Shuxiang Zhang

A phase I clinical trial assessing the safety and tolerability of combretastatin A4 phosphate injections.

Combretastatin A4 phosphate (CA4P) is a prodrug that selectively destroys tumor blood vessels, and has shown efficacy as a targeted anticancer drug in both animal models and clinical trials. The aims of this single-center, open label, phase I clinical trial were to investigate the safety and tolerability of CA4P administered intravenously to patients aged 18–65 years with advanced solid tumors. Using a dose-escalation protocol, patients were assigned to five groups that received injections with 20 (n=3), 33 (n=3), 50 (n=11), 65 (n=6), or 85 (n=2) mg/m2 CA4P. Patients in the 20 and 85 mg/m2 groups received a single dose and the other groups received multiple doses. Adverse events (AE), cardiovascular parameters, and biochemical investigations were studied, and the maximum tolerated dose was determined. Of twenty-five patients enrolled, eight were withdrawn/excluded (not because of AE). There were no deaths. A total of 394 AE occurred in the 25 patients, with 89.3% considered related/possibly related to the drug. AE included headache and dizziness (19.8%), tumor-induced pain (14.2%), vascular vagal excitation (10.7%), and vomiting (9.4%). Ninety-five percent of AE were mild (grades 0–II), with only 5% being grade III–IV. Drug administration was associated with biphasic changes in heart rate and blood pressure, and only limited abnormalities in the laboratory investigations performed. The maximum tolerated dose was 65 mg/m2. We conclude that CA4P is generally well tolerated, with the vast majority of AE that occurred being of mild severity. Further studies will establish the role of CA4P in cancer therapy.

Comparison of CBV, BEAM and BEAC high-dose chemotherapy followed by autologous hematopoietic stem cell transplantation in non-Hodgkin lymphoma: Efficacy and toxicity

Limited data are available to guide the choice of conditioning regimen before autologous hematopoietic stem cell transplantation (AHSCT) for patients with lymphoma.

Phase I study of chimeric anti-CD20 monoclonal antibody in Chinese patients with CD20-positive non-Hodgkin＇s lymphoma

Objective: This study was designed to determine the safety, pharmacokinetics and biologic effects of a human-mouse chimeric anti-CD20 monoclonal antibody (SCT400) in Chinese patients with CD20-positive B-cell non-Hodgkins lymphoma (CD20+ B-cell NHL). SCT400 has an identical amino acid sequence as rituximab, with the exception of one amino acid in the CH1 domain of the heavy chain, which is common in Asians. Methods: Fifteen patients with CD20+ B-cell NHL received dose-escalating SCT400 infusions (250 mg/m2: n=3; 375 mg/m2: n=9; 500 mg/m2: n=3) once weekly for 4 consecutive weeks with a 24-week follow-up period. The data of all patients were collected for pharmacokinetics and pharmacodynamics analyses. Results: No dose-limiting toxicities were observed. Most drug-related adverse events were grade 1 or 2. Two patients had grade 3 or 4 neutropenia. Under premedication, the drug-related infusion reaction was mild. A rapid, profound and durable depletion of circulating B cells was observed in all dose groups without significant effects on T cell count, natural killer (NK) cell count or immunoglobulin levels. No patient developed anti-SCT400 antibodies during the course of the study. SCT400 serum half-life (T1/2), maximum concentration (Cmax) and area under the curve (AUC) generally increased between the first and fourth infusions (P<0.05). At the 375 mg/m2 dose, the T1/2 was 122.5±46.7 h vs. 197.0±75.0 h, respectively, and the Cmax was 200.6±20.2 g/mL vs. 339.1±71.0 g/mL, respectively. From 250 mg/m2 to 500 mg/m2, the Cmax and AUC increased significantly in a dose-dependent manner (P<0.05). Patients with a high tumor burden had markedly lower serum SCT400 concentrations compared with those without or with a low tumor burden. Of the 9 assessable patients, 1 achieved complete response and 2 achieved partial responses. Conclusions: SCT400 is well-tolerated and has encouraging preliminary efficacy in Chinese patients with CD20+ B-cell NHL.

