ORIGINAL ARTICLE From the Albert Einstein Cancer Center, Philadelphia, Pennsylva- nia. Received on March 9, 2006; accepted for publication April 5, 2006. No benefits in any form have been or will be received from a commercial party related directly or indirectly to the subject of this article. Reprint requests: William Tester, MD, FACP , Albert Einstein Can- cer Center, 5501 Old York Road, Philadelphia, PA 19141. E-mail: testerb@einstein.edu Copyright © 2006 Jones and Bartlett Publishers, Inc. 299 Phase I/II Study of Weekly Docetaxel and Vinblastine in the Treatment of Metastatic Hormone-Refractory Prostate Carcinoma William Tester, MD, FACP, Joann Ackler, RN, OCN, Lukman Tijani, MD, John Leighton, MD, Philadelphia, Pennsylvania BACKGROUND Phase II trials have shown that taxanes have clinical activity as single agents as well as in combination with microtubule inhibitors in the treatment of hormone-refractory prostate cancer. Recent phase III trials with docetaxel have reported a survival benefit. Most trials also report significant toxicity, including thromboembolic disease. We conducted a phase I/II study to evaluate the maximum-tolerated dose, re- sponse rate, and effects on quality of life of the combination of docetaxel and vinblastine. METHODS Twenty men with hormone-refractory prostate cancer were treated after experiencing hormonal failure. Patients were enrolled in cohorts of three and treated with three weekly doses of docetaxel (20, 25, 30, 35, or 40 mg/m 2 ) adminis- tered as 30-minute infusion and vinblastine (3 mg/m 2 ) bolus. Treatment cycles were repeated every 28 days. Follow-up assessments included prostate-specific antigen level determinations, computed tomographic scans, bone scans, Brief Pain Inventory, and Functional Assessment of Cancer Therapy-Prostate Instrument (FACT-P). Toxicity was graded by National Cancer Institute common toxicity criteria. RESULTS The maximum tolerated dose of docetaxel was 35 mg/m 2 . Twelve of the 19 patients (63%; 95% CI 38%–84%) evaluable patients achieved a 50% reduction in prostate-specific anti- gen level that persisted for 24–80 weeks. Four of eight pa- tients with measurable soft tissue disease had a partial response. Median time to disease progression was 50 weeks. Sixteen patients completed the Brief Pain Inventory at least three times. Twelve patients reported moderate-to- severe pain scores (≥ 4) at baseline. Of these 12 patients, 11 reported that their worst pain score improved by at least two levels, and five of the 12 reported decreased opioid re- quirements. Seventeen patients completed the FACT-P at baseline and on at least two additional visits. Nine of these 17 (53%) reported improvement in Trial Outcome Index (sum of physical, functional, prostate subscales) by ≥ 6 points. Anemia was common; 12/20 patients required epoetin, and two required transfusions. Venous thrombosis developed in four patients during treatment. Only two patients discontin- ued treatment because of toxicity. CONCLUSIONS This combination of weekly docetaxel and vinblastine is ef- fective, well tolerated, and associated with improved quality of life in most of the patients treated. Although estramus- tine was not given, the risk of thromboembolic disease re- mains significant. (Cancer J 2006;12:299–304) KEY WORDS Docetaxel, hormone-refractory prostate cancer, Brief Pain In- ventory, Trial Outcome Index, FACT-P Prostate cancer is the most commonly diagnosed nonskin cancer and the second leading cause of cancer-related deaths among men in the United States, with 232,090 new cases and 30,350 deaths predicted for the year 2005. 1 For patients with newly diagnosed metastatic prostate cancer, androgen depri- vation is initially effective. However, hormonal ther- apy is not curative, and hormone-refractory prostate