Following definitive treatment , patients were randomized to either cyclophosphamide 1 g/m2 intravenously every 3 weeks for 2 years , estramustine phosphate 600 mg/m2 orally daily for 2 years or to observation only .
Adjuvant therapy for clinical localized prostate cancer treated with surgery or irradiation. Because of efficacy demonstrated with chemotherapy in patients with metastatic disease, the National Prostate Cancer Project in 1978 initiated two protocols evaluating adjuvant therapy following surgery (Protocol 900) and irradiation (Protocol 1000) for patients with localized disease at high risk for relapse. ### methods All patients underwent staging pelvic lymph node dissection. Following definitive treatment , patients were randomized to either cyclophosphamide 1 g/m2 intravenously every 3 weeks for 2 years , estramustine phosphate 600 mg/m2 orally daily for 2 years or to observation only . Accession closed in 1985 and included 184 patients in Protocol 900 (170 evaluable) and 253 in Protocol 1000 (233 evaluable). ### results Nodal involvement was identified in 198 patients (49% of total): 29% in Protocol 900 and 63% in protocol 1000. Median progression-free survival (PFS) and survival have been greater for patients in Protocol 900 regardless of adjuvant, reflecting their lower pathologic stage. Median PFS is significantly greater for patients in Protocol 1000 receiving estramustine (52.2 months) compared to cyclophosphamide (35.0 months). Median PFS for patients with nodal involvement in Protocol 1000 receiving estramustine is increased (43.5 months) compared to no treatment (21.5 months). Patients with limited nodal involvement in Protocol 1000 have a longer median PFS (45.6 months) compared to patients with extensive disease (23.6 months). But in the latter group patients receiving estramustine experienced a significantly longer median PFS (43.5 months) compared to cyclophosphamide (29.1 months) or no adjuvant (13.5 months). Increased PFS with estramustine adjuvant was also noted in stage C patients (only Protocol 900) and in those with high-grade (grade 3) tumors (both protocols). ### conclusions With now over 10 years mean follow-up for this series of patients, we conclude that adjuvant estramustine is beneficial for prostate cancer patients receiving definitive irradiation. This benefit is particularly noted in those patients with extensive nodal involvement (N+, D-1).
### Instruction:
            Given the context about compound efficacy for the given treatment mentioned within the input, mentioned the compounds 
            that can co-occur for the mentioned treatment

            ### Input:
            Adjuvant therapy for clinical localized prostate cancer treated with surgery or irradiation. Because of efficacy demonstrated with chemotherapy in patients with metastatic disease, the National Prostate Cancer Project in 1978 initiated two protocols evaluating adjuvant therapy following surgery (Protocol 900) and irradiation (Protocol 1000) for patients with localized disease at high risk for relapse. ### methods All patients underwent staging pelvic lymph node dissection. Following definitive treatment , patients were randomized to either cyclophosphamide 1 g/m2 intravenously every 3 weeks for 2 years , estramustine phosphate 600 mg/m2 orally daily for 2 years or to observation only . Accession closed in 1985 and included 184 patients in Protocol 900 (170 evaluable) and 253 in Protocol 1000 (233 evaluable). ### results Nodal involvement was identified in 198 patients (49% of total): 29% in Protocol 900 and 63% in protocol 1000. Median progression-free survival (PFS) and survival have been greater for patients in Protocol 900 regardless of adjuvant, reflecting their lower pathologic stage. Median PFS is significantly greater for patients in Protocol 1000 receiving estramustine (52.2 months) compared to cyclophosphamide (35.0 months). Median PFS for patients with nodal involvement in Protocol 1000 receiving estramustine is increased (43.5 months) compared to no treatment (21.5 months). Patients with limited nodal involvement in Protocol 1000 have a longer median PFS (45.6 months) compared to patients with extensive disease (23.6 months). But in the latter group patients receiving estramustine experienced a significantly longer median PFS (43.5 months) compared to cyclophosphamide (29.1 months) or no adjuvant (13.5 months). Increased PFS with estramustine adjuvant was also noted in stage C patients (only Protocol 900) and in those with high-grade (grade 3) tumors (both protocols). ### conclusions With now over 10 years mean follow-up for this series of patients, we conclude that adjuvant estramustine is beneficial for prostate cancer patients receiving definitive irradiation. This benefit is particularly noted in those patients with extensive nodal involvement (N+, D-1).

            ### Response:
            cyclophosphamide, estramustine
            