Estramustine plus docetaxel as second-line therapy in patients with hormone-refractory prostate cancer resistant to docetaxel alone

Objective: Although docetaxel (DOC) plus prednisone is currently the treatment of choice for hormone-refractory prostate cancer (HRPC), no standard therapy is available for those patients who progress during DOC treatment. The aim of this study was to evaluate whether the addition of estramustine (E) can overcome DOC resistance. Methods: Patients who had not responded to DOC in a previous randomised phase II trial received a one-hour intravenous infusion of DOC 70 mg/m(2) on day 2 in combination with oral E 840 mg/day divided into three daily administrations on days 1-5. The primary endpoint was a >50% decrease in PSA; the secondary endpoints were biochemical progression-free survival, overall survival, the objective response rate, and toxicity. Results: A biochemical response was observed in 52% of the 25 patients evaluable for response. The only grade 4 event was a cerebral stroke that occurred a few days after the administration of the first treatment course. Treatment discontinuation due to worsened compliance was observed in the patients who received a higher cumulative number of courses. Conclusions: Our findings suggest that the addition of E may be useful in selected HRPC patients resistant to DOG alone

Predictive value of PSA halving index (PSAHI) in patients (pts) with hormone refractory prostate cancer (HPRC): Results from a randomized phase II trial with docetaxel (D) ± estramustine phopshate (E)

15548 Background: D-based chemotherapy represents the standard treatment for HRPC pts. For several years PSA has been considered as a surrogate endpoint for studies involving pts with HRPC. The possibility of predicting a clinical advantage through the biochemical response rate is controversial. The PSAHI may represent a predictive parameter more than the simple PSA trend. We retrospectively evaluated the role of PSAHI in a consecutive series of patients affected by HRPC and treated in a randomized phase II trial with D±E. Methods: 95 pts affected by HRPC were randomized to D 70 mg/m2 IV d1 q3w (arm A: 49 pts) or D 70 mg/m2 IV d1 q3w + E 280 mg/TID PO starting 1 day prior to D, for 5 consecutive days (arm B: 46 pts). The treatment continued until best PSA response achievement or PSA progression. PSAHI was calculated comparing basal value (the day before first D administration) with those reached after every cycle at 21, 42, 63 and 84 days: each median value was then correlated across all pts. Correlations were made with response, time to progression (TTP) and overall survival (OS). Results: Responses, in terms of PSA? &gt;50% were: 40% in arm A and 75%in arm B with PSA normalization in 5% and 32% respectively. After a median follow-up of 17 months, 65 patients are died (31 in Arm A and 34 in Arm B). Progression free survival (biochemical) was 20 weeks in arm A and 30 in B. Median PSAHI was 2.1 (0.8–8.8) and resulted significantly related to response and TTP: pts with PSAHI less than 1 and more than 1 had a median TTP of 14 and 34 weeks respectively. Between the 4 PSAHI analyzed (after 21, 42, 63 and 84 day), those at 42 and, particularly, 63 day resulted statistically related to response, TTP and OS. After 3 cycles, the PSA decline (63-PSAHI) was highly predicyive of OS which was 63, 72 and 90 weeks respectively (p=0.03), for pts with PSAHI of less than 1, between 1 and 3 and more than 3. Conclusions: PSAHI seems to be highly predictive of TTP and OS. 63-PSAHI seems to be a good surrogate marker of D response and may help in discriminating pts who need to be further treated with D and those who do not. No significant financial relationships to disclose. </jats:p

Docetaxel (D) and estramustine (E) as first-line chemotherapy for patients (pts) with hormone-refractory advanced prostate cancer (HRPC): Final results of a multicentric phase II randomized trial

