Two monoclonal antibodies have demonstrated antitumor activity in clinical trials of men with castrate-resistant prostate cancer.
Orlando, FL-Two monoclonal antibodies have demonstrated antitumor activity in clinical trials of men with castrate-resistant prostate cancer, separate teams of researchers reported at the American Society of Clinical Oncology annual meeting.
The rationale behind cixutumumab's development is the overexpression of IGF-1R in several tumor types and the antitumor activity it has demonstrated in xenograft models and human cell lines, Dr. Higano said.
As in previous trials, hyperglycemia was the most notable adverse event. Seven patients (23%) developed hyperglycemia; four (13%) had grade 3 or higher hyperglycemia, defined as the need for temporary or ongoing insulin therapy. In addition, glucose elevations above the upper limit of normal were observed in 71% of patients. No patient discontinued therapy due to hyperglycemia.
Median composite time to disease progression was 4.8 months. Nine patients were free of progression at 6 or more months. Of 28 patients evaluable for PSA response, one had a response defined as a decrease in PSA of at least 50% from baseline that was confirmed at least 3 weeks later. Three other patients had less than 50% decrease in PSA.
PSA decline: Not the whole story
Five of 15 patients with measurable lesions at baseline had a reduction in tumor size.
"The results of this study illustrate why we are moving away from using PSA decline as a primary endpoint in castrate-resistant prostate cancer," Dr. Higano explained.
"While most patients did not experience a decline in PSA, half of the evaluable patients had stable disease and over half of these lasted at least 6 months. Had PSA decline been the primary endpoint, this promising agent would have been abandoned for prostate cancer. The results of this study support moving forward with cixutumumab in combination with docetaxel in castrate-resistant prostate cancer."
Second agent shows clinical activity
Another monoclonal antibody, this one against interleukin-6, CNTO 328, when given with docetaxel (Taxotere), was associated with a PSA response of 59% in an open-label, phase I study of men with metastatic, castration-resistant prostate cancer, reported Gary Hudes, MD, director, genitourinary malignancies, medical oncology at Fox Chase Cancer Center, Philadelphia.
The dose-escalation study included 38 patients who received a median of six to nine cycles of one of three doses of CNTO 328 in combination with docetaxel.
One dose-limiting toxicity occurred in each of the three treatment cohorts (grade 4 neutropenic infection, grade 3 syncope and dehydration, and grade 3 gastrointestinal bleeding).
The largest dose of CNTO 328 (12 mg/kg every 3 weeks) was safe in combination with docetaxel, and none of the doses affected the pharmacokinetics of docetaxel.
Suppression of C-reactive protein was achieved in 97% of the men, regardless of the CNTO 328 dose. A PSA response was achieved in 64% of patients treated with the lowest dose of CNTO 328 (6 mg/kg every 2 weeks), 50% treated with 9 mg/kg every 3 weeks, and 64% treated with 12 mg/kg every 3 weeks (total: 59%).
In 17 patients with evaluable soft tissue lesions, tumor responses were observed in four men (two partial and two unconfirmed partials).
Dr. Higano is a scientific investigator for Medivation Inc.