Effect of pentoxifylline on colon cancer patients treated with chemotherapy (Part I).

BACKGROUND: Cancer progression is associated with significant systemic clinical manifestations including cachexia induced weight loss and anorexia. Pentoxifylline (PTX) is a drug that has been shown to have multiple beneficial effects in cancer patients through its anti-inflammatory properties. MAIN OBJECTIVE: To evaluate PTX effects on colon cancer patients treated with chemotherapy. PATIENTS AND METHODS: Forty metastatic colon cancer patients receiving chemotherapy were enrolled in this randomized study. 17 patients were treated with a full dose of PTX (400 mg TID), 9 patients with a reduced dose PTX (200 mg TID) and 23 served as controls (no PTX). RESULTS: Follow-up evaluations of patients included the following: physical examination; leukopenia determination; weight determination; stomatitis determination; and survival rate. Patients treated with PTX (both full and reduced doses), experienced a significant increase in weight and a reduction in stomatitis relative to the control group. Treatment with PTX also significantly increased patient survival rate. All patients treated with PTX, had a median overall survival (OS) rate of 20.4 months as compared to 13.2 months in the control group. CONCLUSIONS: PTX treatment of colon cancer patients, in addition to chemotherapy, significantly improved survival rates, induced weight gain and reduced stomatitis occurrence -all important parameters of cachexia.

Efficacy of Aidi Injection and Brucea javanica Oil Emulsion Injection in Rectal Cancer during CapeOX Adjuvant Chemotherapy.

BACKGROUND: Adjuvant chemotherapy with CapeOX regimen is widely used in resected rectal cancer, which brings benefits to patients. But drug-related toxicities are severe during this process; thus, survival outcomes may potentially be affected. This study explored the efficacy of two Chinese herbal injections, Aidi injection (ADI) and Brucea javanica oil emulsion injection (BJOEI), as adjuvant drugs in CapeOX adjuvant chemotherapy on rectal cancer patients. METHODS: A total of 240 cases were enrolled in this retrospective study. 80 cases received CapeOX with ADI (the ADI group), 80 cases received CapeOX with BJOEI (the BJOEI group), and the rest 80 cases received CapeOX alone (the control group). After four cycles' chemotherapy, adverse reactions (ADRs) and quality of life (QOL) were analyzed. Then, patients received follow-up for at least one year, and the endpoint was disease-free survival (DFS). RESULTS: All patients completed at least four cycles' adjuvant chemotherapy. The incidence of leukopenia and thrombocytopenia was significantly lower in the ADI group; the incidence of nausea was significantly lower in the BJOEI group; the incidence of hand-foot syndrome was significantly lower in both the ADI group and BJOEI group. Significant difference was found in the control group regarding the Karnofsky Performance Status (KPS) scores prior and posttreatment. No difference was found among three groups regarding one-year DFS. CONCLUSION: As adjuvant drugs for rectal cancer during CapeOX chemotherapy, ADI shows advantages in decreasing leukopenia and thrombocytopenia, while BJOEI results better in remitting nausea. Both two CHIs had positive impacts on decreasing hand-foot syndrome and the maintenance of patients' QOL. It is worthy of further study and promotion for CHIs.

Risk Factors and Management of Leukopenia After Kidney Transplantation: A Single-Center Experience.

BACKGROUND: Leukopenia is a common complication after kidney transplantation. The etiology is multifactorial, with medication adverse effects and cytomegalovirus infection as main causes. Optimal strategies to prevent or treat posttransplant leukopenia remain unknown. We aimed to identify risk factors for leukopenia and to investigate the benefit of switching the immunosuppressive therapy to hydrocortisone as a continuous infusion. METHODS: We retrospectively evaluated all patients with leukopenia after kidney transplantation between 2007 and 2017 at our center relative to age- and sex-matched controls. RESULTS: Leukopenia was associated with the degree of rejection therapy before leukopenia, the immunosuppressive therapy before transplantation, and an induction therapy with rabbit antithymocyte globulin. Patients with leukopenia exhibited increased mortality, an increased incidence of bacterial and viral infections, and more acute rejections. Switching to hydrocortisone as a continuous infusion in patients with severe leukopenia decreased the duration of leukopenia and the incidence of subsequent viral infections, especially with cytomegalovirus. CONCLUSION: Leukopenia is a risk factor for infectious complications and mortality, and it is associated with acute rejection. Switching immunosuppressive therapy to hydrocortisone as a continuous infusion is a safe approach to reduce the duration of leukopenia and the incidence of viral infections.