15552 Background: Preclinical data showed a synergism between E and D and several studies supported an advantage in associating E and D. Nevertheless, D is considered a standard treatment for HRPC pts and the role of D+E combination remains controversial. Purpose of this study was to evaluate the activity, in terms of PSA decline (PSA↓), the safety and quality of life (QoL) of D±E in HRPC pts. Methods: Eligibility criteria included: HRPC diagnosis, hormone-refractory advanced disease (PSA progression after at least two hormonal therapy), ECOG PS &lt; 2, adequate renal, hepatic and hematological functions, no prior chemotherapy. Pts were randomized to D 70 mg/m2 IV d1 q3w (arm A) or D 70 mg/m2 IV d1 q3w + E 280 mg/TID PO starting 1 day prior to D, for 5 consecutive days (arm B). The treatments were planned until best PSA response achievement or PSA progression. Toxicity was recorded according to NCIC criteria. Qol was assessed by self-filled questionnaires during the treatment. Results: Between 04/2003 and 09/2005, 95 pts (median age 69 years, range 48–86, median PSA 80 ng/ml, range 5–2,166 and measurable disease in 45) were randomized to arm A (49) or arm B (46). In arm A, pts received 321 cycles (median 6, range 0–28) with only 13 (4 %) delays = 7 days. In arm B, pts received 338 cycles (median 7, range 0–20) with only 16 (4.7%) delays. Grade 3–4 hematological toxicities consisted of neutropenia, 4% in arm A and 6% in B. One pt in arm B had febrile neutropenia and grade 3 diarrhea. Grade 3–4 non-hematologic toxicities were vomiting (1 pt in both arms), stomatitis (1 pt in arm A and 2 pts in B) and diarrhoea (1 pt in arm B). Two cases of stroke were reported in arm A. No treatment related death was recorded. Responses, in terms of PSA↓ &gt;50% were: 40% in arm A and 75%in arm B with PSA normalization in 5% and 32% respectively. After a median follow-up of 17 months, 65 patients are died (31 in Arm A and 34 in Arm B). Progression free survival (biochemical) was 20 weeks in arm A and 30 in B. Conclusions: D-based regimens are active in HRPC with a manageable toxicity profile. From this preliminary data, DE combination appears promising, in terms of activity and tolerability so, front-to-front formal comparison in a phase III trial can be recommended. No significant financial relationships to disclose. </jats:p

A multicentric phase II randomized trial of docetaxel (D) plus estramustine (E) versus docetaxel (D) as first line chemotherapy for patients (pts) with hormone-refractory advanced prostate cancer (HRPC)

4625 Background: D is presently considered a standard treatment for HRPC pts. E has shown a synergistic activity with D in vitro, however the role of D+E combination remains to be defined in the clinical practice. We attempted to evaluate the activity, in terms of PSA decline (PSA↓), the safety and quality of life (QoL) of D ± E in HRPC pts. Methods: eligibility criteria were: HRPC diagnosis, hormone-refractory advanced disease (PSA progression after at least two hormonal therapy), ECOG PS ≤ 2, adequate renal, hepatic and hematological functions. Pts were randomized to D 70 mg/m2 IV d1 q3w (arm A) or D 70 mg/m2 IV d1 q3w + E 280 mg/TID PO starting 1 day prior to D, for 5 consecutive days (arm B). The treatments were planned until best PSA response achievement or PSA progression. No anticoagulant prophylaxis was planned in ARM B pts. Qol was assessed by self-filled questionnaires during the treatment. Results: Between 04/2003 and 09/2005, 95 pts (median age 69 years, range 48–86, median PSA 80 ng/ml, range 5–2166 and measurable disease in 45) were randomized to arm A (49) or arm B (46). To date, 9 pts and 6 pts are still on treatment in arm A and B respectively. In arm A, pts received 257 cycles (median 5, range 1–14) with only 10 (3.9%) delays ≥ 7 days. In arm B, pts received 317 cycles (median 7, range 0–20) with only 15 (4.7%) delays. Median follow-up was 19.5 months. Grade 3–4 hematological toxicities consisted of neutropenia, 4% in arm A and 8% in B, anemia, 0% and 2% respectively and 1 pt with febrile neutropenia and grade 3 diarrhea (Arm B). Grade 3−4 non-hematologic toxicities were vomiting (1 pt) in arm A, stomatitis (2 pts) and vomiting (1 pt) in arm B. Two cases of stroke were reported in arm A. Responses, in terms of PSA↓ &gt;50% were: 43% in arm A and 70% in arm B with PSA normalization in 8% and 38% respectively. Progression free survival (biochemical) was 20 weeks in arm A and 31 in B. Analysis concerning QoL outcomes is planned at the treatment completion of all pts. Conclusions: D-based regimens are active in HRPC with a low toxicity profile. From this preliminary data, DE combination appears promising, in terms of activity and tolerability so, front-to-front formal comparison in a phase III trial can be recommended. No significant financial relationships to disclose. </jats:p