Efficacy and safety of low-dose cyclophosphamide combined with lenvatinib, pembrolizumab and TACE for unresectable hepatocellular carcinoma:A single-center, prospective,single-arm clinical trial

Objective: Unresectable hepatocellular carcinoma(uHCC) continues to pose effective treatment options. The objective of this study was to assess the efficacy and safety of combining low-dose cyclophosphamide with lenvatinib, pembrolizumab and transarterial chemoembolization(TACE) for the treatment of uHCC.Methods: From February 2022 to November 2023, a total of 40 patients diagnosed with uHCC were enrolled in this small-dose, single-center, single-arm, prospective study. They received a combined treatment of low-dose cyclophosphamide with lenvatinib, pembrolizumab, and TACE. Study endpoints included progression-free survival(PFS), objective response rate(ORR), and safety assessment. Tumor response was assessed using the modified Response Evaluation Criteria in Solid Tumors(mRECIST), while survival analysis was conducted through KaplanMeier curve analysis for overall survival(OS) and PFS. Adverse events(AEs) were evaluated according to the National Cancer Institute Common Terminology Criteria for Adverse Events(version 5.0).Results: A total of 34 patients were included in the study. The median follow-up duration was 11.2 [95% confidence interval(95% CI), 5.3-14.6] months, and the median PFS(mPFS) was 15.5(95% CI, 5.4-NA) months.Median OS(mOS) was not attained during the study period. The ORR was 55.9%, and the disease control rate(DCR) was 70.6%. AEs were reported in 27(79.4%) patients. The most frequently reported AEs(with an incidence rate >10%) included abnormal liver function(52.9%), abdominal pain(44.1%), abdominal distension and constipation(29.4%), hypertension(20.6%), leukopenia(17.6%), constipation(17.6%), ascites(14.7%), and insomnia(14.7%). Abnormal liver function(14.7%) had the most common grade 3 or higher AEs.Conclusions: A combination of low-dose cyclophosphamide with lenvatinib, pembrolizumab, and TACE is safe and effective for u HCC, showcasing a promising therapeutic strategy for managing uHCC.

UPLC-Q-TOF/MS-based metabolomics reveals modulatory effects of Mesona chinensis Benth polysaccharide in liver injury mice induced by cyclophosphamide

The main purpose of this study was to investigate the improvement effect of Mesona chinensis Benth polysaccharide(MP)on cyclophosphamide(CTX)induced liver injury in mice.To explore metabolic profile of liver tissue and feces among normal group,CTX-induced group and MP management group based on metabolomics method by using UPLC-Q-TOF/MS.The results showed that MP could alleviate liver injury and promote the production of short chain fatty acids(SCFAs),with the best dose of 200 mg/kg·body weight(bw).The principal component analysis(PCA)and orthogonal partial least squares discriminant analysis(OPLSDA)scores plots of the liver and feces samples showed a clear separation among normal,model and highdose of MP(MPH).There were 18 endogenous metabolites in liver and 29 endogenous metabolites in feces,which were mainly involved in 8 metabolic pathways:taurine and hypotaurine metabolism,phenylalanine metabolism,α-linolenic acid metabolism,tricarboxylic acid(TCA)cycle,phenylalanine,tyrosine and tryptophan biosynthesis,arachidonic acid metabolism,sphingolipid metabolism as well as tryptophan metabolism.Moreover,a common metabolite arachidonic acid was observed in liver and feces samples.These endogenous metabolites may be considered to be MP’s response to liver protection.It will help to further understand the mechanism of MP and provide a basis for further research.

Treatment outcome analysis of bevacizumab combined with cyclophosphamide and oxaliplatin in advanced pseudomyxoma peritonei

BACKGROUND Pseudomyxoma peritonei(PMP)is a rare peritoneal malignant tumor syndrome.Cytoreductive surgery combined with hyperthermic intraperitoneal chemotherapy is its standard treatment.However,there are few studies and insufficient evidence regarding systemic chemotherapy of advanced PMP.Regimens for colorectal cancer are often used clinically,but there is no uniform standard for late-stage treatment.AIM To determine if bevacizumab combined with cyclophosphamide and oxaliplatin(Bev+CTX+OXA)is effective for treatment of advanced PMP.The primary study endpoint was progression-free survival(PFS).METHODS Retrospective analysis was conducted on the clinical data of patients with advanced PMP who received Bev+CTX+OXA regimen(bevacizumab 7.5 mg/kg ivgtt d1,oxaliplatin 130 mg/m2 ivgtt d1 and cyclophosphamide 500 mg/m2 ivgtt d1,q3w)in our center from December 2015 to December 2020.Objective response rate(ORR),disease control rate(DCR)and incidence of adverse events were evaluated.PFS was followed up.Kaplan-Meier method was used to draw survival curve,and log-rank test was used for comparison between groups.Multivariate Cox proportional hazards regression model was used to analyze the independent influencing factors of PFS.RESULTS A total of 32 patients were enrolled.After 2 cycles,the ORR and DCR were 3.1%and 93.7%,respectively.The median follow-up time was 7.5 mo.During the follow-up period,14 patients(43.8%)had disease progression,and the median PFS was 8.9 mo.Stratified analysis showed that the PFS of patients with a preoperative increase in CA125(8.9 vs 2.1,P=0.022)and a completeness of cytoreduction score of 2-3(8.9 vs 5.0,P=0.043)was significantly longer than that of the control group.Multivariate analysis showed that a preoperative increase in CA125 was an independent prognostic factor for PFS(HR=0.245,95%CI:0.066-0.904,P=0.035).CONCLUSION Our retrospective assessment confirmed that the Bev+CTX+OXA regimen is effective in second-or posterior-line treatment of advanced PMP and that adverse reactions can be tolerated.A preoperative increase in CA125 is an independent prognostic factor of PFS.

