Xiequn Chen

Multicenter, Randomized, Open-Label Study Comparing the Efficacy and Safety of Micafungin versus Itraconazole for Prophylaxis of Invasive Fungal Infections in Patients undergoing Hematopoietic Stem Cell Transplant

This multicenter, randomized, open-label phase III study compared the efficacy and safety of micafungin and itraconazole in prophylaxis of invasive fungal infections in neutropenic patients undergoing hematopoietic stem cell transplants in China. Micafungin (50 mg/day i.v.) or itraconazole (5 mg/kg/day p.o.) was administered for ≤42 days. The primary endpoint, treatment success, was defined as no proven, probable, or suspected invasive fungal infection through therapy and the absence of proven or probable invasive fungal infection through the end of 4 weeks after therapy. Noninferiority of micafungin against itraconazole was established if the lower boundary of the 95% confidence interval (CI) was >10%. Of 287 patients, 283 were evaluable for efficacy (136 for micafungin, 147 for itraconazole, intent-to-treat population). Treatment success was documented in 92.6% (126 of 136) of micafungin-treated patients and 94.6% (139 of 147) of itraconazole-treated patients (95% CI, -7.562% to 3.482%; P = .48), indicating noninferiority of micafungin against itraconazole. Results were similar for patients treated per protocol. Whereas the rates of proven or probable invasive fungal infection were numerically higher with micafungin than itraconazole at 4.4% (6 of 136) and 1.4% (2 of 147), rates of suspected invasive fungal infection were similar at 5.9% (8 of 136) and 7.5% (11 of 147), respectively. More patients treated with micafungin than itraconazole completed the study (82.9% versus 67.3%, respectively). Significant differences in incidence of withdrawal due to an adverse event (4.4% versus 21.1%) and drug-related adverse events (8% versus 26.5%) were shown between micafungin and itraconazole (P = .00, chi-square test). Micafungin was as effective as itraconazole in preventing invasive fungal infections in patients with neutropenia. In comparison to itraconazole, treatment tolerance was much better with micafungin.

Posaconazole vs. fluconazole as invasive fungal infection prophylaxis in China: a multicenter, randomized, open-label study.

BACKGROUNDnInvasive fungal infection (IFI) is common in neutropenic patients with acute myelogenous leukemia (AML) or myelodysplastic syndrome (MDS). Posaconazole is a broad-spectrum triazole antifungal drug with efficacy in prevention of IFI; however, it has not been previously studied as prophylaxis in a Chinese population.nnnMETHODSnThis multicenter, randomized study in China enrolled AML and MDS patients with persistent chemotherapy-induced neutropenia. Prophylaxis with posaconazole or fluconazole was administered for a maximum of 12 weeks, or until patients recovered from neutropenia and achieved complete remission or an IFI occurred. The primary endpoint was incidence of proven, probable, or possible IFI during treatment. Clinical failure rate, all-cause mortality and time to first systemic antifungal treatment were secondary endpoints.nnnRESULTSnPatients were randomized to receive posaconazole (n = 129) or fluconazole (n = 123); 117 patients in each group were included in the statistical analysis. The incidence of proven, probable or possible IFI was 9.4% (11/117) and 22.2% (26/117) in the posaconazole and fluconazole groups, respectively (p = 0.0114). The clinical failure rate was numerically lower in the posaconazole group (37/117 (31.6%; 95%CI: 23.3 - 40.9)) than in the fluconazole group (49/117 (41.88%; 95% CI: 32.8 - 51.4)) (p = 0.168). Patients receiving posaconazole had a later onset of first systematic antifungal treatment than those receiving fluconazole (p = 0.0139). The most common important adverse events were liver function abnormalities (11 patients (8.8%) on posaconazole and 6 (5.0%) on fluconazole (p = 0.221)).nnnCONCLUSIONSnPosaconazole demonstrates efficacy as prophylaxis against IFI in high-risk neutropenic Chinese patients and is well tolerated during long-term use (ClinicalTrials. gov number, NCT00811928).

A multicenter randomized controlled trial of recombinant human thrombopoietin treatment in patients with primary immune thrombocytopenia

This multicenter, randomized trial assessed the efficacy and safety of a recombinant human thrombopoietin (rhTPO) in patients with persistent primary immune thrombocytopenia (ITP) who had failed glucocorticosteroid treatment. A total of 140 eligible patients were randomized to receive rhTPOxa0+xa0danazol (rhTPO group, 73 patients) or danazol (control group, 67 patients) alone. During the first phase, the increase in the mean maximal platelet counts (101.2xa0×xa0109/L) and the area under curve (749.6) in the rhTPO group were significantly higher compared to control (33.3xa0×xa0109/L and 316.2; Pxa0=xa00.0060 and 0.0000, respectively). The major response rate (MRR) and total response rate (TRR) in the rhTPO group were 38.4 and 60.3xa0%, respectively, significantly higher than in control (MRR 7.9xa0%, Pxa0=xa00.0003; TRR 36.5xa0%, Pxa0=xa00.0104). In the control group, 45 patients with platelet counts <20xa0×xa0109/L were given rhTPO during the second phase and achieved MRR 31.1xa0% and TRR 66.7xa0%. The mean platelet counts in the rhTPO group were still approximately 50xa0×xa0109/L on day 28 of the study. The overall incidence of rhTPO-related adverse events was 13.6xa0%. All the adverse events were generally mild. This study demonstrated that rhTPO was well tolerated, and it markedly increased platelet counts in chronic ITP patients. Stimulation of platelet production by rhTPO may provide a new therapeutic option for patients with ITP.

