Regimen For Cancer Patients Research Articles

Explaining the Experiences of the Reasons for Non-Adherence to Treatment of Leukemia Cancer Patients in the Least Privileged Province of the Country: A Qualitative Study

Introduction: One of the most important challenges in cancer patients is the long treatment period, and as a result, non-compliance with the treatment, considering the cultural and indigenous context of Sistan and Baluchistan province, the importance of this position is felt more. Therefore, the present study was conducted with the aim of explaining the experiences of non-adherence to treatment in Leukemia cancer patients. Methods: This cross-sectional study was conducted qualitatively with a content analysis approach via a purpose-based sampling method on 34 leukemia cancer patients with a mean age of 46±7 in 2022. The data collection tool was a semi-structured interview guide. All interviews were recorded and implemented daily on paper. Finally, the data was coded using conventional content analysis method. Results: In this study, 17 women and 17 men were included in the study. 9 (26/5%) of them were more than 50 years old. After summarizing and coding the issues raised by the participants, 114 initial codes were obtained, five main themes (financial problems, lack of access to medical services, distrust of the health system and treatment, drug interactions and lack of motivation to continue treatment) and 10 sub-themes were extracted. Conclusion: It can be concluded that adherence to drug regimen in cancer patients is a complex issue that depends on many factors. The financial and spiritual support of the government, increasing insurance coverage, and developing infrastructure for better access of patients to medicines and medical centers are among the implementation suggestions of this study.

High glucose reduces anti-tumor activity of aromatase inhibitors in a hormone-dependent breast cancer cell model

One third of breast cancer patients also suffer from diabetes, which is associated with a 40% higher risk of mortality. Patients undergoing anti-cancer treatment are also exposed to xenoestrogens present in everyday life, which may affect the effectiveness of the therapies used. The purpose of our study was to analyzed the effect of metalloestrogens (Al, Cr[III]) on the effectiveness of aromatase inhibitors (AIs) under high glucose conditions prevailing in the cellular model. On two human breast cancer cell lines—MCF-7 and MCF-7/DOX—a cell viability assay, a flow cytometer analysis of apoptosis, and protein activity of BAX, Bcl-2, and VEGF-A by ELISA were carried out. Results were analyzed using one-way ANOVA, followed post hoc by Tukey’s multiple comparisons tests. High glucose conditions reduced the effectiveness of AIs in both cell lines (decreased cytotoxicity, inhibition of apoptosis, increase in Bcl-2/BAX ratio and angiogenesis), regardless of the combination with metalloestrogens. Hyperglycemia may affect the effectiveness of AIs to a greater extent than metalloestrogens alone - the activity of drugs in the presence of high glucose concentrations was significantly lower, regardless of the combination with metalloestrogens, which indicates the key role of hyperglycemia in attenuating their activity. Therefore controlling hyperglycemia and individualized treatment regimens in cancer patients with diabetes may have important therapeutic implications.

A mini-review on anticancer-related properties of azithromycin and its potential activities in overcoming the challenges of glioblastoma.

The resistance, plasticity and heterogeneity of cancer cells, including glioblastoma (GB) cells, have prompted the investigation of various agents for possible adjuncts and alternatives to existing therapies. This includes a macrolide antibiotic, azithromycin (AZI). It possesses intriguing anticancer properties in a range of cancer models in vitro, such as antiproliferative, pro-apoptotic, anti-autophagy and anti-angiogenic effects. In fact, AZI is renowned for its ability to eradicate cancer stem cells by inhibiting mitochondrial biogenesis and respiration. AZI-containing regimens in cancer patients for different purposes have shown favourable (i.e., attributed to its antibacterial activity) and unfavourable outcomes. Whilst its direct anticancer effects have yet to be clinically proven. To that end, this review provides a summary of AZI anticancer studies and delineates its potential activities in overcoming the challenges of GB.

