2119 Systemic Chemotherapy with High Dose Conformal Radiotherapy in High Risk Prostate Cancer

A.A. Elsaid, S. Elassal

Department of Clinical Oncology, Alexandria University, Alexandria, Egypt

Purpose/Objective: The aim of this work is to determine if systemic therapy can improve the outcome of XRT in men withhigh-risk localized prostate cancer.

Materials/Methods: Twenty-two patients with unfavorable-risk prostate cancer were enrolled onto a prospective study todetermine the feasibility of combining DE chemotherapy with 3D- CRT. Patients at high risk for recurrence include those withbiopsy Gleason scores of 8 to 10, prostate specific antigen (PSA) levels � 20 ng/mL, clinical stage T3 disease, any patient withT4N0M0 disease; or patients with TXN1MO disease. Therapy consisted of two 21-day cycles of oral estramustine (280 mgthree times per day on days 1 through 5) with Docetaxel 40 mg/m2 on day 2 followed by concurrent DE chemotherapy (sameregimen) with three-dimensional conformal radiotherapy. Radiation therapy was administered using a three-dimensionalconformal approach to a prescription dose of 77.4 Gy. The median follow-up was 36 months (range, 10 to 40 months). Patientsare monitored with weekly visits, monthly digital rectal examinations, PSA measurement, and testosterone tests, done atbaseline, after two cycles, and again after the whole course. Total hormonal ablation was given only in recurrence or metastasis.

Results: Two patients required discontinuation of chemotherapy due to development of Grade 3 and 4 toxicity. All otherscompleted both components of therapy per protocol guidelines. Minor toxicities included fatigue (100%) alopecia (80% ofpatients), anemia (70%), leukopenia (40%), thrombocytopenia (20%), and nausea (5%) but did not require dose modifications.Mild peripheral edema was seen in 10% of patients and was treated with diuresis. 3D-CRT was tolerated well in these patients.Medications were required for relief of acute grade 2 rectal (gastrointestinal [GI]) and urinary (genitourinary [GU]) symptomsin 20% and 40% of patients, respectively. Three patients developed acute grade 3 GU toxicities. . No grade 4 GU toxicity wasobserved. There were no fatalities. Actuarial 3-year overall survival and disease-free survival (DFS) were 90% and 80%,respectively. Local control rate, assessed by repeated prostate biopsies at 18 months post completion of therapy, was 80%.

Conclusions: Neoadjuvant and concomitant DE with high-dose 3D-CRT is well tolerated in patients with unfavorable-riskprostate cancer. 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.

2120 Prospective Evaluation of Urinary and Intestinal Side Effects After Stereotactic Dose-EscalatedRadiotherapy of Prostate Cancer

P. Fransson1, P. Bergstrom1, P. Lofroth2, A. Widmark1

1Department of Oncology, Institute of Radiation Sciences, Umeå, Sweden, 2Department of Radiation Physics, Institute ofRadiation Sciences, Umeå, Sweden

Purpose/Objective: New data suggest that a higher radiation dose will improve outcome in treatment of localized prostatecancer. External beam radiotherapy (EBRT) may on the other hand induce disturbances in the patient’s urinary and intestinalfunction. Since 1997, 195 patients have been treated with a stereotactic boost of 4-8 Gy added to conventional 70 Gy EBRT.Late side effects were prospectively evaluated 3-years after dose-escalated EBRT.

Materials/Methods: Urinary and intestinal problems were prospectively evaluated with a validated self-assessment question-naire, the Prostate Cancer Symptom Scale, PCSS. Two-hundred-eighty-seven patients completed the questionnaire at the 1-yearfollow-up, and 153 at 3-years after treatment. Pre-treatment mean age was 66 years. One hundred and sixty eight patients weretreated with conformal technique and 195 were treated with dose-escalated stereotactic technique. Mean total dose in theconformal group (�70 Gy) was 66 Gy (60.8-70.4 Gy). The dose-escalated group consists of 3 dose levels, 74 Gy (n�68), 76Gy (n�74), and 78 Gy (n�53).

Results: Analyzing the whole population 3-years after treatment, urgency and starting problems decreased in comparison topre-treatment. A minor increase in urinary incontinence was reported 3-years after treatment in comparison to pre-treatment.No increases in other urinary symptoms were reported.

Intestinal symptoms were slightly increased during the follow-up period in comparison to pre-treatment. Dose-escalation withstereotactic EBRT (74-78 Gy) did not increase gastrointestinal or genitourinary late side effects at 1-year or 3-year incomparison to doses �70 Gy.

Conclusions: The stereotactic EBRT technique facilitates safe dose-escalation of patients with prostate cancer.

2121 The Pattern of Proliferative Index (Ki-67) Following Anti-Androgen Manipulation Reflects the Ability ofIrradiation to Control Locally Advanced Prostate Cancer

B. Hintz1, J.S. Murphy2, C.H. Koo3

1Department of Radiation Therapy , Kaiser Permanente, Los Angeles, CA, 2Department of Urology, Kaiser Permanente,Los Angeles, CA, 3Department of Pathology, Kaiser Permanente, Los Angeles, CA

Purpose/Objective: Anti-Androgen(AA) therapy will cause hormone-sensitive prostate cancer cells to undergo apoptosis and/or enter the resting phase of the cell cycle. Although the decrease of tumor burden would be an advantage for tumor controlwhen irradiation is subsequently added, the cells in resting phase would seemingly be less vulnerable to the usual type of

281Proceedings of the 44th Annual ASTRO Meeting