Docetaxel Versus Surveillance After Radical Prostatectomy for High-risk Prostate Cancer: Results from the Prospective Randomised, Open-label Phase 3 Scandinavian Prostate Cancer Group 12 Trial.

BACKGROUND: Adjuvant chemotherapy is standard treatment for other solid tumours, but to date has not proven effective in prostate cancer. OBJECTIVE: o evaluate whether six cycles of docetaxel alone improve biochemical disease-free survival after radical prostatectomy for high-risk prostate cancer. DESIGN, SETTING, AND PARTICIPANTS: Open-label, randomised multinational phase 3 trial. Enrolment of 459 patients after prostatectomy. INCLUSION CRITERIA: high-risk pT2 margin positive or pT3a Gleason score ≥4+3, pT3b, or lymph node positive disease Gleason score ≥3+4. Patients assigned (1:1) to either six cycles of adjuvant docetaxel 75mg/m2 every 3 wk without daily prednisone (Arm A) or surveillance (Arm B) until endpoint was reached. Primary endpoint was prostate-specific antigen progression ≥0.5 ng/ml. INTERVENTION: Docetaxel treatment after prostatectomy. RESULTS AND LIMITATIONS: Median time to progression, death, or last follow-up was 56.8 mo. Primary endpoint was reached in 190/459 patients-the risk of progression at 5 yr being 41% (45% in Arm A and 38% in Arm B). There was evidence of nonproportional hazards in Kaplan-Meier analysis, so we used the difference in restricted mean survival time as the primary estimate of effect. Restricted mean survival time to endpoint was 43 mo in Arm A versus 46 mo in Arm B (p=0.06), a nonsignificant difference of 3.2 mo (95% confidence interval: 6.7 to -1.5 mo). A total of 116 serious adverse events were recorded in Arm A and 41 in Arm B with no treatment-related deaths. Not all patients received docetaxel by protocol. The endpoint is biochemical progression and some patients received radiation treatment before the endpoint. CONCLUSIONS: Docetaxel without hormonal therapy did not significantly improve biochemical disease-free survival after radical prostatectomy. PATIENT SUMMARY: In this randomised trial, we tested whether chemotherapy after surgery for high-risk prostate cancer decreases the risk of a rising prostate-specific antigen. We found no benefit from docetaxel given after radical prostatectomy.

Weekly docetaxel and prednisolone versus prednisolone alone in androgen-independent prostate cancer: a randomized phase II study.

BACKGROUND: Due to its palliative effect and prostate-specific antigen (PSA) decrease, many clinicians have considered prednisolone monotherapy to be the standard systemic treatment in patients with androgen-independent prostate cancer (AIPC). This approach should be compared with docetaxel (Taxotere)+prednisolone. METHODS: A total of 109 eligible patients were entered into a randomized phase II study (arm A: Taxotere+prednisolone [30 mg m(-2) weekly during 5 of 6 wk+prednisolone 5 mg x 2 per os daily]; arm B: prednisolone [5 mg x 2 per os daily]). Biochemical response (confirmed > or = 50% PSA reduction of the baseline level at 6 wk) was the primary endpoint with subjective progression, quality of life, and progression-free and overall survival as secondary outcomes. RESULTS: Biochemical response at 6 wk was recorded in 29 of 54 evaluable patients in arm A (54%; 95% CI: 40-67%) and 13 of 50 patients in arm B (26%; 95% CI: 14-38%), with similar response rates at 12 wk and if based on all eligible patients. Median progression-free survival was 11 mo (95% CI: 5.8-16.2 mo) in arm A and 4 mo in arm B (95% CI: 2.4-5.6 mo). Median overall survival was 27 mo in arm A (95% CI: 19.8-34.1 mo) and 18 mo in arm B (95% CI: 15.2-20.8 mo). Pain relief and quality-of-life assessment indicated superiority of the arm A treatment, without unacceptable toxicity. CONCLUSION: Docetaxel+prednisolone should become the first-line systemic standard treatment for AIPC as a more effective treatment than prednisolone monotherapy. Weekly applications of docetaxel are well tolerated.

Liposomal doxorubicin (Caelyx) in symptomatic androgen-independent prostate cancer (AIPC)--delayed response and flare phenomenon should be considered.

BACKGROUND: Compared with the native drug, liposomal PEG-coated doxorubicin (Caelyx) enhances tumour activity and reduces toxicity. The formulation may therefore be beneficial in anthracycline-sensitive malignancies, where toxicity represents a major problem, as is the case in androgen-insensitive prostate cancer (AIPC). METHODS: In a multi-centre design 28 patients with advanced AIPC received Caelyx 40 mg/m2 as a 1-hour infusion every month. PSA-based biochemical and subjective response was recorded. RESULTS: Three patients had biochemical responses, a subjective response was recorded in a fourth patient. No Grade 4 toxicity was encountered. Three patients developed a spontaneously recovering plantar-palmar erythema. In 3 of the 4 responding patients, the nadir PSA value was noted after 12 and 16 weeks, respectively. A possible flare phenomenon for PSA was evident in 4 patients. CONCLUSION: Caelyx has limited activity in advanced AIPC. Due to its low toxicity profile the drug may be a worthwhile component of combination treatment of this chemotherapy-resistant condition. In general, clinicians should be aware of possible delay in PSA response as well as possible flare phenomenon during investigational systemic treatment of AIPC. Furthermore, standardization of blood sampling and PSA analyses are necessary in future therapeutic trials of AIPC.