A randomized, double-blind, placebo-controlled phase II study of maintenance therapy with tasquinimod in patients with metastatic castration-resistant prostate cancer responsive to or stabilized during first-line docetaxel chemotherapy.

BACKGROUND: This phase II study was conducted to assess clinical efficacy of tasquinimod maintenance therapy in patients with metastatic castrate-resistant prostate cancer not progressing during first-line docetaxel-based therapy. PATIENTS AND METHODS: Patients were randomly assigned (1 : 1) to receive tasquinimod (0.25-1.0 mg/day orally) or placebo. The primary end point was radiologic progression-free survival (rPFS); secondary efficacy end points included: overall survival (OS); PFS on next-line therapy (PFS 2) and symptomatic PFS, assessed using the Brief Pain Inventory (BPI) questionnaire and analgesic use. Quality of life was measured by the Functional Assessment of Cancer Therapy-Prostate (FACT-P) questionnaire and by the EuroQol-5 Dimension Quality of Life Instrument (EQ-5D). Adverse events were recorded. RESULTS: A total of 219 patients were screened and 144 patients randomized. The median duration of treatment was 18.7 weeks (range 0.6-102.7 weeks) for the tasquinimod arm and 19.2 weeks (range 0.4-80.0 weeks) for the placebo arm. Median (90% CI) rPFS was 31.7 (24.3-53.7) and 22.7 (16.1-25.9) weeks in the tasquinimod and placebo arms, respectively [HR (90% CI) 0.6 (0.4-0.9), P = 0.0162]. The median OS was not reached because only 14 deaths occurred by the cut-off date. No statistically significant differences between treatment arms were noted for symptomatic PFS, PFS 2, BPI score, FACT-P score, or EQ-5D. The incidence of any treatment emergent adverse event (TEAE) was similar in the tasquinimod and placebo arms (97.2% versus 94.3%, respectively), whereas severe TEAEs (NCI-CTC Grade 3-5) incidence was higher in the tasquinimod group (50.7% versus 27.1%). CONCLUSIONS: Randomized trials testing new drugs as maintenance can be successfully conducted after chemotherapy in castrate-resistant prostate cancer. Maintenance tasquinimod therapy significantly reduced the risk of rPFS by 40%. CLINICALTRIALS: gov identifier NCT01732549.

Antioxidative system parameters and level of IL-18 after surgery in patients with renal cell carcinoma according to gender.

Functions of the antioxidative system and cytokines are important factors that can influence the development of cancer. The aim of this study was to determine gender-related differences in the concentration of inflammatory cytokine IL-18 and alterations of antioxidative system parameters after surgical treatment of renal cell carcinoma patients. The study comprised 40 patients (22 women and 18 men). The level of peroxidation product malonodialdehyde (MDA), the status of the antioxidative system and the concentration of interleukin-18 (IL-18) were analyzed. A significant difference in the changes of antioxidative system reflecting parameters was observed according to the gender. In the male group with higher IL-18 concentration after surgery the level of MDA was lower, while in the women group it did not change and the level of catalase activity was higher; superoxide dismutase activity was higher in both groups. It is important to notice that our previous study (where the data were not analyzed in respect of gender) showed that the level of IL-18 was significantly higher after surgical treatment if MDA content was increased. More detailed studies are required to confirm in which cases association between IL-18 concentration and MDA level is related to cancer progression and in which cases - to the better prognosis depending on the patients' gender.