , Orquiectomia , Neoplasias da Próstata/terapia , Compostos Radiofarmacêuticos/uso terapêuticoRESUMO
Enzalutamide (MDV3100), an androgen receptor-signalling inhibitor, represents the most recent compound added to the therapeutic armamentarium for the treatment of metastatic castration-resistant prostate cancer (mCRPC) who progressed to docetaxel. The anti-tumour activity and safety of enzalutamide has been demonstrated in a phase III clinical trial, showing a benefit in overall survival, which was the primary endpoint. There are no head-to-head studies comparing the different treatment options in this subset of patients. In this article, most relevant data published in the literature have been reviewed, with special attention to the therapeutic alternatives currently available for postdocexatel mCRPC patients, emphasising the mechanisms of action of the different drugs, efficacy and quality of life-related aspects.
Assuntos
Antagonistas de Receptores de Andrógenos/farmacologia , Antagonistas de Receptores de Andrógenos/uso terapêutico , Feniltioidantoína/análogos & derivados , Neoplasias de Próstata Resistentes à Castração/tratamento farmacológico , Animais , Antineoplásicos/farmacologia , Antineoplásicos/uso terapêutico , Benzamidas , Humanos , Masculino , Terapia de Alvo Molecular , Nitrilas , Feniltioidantoína/farmacologia , Feniltioidantoína/uso terapêutico , Neoplasias de Próstata Resistentes à Castração/metabolismoRESUMO
A 75-year-old-man, with a 2-month history of abdominal pain, underwent a standard diagnostic workup that included a CT scan that showed a large right renal mass and subcentimeter nodes in the right and left lung lobes. In December 2003, the patient underwent right nephrectomy with adrenalectomy and a diagnosis of renal cell carcinoma (pT3N0M0 stage) was made. No further treatment was proposed and patient was followed up regularly. In October 2006, the annual gastrointestinal endoscopy showed asymptomatic multilobulated and polypoid masses in the gastric fundus and gastric body that corresponded to metastasis of the renal carcinoma that had been resected three years ago. Surgical treatment was refused and oral treatment with sunitinib (50 mg/day consecutively for 4 weeks followed by 2 weeks off) was initiated. Patient completed one cycle and development of acute toxicity (grade 3 asthenia, anorexia and mucositis) led to treatment interruption. After recovering from acute toxicity, the patient was proposed to reinitiate treatment with dose reduction, but he refused any medical treatment. At the follow-up visit, three months later, the gastrointestinal endoscopy showed four unspecific 2 mm nodules without malignant evidence. The whole-body CT did not reveal any other abnormality except for the known lung nodes. PET scan six months after treatment confirmed complete gastric response.
Assuntos
Inibidores da Angiogênese/uso terapêutico , Carcinoma de Células Renais/secundário , Neoplasias Gastrointestinais/tratamento farmacológico , Neoplasias Gastrointestinais/secundário , Indóis/uso terapêutico , Neoplasias Renais/patologia , Inibidores de Proteínas Quinases/uso terapêutico , Pirróis/uso terapêutico , Adrenalectomia , Idoso , Carcinoma de Células Renais/cirurgia , Neoplasias Gastrointestinais/diagnóstico por imagem , Humanos , Neoplasias Renais/cirurgia , Masculino , Metástase Neoplásica , Nefrectomia , Radiografia , Sunitinibe , Resultado do TratamentoRESUMO
A 63-year-old male, ex-smoker since 2000 underwent left radical nephrectomy in June 2004 after being diagnosed with stage II, pT3bN0M0 clear cell carcinoma. In June 2006, a control CT showed a nodule in the superior lobe, on a peripheral location, and another nodule in the base of the right lung. The patient underwent atypical resections of both nodules, confirming the presence of metastatic disease. In August 2006 the patient started treatment with sunitinib (50 mg/day for 4 weeks, with 2 weeks of rest). A total of nine cycles were administered. Periodic monitoring showed good tolerance, only presenting grade 2 erythrodisesthesia and grade 2 thrombocytopenia. CT studies performed every three cycles showed no evidence of disease recurrence. The last cycle was administered in September 2007 and PET imaging confirmed the absence of recurrence. With the patients consent, treatment was interrupted and periodic radiological and clinical examinations were performed. The patient remained asymptomatic until March 2008 when a control CT revealed an objective progression of the disease at the left lung and mediastinum level. Treatment with sunitinib was restarted at the same doses, completing a total of three cycles, achieving a complete response. The patient is still under treatment.