Addition of docetaxel to hormonal therapy in low- and high-burden metastatic hormone sensitive prostate cancer: long-term survival results from the STAMPEDE trial.

BACKGROUND: STAMPEDE has previously reported that the use of upfront docetaxel improved overall survival (OS) for metastatic hormone naïve prostate cancer patients starting long-term androgen deprivation therapy. We report on long-term outcomes stratified by metastatic burden for M1 patients. METHODS: We randomly allocated patients in 2 : 1 ratio to standard-of-care (SOC; control group) or SOC + docetaxel. Metastatic disease burden was categorised using retrospectively-collected baseline staging scans where available. Analysis used Cox regression models, adjusted for stratification factors, with emphasis on restricted mean survival time where hazards were non-proportional. RESULTS: Between 05 October 2005 and 31 March 2013, 1086 M1 patients were randomised to receive SOC (n = 724) or SOC + docetaxel (n = 362). Metastatic burden was assessable for 830/1086 (76%) patients; 362 (44%) had low and 468 (56%) high metastatic burden. Median follow-up was 78.2 months. There were 494 deaths on SOC (41% more than the previous report). There was good evidence of benefit of docetaxel over SOC on OS (HR = 0.81, 95% CI 0.69-0.95, P = 0.009) with no evidence of heterogeneity of docetaxel effect between metastatic burden sub-groups (interaction P = 0.827). Analysis of other outcomes found evidence of benefit for docetaxel over SOC in failure-free survival (HR = 0.66, 95% CI 0.57-0.76, P < 0.001) and progression-free survival (HR = 0.69, 95% CI 0.59-0.81, P < 0.001) with no evidence of heterogeneity of docetaxel effect between metastatic burden sub-groups (interaction P > 0.5 in each case). There was no evidence that docetaxel resulted in late toxicity compared with SOC: after 1 year, G3-5 toxicity was reported for 28% SOC and 27% docetaxel (in patients still on follow-up at 1 year without prior progression). CONCLUSIONS: The clinically significant benefit in survival for upfront docetaxel persists at longer follow-up, with no evidence that benefit differed by metastatic burden. We advocate that upfront docetaxel is considered for metastatic hormone naïve prostate cancer patients regardless of metastatic burden.

Which bowel preparation is best? Comparison of a high-fibre diet leaflet, daily microenema and no preparation in prostate cancer patients treated with radical radiotherapy to assess the effect on planned target volume shifts due to rectal distension.

OBJECTIVE: We evaluated and compared a high-fibre diet leaflet, daily microenema and no preparation to establish how best to achieve consistent bowel preparation in prostate cancer patients being treated with radical radiotherapy. METHODS: 3 cohorts of 10 patients had different dietary interventions: no bowel preparation, high-fibre diet information leaflet and daily microenemas. The available cone beam CT (CBCT) scans of each patient were used to quantify interfractional changes in rectal distension (measured using average cross-sectional area-CSA), prostate shifts relative to bony anatomy compared with that at CT planning scan and rates of geometric miss (i.e. shifts of ≥5 mm). 85 CBCT scans were available in the pre-leaflet cohort, 89 scans in the post-leaflet, and 89 scans in the post-enema group. RESULTS: Mean rectal CSA in the post-enema group was reduced compared with both pre-leaflet (p=0.010) and post-leaflet values (p=0.031). The magnitude of observed mean prostate shifts was significantly reduced in the post-enema group compared with the pre-leaflet group (p=0.014). The proportion of scans showing geometric miss (i.e. shift >5 mm) in the post-enema group (31%) was significantly lower than in the pre-leaflet (62%, p<0.001) or post-leaflet groups (56%, p<0.001). CONCLUSION: This study indicates microenema to be an effective measure to achieve reduction in rectal CSA, prostate shift and reduce geometric miss of ≥5 mm. A further prospective randomised study is advocated to validate the results. ADVANCES IN KNOWLEDGE: The use of microenema is effective in reducing prostate shift and rectal CSA, consequently decreasing the incidence of geographical miss.

Long-term results of a phase II study of synchronous chemoradiotherapy in advanced muscle invasive bladder cancer.

We conducted a phase I/II study investigating synchronous chemoradiotherapy with mitomycin C and infusional 5-fluorouracil (5-FU) in muscle invasive bladder cancer. Early dose escalation results were previously published. We report the long-term toxicity and efficacy results with the optimised regimen. Patients with muscle invasive bladder cancer with glomerular filtration rate >25 ml min(-1) were eligible. Mitomycin (12 mg m(-2) on day 1 only) and infusional 5-FU (500 mg m(-2) day(-1)) for 5 days were administered during weeks 1 and 4 of radiotherapy of 55 Gy in 20 fractions. A total of 41 patients were enrolled, median age was 68 years, 33 were male and eight female patients. Out of the 41 patients, 20 (49%) had hydronephrosis at presentation and 25 (62%) had T3b or T4 disease. Four patients experienced Grade III thrombocytopenia and three patients had Grade III neutropenia. There were no episodes of febrile neutropenia. Four patients experienced Grade III diarrhoea and 1 Grade III urgency and dysuria. Six patients did not undergo cystoscopic evaluation due to early metastatic spread although there was no clinical suggestion of bladder failure. In all, out of 35 evaluable patients, 25 (71%) had macroscopic complete response at 3-month cystoscopy, and biopsy confirmed in 24 out of 25. A total of 16 (39%) patients remain alive with a median follow-up of 50.7 (range 23.5-68.8) months, 14 with a functioning bladder with no reported long-term treatment-related bladder or bowel toxicity. Five out of 41 patients have undergone salvage cystectomy: two for persistent CIS, two T1 and one muscle invasive recurrence. Four patients have received intravesical chemotherapy, of whom two remain alive with a functioning bladder. Overall 12-, 24- and 60-month (m) survival rates were 68, 49 and 36%. Local and distant progression free rates were 82 and 86% at 12-m and 79 and 75% at 24-m. Organ preservation using multimodality therapy is feasible and safe, even in patients with poor renal reserve, and does not compromise salvage therapies. A national phase III trial BC2001 (www.bc2001.org.uk) exploring the effects of synchronous chemoradiotherapy with this regimen is currently recruiting.

Favourable outcome in a patient with central nervous system lupus.

We report a case of paediatric lupus who during her admission developed near fatal central nervous system complication of status eilepticus with respiratory paralysis and was managed with intravenous immunoglobulins, extended course of methyl prednisolone with a favourable outcome.