Researchers report promising results using the drug in combination with docetaxel and prednisone.

STOCKHOLM—Sunitinib used in tandem with docetaxel and prednisone appears to be safe and well tolerated in men with metastatic hormone-refractory prostate cancer (HRPC), investigators announced here at the 33rd Congress of the European Society of Medical Oncology. The combination also shows promising efficacy.

Amado J. Zurita, MD, of The University of Texas MD Anderson Cancer Center in Houston, and colleagues reported the preliminary findings of an ongoing study of sunitinib in combination with docetaxel and prednisone as first-line therapy for metastatic HRPC. The optimal combination dose was established in a phase 1 trial, sunitinib 37.5 mg/day plus docetaxel 75 mg/m2 plus prednisone 5 mg twice daily.

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“Overexpression of vascular endothelial growth factor (VEGF) and platelet-derived growth factor (PDGF) receptors has been implicated in prostate cancer progression and bone metastasis,” the investigators wrote in a poster presentation. “In particular, elevated plasma and urine VEGF levels have shown independent prognostic significance in HRPC patients.”

Sunitinib is an oral, multikinase inhibitor of VEGF and PDGF receptors and thus may enhance the efficacy of chemotherapy in patients with metastatic HRPC.

In the trial, patients received the optimal combination dose on a 21-day cycle, with oral sunitinib given on days 1 through 14, docetaxel on day 1, and prednisone twice daily on days 1 through 21. Dose reductions for treatment toxicity were permitted.

According to the study protocol, patients are to remain in the study until disease progression or for up to 16 cycles, which amounts to roughly a year. Afterward, those patients showing clinical benefit are eligible for continuing sunitinib as monotherapy or combined with chemotherapy in a separate protocol. The primary end point is PSA response, defined as a 50% or greater decline in PSA compared with baseline levels.

Thus far, PSA responses have been documented in 29 (56%) patients. Overall, 68% of patients who have been in the study for at least 12 weeks had at least a 30% drop in PSA by that time, and 23% had a PSA decrease to less than 4.0 ng/mL, according to investigators.

In a cohort of 31 patients with measurable disease at the start of the trial, 14 (45%) have had a partial response, the researchers  reported. Nine (29%) have stable disease, three (10%) have progressive disease, and five (16%) are not evaluable.

The most common treatment-related side effects included diarrhea (65% of patients), neutropenia (48%), fatigue (44%), and nausea (42%), the researchers reported. About a fourth of patients needed to postpone treatment with either docetaxel or sunitinib for a week or two because of low WBC counts.

“Our preliminary findings support the dual inhibition of the VEGF and PDGF signaling pathways in HRPC as critical mediators of disease progression in a significant subset of patients,” Dr. Zurita’s group stated.

These early findings demonstrate efficacy that compares favorably with historical controls in studies of docetaxel and prednisone dual therapy and thus provide a rationale for further research into sunitinib combined with docetaxel and prednisone in metastatic HRPC patients, the researchers stated.