Multinational, double-blind, phase III study of prednisone and either satraplatin or placebo in patients with castrate-refractory prostate cancer progressing after prior chemotherapy: the SPARC trial.

PURPOSE: This multinational, double-blind, randomized, placebo-controlled, phase III trial assessed the efficacy and tolerability of the oral platinum analog satraplatin in patients with metastatic castrate-refractory prostate cancer (CRPC) experiencing progression after one prior chemotherapy regimen. PATIENTS AND METHODS: Nine hundred fifty patients were randomly assigned (2:1) to receive oral satraplatin (n = 635) 80 mg/m(2) on days 1 to 5 of a 35-day cycle and prednisone 5 mg twice daily or placebo (n = 315) and prednisone 5 mg twice daily. Primary end points were progression-free survival and overall survival (OS). The secondary end point was time to pain progression (TPP). RESULTS: A 33% reduction (hazard ratio [HR] = 0.67; 95% CI, 0.57 to 0.77; P < .001) was observed in the risk of progression or death with satraplatin versus placebo. This effect was maintained irrespective of prior docetaxel treatment. No difference in OS was seen between the satraplatin and placebo arms (HR = 0.98; 95% CI, 0.84 to 1.15; P = .80). Compared with placebo, satraplatin significantly reduced TPP (HR = 0.64; 95% CI, 0.51 to 0.79; P < .001). Satraplatin was generally well tolerated, although myelosuppression and GI disorders occurred more frequently with satraplatin. CONCLUSION: Oral satraplatin delayed progression of disease and pain in patients with metastatic CRPC experiencing progression after initial chemotherapy but did not provide a significant OS benefit. Satraplatin was generally well tolerated. These results suggest activity for satraplatin in patients with CRPC who experience progression after initial chemotherapy.

Feasibility of quantifying the effects of epoetin alfa therapy on cognitive function in women with breast cancer undergoing adjuvant or neoadjuvant chemotherapy.

Impaired cognition, fatigue, and diminished quality of life (QOL) are commonly associated with breast cancer chemotherapy. This randomized, double-blind, placebo-controlled pilot trial assessed the feasibility of quantifying the effects of epoetin alfa on cognitive function and mood, and evaluated its effects on fatigue and QOL in patients with breast cancer treated with anthracycline-based adjuvant or neoadjuvant chemotherapy. Patients were randomized to receive epoetin alfa 40,000 U subcutaneously once weekly or placebo at the beginning of 4 cycles of chemotherapy administered over 12 weeks. Cognitive function was assessed by Executive Interview (EXIT25) and Clock Drawing Tasks; mood by Profile of Mood States; anemia-related symptoms, including fatigue, by the Functional Assessment of Cancer Therapy-Anemia (FACT-An) subscale; and QOL by Linear Analog Scale Assessment. Ninety-four patients were evaluable for efficacy and safety. Mean change in EXIT25 scores from baseline to cycle 4 in the epoetin alfa group was 1.3 +/- 3.3; the mean change was 0.3 +/- 2.4 in the placebo group (a negative change indicates improved executive function). There was no difference between groups in mean change in EXIT25 score from baseline to 6-month follow-up assessment. Mean hemoglobin levels were higher in the epoetin alfa group compared with the placebo group after 4 cycles of chemotherapy. Epoetin alfa recipients had less of a decrease in FACT-An subscale scores from baseline to cycle 4 and improvement in FACT-An subscale scores at 6-month follow-up assessment compared with placebo. Epoetin alfa therapy was well tolerated. These data suggest that epoetin alfa may have attenuated the cognitive impairment and fatigue that occurred during adjuvant breast cancer chemotherapy.

Once-weekly dosing of epoetin-alpha increases hemoglobin and improves quality of life in anemic cancer patients receiving radiation therapy either concomitantly or sequentially with chemotherapy.

BACKGROUND: The current study was performed to prospectively evaluate the effectiveness, clinical outcomes, and safety of once-weekly (QW) recombinant human erythropoietin (r-HuEPO [epoetin-alpha]) in anemic cancer patients with nonmyeloid malignancies who were receiving radiation therapy (RT) concomitantly or sequentially with chemotherapy (CT). METHODS: A total of 777 anemic patients (hemoglobin [Hb] < or = 11 g/dL) were enrolled in this multicenter, open-label, nonrandomized, 16-week study. Patients initially received epoetin-alpha at a dose of 40,000 units (U) subcutaneously QW, escalating to a dose of 60,000 U QW if the Hb increased to < or = 1 g/dL after 4 weeks. Endpoints were changes in hematologic and quality of life (QOL) parameters. RESULTS: Among the 442 patients evaluable for hematologic response, the mean increase in Hb from baseline to the time of final evaluation was 1.9 +/- 1.8 g/dL (P < 0.05). An increase in Hb of > or = 2 g/dL, in the absence of blood transfusions, occurred in 68.3% of patients (278 of 407 patients) who were on the study for > or = 30 days. The overall response rate (Hb increase > or = 2 g/dL or Hb > or = 12 g/dL in the absence of blood transfusions) was 74.0% (301 of 407 patients). In 359 patients who were evaluable for QOL assessment, epoetin-alpha therapy was found to significantly (P < 0.05) improve mean Linear Analog Scale Assessment (LASA) scores for energy level, ability to perform daily activities, and overall QOL from baseline to the time of final evaluation. QW epoetin-alpha therapy was found to be well tolerated. CONCLUSIONS: Treatment with QW epoetin-alpha was found to increase Hb levels, decrease transfusion requirements, and improve functional status and QOL in anemic patients with nonmyeloid malignancies who were receiving RT concomitantly or sequentially with CT. Clinical benefits and the safety profile of QW epoetin-alpha in this setting appear to be similar to those observed in anemic cancer patients receiving CT.