Antonio Manganelli

Effect of complete androgen blockade on pathologic stage and resection margin status of prostate cancer: progress pathology report of the Italian PROSIT study

OBJECTIVES To compare the pathologic stage and surgical margin status in patients undergoing either immediate radical prostatectomy or surgery preceded by 3 or 6 months of neoadjuvant hormonal treatment (NHT) in a prospective, randomized study. METHODS Four hundred thirty-one men with prostate cancer were enrolled in the Italian randomized prospective PROSIT study. The whole-mount sectioning technique was used. By May 1999, the reviewing pathologist had evaluated 303 specimens. One hundred seven patients were untreated before radical prostatectomy was performed, and 114 and 82 patients had been treated for 3 and 6 months, respectively, with complete androgen blockade. RESULTS Pathologic organ-confined disease was found in 63.1% of patients with clinical Stage B disease treated with 6 months of NHT versus 61.0% after 3 months of NHT and 37.5% after immediate surgery. Among patients with clinical Stage C tumors, pathologic staging found organ-confined disease in 62.5%, 32.1%, and 11.1% of patients after 6 months of NHT, 3 months of NHT, and immediate surgery, respectively. Three months of NHT produced a significant increase in negative margins both in patients with clinical Stage B and C disease, but the addition of another 3 months of treatment did not significantly improve this result. A lower degree of benefit was observed in patients with clinical Stage C tumors. CONCLUSIONS This study shows that complete androgen blockade before surgery is beneficial in men with clinical Stage B disease. The effects are more pronounced after 6 months of NHT than after 3 months.

Weekly Low-Dose Docetaxel in Advanced Hormone-Resistant Prostate Cancer Patients Previously Exposed to Chemotherapy

Objective: The aim of this study was to evaluate the activity and tolerability of docetaxel in patients with hormone-resistant prostate cancer previously exposed to chemotherapy. Methods: We enrolled 27 patients with hormone-resistant prostatic cancer that had progressed during first-line chemotherapy. The primary end-point was palliative response defined as a 2-point reduction in the 6-point present pain intensity scale, and an improvement in Karnofsky performance status of one 10-point category. The treatment consisted of weekly docetaxel 25 mg/m² body surface area administered by means of a 1-hour intravenous infusion with corticosteroid premedication. Results: The primary criterion of palliative response was met in 13 patients (48%) after eight treatment cycles; its median duration was 6 months (range 1–8). Mean global quality of life improved in 8 and 10 patients after respectively four and eight treatment cycles. After a median follow-up of 8 months, 21 patients had died: the median survival was 9+ months (range 2–18). Weekly docetaxel was very well tolerated: grade 3 neutropenia occurred in 1 patient and grade 3 anemia in 2. Conclusions: Weekly low-dose docetaxel is an effective and well-tolerated treatment for patients with hormone-resistant prostate cancer previously exposed to chemotherapy.

Weekly chemotherapy in advanced prostatic cancer.

This randomised phase II study was performed in order to evaluate the effectiveness of a weekly chemotherapy regimen in advanced prostatic carcinoma patients (stage D2) refractory to hormonal therapy. Seventy-two cases were studied: they were randomised in a 2:1 ratio to receive either epirubicin (30 mg m-2 weekly) or doxorubicin (25 mg m-2 weekly); 48 patients received epirubicin and 24 received doxorubicin. After 12 courses of chemotherapy, the 45 evaluable patients in the epirubicin arm showed a response rate of 37.7% and the 21 evaluable patients in the doxorubicin arm showed a response rate of 33.3% (P = 0.51). Pain intensity, bone and prostatic tumour markers rapidly and significantly decreased in responders. An improvement in physical symptoms, functional conditions and in emotional well-being was observed in the majority of the treated patients. The histological analysis of bone metastases, performed before and after 12 courses of chemotherapy showed a significant reduction in neoplastic invasion and in new bone formation in responders. Cardiac performance worsened in five out of 45 patients and in ten out of 21 during the first 12 courses of epirubicin or doxorubicin respectively (P = 0.014). The median survival was 12.5 months in the epirubicin arm and 8.0 months in the doxorubicin arm (P = 0.042). Our data indicate that in advanced prostatic carcinoma, a weekly epirubicin regimen may give rapid palliative results, similar to that of doxorubicin, but with less side-effects.

Weekly high-dose calcitriol and docetaxel in patients with metastatic hormone-refractory prostate cancer previously exposed to docetaxel.

To evaluate the activity and tolerability of weekly high‐dose calcitriol and docetaxel in patients with metastatic hormone‐refractory prostate cancer (HRPC) previously exposed to docetaxel, as patients who progress after docetaxel treatment might be considered for second‐line chemotherapy, but with no standard salvage therapy available we hypothesised that high‐dose calcitriol might restore sensitivity to chemotherapy.

Weekly epirubicin in patients with hormone-resistant prostate cancer

The aim of this study was to investigate the benefit of weekly epirubicin in the treatment of metastatic hormone-resistant prostate cancer. One hundred and forty-eight patients with metastatic hormone-resistant prostate cancer received weekly 30-min intravenous infusions of epirubicin 30 mg m2 of body surface area. The primary end-point was palliative response, defined as a reduction in pain intensity and an improvement in performance status. The secondary end-points were the duration of the palliative response, quality of life and survival. Fifty-seven (44%) of the 131 evaluable patients met the primary criterion of palliative response after six treatment cycles and 73 (56%) after 12 cycles; the median duration of the response was 9 months (range 1–11). The median global quality of life improved in 52% of the patients after six cycles and in 68% after 12 cycles. The 12- and 18-month survival rates were respectively 56 and 31%, with a median survival of 13+ months (range 1–36). The treatment was well tolerated: grade 3 neutropenia was observed in 8% of the patients, grade 3 anaemia in 7%, and grade 3 thrombocytopenia in 3%. None of the patients developed grade 4 toxicity or congestive heart failure. Weekly epirubicin chemotherapy can lead to a rapid and lasting palliative result in patients with metastatic HRPC, and have a positive effect on the quality of life and survival.

