Mos Of Treatment Research Articles

A phase II trial of celecoxib in PSA recurrent prostate cancer after definitive radiation therapy or radical prostatectomy

4593 Purpose: COX-2 inhibitors have also been shown to have anti-neoplastic effects in a variety of tumor types including prostate cancer. This trial evaluated the efficacy of COX-2 inhibitor celecoxib in PSA-recurrent prostate cancer after radiation therapy (XRT) or radical prostatectomy (RP). Methods: 24 patients with rising PSA after definitive XRT (n=4) or RP (n=20) were treated with celecoxib at 400 mg/day (n=12) or 800 mg/day (n=12) (bid dosing). PSA levels were obtained at 3, 6, and 12 months after initiation of treatment. Data was evaluated by calculating 1) PSA doubling times (PSADT) and 2) slope of logPSA vs. time before and after celecoxib treatment at each time point. Testosterone levels were also obtained. Results: 22 of 24 (92%) patients had an inhibitory effect on their serum PSA after 3 mos of treatment: 8/24 had a decline and 3/24 had stabilization of their PSA. Of the remaining 13 patients, 11 had slowing of their PSADT - mean increase (i.e. slowing) in PSADT of 4.5-fold from pre-treatment. Only 2 patients (12%) had no initial change in their PSADT at 3 mos., yet both patients eventually showed increase of PSADT (2.2-fold and 4.0-fold) by 12 mos. Short-term responses at 3 mos. continued at 6 and 12 mos. of treatment. There was a significant shift of patients with rapid towards slower/stable PSADT at all time points (p = 0.008) (table). Comparison of rate of PSA rise before vs. after celecoxib treatment showed significant flattening of mean slope of logPSA vs. time from pre-treatment (1.48) vs. 3 mos. (0.09), 6 mos. (0.35) and 12 mos. (0.46) (p < 0.05 for each time point), There was no significant change in testosterone levels suggesting an androgen-independent mechanism. Conclusions: COX-2 inhibitors may decrease serum PSA levels in patients with biochemical progression after XRT or RP. These results suggest that COX-2 inhibitors may help delay disease progression in these patients. No significant financial relationships to disclose.

719 Doxifluridine in advanced colorectal carcinoma. Parallel multicentre randomized phase II trial

Doxifluridine (5-dFUR) is a fluoropyrimidine derivative with a better therapeutic index than FU (Bajetta, <i>Eur J Cancer</i>, 1993). This study independently evaluated the activity of two different schedules of oral or i.v. 5-dFUR plus levo-Ieucovorin. Between April 1993 and September 1994, a total of 130 untreated (in an adjuvant and metastatic setting) pts with measurable colorectal cancer were randomized to 5-dFUR 750mg/m² p.o. on days 1→4 and levo-leucovorin 25mg/dose p.o. two hours before 5-dFUR, repeated every 12 days (Arm A); or 5-dFUR 3000mg/m² as a one hour i.v. infusion for 5 consecutive days combined with levo-leucovorin 25mg/dose i.v. immediately before 5-dFUR every 21 days (Arm B). The first response evaluation was made after 2 mos of treatment. The two arms were well balanced in terms ofage (median 61 yrs, range 31–80), sex (M/F: 69/61) and disease extension. A preliminary intent-to-treat analysis was made of 126 adequately treated pts (4 too early to evaluate), of whom 67 were in Arm A and 59 in Arm B. The response rates were 15% in Arm A (2 CR, 8 PR, 29 SD, 28 PD) and 39% in Arm B (5 CR, 15 PR, 15 SD, 21 PD). Toxicity included WHO grade 3 and 4 diarrhea in respectively 16% and 7% of Arm A and 16% and 15% of Arm B respectively. Mucositis was mainly observed in Arm B (grade 3 in 13% and grade 4 in 1%). The preliminary data confirm the good tolerability profile of both the oral and the i.v. schedule. The oral route seems to be promising and is interesting, because it could be benefit for pts suitable for home treatment. Moreover, this study confirms the efficacy of i.v. doxifluridine as a fast line therapy in advanced colorectal cancer. <i>Data management by I.T.M.O. (ltalian Trials in Medical Oncology) Scietific Service</i>.