New Drug Protects Against Myelosuppression Secondary to Lung Cancer Chemotherapy.

Trilaciclib (Cosela) is approved to protect normal bone marrow cells from damage secondary to chemotherapy in adults receiving a platinum-etoposide chemotherapy regimen or a topotecan chemotherapy regimen for extensive-stage small cell lung cancer.

Conversion from cytomegalovirus universal prophylaxis with valganciclovir to the preemptive monitoring approach to manage leukopenia after kidney or pancreas transplantation.

PURPOSE: In clinical practice, conversion from universal cytomegalovirus prophylaxis (CMV PPX) with valganciclovir (VGC) to targeted therapy (preemptive monitoring, PEM) is often pursued in the setting of leukopenia. It is unknown if this is an effective strategy. METHODS: Adult patients receiving a kidney and/or pancreas transplant were included if converted from PPX to PEM between 9/1/19 and 3/1/20 due to leukopenia. A positive CMV viral load (VL) was defined as CMV PCR greater than the lower limit of quantification (LLOQ) based on local lab testing. A CMV VL of >500 IU/mL was chosen as the preemptive treatment (PET) threshold. Primary objective was to describe the impact of conversion on resolution of leukopenia. Secondary objectives were to assess PEM associated outcomes. RESULTS: There were 49 patients converted from PPX to PEM due to leukopenia in the study period; 88% were KTRs and 96% received lymphocyte-depleting induction; 84% were seropositive at transplant (R+) and 16% were high-risk (D+/R-). Mean WBC at time of enrollment was 1.4 ± 0.4. After PEM conversion, WBC recovered to >3 in 87.8% of the population in a mean of 26.8 ± 24.5 days. Immunosuppression was modified in 96% of the population and GCSF was required in 46.9% of patients. CMV viremia occurred in 36.7% of the population; 78% were KTRs and 94% were R+. Time from PEM enrollment to PET was 64 ± 34 days. Median VL at first detection was 587 IU/mL, median peak was 1920 IU/mL. Five patients (27.8%) presented with symptoms consistent with CMV syndrome, none had end organ disease. Six patients (33%) presented with a VL <500 IU/mL at first detection, but all subsequently surpassed the threshold and required PET. Mean duration of PET was 25 ± 11 days. Mean change in WBC in response to PET was -0.4 ± 1.3. Immunosuppression required further adjustment in 61% of patients. There were no deaths or graft loss due to CMV at last follow-up. CONCLUSION: In kidney and pancreas transplant recipients who undergo PEM conversion due to leukopenia, withholding of VGC can improve leukopenia, but other concomitant measures are necessary. This population should be considered fairly high risk, with a threshold of treatment of first quantifiable replication. Our findings suggest lack of harm from this approach but highlight the importance of close monitoring to prevent symptomatic replication. Larger studies with longer follow-up are needed to better evaluate the impact of PEM conversion on late-onset CMV and patient and graft outcomes.

Cabazitaxel schedules in metastatic castration-resistant prostate cancer: a review.

Cabazitaxel (25 mg/m2 every 3 weeks) is the standard second-line chemotherapy for patients with metastatic castration-resistant prostate cancer previously treated with docetaxel. It is associated with a risk of neutropenic complications, which may be a barrier to its use in daily clinical practice, particularly in frail elderly patients. Here the authors reviewed key studies conducted with cabazitaxel (TROPIC, PROSELICA, AFFINITY, CARD and the European compassionate use program) and pilot studies with adapted schedules. Based on this review, the use of prophylactic granulocyte colony-stimulating factor from cycle 1 appears crucial to maximize the benefit-risk ratio of cabazitaxel in metastatic castration-resistant prostate cancer. Preliminary data with alternative schedules look promising, especially for frail patients. Results of the ongoing Phase III CABASTY trial (ClinicalTrials.gov: NCT02961257) are awaited.