Prednisone plus Gefitinib versus Prednisone plus Placebo in the Treatment of Hormone-Refractory Prostate Cancer: A Randomized Phase II Trial

Background: Abnormal epidermal growth factor receptor expression and pre-clinical data prompted us to investigate the activity of gefitinib, a selective epidermal growth factor receptor tyrosine kinase inhibitor, in hormone-refractory prostate cancer. Methods: Eighty-two patients were randomly assigned to receive prednisone plus gefitinib (pG; n = 44) or prednisone plus placebo (ppl; n = 38). On progression, patients initially assigned to placebo were offered the possibility to receive gefitinib. Best prostate-specific antigen response was the primary endpoint. Results: At a median follow-up time of 29.0 months (26.0–32.0), 77 patients progressed and 51 died. Prostate-specific antigen response was recorded in 6/38 (15.8%; 95% CI 4.2–27.4) and in 5/44 (11.4%; 95% CI 2.0–20.8) patients in pG and ppl groups, respectively. There was no difference between groups in time to progression (median pG 4.0 months, range 3.5–4.5; median ppl 4.5 months, range 3.5–5.0) and survival (median pG 26.5 months, range 16.0–37.0; median ppl 20.5 months, range 14.0–27.0). Adverse events occurred in 19 patients in each arm and were generally mild. Conclusions: pG showed a good tolerability profile but only a limited therapeutic activity in hormone-refractory prostate cancer.

Bevacizumab and Weekly Docetaxel in Patients with Metastatic Castrate-Resistant Prostate Cancer Previously Exposed to Docetaxel

Background. The aim of this paper was to evaluate the activity and tolerability of docetaxel (D) and bevacizumab (Bev) in patients with metastatic castrate-resistant prostate cancer (CRPC) previously exposed to D. Methods. Treatment consisted of D 30 mg/m2 i.v. for four consecutive weekly administrations followed by a 2-week rest interval, in addition to Bev 5 mg/kg i.v. every 2 weeks. Results. Forty-three patients were enrolled: a PSA response was observed in 27 patients (62.7%, 95% CI: 0.41 to 0.91), and a palliative response was achieved in 31 patients (72.1%, 95%CI: 0.48 to 1.02). After a median followup of 11.3 months, only five patients had died. The regimen was generally well tolerated. Conclusion. Weekly D + biweekly Bev seems to be an effective and well-tolerated treatment option for patients with metastatic CRPC previously exposed to D-based chemotherapy.

Capecitabine as third-line treatment in patients with metastatic renal cell carcinoma after failing immunotherapy.

The aim of this study was to evaluate the activity and toxicity of capecitabine as third-line treatment in patients with advanced renal cell carcinoma for whom immunotherapy had failed. Twenty-one patients with metastatic clear renal cell carcinoma were enrolled. Capecitabine was administered orally twice daily at a dosage of 2500 mg/m2 for 14 days, followed by 7 days of rest. The median number of administered cycles was five (1–13). One patient (4.8%) achieved a remission after eight treatment cycles. Stable disease was observed in nine patients (42.8%), whereas 11 progressed (52.4%). The estimated median time to progression was 3.6 months (confidence interval: 1.4 to 5.2). The estimated median overall survival was 7.2 months (confidence interval: 4.6 to 8.8). The regimen was well tolerated and no unexpected toxic effects were observed. Capecitabine as third-line treatment showed a favourable toxicity profile, but exhibited low activity in patients with advanced renal cell carcinoma after failing immunotherapy.

Docetaxel and epirubicin compared with docetaxel and prednisone in advanced castrate-resistant prostate cancer: a randomised phase II study

Background:This randomised phase II study compared the activity and safety of the combination docetaxel (D)/epirubicin (EPI) with the conventional treatment D/prednisone (P) in advanced castrate-resistant prostate cancer (CRPC) patients.Materials and methods:Patients were randomly assigned to D 30 mg m−2 as intravenous infusion (i.v.) and EPI 30 mg m−2 i.v. every week (D/EPI arm), or D 70 mg m−2 i.v. every 3 weeks and oral P 5 mg twice daily (D/P arm). Chemotherapy was administered until disease progression or unacceptable toxicity.Results:A total of 72 patients were enrolled in the study and randomly assigned to treatment: 37 to D/EPI and 35 to D/P. The median progression-free survival (PFS) was 11.1 months (95% CI 9.2–12.6 months) in the D/EPI arm and 7.7 months (95% CI 5.7–9.4 months) in the D/P arm (P=0.0002). The median survival was 27.3 months (95% CI 22.1–30.8 months) in the D/EPI arm and 19.8 months (95% CI 14.4–24.8 months) in the D/P arm (P=0.003). Both regimens were generally well tolerated.Conclusion:The treatment of advanced CRPC with weekly D combined with weekly EPI was feasible and tolerable, and led to superior PFS than the treatment with 3-weekly D and oral P.

Transitional cell carcinoma of the ureteral stump 13 years after nephrectomy for benign disease.

A case of primary carcinoma of the ureteral stump occurring 13 years after nephrectomy for benign disease is reported. The literature is reviewed.