No Improved Outcomes in Prostate Cancer With ADT Plus Mitoxantrone/Prednisone

Combining mitoxantrone and prednisone (MP) with adjuvant androgen deprivation therapy (ADT) failed to improve overall survival over ADT alone in patients with high-risk prostate cancer after radical prostatectomy, and increased the risk of other malignancies.

“On the basis of the totality of data in 1999, we hypothesized that adjuvant MP combined with 2 years of ADT could further reduce mortality and improve overall survival,” wrote study authors led by Maha Hussain, MD, of Northwestern University in Chicago. The SWOG S9921 trial included a total of 961 patients with prostate cancer with one or more high-risk factors after radical prostatectomy, randomized to receive either ADT + MP (480 patients) or ADT alone (481 patients).

The median age in the study was 60 years, and most patients were white (84%). Most patients (63%) had positive margins after surgery; 45% had a Gleason score of 7, and 52% had a score of 8 to 10. Accrual to the study was stopped early, in 2007, as a result of a higher leukemia incidence seen with the combination approach. The results of the study were published in the Journal of Clinical Oncology.

After a median follow-up of 11.2 years, the 10-year overall survival rate was 86% for ADT + MP and 87% for ADT alone, for a hazard ratio (HR) of 1.06 (95% CI, 0.79–1.43; P = .70). The 10-year disease-free survival (DFS) rate was the same in both arms, at 72%, for an HR of 1.01 (95% CI, 0.80–1.27; P = .94). When patients were stratified by risk group, there were still no differences with regard to 10-year overall survival or DFS.

Prostate cancer was the cause of death in 18% of the ADT monotherapy patients and in 22% of the ADT + MP patients. More patients in the combination group died of other cancers, at 36% compared with 18%; these included leukemia, lung cancer, pancreatic cancer, and others.

“In high-risk patients with prostate cancer, ADT + MP did not improve survival compared with ADT,” the authors concluded, noting that the mortality rates in both arms of the trial were higher than anticipated. “In a rapidly changing genomics and therapeutic landscape, the way forward in the adjuvant setting will include incorporating genomic predictors of poor outcome, use of surrogate intermediate endpoints of clinical benefit, and incorporation of novel therapies including new androgen receptor–targeted agents with demonstrated effect on overall survival in metastatic prostate cancer.”