Ziyuglycoside II alleviates cyclophosphamide-induced leukopenia in mice via regulation of HSPC proliferation and differentiation.

Ziyuglycoside II (ZGS II) is a major bioactive ingredient of Sanguisorbae officinalis L., which has been widely used for managing myelosuppression or leukopenia induced by chemotherapy or radiotherapy. In the current study, we investigated the pro-hematopoietic effects and underlying mechanisms of ZGS II in cyclophosphamide-induced leukopenia in mice. The results showed that ZGS II significantly increased the number of total white blood cells and neutrophils in the peripheral blood. Flow cytometry analysis also showed a significant increase in the number of nucleated cells and hematopoietic stem and progenitor cells (HSPCs) including ST-HSCs, MPPs, and GMPs, and enhanced HSPC proliferation in ZGS II treated mice. The RNA-sequencing analysis demonstrated that ZGS II effectively regulated cell differentiation, immune system processes, and hematopoietic system-related pathways related to extracellular matrix (ECM)-receptor interaction, focal adhesion, hematopoietic cell lineage, cytokine-cytokine receptor interaction, the NOD-like receptor signaling pathway, and the osteoclast differentiation pathway. Moreover, ZGS II treatment altered the differentially expressed genes (DEGs) with known functions in HSPC differentiation and mobilization (Cxcl12, Col1a2, and Sparc) and the surface markers of neutrophilic precursors or neutrophils (Ngp and CD177). Collectively, these data suggest that ZGS II protected against chemotherapy-induced leukopenia by regulating HSPC proliferation and differentiation.

Amelioration of cyclophosphamide-induced myelosuppression during treatment to rats with breast cancer through low-intensity pulsed ultrasound.

To investigate the alleviating effects of low-intensity pulsed ultrasound (LIPUS) on myelosuppression of Sprague-Dawley rats with breast cancer induced by cyclophosphamide (CTX). Breast cancer in rats was triggered by intragastric gavage with 7,12-dimethylbenz[a]anthracene (150 mg/kg). Then, the rats with breast cancer were randomly allocated to the LIPUS group (n=50) and the control group (n=50). The LIPUS group was injected intraperitoneally with CTX (50 mg/kg) for 4 consecutive days and underwent LIPUS treatment at femoral metaphysis 20 min per day from the first day of injection for 7 consecutive days. The control group was injected with CTX (50 mg/kg) and treated with LIPUS without energy output. Blood, enzyme-linked immunosorbent assay (ELISA), real-time quantitative polymerase chain reaction, Hematoxylin and Eosin (H&E) staining, and scanning electron microscopy were applied to detect the changes. The results indicated that LIPUS significantly promoted the proliferation of bone marrow nucleated cells, white blood cells (WBCs), IgA, IgG, and IgM in the peripheral blood (P<0.05) without the damage to liver and kidney function simultaneously. The mechanisms may result from the LIPUS alleviation effect on bone marrow hematopoietic function through regulating cytokines such as LIPUS can increase the expression of granulocyte colony-stimulating factor (G-CSF), stem cell factor, transforming growth factor-ß, and intercellular cell adhesion molecule-1, meanwhile LIPUS will decrease the expression of interleukin-6, tumor necrosis factor-α, and vascular cell adhesion molecule-1. LIPUS has potential to be a new adjuvant therapy method in clinic for ameliorating chemotherapy-induced myelosuppression.

Sulfated polymannuroguluronate TGC161 ameliorates leukopenia by inhibiting CD4+ T cell apoptosis.

Polysaccharides have aroused considerable interest due to their diverse biological activities and low toxicity. In this study, we evaluated the effect of marine polysaccharide sulfated polymannuroguluronate (TGC161) on the leukopenia induced by chemotherapy. It is found that TGC161 ameliorates the leukopenia. Besides, TGC161 would promote CD4+ T cell differentiation and maturation in the thymus, but does not have a significant effect on precursor cells in bone marrow. Furthermore, TGC161 inhibits CD4+ T cell apoptosis in vitro. Collectively, our findings offer a natural and harmless polysaccharide to ameliorate leukopenia.

