Fatal neutropenic enterocolitis associated with docetaxel use: A review of cases reported to the United States Food and Drug Administration Adverse Event Reporting System.

Docetaxel is a microtubule inhibitor indicated for the treatment of multiple cancers as a single agent or in combination with other antineoplastics. The U.S. Food and Drug Administration (FDA) conducted a postmarketing review of fatal neutropenic enterocolitis cases reported with docetaxel using the FDA Adverse Event Reporting System (FAERS) and literature to determine whether the drug was a potential cause. We searched FAERS and the literature for reports of fatal neutropenic enterocolitis with docetaxel-based treatment reported between 14 May 1996 and 13 March 2017. We characterized the clinical course and severity of neutropenic enterocolitis and utilized the World Health Organization-Uppsala Monitoring Centre rubric to assess drug causality. We identified 41 fatal cases of neutropenic enterocolitis with docetaxel from FAERS and the literature. The median time to onset of neutropenic enterocolitis from last docetaxel dose was seven days (range 2-13 days), and median time to death was nine days (range 3-23 days). The cause of death in 83% (34/41) of patients was neutropenic enterocolitis. We determined the drug-event association as probable in seven cases. Neutropenic enterocolitis with docetaxel monotherapy occurred in six cases; however, in 85% (35/41) of cases, neutropenic enterocolitis occurred when docetaxel was used in combination with other cytotoxic chemotherapy. In some cases, neutropenic enterocolitis occurred despite use of granulocyte colony-stimulating factors. Neutropenic enterocolitis is a severe and potentially fatal complication of docetaxel-based treatment, especially when combined with other antineoplastic treatments known to cause neutropenia. Practitioners should be aware of this safety risk to promptly recognize and manage patients.

Randomized phase II trial of docetaxel plus thalidomide in androgen-independent prostate cancer.

PURPOSE: Both docetaxel and thalidomide have demonstrated activity in androgen-independent prostate cancer (AIPC). We compared the efficacy of docetaxel to docetaxel plus thalidomide in patients with AIPC. METHODS: Seventy-five patients with chemotherapy-naïve metastatic AIPC were randomly assigned to receive either docetaxel 30 mg/m(2) intravenously every week for 3 consecutive weeks, followed by a 1-week rest period (n = 25); or docetaxel at the same dose and schedule, plus thalidomide 200 mg orally each day (n = 50). Prostate-specific antigen (PSA) consensus criteria and radiographic scans were used to determine the proportion of patients with a PSA decline, and time to progression. RESULTS: After a median potential follow-up time of 26.4 months, the proportion of patients with a greater than 50% decline in PSA was higher in the docetaxel/thalidomide group (53% in the combined group, 37% in docetaxel-alone arm). The median progression-free survival in the docetaxel group was 3.7 months and 5.9 months in the combined group (P =.32). At 18 months, overall survival in the docetaxel group was 42.9% and 68.2% in the combined group. Toxicities in both groups were manageable after administration of prophylactic low-molecular-weight heparin in the combination group. CONCLUSION: In this randomized phase II trial, the addition of thalidomide to docetaxel resulted in an encouraging PSA decline rate and overall median survival rate in patients with metastatic AIPC. After the prophylactic low-molecular-weight heparin was instituted to prevent venous thromboses, the combination regimen was well tolerated. Larger randomized trials are warranted to assess the impact of this combination.