Chemotherapy research for metastatic prostate cancer

Abstract

Declines in quality of life with early docetaxel treatment may be offset by long-term gains for men with metastatic hormone-sensitive prostate cancerIn 2004, docetaxel was recognized as the first agent to confer an overall survival (OS) benefit in men with metastatic prostate cancer; 1,2 however, docetaxel is also associated with known side effects that can diminish quality of life (QOL).3,4 The CHAARTED study, which showed an OS benefit of docetaxel in metastatic, hormone-sensitive prostate cancer, 5 also included global measures of QOL that account for disease-related symptoms, as well as treatment-related symptoms. Dr. Linda Patrick-Miller presented the QOL results from CHAARTED at ASCO 2016. 6 The 790 patients in CHAARTED who were randomly assigned to androgendeprivation therapy (ADT) plus docetaxel (n=397) or ADT alone (n=393) underwent QOL assessment at baseline, three, six, nine, and 12 months following randomization. Compared with those who received ADT alone, the patients who received the combination of ADT plus docetaxel had significantly worse overall QOL, as measured by Functional Assessment of Cancer Therapy-Prostate (FACT-P) scores, at three months (p=0.02); however, by Month 12, their FACT-P scores were significantly better (p=0.04). As expected, fatigue was significantly worse at three months in the docetaxel group, as measured by Functional Assessment of Chronic Illness Therapy-Fatigue (FACIT-F) scores (p<0.001); however, by six months, FACIT-F scores had returned to baseline and were no different from those who received ADT alone. FACT-Taxane scores were significantly worse in the docetaxel group at all time points, but Brief Pain Inventory (BPI) scores did not differ between the two groups at any time. Emotional well-being was significantly greater in the docetaxel group at all time points. Coupled with the OS benefit observed in metastatic hormone-sensitive prostate cancer, these results suggest that early docetaxel treatment offers a clinically meaningful benefit in men with newly diagnosed advanced prostate cancer.Intermittent docetaxel is non-inferior to continuous docetaxel treatment in one-year survival of men with metastatic castrate-resistant prostate cancer.Intermittent docetaxel treatment offers patients the benefit of a "treatment holiday" -reducing their overall exposure to docetaxel and cumulative toxicity, and potentially delaying resistance to taxanes.7 However, data on the noninferiority of intermittent vs. continuous docetaxel in men with castrate-resistant prostate cancer (CRPC) are lacking. The PRINCE study randomly assigned men with chemotherapy-naïve metastatic CRPC (mCRPC) to either intermittent (n=78) or continuous (n=78) treatment with docetaxel.8 Men in the intermittent treatment arm were started on a 12-week sequence of either four cycles given in a three-weekly regimen or three cycles in a weekly regimen, followed by a treatment holiday until disease progression. The continuous arm received docetaxel in either a three-weekly or weekly regimen until death. Patients in...

Unbiased Phenotype-Based Screen Identifies Therapeutic Agents Selective for Metastatic Prostate Cancer

“…Paclitaxel-based chemotherapy is frequently used to treat patients with metastatic prostate cancer who develop resistance to hormone deprivation therapy; however, they often succumb within months as a result of taxane resistance ( 9 ). Paclitaxel-resistant prostate cancer cells (PC-3TxR and DU-145TxR) responded to fenbendazole in a dose-dependent manner in vitro , but were refractory to paclitaxel treatment ( Figure 5A ).…”

“…The management of hormone refractory metastatic prostate cancer has been limited to palliation of symptoms due to a lack of effective treatments. Taxane-based chemotherapy has improved survival in some men with metastatic disease ( 8 , 9 ). Although most patients initially respond to docetaxel, the majority of these cancers eventually develop insensitivity, resulting in a more aggressive, chemotherapy-resistant disease ( 10 ).…”

Safety and Efficacy of First-Line Treatments for Chemotherapy-Naive Metastatic Castration-Resistant Prostate Cancer: A Systematic Review and Indirect Comparison

“…A total of 2533 potentially relevant articles were identified after the initial database search. After excluding 2510 articles not meeting inclusion criteria, 23 full-text articles which described 10 CTs, including 3 for docetaxel [ 10 – 12 ], 3 for sipuleucel-T [ 13 – 15 ], 1 for abiraterone [ 16 , 17 ], 1 for enzalutamide [ 18 , 19 ], 1 for mitoxantrone [ 20 ], and 1 for cabazitaxel [ 8 ], were included in the final analysis ( Figure 1 ). Agreement between the two researchers was 100% for quality assessment of included CTs.…”

“…Considering the goals of this research, only trials that used the dosages recommended by the EAU were included. A lower dose of cabazitaxel (20 mg/m 2 ) was included because efficacy was similar to a higher dose (25 mg/m 2 ) but with lower toxicity in one study [ 8 ].…”