Standardized fluorescence in situ hybridization testing based on an appropriate panel of probes more effectively identifies common cytogenetic abnormalities in myelodysplastic syndromes than conventional cytogenetic analysis: A multicenter prospective study of 2302 patients in China

In an attempt to establish the advantages of fluorescence in situ hybridization (FISH) studies over conventional cytogenetic (CC) analysis, a total of 2302 de novo MDS patients from 31 Chinese institutions were prospectively selected in the present study for both CC and standardized FISH analysis for +8, -7/7q-, -5/5q-, 20q- and-Y chromosomal abnormalities. CC analysis was successful in 94.0% of the patients; of these patients, 35.9% of the cases were abnormal. FISH analysis was successful in all 2302 patients and detected at least one type of common cytogenetic abnormality in 42.7% of the cases. The incidences of +8, -7/7q-, -5/5q-, 20q- and-Y chromosomal abnormalities by FISH were 4.1% to 8.7% higher than those by CC. FISH identified abnormalities in 23.6% of the patients exhibiting normal CC results and revealed that 20.7% of the patients with adequate normal metaphases (≥20) had abnormal clones. FISH identified cytogenetic abnormalities in 50.4% of the patients with failed CC analysis. In summary, our multicenter studies emphasised and confirmed the importance of applying standardized FISH testing based on an appropriate panel of probes to detect common cytogenetic abnormalities in Chinese de novo MDS patients, particularly those with normal or failed CC results.

Ibrutinib versus rituximab in relapsed or refractory chronic lymphocytic leukemia or small lymphocytic lymphoma: a randomized, open-label phase 3 study

In the Asia‐Pacific region, treatment options are limited for patients with relapsed/refractory chronic lymphocytic leukemia (CLL)/small lymphocytic lymphoma (SLL). Rituximab is widely used in this setting when purine analog‐based therapies are not appropriate. We evaluated the efficacy and safety of ibrutinib compared with rituximab in a randomized, open‐label phase 3 study in predominantly Asian patients with relapsed/refractory CLL/SLL. Patients (N = 160) were randomly assigned 2:1 to receive 420 mg ibrutinib (n = 106) until disease progression (PD) or unacceptable toxicity or up to six cycles of rituximab (n = 54). The primary endpoint was investigator‐assessed progression‐free survival (PFS); key secondary endpoints were overall response rate (ORR), overall survival (OS), and safety. Rituximab‐treated patients could crossover to receive ibrutinib after confirmed PD. At data cutoff, median treatment duration was 16.4 months for ibrutinib and 4.6 months for rituximab. Ibrutinib significantly improved PFS (hazard ratio [HR] = 0.180, 95% confidence interval [CI]: 0.105–0.308). ORR was significantly higher (P < 0.0001) with ibrutinib (53.8%) than with rituximab (7.4%). At a median follow‐up of 17.8 months, ibrutinib improved OS compared with rituximab (HR = 0.446; 95% CI: 0.221–0.900; P = 0.0206). Overall incidence of adverse events (AEs) was similar between treatments and was not exposure‐adjusted. With ibrutinib, most common AEs were diarrhea and platelet count decreased; with rituximab, most common AEs were neutrophil count decreased and platelet count decreased. Grade ≥3 AEs were reported in 82.7% of ibrutinib‐treated patients and 59.6% of rituximab‐treated patients. Ibrutinib improved PFS, ORR, and OS compared with rituximab and displayed a manageable safety profile in Asian patients with relapsed/refractory CLL/SLL.

First-line gemcitabine, oxaliplatin, and l-asparaginase chemotherapy followed by involved field radiation in stage IE/IIE extranodal NK/T-cell lymphoma.

e18540 Background: Now, there is lack of consensus on treatment of Extranodal NK/T cell lymphoma (ENKTL), and no therapy is considered standard. ENKTL shows a poor response to anthracycline-based chemotherapy, such as CHOP or CHOP-like regimens, because of the frequent expression of a multidrug-resistant P-glycoprotein. Thus, we designed an induce chemotherapy regimen consisted of gemcitabine, oxaliplatin and l-asparaginase(GELOX), which are not affected by P-glycoprotein. In addition, we added involved field radiation. The objective of this study is to investigate the efficacy and safety of GELOX followed by involved field radiation.nnnMETHODSnFrom January 2008 to April 2010, 17 newly diagnosed patients with stage IE/IIE ENKTL were frontline treated with GELOX chemotherapy (gemcitabine 1000 mg/m2 intravenous drip on day 1,8; oxaliplatin 130mg/m2 intravenous drip on day 1; and l-asparaginase 5000IU/ m2 intravenous drip on days 1-7) followed by involved field radiation ( radiation 46 Gy to 56 Gy) in Sun Yat-sen University Cancer Center.nnnRESULTSnAfter treatment of GELOX regimen, there were 12 CRs (70.5%, 12/17) and 5 PRs (29.5%, 5/17), which is a 100% response rate. No patient was disease progression or stable during chemotherapy. All patients achieved CRs after involved field radiation, which is a 100% CR rate. At a median follow-up of 18.6 months (range 5-31), 2 (11.8%) of 17 patients experienced disease progression. the estimated median disease-free survival (DFS) is 30.0 months (95% CI, 26.2 to 38.9). Grades 1 to 2 toxicities were frequent during GELOX, but grades 3 to 4 toxicities were rare (5.9%).nnnCONCLUSIONSnIn conclusion, GELOX followed by involved field radiation can be a feasible and effective treatment strategy for stages IE to IIE ENKTL.