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- A meta-analysis of randomized controlled trials comparing early and late concurrent thoracic radiotherapy with etoposide and cisplatin/carboplatin chemotherapy for limited-disease small-cell lung cancer. [JOURNAL ARTICLE]
- Mol Clin Oncol 2014 Sep; 2(5):805-810.
The aim of the present study was to determine the optimal time for concurrent thoracic radiotherapy (TRT) with etoposide and cisplatin/carboplatin (EP/EC) chemotherapy for the treatment of limited-disease small-cell lung cancer (LD SCLC). Randomized controlled trials comparing early and late concurrent TRT with EP/EC chemotherapy for the treatment of patients with LD SCLC were identified through searching databases such as MEDLINE, the Cochrane Central Register of Controlled Trials and Embase. Early thoracic radiotherapy (ERT) was defined as initiating irradiation within 30 days after chemotherapy initiation. A total of 3 eligible randomized controlled trials were identified. No significant differences in the objective response rate were detected between early and late concurrent TRT [risk ratio (RR)=1.01; 95% confidence interval (CI): 0.86-1.18; P=0.90]. Similar results were observed in the 1-, 2-, 3- and 5-year survival rates between early and late concurrent TRT (RR=1.06, 95% CI: 0.88-1.27, P=0.56; RR=1.15, 95% CI: 0.77-1.71, P=0.49; RR=0.90, 95% CI: 0.66-1.22, P=0.49; and RR=1.18, 95% CI: 0.64-2.16, P=0.60, respectively). The total incidence of grade 3-4 adverse events, including anemia, leukopenia, neutropenia, thrombocytopenia, nausea and vomiting, infection, esophageal toxicity, pulmonary toxicity, alopecia and hemorrhage with early concurrent TRT was significantly higher compared to that with late concurrent TRT (RR=1.21, 95% CI: 1.03-1.43, P=0.02). Thus, the results of our study indicated that the prognosis of LD SCLC treated with late concurrent TRT and EP/EC chemotherapy is similar to that with early concurrent TRT, although the incidence of grade 3-4 adverse events was lower in LD SCLC patients treated with late concurrent TRT combined with EP/EC chemotherapy.
- Carboplatin plus etoposide in heavily pretreated castration-resistant prostate cancer patients. [Journal Article]
- Future Oncol 2014 Jun; 10(8):1353-60.
Aims:Carboplatin plus etoposide has modest efficacy in docetaxel-pretreated castration-resistant prostate cancer patients. We hypothesized that carboplatin-etoposide could still exert some therapeutic activity after docetaxel, cabazitaxel and either abiraterone or enzalutamide. Patients & methods: We enrolled 15 patients in the first step of a Phase II trial. The target sample size is 46 patients. The primary end point of the study was progression-free survival after 12 weeks.
Results:The median progression-free survival was 11 weeks (range: 8-18), while median overall survival was 18 weeks (range: 12-26). Of seven patients with measurable disease, two had a partial response, two showed stable disease and the remaining three had progressive disease as the best radiological response. Five patients were considered progression-free after 12 weeks, prompting continuation of the trial.
Conclusion:Our preliminary findings support the hypothesis that carboplatin plus etoposide may yield some clinical benefit in a population of patients who failed all currently approved therapeutic options for prostate cancer.
- [Effect of intermediate-dose cytarabine on mobilization of peripheral blood hematopoietic stem cell in acute myeloid leukemia]. [English Abstract, Journal Article]
- Zhonghua Xue Ye Xue Za Zhi 2014 Jul 14; 35(7):587-91.
