Neoadjuvant chemo is well tolerated in high-risk PCa

Atlanta-Neoadjuvant docetaxel added to androgen suppression therapy and radiation therapy appears to be safe and active in patients with high-risk localized prostate cancer, according to findings of a new phase II study from Canada reported here at the American Society of Clinical Oncology annual meeting.

The current study, a seven-center trial led by Michael R. McKenzie, MD, a radiation oncologist at the British Columbia Cancer Agency, Vancouver Cancer Centre, sought to assess the tolerability of neoadjuvant docetaxel with androgen suppression therapy and radiation therapy in men with high-risk localized prostate cancer.

All of the men received 3 years of androgen suppression therapy consisting of an LHRH agonist plus an anti-androgen for 4 weeks followed by chemotherapy starting at week 5. Twenty-four men received weekly docetaxel, 35 mg/m² for 6 weeks, given every 8 weeks for two cycles. Radiation therapy was started at week 25.

After a revision of the protocol, 30 men received docetaxel, 75 mg/m² every 3 weeks for 4 cycles, followed by radiation therapy starting at week 21.

The primary endpoint was unacceptable toxicity, defined as greater than grade 3 nonhematologic toxicity, grade 4 neutropenia lasting beyond 7 days, febrile neutropenia, or toxicity-related radiation therapy change (a delay greater than 2 weeks or a dose reduction of 25%).

An analysis of the data after all men had completed radiation therapy indicated that neoadjuvant androgen suppression therapy and docetaxel in combination with radiation therapy was generally well tolerated.

Of the 54 men, eight (14.8%) were classified as having unacceptable toxicity. Among these were five patients who were receiving once-weekly docetaxel: three developed grade 3 acute radiation therapy-related genitourinary toxicity, one had grade 3 docetaxel hypersensitivity, and one had grade 3 fatigue for more than 2 weeks.

In three patients receiving docetaxel every 3 weeks, unacceptable toxicities included grade 3 acute radiation therapy-related genitourinary toxicity (one patient), febrile neutropenia (one patient), and grade 4 neutropenia for more than 7 days (one patient).

Approximately one-third of the men (35.2%) achieved PSA levels between 0.1 and 0.5 μg/L in response to neoadjuvant treatment; 23 patients (42.6%) achieved PSA levels between 0.5 μg/L and 2.0 μg/L; and three (5.6%) patients had PSA levels >2.0 μg/L.

The combination of radiation therapy and hormone therapy is better than radiation therapy alone, but a significant proportion of patients still relapse on therapy, according to Dr. McKenzie.

"Given the results of docetaxel in hormone-refractory and hormone-sensitive disease, it seemed logical to explore the potential benefits of docetaxel in this setting," he told Urology Times.

He added that the researchers were concerned about whether the combination would be tolerable in a relatively older population of men, and "we were able to show that it was."