Impact of Granulocyte Colony-Stimulating Factor (G-CSF) and Epoetin (EPO) on Hematologic Toxicities and Quality of Life in Patients During Adjuvant Chemotherapy in Early Breast Cancer: Results From the Multi-Center Randomized ADEBAR Trial.

BACKGROUND: Hematologic toxicities are one of the greatest challenges in adjuvant chemotherapy for breast cancer. This analysis of the ADEBAR trial aims to evaluate application and effect of granulocyte colony-stimulating factor (G-CSF) and epoetin alfa (EPO) on hematologic parameters and fatigue in patients with breast cancer during chemotherapy. PATIENTS AND METHODS: In the ADEBAR trial, 1493 patients with node-positive primary breast cancer were randomized to either 6 × 5-fluorouracil, epirubicin, and cyclophosphamide (FEC120) or 4 × epirubicin and cyclophosphamide followed by 4 × docetaxel (EC-DOC). Co-medication with G-CSF or EPO was applied to treat chemotherapy-induced leukopenia or anemia. Fatigue was assessed at baseline and after one-half of the chemotherapy. RESULTS: In total, 899 patients could be included in the analysis. There was no evidence for an association between leucocyte or hemoglobin levels and application of G-CSF and EPO in the preceding cycle, respectively. Hemoglobin levels (B = -0.41; P < .001) were affected by treatment regimen. Fatigue during chemotherapy was mostly affected by the level of fatigue before the start of chemotherapy (B = 0.41; P < .001). Patients with G-CSF application in the preceding cycle showed an increased fatigue score (B = 5.43; P = .02). CONCLUSION: We showed that fatigue during adjuvant chemotherapy was mostly affected by the level of fatigue present before the start of chemotherapy. This result suggests that the level of fatigue before the start of treatment should be included as an important factor when deciding on type and toxicity of chemotherapy in early breast cancer.

Adjustment of azathioprine dose should be based on a lower 6-TGN target level to avoid leucopenia in NUDT15 intermediate metabolisers.

BACKGROUND: The association between NUDT15 polymorphisms and thiopurine-induced leucopenia is well known. AIM: To investigate the association between NUDT15 polymorphisms and time-to-leucopenia in paediatric patients with inflammatory bowel disease (IBD) receiving azathioprine and to determine the relationship between NUDT15 polymorphisms and 6-thioguanine nucleotide (6-TGN) levels. METHODS: This retrospective observational study included Korean paediatric patients with IBD who were treated with azathioprine and underwent NUDT15 and TPMT genotyping. Azathioprine doses were adjusted by regular thiopurine metabolite monitoring. Factors associated with time-to-leucopenia and the relationship between NUDT15 polymorphisms and 6-TGN levels were analysed. RESULTS: Among the 167 patients included, leucopenia was observed in 16% (19/119), 44% (20/45) and 100% (3/3) of the NUDT15 normal, intermediate and poor metabolisers respectively (P < 0.001). NUDT15 polymorphism was significantly associated with time-to-leucopenia (HR = 5.26, 95% CI = 2.74-10.09, P < 0.001). There was a positive association between 6-TGN levels and leucopenia among the NUDT15 intermediate/TPMT normal metabolisers (median 361.3 vs 263.8 pmol/8 × 108 RBC, P = 0.013). The most accurate 6-TGN cut-off level associated with leucopenia was 308.2 pmol/8 × 108 RBC (AUC = 0.742, 95% CI = 0.569-0.915, sensitivity 80.0%, specificity 72.7%, P < 0.001) in this subgroup. When the specificity was set to <15%, the 6-TGN cut-off level was 167.1 pmol/8 × 108 RBC (sensitivity 93.3%, specificity 13.6%). CONCLUSIONS: NUDT15 polymorphisms were associated with time-to-leucopenia during azathioprine treatment in Korean paediatric patients with IBD. In order to reduce the development of thiopurine-induced leucopenia (<15%) in NUDT15 intermediate metabolisers, adjustment of azathioprine doses should be based on a lower 6-TGN target level (<167.1 pmol/8 × 108 RBC).