To explore the impact of courses of intermediate-dose cytarabine (ID-Ara-C) chemotherapy on the efficiency of hematopoietic stem cell mobilization in acute myeloid leukemia (AML) patients with autologous hematopoietic stem cell transplantation (auto-HSCT).90 patients with de novo AML undergoing auto-HSCT between August 1999 and November 2012 were enrolled. All patients received the mobilization regimen of cytarabine and etoposide chemotherapy in combination with recombinant human granulocyte-colony stimulating factor (rhG-CSF). Stem cell apheresis was scheduled when blood leukocyte count recovered greater than 4.0×10⁹/L or the proportion of CD34⁺ cells greater than 1% in peripheral blood. The impact of ID-Ara-C courses on the mobilization efficiency was analyzed retrospectively.According to the ID-Ara-C courses, patients were divided into group A (<2 courses), B(2 courses), and C(>2 courses). The median doses of CD34⁺ cells (×10⁶/kg) in three groups were 4.7, 2.7, 2.3, respectively (P=0.003). Of the available 87 patients who could be evaluated, 61 (70.1%) cases had CD34⁺ cells greater than 2.0 × 10⁶/kg, and 26 (29.9%) cases less than 2.0 × 10⁶/kg. Of the 26 patients without satisfactory mobilization efficiency, 7 (15.2%) were in group A, 10 (47.6%) in group B, and 9 (45.0%) in group C (χ²=10.05, P=0.007). In addition, patients with satisfactory mobilization efficiency (CD34⁺ cells ≥2.0×10⁶/kg) in groups C needed more times of collection, more volume of blood processed, and even high-dose and longer course of rhG-CSF (P<0.05). In univariate analysis. The ID-Ara-C courses and the cumulative dose were significant correlate with mobilization efficiency. In multivariate analysis, the ID-Ara-C courses was an independent correlation factor for mobilization efficiency (odd ratio=0.623, 95% confidence interval=0.418-0.926, P=0.019). The sex, age, cytogenetic risk, the standard chemotherapy courses did not correlate with mobilization efficiency.The number of ID-Ara-C courses was independent factor for the mobilization efficiency and should be taken seriously in AML patients with auto-HSCT.
- Resistance Training Does Not Protect Against Increases in Plasma Cytokine Levels Among Germ Cell Cancer Patients During and After Chemotherapy. [JOURNAL ARTICLE]
- J Clin Endocrinol Metab 2014 Jul 22.:jc20134495.
Context: Testicular germ cell cancer (GCC) patients treated with cisplatin-etoposide-bleomycin chemotherapy (BEP) have excellent prognosis but have an increased risk of late-occurring morbidities, which may be associated with changes in the inflammatory profile. Objective: The objective of the study was to explore plasma cytokine concentrations in GCC patients randomized to resistance training or usual care during BEP, in comparison with healthy controls. Design/Setting: This was a randomized controlled trial in GCC patients enrolled from an oncology clinic, including a healthy reference group for comparison purposes. Outcome Measures: Plasma granulocyte macrophage colony-stimulating factor, interferon-γ, IL-1β, IL-2, IL-6, IL-8, IL-10, IL-12, and TNF-α were measured in fasting blood samples from GCC patients randomized to resistance training (INT; n = 15) or usual care (CON; n = 15) and healthy age-matched controls (REF; n = 19). Clinical toxicity assessments and patient-reported end points were also recorded. Results: CON and INT were balanced at baseline. Compared with REF, CON had higher concentrations of IL-10, IL-6, and interferon-γ, and INT had higher concentrations of IL-6, IL-8 and TNF-α (all P < .05). At the end of therapy, concentrations of IL-6, IL-8, and IL-10 increased in both GCC groups (all P < .01). Three months after therapy, all cytokine concentrations were comparable with the pretreatment levels in both GCC-groups but remained elevated compared with REF (P < .05). Changes in TNF-α correlated with pulmonary toxicity (P < .01). At the end of therapy, IL-6 concentrations correlated with quality of life (P < .05) and fatigue (P < .01). Conclusion: GCC patients treated with BEP display consistently elevated levels of systemic inflammatory markers compared with healthy controls. Resistance training during therapy has no impact on plasma cytokine concentrations.
- Cytotoxic effect of the biotechnologically-derived justicidin B on human lymphoma cells. [JOURNAL ARTICLE]
- Biotechnol Lett 2014 Jul 22.
