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Abstract Background Canfosfamide is a novel glutathione analog activated by glutathione S-transferase P1-1. This study evaluated the safety and efficacy of canfosfamide in combination with pegylated liposomal doxorubicin (PLD) in patients with platinum resistant ovarian cancer. Patients with platinum resistant ovarian carcinoma and measurable disease received canfosfamide at 960 mg/m2 in combination with PLD at 50 mg/m2, intravenously day 1 in every 28 day cycles until tumor progression or unacceptable toxicities. The primary endpoints were objective response rate (ORR) and progression-free survival (PFS). Results Canfosfamide plus PLD combination therapy was administered at 960/50 mg/m2, respectively. Thirty-nine patients received a median number of 4 cycles (range 1.0-18.0). The ORR was 27.8% (95% CI, 14.2-45.2) with a disease stabilization rate of 80.6% (95% CI, 64.0-91.8) in the evaluable population. The CA-125 marker responses correlated with the radiological findings of complete response or partial response. The median PFS was 6.0 months (95% CI, 4.2-7.9) and median survival was 17.8 months. The combination was well tolerated. Myelosuppression was managed with dose reductions and growth factor support. Grade 3 febrile neutropenia was observed in 2 patients (5.1%). Non-hematologic adverse events occurred at the expected frequency and grade for each drug alone, with no unexpected or cumulative toxicities. Conclusions Canfosfamide in combination with PLD is well tolerated and active in platinum and paclitaxel refractory or resistant ovarian cancer. A randomized phase 3 study was conducted based on this supportive phase 2 study. Trial Registration This study was registered at www.clinicaltrials.gov: NCT00052065.

Background: Canfosfamide is a novel glutathione analog activated by glutathione S-transferase P1-1. This study evaluated the safety and efficacy of canfosfamide in combination with pegylated liposomal doxorubicin (PLD) in patients with platinum resistant ovarian cancer. Patients with platinum resistant ovarian carcinoma and measurable disease received canfosfamide at 960 mg/m2 in combination with PLD at 50 mg/m2, intravenously day 1 in every 28 day cycles until tumor progression or unacceptable toxicities. The primary endpoints were objective response rate (ORR) and progression-free survival (PFS). Results: Canfosfamide plus PLD combination therapy was administered at 960/50 mg/m2, respectively. Thirty-nine patients received a median number of 4 cycles (range 1.0-18.0). The ORR was 27.8% (95% CI, 14.2-45.2) with a disease stabilization rate of 80.6% (95% CI, 64.0-91.8) in the evaluable population. The CA-125 marker responses correlated with the radiological findings of complete response or partial response. The median PFS was 6.0 months (95% CI, 4.2-7.9) and median survival was 17.8 months. The combination was well tolerated. Myelosuppression was managed with dose reductions and growth factor support. Grade 3 febrile neutropenia was observed in 2 patients (5.1%). Non-hematologic adverse events occurred at the expected frequency and grade for each drug alone, with no unexpected or cumulative toxicities. Conclusions: Canfosfamide in combination with PLD is well tolerated and active in platinum and paclitaxel refractory or resistant ovarian cancer. A randomized phase 3 study was conducted based on this supportive phase 2 study. Trial Registration: This study was registered at www.clinicaltrials.gov: NCT00052065. [ABSTRACT FROM AUTHOR]

Context: To date, there has not been clear evidence regarding interventions that are effective in addressing the specific needs of homeless youth. A systematic and comprehensive international review on effective interventions for homeless youth is presented. This study seeks to provide an accurate and complete picture of effective interventions for homeless youth by collecting, summarizing, categorizing, and evaluating quantitative studies (i.e., those that have assessed treatment outcomes). EVIDENCE ACQUISTION: The following databases were searched in 2008: PsycINFO, ERIC, MEDLINE, and Cochrane were searched from 1985 through 2008 using specific key words: interventions and programs, with homeless youth (s), homeless adolescents, street youth (s), runaways and throwaways. In addition, references of key articles were searched by hand. Eleven studies met pre-established inclusion criteria. To determine study quality, a set of operational parameters was formulated to rate each study as either good, fair, or poor., Evidence Synthesis: There is no compelling evidence that specific interventions are effective for homeless youth, owing to moderate study quality and the small number of intervention studies. Conclusions that can be drawn from the studies are limited by the heterogeneity of interventions, participants, methods, and outcome measures. Many interventions focused on reduction of substance abuse, whereas other important outcomes, such as quality of life, have received little attention. No study received a quality rating of good, and four studies were rated as fair. Most convincing, but still marginal, were results of interventions based on cognitive-behavioral approaches, which revealed some positive results on psychological measures., Conclusions: More methodologically sound research is needed to determine what specific interventions are beneficial for subgroups of homeless youth. Implications for future research are discussed., (2010 American Journal of Preventive Medicine. Published by Elsevier Inc. All rights reserved.)