Comparative study of changes in renal and electrolyte profiles induced by liposomal doxorubicin versus conventional doxorubicin-based regimens in cancer patients

Comparative study of changes in renal and electrolyte profiles induced by liposomal doxorubicin versus conventional doxorubicin-based regimens in cancer patients

Preclinical development of a vaccine-based immunotherapy regimen (VBIR) that induces potent and durable T cell responses to tumor-associated self-antigens.

The development of therapeutic cancer vaccines remains an active area, although previous approaches have yielded disappointing results. We have built on lessons from previous cancer vaccine approaches and immune checkpoint inhibitor research to develop VBIR, a vaccine-based immunotherapy regimen. Assessment of various technologies led to selection of a heterologous vaccine using chimpanzee adenovirus (AdC68) for priming followed by boosts with electroporation of DNA plasmid to deliver T cell antigens to the immune system. We found that priming with AdC68 rapidly activates and expands antigen-specific T cells and does not encounter pre-existing immunity as occurs with the use of a human adenovirus vaccine. The AdC68 vector does, however, induce new anti-virus immune responses, limiting its use for boosting. To circumvent this, boosting with DNA encoding the same antigens can be done repetitively to augment and maintain vaccine responses. Using mouse and monkey models, we found that the activation of both CD4 and CD8 T cells was amplified by combination with anti-CTLA-4 and anti-PD-1 antibodies. These antibodies were administered subcutaneously to target their distribution to vaccination sites and to reduce systemic exposure which may improve their safety. VBIR can break tolerance and activate T cells recognizing tumor-associated self-antigens. This activation lasts more than a year after completing treatment in monkeys, and inhibits tumor growth to a greater degree than is observed using the individual components in mouse cancer models. These results have encouraged the testing of this combination regimen in cancer patients with the aim of increasing responses beyond current therapies.

Abstract 84: Sensitive and unbiased detection of clinically actionable gene fusions from FFPE tumor biopsies using the Arima-HiC platform

Abstract Accurate and sensitive identification of gene fusions is critical to understanding disease mechanisms and the development and selection of optimal treatment regimens for cancer patients. Typically, these fusions are detected using low-resolution karyotyping, low throughput and biased FISH assays, or RNA sequencing approaches; however, the accuracy and sensitivity of gene fusion detection can be limited by factors such as low transcript abundance, transcript length, RNA degradation from formalin fixed paraffin embedded (FFPE) tissues, or the limited availability of fresh biopsy samples for RNA extraction. To address these limitations, we developed a novel approach to identifying gene fusions from FFPE samples using the Arima-HiC platform and short-read sequencing. We performed pan-cancer analysis on 12 FFPE adult tumor biopsies, each with gene fusions known to be clinically actionable. With this newly developed Hi-C workflow we identified all the known gene fusions with 100% sensitivity in the samples including those involving ALK, NTRK3, ROS1, FGFR2, and SS18 genes. This approach also revealed that the NTRK3 gene fusion was the result of a more complex rearrangement within chr12, within chr15, and between chr12 and chr15. Additionally, we detected the presence of numerous structural variants per sample in addition to the known gene fusion in each sample. For example in a bile duct tumor, Arima-HiC detected an FGFR2-EEA1 gene fusion, as well as 25 other structural variants genome-wide including in a CPD-LASP1 gene fusion This gene fusion has not been reported to our knowledge, however, LASP1 is a reported 3’ fusion partner with MLL in leukemia. While these findings are not clinically actionable today, the unbiased, accurate, and sensitive detection of structural variants from frozen and FFPE solid tumor biopsies may facilitate further research into their relationship between disease mechanisms and clinical outcomes. Taken together, these findings demonstrate the analytical utility of Arima Hi-C sequencing technology to provide both chromosome-scale and gene-level resolution for the detection of structural variants in tumor biopsies samples. This workflow can provide improved access to critical genomic information from FFPE blocks for the identification of pathognomonic and druggable gene fusion events and other structural variants across tumor types. Citation Format: David Jacob Hermel, Kristin Sikkink, Derek Reid, Anthony Schmitt, Darren S. Sigal. Sensitive and unbiased detection of clinically actionable gene fusions from FFPE tumor biopsies using the Arima-HiC platform [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2022; 2022 Apr 8-13. Philadelphia (PA): AACR; Cancer Res 2022;82(12_Suppl):Abstract nr 84.