Purpose of work: The study was aimed to assess the antineoplastic activity of justicidin B in vitro and to search for its general toxicological profile in vivo. The anti-neoplastic activity of the arylnaphthalene lignin, justicidin B, was assessed in a panel of human lymphoma cell lines and compared with etoposide as a reference compound. A screening of the cytotoxicity after 24, 48 and 72 h exposure was performed by the MTT-dye reduction assay. Dose- and time-dependent cytotoxic effect was observed and the IC50 values ranged from 0.17 µM (RPMI-8226, 72 h) to 183 µM (U-266, 24 h) and more than 200 µM (HD-MY-Z, 24 and 48 h). Activation of caspase 3 and 8 was involved in the induction of programmed cell death in DOHH-2 cell line. NF-κB modulation occurred in DOHH-2 and HH cells. The general toxicity in mice after i.p. injection was also tested. The highest applied dose (50 mg/kg = 137.25 µM) did not show any toxicity. Justicidin B possesses definite and potent selective antineoplastic activity, related to its ability to induce programmed cell death in NHL-derived human cell lines at concentrations that can be reached in mice without toxicity.
- Production of IL-1β by bone marrow-derived macrophages in response to chemotherapeutic drugs: Synergistic effects of doxorubicin and vincristine. [JOURNAL ARTICLE]
- Cancer Biol Ther 2014 Jul 21; 15(10)
Cytotoxic chemotherapeutic drugs, especially when used in combination, are widely employed to treat a variety of cancers in patients but often lead to serious symptoms that negatively affect physical functioning and quality of life. There is compelling evidence that implicates cytotoxic chemotherapy-induced inflammation in the etiology of these symptoms. Because IL-1β plays a central role as an initiator cytokine in immune responses, we compared doxorubicin, a drug known to induce IL-1β production, with ten other commonly prescribed chemotherapeutic drugs in their ability to lead to processing and secretion of IL-1β by primary mouse macrophages. Seven of them (melphalan, cisplatin, vincristine, etoposide, paclitaxel, methotrexate, and cytarabine) caused the production of IL-1β in cells pretreated with lipopolysaccharide. When delivered in combination with doxorubicin, one of the drugs, vincristine, was also capable of synergistically activating the NLRP3-dependent inflammasome and increasing expression of IL-1β, IL-6 and CXCL1. The absence of TNF-α and IL-1 signaling caused a partial reduction in the production of mature IL-1β. Three small-molecule inhibitors known to suppress activity of kinases situated upstream of mitogen-activated kinases (MAPKs) inhibited the expression of IL-1β, IL-6 and CXCL1 when doxorubicin and vincristine were used singly or together. Kinase inhibitors may be useful in reducing inflammation in patients receiving chemotherapy.
- Autologous Hematopoietic Stem Cell Transplantation for High-risk Acute Lymphoblastic Leukemia: non-Randomized Study with a maximum Follow-up of more than 22 Years. [Journal Article]
- Mediterr J Hematol Infect Dis 2014; 6(1):e2014047.
To evaluate the efficacy and toxicity of autologous hematopoietic stem cell transplantation (AHSCT) for high-risk acute lymphoblastic leukemia (ALL).Overall, 128 high-risk ALL patients at a median age of 26 years (range 18-56 years) at diagnosis received AHSCT between 1991-2008. Induction treatment was anthracycline-based in all patients. Conditioning regimen consisted of CAV (cyclophosphamide, cytarabine, etoposide) in 125 patients whereas 3 subjects received cyclophosphamide and TBI (total body irradiation). Bone marrow was stored for 72 hours in 4°C and re-infused 24 hours after conditioning completion. Bone marrow was a source of stem cells in 119 patients, peripheral blood in 2 and 7 subjects received both bone marrow and peripheral blood.With a median follow-up after AHSCT of 1.6 years (range 0.1-22.3 years), the probability of leukemia-free survival (LFS) for the whole group at 10 years was 27% and 23% at 20 years. Transplant-related mortality at 100 days after AHSCT was 3.2%. There was a strong tendency for better LFS for MRD-negative patients if compared with patients who had positive or unknown MRD status at AHSCT (32% vs 23% and 25%, respectively; p=0.06). There was no difference in LFS between B- and T-lineage ALL as well as between patients transplanted in first complete remission (CR1) and CR2. LFS at 10 years for patients with Philadelphia-positive (Ph+) ALL at transplant was 20% and this was comparable with subjects with negative and missing Ph status (26% and 28%; p=0.97).The results of AHSCT for high-risk ALL remains unsatisfactory with low probability of long-term LFS.
