ANAHEIM, CA (UroToday.com) - This session dealt with aspects of systemic therapy of advanced disease. The impact of the PSA flare with docetaxel therapy was evaluated by Nelius and associates [ ABST 1010]. Eight patients from a treatment cohort of 74 were identified as demonstrating a PSA flare. Tumor progression and median survival did not differ in this group. A flare of 3-28.3% was noted during the 3-6 weeks into treatment yet 7 of 8 patients did demonstrate a >50 reduction in baseline PSA thereafter. These data suggested that while a PSA flare may occur in a subset of patients they should be continued on treatment for a minimum of 6 weeks. Additionally, co-administration of steroids with therapy may propogate a flare through androgen receptor mutation activity.

The combination of docetaxel and mitoxantron was described by Ohlmann and co investigators. 97 patients with androgen independent disease and asymptomatic PSA progression were enrolled in this phase II study [ABST 1011]. The mean age of the patients was 65.9 and mean PSA 182. 67% of patients had osseous metastases. Time to progression was 14.4 months (4-23 months) and mean survival was 17.6 months. Treatment associated side effects included neutropenia , and sepsis. Three deaths were observed. The data so far suggest that this is an active regimen.

The use of chemotherapy and adjuvant androgen blockade in radical prostatectomy patients with high risk of progression was described by DeLaTaille and associates [ABST 1012]. Patients received either docetaxel and androgen blockade for three years versus androgen blockade for three years. Patients received 100ng/m2 of paclitaxel once a week for 8 weeks. Data on 38 patients with a mean follow up of 6 months demonstrated undetectable PSAs in all patients. All patients receiving paxlitaxel experienced alopecia 4 patients demonstrated distal neuropathy. No hematologic side effects were noted. At this time is was noted that this combination is tolerable in this patient population. The protocol is ongoing.

In an adjuvant multimodal trial of androgen blockade, zolendronic acid and docetaxel in high risk patients after radical prostatectomy 25 patients underwent therapy and followed for a mean period of 20.5 months [Sahi, et al ABST 1013]. High risk was defined as a 70% chance of biochemical failure by the Kattan nomogram. Patients received one year of androgen deprivation, zoledronic acid at 4 mg evey 3 months and docetaxel at 75 mg/qm for 6 consecutive cycles. The regimen was well tolerated with level ¾ hematological toxicity in 12% of patients and GI toxicity in 20 percent of patients. At this time 20 percent of patients have experienced a biochemical failure with 3 of 5 patients demonstrating bone disease. Two cancer related deaths have occurred. The data demonstrate a lower than expected effect, with a 20% progression and 8% mortality rate.

The phase III SPARC trial was presented by Sartor and associates [ABST 1014]. 950 patients were accrued over 28 months. Patients had stage D2 disease and had failed 1 prior chemotherapy regimen. Treatment resulted in a 40% reduction in the risk of disease progression over placebo (HR 0.6; 95%CI 0.5-0.7, p<0.01). The progression free survival improvement was 13 percent (11 vs 9.7 weeks) reaching 89% in the 75th PFS percentile [36 vs 19 weeks]. Pain response was significantly greater in patients receiving satraplatin (24 vs 13.8 percent) as was PSA response (25% vs 12%). The most common toxicity was myelosupression and GI toxicities which were mild. The results of this phase III study demonstrate that oral satraplatin is well tolerated and has clinically relevant activity in patients with AIPC.

Smith and associates described and interim analysis of a phase III study evaluating the effectiveness of toremifene ( a synthetic estrogen receptor modulator; SERM) in increasing bone mineral density in men on ADT [ABST 1015]. In a 24 month prospective study 1392 men receiving ADT for at least 6 months received either toremifene citrate 80 mg daily or placebo. The the sub group of the first 197 patients, the treatment arm significantly increased bone mineral density of the lumbar spine, total hip and femoral neck compared to placebo. Loss of bone mineral density was seen at all sites for men on placebo. The degree of improvement noted has translated into fracture protection in women on SERMS. The full data set will be necessary before realizing the fracture benefit in this cohort of patients.

Wadhwa and associates investigated the impact of zoledronic acid administration to adequately treat bone loss for men receiving ADT by either LHRH agents or bicalutamide [ABST 1017]. Patients received 4mgZA iv every 3 months for a year. Bone mineral increase was improved by DEXA scan in all patients and in the bicalutamide patients in particular. 16% of patients had lumbar compression fractures at base line and this did not worsen. One patient experienced osteonecrosis of the mandible. After one year however a decline in BMD was noted suggesting that optimal dosage is somewhere between 3 and 12 months

UroToday.com Full Conference Reports

Written by S.Bruce Malkowicz, MD, a Contributing Editor with UroToday.

Please log-in or register in order to submit comments.

Powered by AkoComment!