The coffee ingredients caffeic acid and caffeic acid phenylethyl ester protect against irinotecan-induced leukopenia and oxidative stress response.

BACKGROUND AND PURPOSE: Irinotecan, used in colorectal cancer therapy, is metabolized by glucuronidation involving different UDP-glucuronosyltransferase (UGT)1A isoforms leading to facilitated elimination from the body. Individuals homozygous for the genetic variants UGT1A1*28 (Gilbert syndrome) and UGT1A7*3 are more susceptible to irinotecan side effects, severe diarrhoea and leukopenia. The aim of this study was to investigate the protective effects and active constituents of coffee during irinotecan therapy using humanized transgenic (htg)UGT1A-WT and htgUGT1A-SNP (carry UGT1A1*28 and UGT1A7*3 polymorphisms) mice. EXPERIMENTAL APPROACH: HtgUGT1A mice were pretreated with coffee or caffeic acid (CA) + caffeic acid phenylethyl ester (CAPE) and injected with irinotecan. The effects of coffee and CA + CAPE were investigated using reporter gene assays, immunoblot, TaqMan-PCR, siRNA analyses and blood counts. KEY RESULTS: Only the combination of the two coffee ingredients, CA and CAPE, mediates protective effects of coffee in a model of irinotecan toxicity by activation of UGT1A genes. Coffee and CA + CAPE significantly increased UGT1A expression and activity along with SN-38 glucuronide excretion in irinotecan-injected htgUGT1A mice, resulting in significant improvement of leukopenia, intestinal oxidative stress and inflammation. CONCLUSION AND IMPLICATIONS: In this study, we identify the compounds responsible for mediating the previously reported coffee-induced activation of UGT1A gene expression. CA and CAPE represent key factors for the protective properties of coffee which are capable of reducing irinotecan toxicity, exerting antioxidant and protective effects. Provided that CA + CAPE do not affect irinotecan efficacy, they might represent a novel strategy for the treatment of irinotecan toxicity.

The potential agents from food for preventing leukopenia induced by benzene: garlic preparations.

Leukopenia is the early clinical manifestation of benzene poisoning. The aim of our research was to evaluate the preventive effects of three kinds of garlic preparations on benzene induced leukopenia. The mouse model of Leukopenia was established with benzene orally. At the same time, mice were administrated with garlic homogenate (GH), garlic oil (GO) or diallyl trisulfide (DATS) as preventional measures. The counts of white blood cells (WBC), the organ indexes, pathological examinations, blood biochemical parameters, weight gains, and food intakes were evaluated to observe the protective effect and potential adverse events. The results demonstrated that the counts of WBC increased by 144.04%, 140.07%, and 148.34%, respectively, after intervention by GH (400 mg/kg), GO (60 mg/kg) and DATS (30 mg/kg), compared with that in the model group. The spleen and thymus indexes in the benzene model group were 44.99% and 54.04% lower than those in the blank control group, the number of spleen nodules reduced and the thymus atrophy, which were restored by three garlic preparations at different degree. The results suggested that the three preparations all could prevent the leukopenia and protect the organ injuries induced by benzene. However, the spleen index and weight gains revealed that GH and GO brought more adverse events than DATS.

Protective and adaptogenic role of peroxiredoxin 2 (Prx2) in neutralization of oxidative stress induced by ionizing radiation.