The application and research advances of organoids in clinical medicine

<p indent="0mm">Three-dimensional cultured organoids recapitulate histopathologic and molecular characteristics of the primary tissues. The rise and development of organoids provide an important platform for clinical medicine research. Patient-derived organoids could be used as models to help clinicians to better understand the pathophysiology of related diseases and formulate corresponding treatment strategies; Organoids derived from tumors could be utilized as a drug screening system for precision medicine, helping clinicians to select the most appropriate regimen for cancer patients and to improve the clinical outcome. This review would summarize the application and research advances of organoids in clinical medicine.

Oral Versus Intravenous Chemotherapy in COVID-19 Epidemic

The novel coronavirus has a significant impact on the routine clinical practice for cancer patients in China since December 2019. During the epidemic in mainland China, especially Wuhan, the intravenous chemotherapies of cancer patients were considerably delayed. Up to now, cancer patients throughout the world directly encounter similar obstacles. For patients who have the right to choose chemotherapeutic regimens with different administration routes, oral drugs can be considered to be applied. In this mini-review, oral chemotherapeutic drugs were compared with intravenous drugs in seven types of tumors. Accordingly, we intended to provide useful suggestions for clinicians to balance the benefits and risks of oral against intravenous chemotherapies and to choose properly substituted oral chemotherapeutic regimens for cancer patients amid the coronavirus disease 2019 (COVID-19) pandemic.

The importance of developing new mannan tests in the diagnosis of invasive candidiasis in oncology patients

The regimens of anticancer therapy have been intensified and methods of high-dose chemotherapy (HDCT) have been introduced for recent years which made it possible to achieve significant progress in the results of tumor treatments. Intensification of chemotherapy regimens in cancer patients leads to the emergence of risk factors of invasive candidiasis (IC) development: agranulocytosis, disruption of the integrity of the mucous membranes, prolonged use of CVC, repeated antibiotic therapy, long-term parenteral nutrition. Thus, intensification of anticancer therapy may be accompanied by an increase in infection-mediated mortality.IC is the most common invasive mycosis in Russia. More than 11 thousand cases of IC occur in our country every year. The frequency IC in Russia is 8.29 per 100 thousand of the population, which corresponds to the results of the LIFE study in European countries where this indicator varies from 2.2 to 11 per 100 thousand of the population. There are no clinical signs or symptoms specific for IC. It develops in patients with concomitant diseases, which significantly complicates the diagnosis. In this regard, an urgent issue is to improve the diagnosis of candidal infectious complications in cancer patients in order to optimize treatment by studying serological markers that have the greatest value in the diagnosis of infectious complications in cancer patients.

1868P Real-world safety of the 6-weekly pembrolizumab regimen in cancer patients treated in South East London

Pembrolizumab (pembro) is a PD-1 inhibitor indicated for the treatment (tx) of a several malignancies. Most clinical trials used a 3-weekly tx (Q3W) but a 6-weekly 400mg regimen (Q6W) is now approved, based on pharmacokinetic data, also supported by the KEYNOTE-555 trial. The real world tolerability of the Q6W remains unknown. The COVID-19 pandemic led to rapid adoption of the Q6W tx, usually in patients (pts) previously receiving Q3W tx, as it facilitates less hospital visits. We report the toxicity profile of pts treated with Q6W pembro and the comparison of the preceding Q3W tx.

Published randomized controlled trials of surveillance in cancer patients - a systematic review.

