Neoadjuvant estramustine and etoposide followed by concurrent estramustine and definitive radiotherapy for locally advanced prostate cancer: feasibility and preliminary results.
OBJECTIVE
Current therapy for locally advanced prostate cancer is suboptimal. A treatment regimen was designed to improve systemic control by neoadjuvant targeting of hormone-sensitive and -insensitive micrometastatic disease and to improve local control by escalating the biologic effective dose to the prostate using estramustine (EMP) concurrently with radiotherapy.


METHODS
Eighteen patients with locally advanced prostate cancer (Stages T3/T4 or T1c/T2b/T2c with a Gleason score of > or =7 and a serum PSA >15 ng/ml) were entered onto this trial. Therapy consisted of two 21-day cycles of oral estramustine (10 mg/kg/day) in three divided doses and oral etoposide (50 mg/m(2)/day, in two divided doses), followed by concurrent estramustine (10 mg/kg/day, PO) and three-dimensional conformal radiotherapy.


RESULTS
Two patients required discontinuation of chemotherapy due to development of Grade 3 and 4 toxicity. All others completed both components of therapy per protocol guidelines. Minor toxicities included alopecia (100% of patients), anemia (69%), leukopenia (37%), thrombocytopenia (19%), and nausea (6%) but did not require dose modifications. There were no fatalities. Actuarial 3-year overall survival and disease-free survival (DFS) were 88% and 73%, respectively. Local control rate, assessed by repeated prostate biopsies at 18 months post completion of therapy, was 71%.


CONCLUSIONS
The described regimen is well tolerated, and preliminary efficacy data are encouraging. The underlying concepts of early targeting of both hormone-sensitive and -insensitive micrometastatic clones, in combination with aggressive local therapy, warrant further investigation.
Ben-Josef
E
E
Department of Radiation Oncology, Barbara Ann Karmanos Cancer Institute and Wayne State University, Detroit, MI 48201, USA. benjosef@kci.wayne.edu
Porter
A T
AT
Han
S
S
Mertens
W
W
Chuba
P
P
Fontana
J
J
Hussain
M
M
D000368:Aged; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use*; D017024:Chemotherapy, Adjuvant; D004961:Estramustine / Q000008:administration & dosage / Q000009:adverse effects; D005047:Etoposide / Q000008:administration & dosage; D005240:Feasibility Studies; D006801:Humans; D008297:Male; D008875:Middle Aged; D009367:Neoplasm Staging; D010865:Pilot Projects; D017430:Prostate-Specific Antigen / Q000097:blood; D011471:Prostatic Neoplasms / Q000188:drug therapy* / Q000473:pathology / Q000532:radiotherapy*; D011837:Radiation-Protective Agents / Q000008:administration & dosage / Q000009:adverse effects; D020266:Radiotherapy, Conformal; D016019:Survival Analysis
D011837:Radiation-Protective Agents; D004961:Estramustine; D005047:Etoposide; D017430:Prostate-Specific Antigen