Phase 2 study of granulocyte-macrophage colony-stimulating factor plus thalidomide in patients with hormone-naïve adenocarcinoma of the prostate.

OBJECTIVE

To assess the efficacy of granulocyte macrophage colony-stimulating factor (GM-CSF) in combination with thalidomide on prostate-specific antigen (PSA) reduction in hormone-naïve prostate carcinoma (HNPC) patients with rising PSA levels after definitive local treatment.

MATERIALS AND METHODS

HNPC patients (n = 21) with evidence of progression demonstrated by 3 consecutive rises in PSA and no evidence of radiographic involvement were treated on a chronic dosing schedule with GM-CSF. Patients received 250 microg/m2 (maximum 500 microg) 3 times a wk by subcutaneous injection, with injections at least 24 h apart. Thalidomide administration began concurrently with an initial dose of 100 mg daily for 7 consecutive days. During wk 2 to 4, the dose was escalated every 7 d by 100 mg per individual tolerance to a maximum of 400 mg. The maximum tolerated dose of thalidomide was continued without interruption. PSA, testosterone, and routine laboratory parameters were measured every 6 wk.

RESULTS

One patient was not evaluable because of noncompliance. For the 20 evaluable patients, baseline PSA levels ranged from 1.3 to 61.0 ng/ml. Nineteen patients left the study at 3.0 to 33.3 mo, secondary to individual tolerance, progressive disease, or development of a second primary tumor. One patient continues to receive therapy at 33.8 mo. Two patients did not respond to the therapy. For the 18 patients who did respond, the median reduction in PSA level was 59% (range 26%-89%), and the median duration of response was 11 mo (range 4.5-36). Grades 1-2 toxicity included peripheral neuropathy, fatigue, skin rash, and constipation. One patient had deep-vein thrombosis/pulmonary embolism.

CONCLUSIONS

GM-CSF plus thalidomide can be administered successfully with encouraging antitumor activity and reversible toxicity. This may represent an alternative to hormonal therapy.