With solid tumor cancer survivorship increasing, the number of patients requiring post-treatment surveillance also continues to increase. This highlights the need for evidence-based cancer surveillance guidelines. Ideally, these guidelines would be based on combined high-quality data from randomized controlled trials (RCTs). We present a systematic review of published cancer surveillance RCTs in which we sought to determine the feasibility of data pooling for guideline development.We carried out a systematic search of medical databases for RCTs in which adult patients with solid tumors that had undergone surgical resection with curative intent and had no metastatic disease at presentation, were randomized to different surveillance regimens that assessed effectiveness on overall survival (OS). We extracted study characteristics and primary and secondary outcomes, and assessed risk of bias and validity of evidence with standardized checklist tools.Our search yielded 32,216 articles for review and 18 distinct RCTs were included in the systematic review. The 18 trials resulted in 23 comparisons of surveillance regimens. There was a highlevel of variation between RCTs, including the study populations evaluated, interventions assessed and follow-up periods for the primary outcome. Most studies evaluated colorectal cancer patients (11/18, [61%]). The risk of bias and validity of evidence were variable and inconsistent across studies.This review demonstrated that there is tremendous heterogeneity among RCTs that evaluate effectiveness of different postoperative surveillance regimens in cancer patients, rendering the consolidation of data to inform high-quality cancer surveillance guidelines unfeasible. Future RCTs in the field should focus on consistent methodology and primary outcome definition.

Abstract 4239: Immunomodulatory effects of topotecan augment the effectiveness of chemotherapy-immunotherapy combination

Abstract Combination therapy is a cornerstone of anticancer therapy, suggesting potential therapeutic benefit to nonresponders to single-agent treatment. BVAC, a B-cell-and-monocyte-based vaccine loaded with alpha-galactosylceramide(α-GC) and tumor antigen as reported in our previous studies, can be successfully combined with other treatments. Here we found out a novel synergistic regimen in TC-1 tumor model which combines BVAC with topotecan, a chemotherapeutic agent as a topoisomerase I inhibitor. We demonstrated some significant alteration in the immunoprofiles of topotecan-treated mice. We observed increased tumor recruitment of monocytes and CD8+ T cells, and decreased frequencies in regulatory T cells in tumor. Accordingly, we are currently investigating how topotecan-induced changes in immune cell composition could lead to improvement of antitumor effect. These data indicate that topotecan not only has cytotoxicity to tumor but can contribute to modulating tumor immune microenvironment. We anticipate that this study could provide a rationale for combination of cancer vaccine and chemotherapy and define future optimal treatment regimens in cancer patients. Citation Format: Jeong-Mi Lee, Kwang-Soo Shin, Choong-Hyun Koh, Insu Jeon, Tae-Seung Kang, Boyeong Song, Chang-Yuil Kang. Immunomodulatory effects of topotecan augment the effectiveness of chemotherapy-immunotherapy combination [abstract]. In: Proceedings of the Annual Meeting of the American Association for Cancer Research 2020; 2020 Apr 27-28 and Jun 22-24. Philadelphia (PA): AACR; Cancer Res 2020;80(16 Suppl):Abstract nr 4239.

Immunomodulatory effects of topotecan augment the effectiveness of chemotherapy-immunotherapy combination

Abstract Combination therapy is a cornerstone of anticancer therapy, suggesting potential therapeutic benefit to nonresponders to single-agent treatment. BVAC, a B-cell-and-monocyte-based vaccine loaded with alpha-galactosylceramide (α-GC) and tumor antigen as reported in our previous studies, can be successfully combined with other treatments. Here we found out a novel synergistic regimen in TC-1 tumor model which combines BVAC with topotecan, a chemotherapeutic agent as a topoisomerase I inhibitor. We demonstrated some significant alteration in the immunoprofiles of topotecan-treated mice. We observed increased tumor recruitment of monocytes and CD8+ T cells, and decreased frequencies in regulatory T cells in tumor. Accordingly, we are currently investigating how topotecan-induced changes in immune cell composition could lead to improvement of antitumor effect. These data indicate that topotecan not only has cytotoxicity to tumor but can contribute to modulating tumor immune microenvironment. We anticipate that this study could provide a rationale for combination of cancer vaccine and chemotherapy and define future optimal treatment regimens in cancer patients.

