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

Int J Radiat Oncol Biol Phys. 2009 Mar 1;73(3):672-8. doi: 10.1016/j.ijrobp.2008.05.020. Epub 2008 Nov 5.


Purpose: 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 and materials: 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.

Conclusion: 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.

Publication types

  • Clinical Trial, Phase III
  • Multicenter Study
  • Randomized Controlled Trial
  • Research Support, N.I.H., Extramural

MeSH terms

  • Adult
  • Aged
  • Aged, 80 and over
  • Androgen Antagonists / administration & dosage
  • Androgen Antagonists / adverse effects
  • Antineoplastic Combined Chemotherapy Protocols / adverse effects*
  • Chemotherapy, Adjuvant / adverse effects
  • Combined Modality Therapy / adverse effects
  • Drug Administration Schedule
  • Estramustine / administration & dosage
  • Estramustine / adverse effects
  • Etoposide / administration & dosage
  • Etoposide / adverse effects
  • Follow-Up Studies
  • Humans
  • Leukemia, Myeloid, Acute / chemically induced
  • Male
  • Middle Aged
  • Myelodysplastic Syndromes / chemically induced
  • Paclitaxel / administration & dosage
  • Paclitaxel / adverse effects
  • Prostatic Neoplasms / drug therapy*
  • Prostatic Neoplasms / radiotherapy
  • Thromboembolism / chemically induced*
  • Thromboembolism / prevention & control


  • Androgen Antagonists
  • Estramustine
  • Etoposide
  • Paclitaxel