Ifosfamide, Cisplatin or Carboplatin, and Etoposide (ICE)-based Chemotherapy for Mobilization of Autologous Peripheral Blood Stem Cells in Patients with Lymphomas.

Background: High-dose chemotherapy followed by autologous stem cell transplantation (ASCT) is a promising approach for lymphomas. This study aimed to evaluate the effect of ifosfamide, cisplatin or carboplatin, and etoposide (ICE)-based regimen as a mobilization regimen on relapsed, refractory, or high-risk aggressive lymphoma. Methods: From June 2001 to May 2013, patients with lymphomas who mobilized by ICE-based regimen for ASCT were analyzed in this retrospective study. The results of the autologous peripheral blood stem cells collection, toxicity, engraftment after ICE-based mobilization regimen were analyzed in this study. Furthermore, risk factors for overall survival (OS) and progression free survival (PFS) were evaluated by univariate analysis. Results: The stem cells were mobilized using ICE-based regimen plus rituximab or ICE-based regimen alone in 12 patients and 54 patients, respectively. The results of stem cell mobilization were excellent. Ninety-seven percentages of the patients had the stem cell collection of at least 2.0 × 106 CD34+ cells/kg and 68% had at least 5 × 106 CD34+ cells/kg. Fifty-eight percentage of the patients experienced Grade 4 neutropenia, 20% developed febrile neutropenia, and only 12% had Grade 4 thrombocytopenia. At a median follow-up of 63.8 months, the 5-year PFS and OS were 64.4% and 75.3%, respectively. Conclusion: ICE is a powerful regimen for stem cell mobilization in patients with lymphomas.

A phase I study of different doses and frequencies of pegylated recombinant human granulocyte-colony stimulating factor (PEG rhG-CSF) in patients with standard-dose chemotherapy-induced neutropenia

Objective The recommended dose of prophylactic pegylated recombinant human granulocyte-colony stimulating factor (PEG rhG-CSF) is 100 μg/kg once per cycle for patients receiving intense-dose chemotherapy. However, few data are available on the proper dose for patients receiving less-intense chemotherapy. The aim of this phase I study is to explore the proper dose and administration schedule of PEG rhG-CSF for patients receiving standard-dose chemotherapy. Methods Eligible patients received 3-cycle chemotherapy every 3 weeks. No PEG rhG-CSF was given in the first cycle. Patients experienced grade 3 or 4 neutropenia would then enter the cycle 2 and 3. In cycle 2, patients received a single subcutaneous injection of prophylactic PEG rhG-CSF on d 3, and received half-dose subcutaneous injection in cycle 3 on d 3 and d 5, respectively. Escalating doses (30, 60, 100 and 200 μg/kg) of PEG rhG-CSF were investigated. Results A total of 26 patients were enrolled and received chemotherapy, in which 24 and 18 patients entered cycle 2 and cycle 3 treatment, respectively. In cycle 2, the incidence of grade 3 or 4 neutropenia for patients receiving single-dose PEG rhG-CSF of 30, 60, 100 and 200 μg/kg was 66.67%, 33.33%, 22.22% and 0, respectively, with a median duration less than 1 (0-2) d. No grade 3 or higher neutropenia was noted in cycle 3 in all dose cohorts. Conclusions The pharmacokinetic and pharmacodynamic profiles of PEG rhG-CSF used in cancer patients were similar to those reported, as well as the safety. Double half dose administration model showed better efficacy result than a single dose model in terms of grade 3 neutropenia and above. The single dose of 60 μg/kg, 100 μg/kg and double half dose of 30 μg/kg were recommended to the phase II study, hoping to find a preferable method for neutropenia treatment.