Significant Anticancer Activity of a Venom Fraction Derived from the Persian Gulf Sea Anemone, Stichodactyla haddoni.

Chemotherapy is still one of the main therapeutic regimens in cancer patients but its toxicity is a hard challenge for every patient yet. One of the available solutions is tracing for non-toxic anticancer agents from natural resources. Numerous proteins and peptides in the venom of sea anemones are potentially useful agents with pharmacological properties. Concerning to significance of this issue, the current study was aimed to finding a non-toxic anticancer fraction from the venom of the Persian Gulf sea anemone, Stichodactyla haddoni. Anticancer and hemolytic activity of crude venom was evaluated and followed by fractionation using RP-HPLC. Breast, Brain, and Colon cancer cell lines were selected to assessment of anticancer activity and toxicity. IC50 of crude venom on the abovementioned cancer cell lines was as 4.13, 6.58, and 31.54 µg, respectively. According to the results obtained by paired sample t-test and comparison of toxicity of the fractions in normal cell line, F10, designated as hadonin, was determined as the candidate anti-cancer fraction. The non-toxic dose of F10 was 20 ng in which showed respectively 66, 29, and 7 anticancer activities on breast, brain, and colon cancer cell lines. According to results, anticancer activity of hadonin is of high pharmaceutical value to follow its therapeutic potency in animal model. In conclusion, the venom of the Persian Gulf sea anemone contains a potential anticancer agent with reasonable activity at nanogram level against three kinds of cancer cells with no toxicity on normal cells.

Линейно-квадратичная модель в планировании нейтронной терапии на циклотроне У-120

Purpose: To estimate the feasibility of using linear-quadratic model (LQM) for planning neutron therapy regimens by the criterion of early radiation-induced reactions. &#x0D; Material and methods: The LQM, which described the reaction of tissues to fractionated irradiation, was used. The results obtained were compared with similar results found on the basis of the TDF model successfully used for neutron therapy planning.&#x0D; Results: The LQM parameters αn and βn for radiation induced skin damage were found. The dependence of a single dose of neutrons on the number of therapy sessions was obtained. This dependence was in good agreement with the analogous dependence found by the TDF model, which indicated the correctness of the method for calculating it. When using LQM for planning neutron therapy, the issue related with the time intervals between sessions was considered. For this purpose, the comparative calculations of the ratio of the total effect, determined by the LQM, and the TDF factor were carried out. The difference between the compared values did not exceed 6 %, thus allowing the time interval for planning neutron therapy using LQM to be excluded. &#x0D; Two methods to control the damage to normal tissue using LQM were considered. The first method was based on the evaluation of part of the used tolerance of the irradiated tissue, and the second one was carried out by transferring the applied dose fractionation regimen of neutron therapy to the isoeffective standard regimen of photon therapy.&#x0D; Conclusion: It was shown that LQM can be used for planning neutron therapy regimens in cancer patients by the criterion of early radiation-induced reactions. The results obtained extend the potential of radiobiological planning of neutron therapy and can serve as a basis for the development of the method of using LQM in prediction of late radiation-induced complications.

RATIONAL SUPPORTIVE THERAPY FOR CHEMOTHERAPY INDUCED ANEMIA: A PHARMACO-ECONOMIC ANALYSIS OF ERYTHROPOIETIN THERAPY IN CANCER PATIENTS IN RUSSIAN FEDERATION

