Locally advanced prostate cancer treated with concomitant radiation and 5-fluorouracil: Southwest Oncology Group Study 9024.
ABSTRACT Radiation is considered the standard treatment for locally advanced (T3 and T4) prostate cancer but cure with radiation alone is infrequent. Studies have shown that adding androgen ablation improves the results but there is still much room for improvement. We performed a phase II multi-institutional study to explore the feasibility of concomitant chemoradiotherapy.
Eligible patients had prostate cancer with clinical evidence of invasion through the prostatic capsule or into the seminal vesicles without evidence of nodal or distant metastasis. Prior prostatectomy was not allowed and patients could not be candidates for surgical resection due to medical reasons or refusal of surgery. Radiation consisted of 7,020 cGy in 39 fractions. Continuous infusion 5-fluorouracil at a dose of 200 mg/m2 daily was started on day 1 and continued 7 days weekly until the last day of radiation.
All 30 eligible patients were evaluated for toxicity. Diarrhea was the most common toxicity with grade 3 and 4 diarrhea in 2 and 1 patients, respectively. The only other grade 4 toxicity was hemorrhagic cystitis in 1 patient. There was 1 incident each of grade 3 stomatitis, congestive heart failure, edema, proctitis and hematuria. No patient with grade 3 or 4 toxicity required treatment delay. Ten patients (33%) achieved a negative biopsy and 13 (43%) achieved prostate specific antigen less than 1.0 ng/ml. Six patients (20%) achieved a complete response, defined as negative biopsy and prostate specific antigen less than 1.0 (95% CI 8 to 39). Patients without any biopsies or without prostate specific antigen followup were assumed to be nonresponders.
Toxicity was acceptable. The modest response rate indicates that better chemotherapy that improves local and systemic failure is necessary to improve the results. This study confirms the feasibility of a combined chemoradiotherapy approach.
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ABSTRACT: Historically advanced prostate cancer had been treated with androgen ablation. With the evolution of radiation therapy it was shown that some patients with advanced but nonmetastatic disease could be cured or at least have progression delayed. Subsequently a series of studies demonstrated that the combination of radiation and androgen ablation resulted in improved results over those of radiation therapy alone, although the failure rate was still high. This review explores the continued evolution in the treatment of high risk disease. The published literature on treatment for high risk prostate cancer was reviewed. Adding androgen ablation to radiation decreased the failure rate from 79% to 67% in older studies and 55% to 25% in more recent studies. Most contemporary studies of higher radiation doses showed further improvement with a failure rate of 20% to 40%. The results of adding an implant boost appears to have decreased the failure rate further to 30% or less in most studies. There is now great interest in exploring chemotherapy or biological agents as adjuvant therapy to try to improve the results further. The role of surgery in these patients is also awaiting further clarification. Radiation therapy has been the primary mode of curative therapy for high risk prostate cancer for 3 decades. Much progress has been made. Evolving data suggest that radiation will continue to have the primary role in treatment in these patients in the future.The Journal of Urology 01/2007; 176(6 Pt 2):S34-41. · 3.75 Impact Factor