A radioprotective effect of exogenous recombinant peroxiredoxin 2 (Prx2) was revealed and characterized using an animal model of whole body X-ray irradiation at sublethal and lethal doses. Prx2 belongs to an evolutionarily ancient family of peroxidases that are involved in enzymatic degradation of a wide variety of organic and inorganic hydroperoxides. Apart from that, the oxidized form of Prx2 also exhibits chaperone activity, thereby preventing protein misfolding and aggregation under oxidative stress. Intravenous administration of Prx2 in animals at a concentration of 20 µg/g 15 min before exposure to ionizing radiation contributes to a significantly higher survival rate, suppresses the development of leucopenia and thrombocytopenia, as well as protects the bone marrow cells from genome DNA damage. Moreover, injection of Prx2 leads to suppression of apoptosis, stimulates cell proliferation and results in a more rapid recovery of the cell redox state. Exogenous Prx2 neutralizes the effect of the priming dose on the second irradiation of the cells. The radioprotective properties of exogenous Prx2 are stipulated by its broad substrate peroxidase activity, chaperone activity in the oxidized state, and are also due to the signal-regulatory function of Prx2 mediated by the regulation of the level of hydroperoxides as well as via interaction with redox-sensitive regulatory proteins.

Using PARP Inhibitors in Advanced Ovarian Cancer.

Poly(ADP-ribose) polymerase (PARP) proteins are used by cells in several DNA repair processes. PARP inhibition can result in preferential death of cancer cells when another mechanism for repairing DNA is defective. Two PARP inhibitors, olaparib and rucaparib, have been approved by the US Food and Drug Administration (FDA) for the treatment of recurrent, BRCA-associated ovarian cancer. More recently, these two and a third PARP inhibitor, niraparib, were approved by the FDA as maintenance therapy following platinum-based chemotherapy for recurrent ovarian cancer. This has caused a paradigm shift in disease management and a challenge for clinicians, who must decide how best to use these agents in individualized treatment. The oral formulation is attractive to patients, but adverse effects such as nausea and fatigue can impact quality of life. As clinicians become comfortable selecting PARP inhibitors and managing associated toxicities, future steps will be to investigate how to safely administer them in combination with other therapies.

Local innate responses and protective immunity after intradermal immunization with bovine viral diarrhea virus E2 protein formulated with a combination adjuvant in cattle.

Bovine viral diarrhea virus (BVDV) is one of the most serious pathogens in cattle. Recently, we developed a novel adjuvant platform (TriAdj) that includes a toll-like receptor 3 agonist, poly (I:C); an innate defense regulatory peptide; and water-soluble polymer, poly[di(sodiumcarboxylatoethylphenoxy)]-phosphazene (PCEP). To develop a needle-free intradermal (ID) subunit vaccine, the BVDV type-2 E2 protein was formulated with TriAdj, and immune protection was evaluated in calves against a BVDV-2 strain. Intradermal delivery of E2/TriAdj elicited robust virus neutralizing antibodies and cell-mediated immune responses including CD4+ and CD8+ T-cell responses. The development of CD8+ T-cell responses in vaccinated calves indicates that TriAdj promotes cross-presentation. Upon challenge with virulent BVDV-2, the vaccinated calves showed no weight loss, leukopenia or virus shedding, and almost no temperature increase, in contrast to the control animals, which had severe clinical disease and shed virus for three to six days in nasal fluids and white blood cells. Intradermal vaccination was shown to attract various immune cell populations including dendritic cells, the most important antigen presenting cells. These data demonstrate that ID delivery is suitable as an administration route in cattle and that ID delivered, TriAdj-formulated E2 can protect cattle from BVDV-2.

Early Assessment of Thiopurine Metabolites Identifies Patients at Risk of Thiopurine-induced Leukopenia in Inflammatory Bowel Disease.