Modern anticancer therapy due to its intensity and molecular biology orientation allows achieving higher efficiency and theoretically reducing the incidence of complications. However, the increase in efficacy in the modern oncology really exists, but reducing complication frequency, unfortunately, is far from being solved. In many respects the problems of diagnosis, treatment and complications monitoring are associated with the impact on the complex physiological processes occurring in oncological patient. Timely implementation of modern and adequate programs for the prevention and treatment of these complications defines the concept of “supportive therapy”, which provides at least half the effectiveness of antitumor treatment.To date, according to most studies, the most frequent complications of antitumor therapy are hematologic, in particular – anemia. In clinical practice, blood transfusions, recombinant human erythropoietins, hemopoiesis stimulating cofactors are used to correct this type of complications. The need for anemia treatment is determined by its negative impact on quality of life, as well as a negative prognostic impact on the life expectancy of cancer patients, because hypoxia of tumor tissue can be associated with resistance to chemoand radiation therapy, the stimulation of genetic mutations and neoangiogenesis, which make it difficult to control of tumor growth. In numerous studies using multivariate analysis confirmed the association of low hemoglobin levels and/or tumor tissue hypoxia with worsening prognosis and overall survival in many types of tumors. The modern anemia treatment should not be determined only by increased in hemoglobin level, but should be considered as an active prophylaxis for its reducing. Recombinant forms of human erythropoietin and intravenous forms of iron preparations should be the most popular correction methods in everyday practice.The high cost of complex anemia therapy and the social significance of oncological diseases necessitate a pharmaco-economic analysis of registered in Russia erythropoietin preparations and the optimization of existing anemia treatment regimens in cancer patients in order to reduce the expenditures of the health budget. At present, an active import substitution program is underway in the Russian Federation to support the development of the Russian pharmaceutical industry and provide the population with more affordable medicines while maintaining its quality and efficiency. The need to address these issues, and the effective use of the domestic biological analogue epoetin alfa, served as an excuse for performing a comparative clinical and economic analysis. They were selected drugs that differ in pharmacokinetic properties: Eralfon® – analogue of epoetin alfa and Aranesp® – darbepoetin alfa.The treatment model of adults oncological patients with anemia receiving chemotherapy was created, which takes into account various therapies using erythropoietin preparations. The total therapy cost for an oncological patient with anemia is less when using short-acting erythropoietin – epoetin alfa – 131 609 rubles in comparison with the long-acting erythropoietin – darbepoetin alfa – 245 159.2 rubles, the difference was 113 550.2 rubles (–46 %) in favor of the epoetin alfa.According to pharmaco-economic analysis, the treatment of anemia with a Russian-produced drug epoetin alfa (Eralfon®) is preferred in comparison to darbepoetin alfa (Aranesp) in adult cancer patients with nonmyeloid malignancies in the Russian Federation, as it allows increasing the number of treated patients at a cost reduction.

Abstract 567: CD38 blockade overcomes the immune resistance to anti-PD-L1 therapy by boosting CD8 T cell response

