Randomization reveals unexpected acute leukemias in Southwest Oncology Group prostate cancer trial

J Clin Oncol. 2008 Mar 20;26(9):1532-6. doi: 10.1200/JCO.2007.13.4197.

Abstract

Purpose: Southwest Oncology Group (SWOG) study 9921 is a randomized, phase III, intergroup study to define the role of adjuvant chemotherapy in patients with high-risk prostate cancer.

Patients and methods: We allocated 983 patients with prostate cancer with high-risk features to receive 2 years of androgen-deprivation therapy (ADT) with or without six cycles of mitoxantrone (12 mg/m(2)) after prostatectomy.

Results: In January 2007, SWOG 9921 was closed to further accrual after three cases of acute myelogenous leukemia (AML) were reported of a total of 487 patients in the mitoxantrone treatment arm. The key cytogenetic features of these cases included inv(16) in the first case, t(15;17) in the second, and del(5) in the third case. Time from the start of mitoxantrone to the detection of AML was 13, 48, and 72 months, respectively. Before SWOG 9921, there were no cases of mitoxantrone-induced AML reported in patients treated for prostate cancer.

Conclusion: The emergence of this possible pattern of secondary malignancy emphasizes the importance of randomized controlled trials in defining safety and efficacy of new approaches for patients in the adjuvant setting.

Publication types

  • Case Reports
  • Clinical Trial, Phase III
  • Randomized Controlled Trial
  • Research Support, N.I.H., Extramural

MeSH terms

  • Adenocarcinoma / drug therapy
  • Adult
  • Aged
  • Aged, 80 and over
  • Anilides / administration & dosage
  • Antineoplastic Combined Chemotherapy Protocols / administration & dosage*
  • Antineoplastic Combined Chemotherapy Protocols / adverse effects*
  • Chemotherapy, Adjuvant / adverse effects
  • Fatal Outcome
  • Goserelin / administration & dosage
  • Humans
  • Leukemia, Myeloid, Acute / chemically induced*
  • Leukemia, Myeloid, Acute / diagnosis*
  • Leukemia, Myeloid, Acute / ethnology
  • Male
  • Middle Aged
  • Mitoxantrone / administration & dosage*
  • Mitoxantrone / adverse effects*
  • Nitriles / administration & dosage
  • Prednisone / administration & dosage
  • Prostatectomy*
  • Prostatic Neoplasms / drug therapy*
  • Prostatic Neoplasms / ethnology
  • Prostatic Neoplasms / pathology
  • Risk Assessment
  • Risk Factors
  • Southwestern United States / epidemiology
  • Survival Analysis
  • Tosyl Compounds / administration & dosage

Substances

  • Anilides
  • Nitriles
  • Tosyl Compounds
  • Goserelin
  • bicalutamide
  • Mitoxantrone
  • Prednisone