Phase I trial of docetaxel given every 3 weeks and daily lenalidomide in patients with advanced solid tumors.

PURPOSE: Cytotoxic and anti-angiogenic drugs are efficacious in malignancies. This trial was undertaken to evaluate the toxicity of a novel regimen combining docetaxel and lenalidomide. PATIENTS AND METHODS: Patients with advanced solid tumors were eligible. Docetaxel was administered on day 1, and lenalidomide was given on days 1-14 of each 21-day cycle. Since significant myelosuppression occurred, pegfilgrastim was added on day 2. Dose limiting toxicity (DLT) was defined as >or=grade 3 non-hematologic toxicity, grade 4 neutropenia with fever, or grade 4 anemia or thrombocytopenia. RESULTS: Thirty-three patients were enrolled. DLTs included neutropenia, nausea/vomiting, and dyspnea. Of the evaluable patients, 69% had stable disease, and 3% had partial response. CONCLUSIONS: This regimen was well tolerated and provided stable disease in the majority of advanced cancer patients. The recommended phase II dosing is docetaxel 75 mg/m(2) on day 1, lenalidomide 25 mg on days 1-14, and pegfilgrastim 6 mg on day 2, given every 3 weeks.

Development of a modified surveillance definition of central line-associated bloodstream infections for patients with hematologic malignancies.

OBJECTIVE: To develop a modified surveillance definition of central line-associated bloodstream infection (mCLABSI) specific for our population of patients with hematologic malignancies to better support ongoing improvement efforts at our hospital. DESIGN: Retrospective cohort study. PATIENTS: Hematologic malignancies population in a 1,200-bed tertiary care hospital on a 22-bed bone marrow transplant (BMT) unit and a 22-bed leukemia unit. METHODS: An mCLABSI definition was developed, and pathogens and rates were compared against those determined using the National Healthcare Safety Network (NHSN) definition. RESULTS: By the NHSN definition the CLABSI rate on the BMT unit was 6.0 per 1,000 central line-days, and by the mCLABSI definition the rate was 2.0 per 1,000 line-days ([Formula: see text]). On the leukemia unit, the NHSN CLABSI rate was 14.4 per 1,000 line-days, and the mCLABSI rate was 8.2 per 1,000 line-days ([Formula: see text]). The top 3 CLABSI pathogens by the NHSN definition were Enterococcus species, Klebsiella species, and Escherichia coli. The top 3 CLABSI pathogens by the mCLABSI definition were coagulase-negative Staphylococcus (CONS), Pseudomonas aeruginosa, and Staphylococcus aureus. The difference in the incidence of CONS as a cause of CLABSI under the 2 definitions was statistically significant ([Formula: see text]). CONCLUSIONS: A modified surveillance definition of CLABSI was associated with an increase in the identification of staphylococci as the cause of CLABSIs, as opposed to enteric pathogens, and a decrease in CLABSI rates.

Dose-modified oral chemotherapy in the treatment of AIDS-related non-Hodgkin's lymphoma in East Africa.

PURPOSE Africa is burdened by the AIDS epidemic and attendant increase in HIV/AIDS-related malignancies. Pragmatic approaches to therapeutic intervention could be of great value. Dose-modified oral chemotherapy for AIDS-related non-Hodgkin's lymphoma is one such approach. PATIENTS AND METHODS The oral regimen consisted of lomustine 50 mg/m(2) on day 1 (cycle 1 only), etoposide 100 mg/m(2) on days 1 to 3, and cyclophosphamide/procarbazine 50 mg/m(2) each on days 22 to 26 at 6-week intervals (one cycle) for two total cycles in HIV-infected patients with biopsy-proven non-Hodgkin's lymphoma. Results Forty-nine patients (21 in Uganda and 28 in Kenya) were treated. The majority of patients were female (59%) and had a poor performance status (63%); 69% of patients had advanced-stage disease; and 18 patients (37%) had access to antiretroviral therapy. In total, 79.5 cycles of therapy were administered. The regimen was well tolerated, had modest effects (decline) on CD4(+) lymphocyte counts (P = .077), and had negligible effects on HIV-1 viral replication. Four febrile neutropenia episodes and three treatment-related deaths (6% mortality rate) occurred. The overall objective response rate was 78% (95% CI, 62% to 88%); median follow-up time was 8.2 months (range, 0.1 to 71 months); median event-free and overall survival times were 7.9 months (95% CI, 3.3 to 13.0 months) and 12.3 months (95% CI, 4.9 to 32.4 months), respectively; and 33% of patients survived 5 years. CONCLUSION Dose-modified oral chemotherapy is efficacious, has comparable outcome to that in the United States in the pre-highly active antiretroviral therapy setting, has an acceptable safety profile, and is pragmatic in sub-Saharan Africa. The international collaboration has been highly successful, and subsequent projects should focus on strategies to optimize combination antiretroviral therapy and chemotherapy and follow-up tissue correlative studies.