Abstract Although strategies incorporating immune checkpoint inhibition, e.g. PD-1/PD-L1 blockade, are achieving unprecedented successes and increasingly becoming incorporated into standard of care regimens for cancer patients, high rates of resistance still limit the potential efficacy. Therapeutic improvement requires a thorough understanding of the biological process of resistance. To date there have been few studies reporting mechanisms of resistance to PD-L1 blockade. We have explored the resistance mechanisms to functional PD-L1 loss in preclinical lung cancer models by using pharmacological and genetic approaches (PD-L1 blocking antibody treatment or CRISPR/Cas9-mediated deletion of PD-L1 on tumor cells). The molecular and immune profiles of the tumor microenvironment were evaluated in mutant K-ras/p53 (KP) GEM lung cancer models and multiple immunocompetent syngeneic models (both KP and Lewis lung cancer). Additionally, to determine the applicability of the results to patients with lung cancer, we analyzed 259 patient tumor specimens with IHC staining and evaluated the immune markers in TCGA datasets (adenocarcinoma and squamous) and the MD Anderson PROSPECT dataset. We observed that lung tumors gained resistance to anti-PD-L1 antibody treatment over time, and that the up-regulation of CD38 on tumor cells accounted for the treatment resistance. We also observed the same resistance mechanism caused by CD38 up-regulation in PD-L1 KO mice bearing PD-L1 KO Lewis lung tumors generated with the CRISPR/Cas9 system. Manipulation of CD38 on a panel of lung cancer cell lines, demonstrated that CD38 inhibits CD8+ T cell proliferation, antitumor cytokine secretion, and tumor cell killing capability in vitro and in vivo. Furthermore, to test whether CD38 blockade might be therapeutically efficacious to counter anti-PD-L1 resistance, we applied the combination therapy of anti-CD38 and anti-PD-L1 in lung cancer animal models and demonstrated dramatic therapeutic benefit on primary tumor growth and metastasis. Bioinformatic analyses of the patient tumor databases revealed a strong correlation between CD38 expression and an immune suppressive inflammatory signature. Finally, in 259 lung cancer specimens, 18.5% of cases exhibited positive staining for CD38 on tumor cells. Based upon our studies, we conclude that the up-regulation of CD38 on tumor cells is a major mechanism of resistance to anti-PD-L1 therapy, and that CD38 is a novel immune checkpoint that inhibits CD8+ T cell function. The blockade of CD38 and PD-L1 is a rational combination to prevent immune resistance and increase the response rate for lung cancer patients. Citation Format: Limo Chen, Lixia Diao, Yongbin Yang, Xiaohui Yi, Jaime Rodriguez, Youhong Fan, Leticia Rodriguez, Jared Fradette, Christin Ungewiss, Jonothan Roybal, Jingfen Zhu, Jing Wang, Lauren Byers, Stephen Ullrich, Ignacio Wistuba, John Heymach, Xiao-Feng Qin, Don Gibbons. CD38 blockade overcomes the immune resistance to anti-PD-L1 therapy by boosting CD8 T cell response [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2017; 2017 Apr 1-5; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2017;77(13 Suppl):Abstract nr 567. doi:10.1158/1538-7445.AM2017-567

Low Doses of Eltrombopag Are Safe and Effective in the Prophylaxis of the Chemotherapy-Induced Thrombocytopenia (CIT)

Chemotherapy-induced-thrombocytopenia (CIT) can prevent the administration of the optimal dose and schedule of anticancer treatment and limit its benefits in the adjuvant or metastatic setting. Therapeutic approaches will include dose delays or reduction ,platelet transfusion and consideration of platelet-stimulating agents. In a review of chemotherapy-induced thrombocytopenia including >47 000 patients with solid tumors, CRC was associated with the highest prevalence of thrombocytopenia by cancer type, and most patients had received a platinum-based chemotherapy regimen. Experimental data demonstrated that Platinum is one of the heavy metals which may induce immune manifestations in humans and in experimental animals. However, novel mechanisms of oxaliplatin-related thrombocytopenia have been implicated and include an immune-dependent mechanism, as well as portal hypertension related to sinusoidal injury yielding splenic sequestration of platelets.Eltrombopag is an oral, non-peptide thrombopoietin receptor agonist that has been shown efficacy and safety in chronic immune thrombocytopenia (ITP) patients not responding to previous therapy .Moreover,some clinical studies demonstrate a role for thrombopoietin agonists in improving compliance with cytotoxic regimens in cancer patients whose chemotherapy was delayed due to thrombocytopenia,[and they suggest that prophylactic use of eltrombopag or romiplostim might reduce the degree and duration of chemotherapy-induced thrombocytopenia. Here, we report on a series of 22 patients at high risk of CIT because of platinum chemotherapy schedules who received low doses eltrombopag as prophilaxis .The aim of the study was to prevent CIT in patients who cannot be supported by platelet transfusions and for whom the maintenance of dose intensity is crucial for remission or survivalMethodsA total of 22 consecutive adult patients, female (60 %), median age 47 years (range 28 - 67) were enrolled in the study. The reason of chemotherapy has been ovary cancer in 5 patients, colon cancer in 8 patients, relapsed DLBC lymhoma in 4 patients, TNBC in 2 patients, pancreatic cancer in 3 pts. All patients received eltrombopag 25 mg by mouth twice a weekly as soon as the platelet count falls below 80000 mmc, and continued on treatment until completion of cycles of chemotherapy.ResultsThe mean platelet count nadir was 60000 mmc; the number of days with platelet count < 80000/µL was 4 days; The maximum value reached was 270,000 mmc. No treatment-related toxicity was observe. 1 out of 22 pts , did not respond to the planned dose and received 50 mg for eight consecutive days before each course of chemotherapy.The principal endpoints of the study : avoid nadir platelet counts < 50,000/µL,platelet transfusions, bleeding events, chemotherapy dose reductions , chemotherapy delays. were achieved in all patients.ConclusionIn our opinion low dose eltrombopag prophilaxis can be an effective and safe strategy for preventing the CIT. DisclosuresNo relevant conflicts of interest to declare.

