Optimizing the time of co-administration of docetaxel and samarium-153

New treatment modalities for androgene independent prostate cancer are warranted. Ongoing randomized studies are testing new chemotherapy drugs.

Citation: Proc Am Soc Clin Oncol 22: page 433, 2003 (abstr 1739)

Author(s): A. Widmark, T. Linne, H. Modig, L. Johansson; Department of RadiationSciences, Umea, Sweden; Aventis, Stockholm, Sweden

Abstract: New treatment modalities for androgene independent prostate cancer are warranted. Ongoing randomized studies are testing new chemotherapy drugs. A recent publication by Tu and co-workers in Lancet in 2001 indicates astonishing effect by the combination of radioisotope and chemotherapy. To further evaluate the combination of radioisotopes(153Sm; Quadramet) and chemotherapy (docetaxel; Taxotere) we have evaluated the optimal time frame for pre-treatment with, samarium-153,prior to the treatment with docetaxel (TAXAM). Six patients were included in a pilot study after informed concent. Six patients received afive weeks schedule of docetaxel 30 mg/m2 iv. 30 minutes weekly. 24 hours prior to the fourth week treatment with docetaxel, 37 MBq/kg ofsamarium was injected. Five of the 6 patients received a 2:nd cycle when progressing. We than studied the uptake and retention of samarium in the skeleton and metastasis with gamma-camera. Within three minutes after the injection the accumulation of the isotope in normal bone started to level off reaching a stable level after 10 minutes. The uptake of the radioisotope in the bone metastasis continued to increase and was doubled after 30 minutes. Eight hours after the injection, the concentration in bone metastasis was 3-4 times higher than in normalbone. This ratio was maintained during the evaluated time frame (7 days). The retention of samarium in soft tissue was negligible after 24 h. Five out of 6 patients responded with > 50% decrease in PSA. 3/5 reaching this level within three weeks. Four out of the six patients reached a PSA decline of >80% and four of them remained with > 50% decrease PSA more than six months. Toxicity was low, with only one episode of fever.To obtain a maximal radio sensitizing effect on tumor, while protecting normal tissue, the optimal time period between administration ofsamarium-153 and docetaxel is 8-24 hours. The response is promising, and a phase II study is in progress.