- Peripheral primitive neuroectodermal tumor of the dura in a 51-year-old woman following intensive treatment for breast cancer. [Journal Article]
- Am J Case Rep 2014.:294-9.
Patient: Female, 51 Final Diagnosis: Ewing sarcoma Symptoms: Visual disturbances Medication: - Clinical Procedure: - Specialty: Oncology.Rare disease.Primitive neuroectodermal tumor/Ewing sarcoma (PNET/EWS) is a round blue cell sarcoma that shows varying degrees of neuroectodermal differentiation. PNET/EWS as a primary intracranial tumor is extremely uncommon.We report a unique case of peripheral PNET presenting as an intracranial mass in an adult following chemotherapy and radiotherapy for a solid tumor. A 51-year-old woman with previously treated left breast cancer was evaluated for a newly developed brain mass. She underwent craniotomy with resection. Surgical pathology was consistent with a peripheral PNET/EWS with Ewing sarcoma gene translocation. She was treated appropriately with vincristine, cyclophosphamide, and doxorubicin (later dactinomycin) alternating with ifosfamide and etoposide.Although development of PNET/EWS presenting along the CNS is exceedingly rare in adults, establishing the proper diagnosis of this "small blue cell tumor" is critical. The further distinction between central PNET and peripheral PNET can greatly impact both prognosis and treatment. Our case also highlights the importance of considering the impact of prior intensive therapies, including radiation and chemotherapy, on predisposing to future PNET/EWS.
- Etoposide interferes with the process of chromatin condensation during alga Chara vulgaris spermiogenesis. [Journal Article]
- Micron 2014 Oct.:45-50.
DNA topoisomerase II plays an essential role in animal spermiogenesis, where changes of chromatin structure are connected with appearance of transient DNA breaks. Such topo II activity can be curtailed by inhibitors such as etoposide and suramine. The aim of the present study was to investigate, for the first time, the effect of etoposide on spermatid chromatin remodeling in the green alga Chara vulgaris. This inhibitor prolonged the early spermiogenesis stages and blocked the formation of the phosphorylated form of histone H2AX at stages VI-VII. The lack of transient DSBs at these stages impairs the elimination of supercoils containing nucleosomes which lead to disturbances in nucleoprotein exchange and the pattern of spermatid chromatin fibrils at stages VI-VIII. Immunofluorescent and ultrastructural observations revealed that during C. vulgaris spermiogenesis topo II played an important role similar to that in mammals. Some corresponding features had been pointed out before, the present studies showed further similarities.
- High-dose chemotherapy with autologous stem cell rescue for treatment of retinoblastoma: Report of five cases. [JOURNAL ARTICLE]
- Pediatr Transplant 2014 Jul 14.
RB is a primarily pediatric cancer arising from the retina, initiated by biallelic loss of the RB1 gene. We report five children with bilateral RB (n = 3), extra-ocular disseminated RB, or disseminated relapsed RB, who were treated with tandem high-dose chemotherapy and autologous stem cell rescue. All patients received at least 2.2 × 10(6) /kg CD34(+) (median, 3.9 × 10(6) /kg) cells. The preparative regimen for course 1 was carboplatin, thiotepa, etoposide, and for course 2, CM and melphalan. ANC of at least 0.5 × 10(9) /L occurred at a median of 11 days (range, 10-12) and 15 days (range, 12-16) after the first and second procedure, respectively. Platelet engraftment occurred at a median of 13 days (range, 12-17) and 15 days (range, 14-22) after the first and second procedure, respectively. All of the five patients treated remain alive and disease free at the last follow-up time, ranging between 21 and 44 months after completion of autologous transplant. Additional therapy was required in one patient, in whom enucleation had to be performed because of early disease relapse, refractory to local therapy. Intensification of chemotherapy with repeated high-dose chemotherapy and autologous rescue appears an acceptable choice in selected cases with bilateral or extra-ocular disease, either recurrent or refractory.