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/m² 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.

Purpose: Antiproliferative and antiosteoclastic activity from preclinical models show potential for dasatinib, an oral SRC and SRC family kinase inhibitor, as a targeted therapy for patients with prostate cancer. This phase II study investigated the activity of dasatinib in patients with metastatic castration-resistant prostate cancer (CRPC). Experimental Design: Chemotherapy-naive men with CRPC and increasing prostate-specific antigen were treated with dasatinib 100 or 70 mg twice daily. Endpoints included changes in prostate-specific antigen, bone scans, measurable disease (Response Evaluation Criteria in Solid Tumor), and markers of bone metabolism. Following Prostate Cancer Working Group 2 guidelines, lack of progression according to Response Evaluation Criteria in Solid Tumor and bone scan was determined and reported at 12 and 24 weeks. Results: Forty-seven patients were enrolled and received dasatinib (initial dose 100 mg twice daily, n = 25; 70 mg twice daily, n = 22), of whom 41 (87%) had bone disease. Lack of progression was achieved in 20 (43%) patients at week 12 and in 9 (19%) patients at week 24. Of 41 evaluable patients, 21 (51%) patients achieved ≥40% reduction in urinary N-telopeptide by week 12, with 33 (80%) achieving some level of reduction anytime on study. Of 15 patients with elevated urinary N-telopeptide at baseline, 8 (53%) normalized on study. Of 40 evaluable patients, 24 (60%) had reduction in bone alkaline phosphatase at week 12 and 25 (63%) achieved some reduction on study. Dasatinib was generally well tolerated and treatment-related adverse events were moderate. Conclusions: This study provides encouraging evidence of dasatinib activity in bone and reasonable tolerability in chemotherapy-naive patients with metastatic CRPC. (Clin Cancer Res 2009;15(23):7421–8)

BACKGROUND An every‐2‐week regimen of gemcitabine and paclitaxel was adapted for patients with advanced transitional cell carcinoma (TCC) who had received prior cisplatin‐based chemotherapy. METHODS Forty‐one patients with advanced or metastatic TCC who had received prior cisplatin‐based systemic chemotherapy were treated with an outpatient regimen of gemcitabine 2500–3000 mg/m² and paclitaxel 150 mg/m² every 2 weeks. RESULTS Forty of 41 patients had measurable disease. Response was observed in 24 patients (60%; 95% confidence interval [CI], 45–75%). Eleven (28%) achieved complete response, and 13 (33%) obtained partial response. Twenty of 25 patients (80%; 95% CI, 64–96%) who had been previously treated in the neoadjuvant or adjuvant setting responded versus 4 of 15 (27%; 95% CI, 5–49%) in patients who received prior methotrexate, vinblastine, doxorubicin, cisplatin (M‐VAC) for metastatic disease. The median duration of survival for patients given gemcitabine and paclitaxel after failing neoadjuvant or adjuvant M‐VAC was 12 months (range, 2–43+), as compared with only 8 months (range, 2–28) for patients who had been treated after failure of prior therapy for metastatic disease. For all patients, the median duration of response was 6.4 months (range, 2–43.3+ months), and the median survival was 14.4 months (range, 2–43+). Thirteen patients (32%) developed World Health Organization Grade 3–4 neutropenia, with febrile neutropenia in 3 (7%) patients. Granulocyte colony‐stimulating factor was given to 10 (24%) patients. There was no Grade 3–4 anemia or thrombocytopenia. CONCLUSIONS The combination of gemcitabine and taxol in previously treated patients with recurrent TCC is highly effective and produces objective durable responses. This every‐2‐week schedule is a well tolerated outpatient regimen with minimal toxicity. Cancer 2001;92:2993–8. © 2001 American Cancer Society.

BACKGROUND: Neoadjuvant chemotherapy for patients with muscle‐invasive bladder carcinoma is given to treat micrometastases and to preserve the bladder. The objective of this study was to evaluate the possibility of bladder preservation in patients with muscle‐invasive bladder carcinoma who were treated with neoadjuvant methotrexate, vinblastine, doxorubicin, and cisplatin (M‐VAC) chemotherapy.METHODS: One hundred four consecutive patients with T2–T4,N0,M0 transitional cell carcinoma of the bladder were treated with 3 cycles of neoadjuvant M‐VAC chemotherapy. After clinical restaging, 52 patients underwent transurethral resection of the bladder (TURB) alone, 13 patients underwent partial cystectomy, and 39 patients underwent radical cystectomy.RESULTS: The median survival for the entire group was 7.49 years (95% confidence interval, 4.86–10.0 years). Forty‐nine patients (49%) were T0 at the time of TURB after receiving M‐VAC. Thirty‐one of 52 patients (60%) who received chemotherapy and underwent TURB alone were alive at a median follow‐up of 56 + months (range, 10–160 + months): Twenty‐three patients (44%) in that TURB group maintained an intact bladder. Of 13 responding patients with monofocal lesions who underwent partial cystectomy, only 1 patient required salvage cystectomy, and survival generally was good. The 5‐year survival rate for this group was 69%. With a long median follow‐up of 88 + months (range, 16–158 months), 4 patients (31%) were alive with a functioning bladder. In the radical cystectomy group, the median follow‐up was 45 months (range, 4–172 + months), and 15 of 39 patients (38%) patients remained alive. In 77 patients who had their tumors down‐staged to T0 or superficial disease, the median follow‐up was 63 months (range, 4–172 + months), and the 5‐year rate survival was 69%. This is in contrast to a 5‐year survival rate of only 26% in 27 patients who failed to respond and had a status ≥ T2 after receiving chemotherapy (median follow‐up, 31 months; range, 7–156 + months). The median survival for 27 elderly patients (age ≥ 70 years; median age, 73 years; range, 70–82 years) was 90 months (7.5 years). For elderly patients who underwent TURB and partial cystectomy, the 5‐year survival rate was 67% with a 109‐month (9‐year) median survival; 47% of patients preserved their bladders intact. The median follow‐up of the living elderly patients was 61 months (range, 20–120 + months).CONCLUSIONS: Bladder sparing in selected patients on the basis of response to neoadjuvant chemotherapy is a feasible approach that should be confirmed in prospective, randomized trials. Selected elderly patients are candidates for this approach. Cancer 2003;97:1644–52. © 2003 American Cancer Society.DOI 10.1002/cncr.11232

Background: This randomized, phase II study assessed the activity of oblimersen sodium, a Bcl-2 antisense oligonucleotide, administered before docetaxel (Taxotere) to patients with castration-resistant prostate cancer. Patients and methods: Chemotherapy-naive patients with prostate-specific antigen (PSA) progression and testosterone ≤0.5 ng/ml received docetaxel 75 mg/m² on day 1 or oblimersen 7 mg/kg/day continuous i.v. infusion on days 1–7 with docetaxel 75 mg/m² on day 5 every 3 weeks for ≤12 cycles. Primary end points were confirmed PSA response (Bubley criteria) and major toxic events. Results: Confirmed PSA response was observed in 46% and 37% of 57 and 54 patients treated with docetaxel and docetaxel–oblimersen, respectively. Partial response (RECIST) was achieved in 18% and 24%, respectively. Oblimersen added to docetaxel was associated with an increase in the incidence of grade ≥3 fatigue, mucositis, and thrombocytopenia. Major toxic events were reported in 22.8% and 40.7% of patients with docetaxel and docetaxel–oblimersen, respectively. Conclusions: The primary end points of the study were not met: a rate of confirmed PSA response >30% and a major toxic event rate <45% were not observed with docetaxel–oblimersen.