BACKGROUND AND AIMS: Only a quarter of thiopurine-induced myelotoxicity in inflammatory bowel disease [IBD] patients is related to thiopurine S-methyltransferase deficiency. We determined the predictive value of 6-thioguanine nucleotide [6-TGN] and 6-methylmercaptopurine ribonucleotide [6-MMPR] concentrations 1 week after initiation [T1] for development of leukopenia during the first 8 weeks of thiopurine treatment. METHODS: The study was performed in IBD patients starting thiopurine therapy as part of the Dutch randomized controlled TOPIC trial [ClinicalTrials.gov NCT00521950]. Blood samples for metabolite measurement were collected at T1. Leukopenia was defined by leukocyte counts of <3.0 × 109/L. For comparison, patients without leukopenia who completed the 8 weeks on the stable dose were selected from the first 272 patients of the TOPIC trial. RESULTS: Thirty-two patients with, and 162 patients without leukopenia were analysed. T1 threshold 6-TGN concentrations of 213 pmol/8 × 108 erythrocytes and 3525 pmol/8 × 108 erythrocytes for 6-MMPR were defined: patients exceeding these values were at increased leukopenia risk (odds ratio [OR] 6.2 [95% CI: 2.8-13.8] and 5.9 [95% CI: 2.7-13.3], respectively). Leukopenia rates were higher in patients treated with mercaptopurine, compared with azathioprine (OR 7.3 [95% CI: 3.1-17.0]), and concurrent anti-TNF therapy (OR 5.1 [95% CI: 1.6-16.4]). Logistic regression analysis of thiopurine type, threshold concentrations, and concurrent anti-tumour necrosis factor [TNF] therapy revealed that elevations of both T1 6-TGN and 6-MMPR resulted in the highest risk for leukopenia, followed by exceeding only the T1 6-MMPR or 6-TGN threshold concentration (area under the curve 0.84 [95% CI: 0.76-0.92]). CONCLUSIONS: In ~80% of patients, leukopenia could be explained by T1 6-TGN and/or 6-MMPR elevations. Validation of the predictive model is needed before implementing in clinical practice.

[Clinical Efficacy of Cepharanthin(R)for Radiotherapy-Induced Leukopenia - A Nationwide, Multicenter, and Observational Study].

The clinical efficacy and safety of cepharanthin for the treatment of radiotherapy-induced leukopenia were reevaluated at multiple institutions.Clinical data of cancer patients aged over 20 years old, who received a total radiotherapy dose above 40 Gy, and who were treated with cepharanthin for more than 2 weeks between April 2007 and November 2012, were evaluated. Data from 65 patients(males: 31, females: 34)from 7 facilities were analyzed to assess efficacy and adverse events.The mean leukocyte count was significantly higher at the end of the treatment compared with the initial data.However, no significant differences were observed in erythrocyte and platelet counts.No adverse events attributed to cepharanthin were reported.Although this was a retrospective study, cepharanthin was found to be safe and significantly effective for the management of leukopenia caused by radiotherapy.

Seminiferous epithelium damage after short period of busulphan treatment in adult rats and vitamin B12 efficacy in the recovery of spermatogonial germ cells.

Several different strategies have been adopted in attempt to recover from chemotherapy-damaged spermatogenesis that is often seen in oncologic patients. In this study, we have evaluated the impact of short period of exposure to busulphan on the haemogram and seminiferous epithelium of adult rats, focusing on spermatogonial depletion and Sertoli cell (SC) integrity. We then examined whether vitamin B12 supplementation improves the haematological parameters and spermatogonia number. The animals received 10 mg/kg of busulphan (BuG) or busulfan+vitamin B12 (Bu/B12 G) on the first and fourth days of treatment. In H.E.-stained testicular sections, the areas of the seminiferous tubule (ST) and seminiferous epithelium were measured. The number of spermatogonia in H.E-stained and PCNA-immunolabelled testicular sections was quantified. The frequency of tubules with abnormal SC nuclei or TUNEL-positive SC was evaluated. Vimentin immunofluorescence in ST was also evaluated. In BuG and Bu/B12 G, the animals showed leukopenia and thrombocytopenia, but the body weight reduced only in BuG. The areas of ST and seminiferous epithelium decreased in Bu/B12 G and BuG. In BuG, the number of H.E.-stained and PCNA-immunolabelled spermatogonia reduced significantly. The frequency of tubules containing abnormal SC nuclei and TUNEL-positive SC increased and the vimentin immunoexpression pattern changed. In Bu/B12 G, the number of H.E.-stained or PCNA-immunolabelled spermatogonia increased fourfold in comparison with BuG. The structural changes in ST after 6 days of busulphan exposure may be associated with the potential effect of this anti-neoplastic agent on SC. The increased number of spermatogonia in the busulphan-treated animals receiving vitamin B12 indicates that this vitamin can be an adjuvant therapy to improve the fertility in male cancer patients.