ABSTRACT
BACKGROUND: This multicentre, randomised, open label, phase II/III study aimed to investigate the potential benefit of adding risedronate (R) to docetaxel (D) in patients with metastatic Castration Resistant Prostate Cancer (CRPC). PATIENTS AND METHODS: CRPC patients with bone metastasis were randomly assigned to receive D 75 mg/m(2) every 3 weeks and prednisone as first line chemotherapy, with or without R 30 mg oral once daily. The primary end-point was time to progression (TTP). A composite end-point of objective progression by RECIST criteria, PSA progression, or pain progression, whichever occurred first, was applied. The study had 80% power to detect an improvement of 30% in median TTP in the DR group (two-sided α=0.05). RESULTS: Five hundred and ninety-two men (301 D versus 291 DR) were randomised. TTP was 7.4 [D] versus 6.5 [DR] months (p=0.75). PSA and pain response rates were similar, 66.3% [D] versus 65.9% [DR] and 27.9% [D] versus 31.2% [DR], respectively. Median overall survival (OS) was 18.4 [D] versus 19.2 [DR] months (p=0.33). There were no differences in toxicity. CONCLUSION: The addition of the third generation bisphosphonate, risedronate, in the setting of effective first line docetaxel based chemotherapy did not increase efficacy, as indicated by the lack of improvement in TTP, OS, PSA- and pain response.
Subject(s)
Androgen Antagonists/therapeutic use , Antineoplastic Agents, Phytogenic/administration & dosage , Antineoplastic Combined Chemotherapy Protocols/therapeutic use , Bone Neoplasms/drug therapy , Castration , Prostatic Neoplasms/drug therapy , Taxoids/administration & dosage , Aged , Aged, 80 and over , Antineoplastic Agents, Phytogenic/adverse effects , Antineoplastic Combined Chemotherapy Protocols/adverse effects , Bone Density Conservation Agents/administration & dosage , Bone Neoplasms/blood , Bone Neoplasms/mortality , Bone Neoplasms/secondary , Disease Progression , Docetaxel , Etidronic Acid/administration & dosage , Etidronic Acid/analogs & derivatives , Humans , Kaplan-Meier Estimate , Male , Middle Aged , Netherlands , Norway , Pain/prevention & control , Prednisone/administration & dosage , Proportional Hazards Models , Prostate-Specific Antigen/blood , Prostatic Neoplasms/blood , Prostatic Neoplasms/mortality , Prostatic Neoplasms/pathology , Prostatic Neoplasms/surgery , Risedronic Acid , Risk Assessment , Risk Factors , Taxoids/adverse effects , Time Factors , Treatment OutcomeABSTRACT
BACKGROUND: Delayed gastric emptying (DGE) is a main complication with unknown origin after a cytoreductive surgery and hyperthermic intra-peritoneal chemotherapy (CRS-HIPEC). The aim of this study was to investigate if preservation of the right gastro-epiploic artery (GEA) during standard omentectomy would have a positive effect on gastric emptying after CRS-HIPEC. METHODS: Forty-two patients subjected to a CRS-HIPEC were randomized into two groups perioperatively before performing an omentectomy: in Group I (N = 21) omentectomy was performed with preservation of the GEA; in Group II (N = 21) omentectomy was performed with resection of the GEA. The primary endpoint was the number of days to full oral intake of solid food. Secondary endpoints were number of days to intended occlusion of gastrostomy catheter and total hospital admission time. RESULTS: No significant differences were discovered between both groups in any of the study endpoints after CRS-HIPEC. No significant differences were observed in patient or operation characteristics between the randomized groups. CONCLUSIONS: No association was demonstrated between preservation of the gastro-epiploic artery during omentectomy and gastric emptying after CRS-HIPEC. The extensive intestinal manipulation or the heated intra-peritoneal chemotherapy during surgery are more plausible causes of this phenomenon. This clinical trial was registered in the Netherlands at the Central Committee on Research involving Human Subjects (CCMO) under registration number P06.0301L.