A prospective study on the efficacy of two-dose influenza vaccinations in cancer patients receiving chemotherapy.

Cancer patients receiving chemotherapy are at risk of acquiring influenza infections. Two-dose vaccination is a proposed strategy for increasing vaccination efficacy; however, this has yet to be confirmed in this population. The purpose of this study was to clarify the efficacy and safety of this strategy. We conducted a multicentre prospective study on a two-dose vaccination regimen in cancer patients receiving chemotherapy. Second vaccinations were performed in patients who did not respond to all three viral strains after the first vaccination. Serum haemagglutination inhibition titres were measured to determine the patients' immunological response, 2 weeks prior to the first vaccination, 3-5 weeks after each vaccination, and at the end of the influenza season. We enrolled 109 patients, including 70 with solid tumours, 36 with haematological malignancies, and 3 with both cancer types. Among the total patients, the proportion of patients with protective titres against the three viral strains increased significantly from 3 to 27% (P < 0.01) following vaccination. Among the 79 patients who received a second vaccination, the proportion of those with protective titres against the individual strains increased by 10% (H1N1), 8% (H3N2), and 3% (B) compared with after the first vaccination. Serious adverse events were not observed. We recommend influenza vaccinations for cancer patients, including those receiving chemotherapy. Also, the additional benefit of the second vaccination may be limited.

Predicting response to multidrug regimens in cancer patients using cell line experiments and regularised regression models.

BackgroundPatients suffering from cancer are often treated with a range of chemotherapeutic agents, but the treatment efficacy varies greatly between patients. Based on recent popularisation of regularised regression models the goal of this study was to establish workflows for pharmacogenomic predictors of response to standard multidrug regimens using baseline gene expression data and origin specific cell lines. The proposed workflows are tested on diffuse large B-cell lymphoma treated with R-CHOP first-line therapy.MethodsFirst, B-cell cancer cell lines were tested successively for resistance towards the chemotherapeutic components of R-CHOP: cyclophosphamide (C), doxorubicin (H), and vincristine (O). Second, baseline gene expression data were obtained for each cell line before treatment. Third, regularised multivariate regression models with cross-validated tuning parameters were used to generate classifier and predictor based resistance gene signatures (REGS) for the combination and individual chemotherapeutic drugs C, H, and O. Fourth, each developed REGS was used to assign resistance levels to individual patients in three clinical cohorts.ResultsBoth classifier and predictor based REGS, for the combination CHO, were of prognostic value. For patients classified as resistant towards CHO the risk of progression was 2.33 (95% CI: 1.6, 3.3) times greater than for those classified as sensitive. Similarly, an increase in the predicted CHO resistance index of 10 was related to a 22% (9%, 36%) increased risk of progression. Furthermore, the REGS classifier performed significantly better than the REGS predictor.ConclusionsThe regularised multivariate regression models provide a flexible workflow for drug resistance studies with promising potential. However, the gene expressions defining the REGSs should be functionally validated and correlated to known biomarkers to improve understanding of molecular mechanisms of drug resistance.Electronic supplementary materialThe online version of this article (doi:10.1186/s12885-015-1237-6) contains supplementary material, which is available to authorized users.