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

Journal Article · Sun Mar 01 04:00:00 UTC 2009 · International Journal of Radiation Oncology, Biology and Physics

DOI:https://doi.org/10.1016/j.ijrobp.2008.05.020· OSTI ID:21172614

Rosenthal, Seth A ^[1]; Bae, Kyoungwha ^[2]; Pienta, Kenneth J ^[3]; Sobczak, Mark L ^[4]; Asbell, Sucha O ^[5]; Rajan, Raghu ^[6]; Kerlin, Kevin J ^[7]; Michalski, Jeff M ^[8]; Sandler, Howard M ^[9]

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1. Radiation Oncology Center, Radiological Associates of Sacramento, Sacramento, CA (United States)
2. Department of Statistics, Radiation Therapy Oncology Group, Philadelphia, PA (United States)
3. Division of Medical Oncology, University of Michigan, Ann Arbor, MI (United States)
4. Section of Radiation Oncology, Department of Medicine, Dartmouth-Hitchcock Medical Center, Lebanon, NH (Lebanon)
5. Department of Radiation Oncology, Albert Einstein Medical Center, Philadelphia, PA (United States)
6. Department of Medical Oncology, McGill University, Montreal, QB (Canada)
7. Wayne Radiation Oncology Center, Goldsboro, NC (United States)
8. Department of Radiation Oncology, Washington University, St. Louis, MO (United States)
9. Department of Radiation Oncology, University of Michigan, Ann Arbor, MI (United States)

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 {>=}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.

• OSTI ID: 21172614
• Journal Information: International Journal of Radiation Oncology, Biology and Physics, Journal Name: International Journal of Radiation Oncology, Biology and Physics Journal Issue: 3 Vol. 73; ISSN IOBPD3; ISSN 0360-3016
• Country of Publication: United States
• Language: English

Related Subjects

62 RADIOLOGY AND NUCLEAR MEDICINE
ANDROGENS
ANTIGENS
CHEMOTHERAPY
CLINICAL TRIALS
INHIBITION
LEUKEMIA
PATIENTS
PROSTATE
RADIATION HAZARDS
RADIOTHERAPY
TOXICITY