title: Phase III multi-institutional trial of adjuvant chemotherapy with paclitaxel, estramustine, and oral etoposide combined with long-term androgen suppression therapy and radiotherapy versus long-term androgen suppression plus radiotherapy alone for high-risk prostate cancer: preliminary toxicity analysis of RTOG 99-02.
abstract: OBJECTIVE
  Long-term androgen suppression plus radiotherapy (AS+RT) is standard treatment of high-risk prostate cancer. A randomized trial, Radiation Therapy Oncology Group trial 9902, was undertaken to determine whether adjuvant chemotherapy with paclitaxel, estramustine, and etoposide (TEE) plus AS+RT would improve disease outcomes with acceptable toxicity.
  
  
  METHODS
  High-risk (prostate-specific antigen 20-100 ng/mL and Gleason score >or=7; or Stage T2 or greater, Gleason score 8, prostate-specific antigen level <100 ng/mL) nonmetastatic prostate cancer patients were randomized to AS+RT (Arm 1) vs. AS+RT plus four cycles of TEE (Arm 2). TEE was delivered 4 weeks after RT. AS continued for 2 years for both treatment arms. RT began after 8 weeks of AS began.
  
  
  RESULTS
  The Radiation Therapy Oncology Group 9902 trial opened January 11, 2000. Excess thromboembolic toxicity was noted, leading to study closure October 4, 2004. A total of 397 patients were accrued, and the data for 381 were analyzable. An acute and long-term toxicity analysis was performed. The worst overall toxicities during treatment were increased for Arm 2. Of the 192 patients, 136 (71%) on Arm 2 had RTOG Grade 3 or greater toxicity compared with 70 (37%) of 189 patients on Arm 1. Statistically significant increases in hematologic toxicity (p < 0.0001) and gastrointestinal toxicity (p = 0.017) but not genitourinary toxicity (p = 0.07) were noted during treatment. Two Grade 5 complications related to neutropenic infection occurred in Arm 2. Three cases of myelodysplasia/acute myelogenous leukemia were noted in Arm 2. At 2 and 3 years after therapy completion, excess long-term toxicity was not observed in Arm 2.
  
  
  CONCLUSIONS
  TEE was associated with significantly increased toxicity during treatment. The toxicity profiles did not differ at 2 and 3 years after therapy. Toxicity is an important consideration in the design of trials using adjuvant chemotherapy for prostate cancer.
authors.affiliation: Radiation Oncology Center, Radiological Associates of Sacramento, Sacramento, CA 95815, USA. rosenthals@radiological.com
authors.forename: Seth A
authors.initials: SA
authors.lastname: Rosenthal
authors.forename: Kyoungwha
authors.initials: K
authors.lastname: Bae
authors.forename: Kenneth J
authors.initials: KJ
authors.lastname: Pienta
authors.forename: Mark L
authors.initials: ML
authors.lastname: Sobczak
authors.forename: Sucha O
authors.initials: SO
authors.lastname: Asbell
authors.forename: Raghu
authors.initials: R
authors.lastname: Rajan
authors.forename: Kevin J
authors.initials: KJ
authors.lastname: Kerlin
authors.forename: Jeff M
authors.initials: JM
authors.lastname: Michalski
authors.forename: Howard M
authors.initials: HM
authors.lastname: Sandler
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000726:Androgen Antagonists / Q000008:administration & dosage / Q000009:adverse effects; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000009:adverse effects*; D017024:Chemotherapy, Adjuvant / Q000009:adverse effects; D003131:Combined Modality Therapy / Q000009:adverse effects; D004334:Drug Administration Schedule; D004961:Estramustine / Q000008:administration & dosage / Q000009:adverse effects; D005047:Etoposide / Q000008:administration & dosage / Q000009:adverse effects; D005500:Follow-Up Studies; D006801:Humans; D015470:Leukemia, Myeloid, Acute / Q000139:chemically induced; D008297:Male; D008875:Middle Aged; D009190:Myelodysplastic Syndromes / Q000139:chemically induced; D017239:Paclitaxel / Q000008:administration & dosage / Q000009:adverse effects; D011471:Prostatic Neoplasms / Q000188:drug therapy* / Q000532:radiotherapy; D013923:Thromboembolism / Q000139:chemically induced* / Q000517:prevention & control
chemical_list: D000726:Androgen Antagonists; D004961:Estramustine; D005047:Etoposide; D017239:Paclitaxel