Effect of Rituximab Versus Mycophenolate Mofetil or Cyclophosphamide as Control in Lupus Nephritis:A Meta-Analysis

Objective:To evaluate the effects of rituximab versus mycophenolate mofetil or cyclophosphamide as control in lupus nephritis by meta-analysis.Methods:A systematic search was carried out up to January 2022,obtaining 7 studies involving 645 participants with lupus nephritis at the commencement of the investigation;198 of them were treated with rituximab,while 447 were treated with mycophenolate mofetil or cyclophosphamide.We determined the odds ratio(OR)and mean difference(MD)with 95%confidence index(CI)to compare rituximab’s efficacy to that of mycophenolate mofetil or cyclophosphamide as control in lupus nephritis using random-or fixed-effects model by dichotomous or continuous techniques.Results:The rituximab group showed significantly higher complete renal remission rate(OR=2.52;95%CI 1.30-4.91,P=0.006)and total renal remission rates(OR=2.22;95%CI 1.36-3.63,P=0.001)than the control group.However,there was no significant difference in terms of end Systemic Lupus Erythematosus Disease Activity Index(SLEDAI)score(MD-1.16;95%CI-2.88-0.57,P=0.19),proteinuria(MD-0.31;95%CI-0.70-0.09,P=0.013),and serum creatinine(MD 0.01;95%CI-0.04-0.07,P=0.64)between the rituximab group and the control.Conclusion:Rituximab exhibited significantly greater complete renal remission rate and total renal remission rates,with no significant difference in terms of shorter-end SLEDAI,proteinuria,and serum creatinine,compared with the control in individuals with lupus nephritis.

Protective effect of ascorbic acid on cyclophosphamide induced testicular gametogenic and androgenic disorders in male rats

Aim: To study the detrimental effects of cyclophosphamide on the testicular androgenic and gametogenic activities through endocrine inhibition and/or induction of oxidative stress in male albino rats and to evaluate the protective effect of ascorbic acid. Methods: The testicular △~5, 3β-hydroxysteroid dehydrogenase (HSD), 17β-HSD, peroxidase and catalase activities along with the levels of malondialdehyde (MDA) and conjugated dienes in testicular tissue were measured for the evaluation of testicular oxidative stress. The plasma testosterone (T) level was measured by immunoassay. Various germ cells at stage Ⅶ of spermatogenic cycle were quantified from testicular stained sections. Results: Cyclophosphamide treatment results in a significant inhibition in the testicular △~5, 3β-HSD and 17β-HSD activities, a decrease in plasma T level and a diminution in the counts of various germ cells. Moreover, this treatment was also associated with a significant inhibition of the peroxidase and catalase activities along with high levels of MDA and conjugated dienes in the testis. All these changes were reversed by ascorbic acid co-administration. Conclusion: Cyclophosphamide treatment at the dosage used caused testicular gametogenic and androgenic disorders as well as induced testicular oxidative stress that can be reversed by ascorbic acid co-administration.

Effect of combined treatment with cyclophosphamidum and allicin on neuroblastoma-bearing mice

Objective:To evaluate the efficacy of allicin combined with cyclophosphamide on neuroblastoma(NB)-bearing mice and explore the immunological mechanism in it.Methods:A total of 30NB-bearing mice were equally randomized into model group,cyclophosphamide group and combined therapy group,10 nudemice were set as normal saline(NS) group.Cyclophosphamide group and combined therapy group were weekly injected with 60 mg/kg cyclophosphamide for four weeks;besides,combined therapy group was given with allicin(10 mg/kg/d) by gastric perfusion for 4 weeks;model group and NS group were given with the same volume of NS.Serum VEGF content was detected by ELISA pre-treating(0 d) and on the 3rd d.14 th d and 28 th d;on29th d,all mice were sacrificed and the tumor,liver,spleen and thymic tissues were weighted.Tumors were made into paraffin section for detecting tumor cell apoptosis and proliferation by TUNEI.and BrdU method,respectively.Survival curves were drawn by Kaplan-Meier method.Results:After treatment,both treatment groups relieved on viscera indexes,VEGF level,T cell subsets distribution and tumor growth and each index of combined therapy group was better than cyclophosphamide group(P【0.05 or 0.01);only combined therapy group could significantly increase the lifetime of NB-bearing mice(χ~2=5.667,P=0.017).Conclusions:Allicin can improve T cell subsets distribution and inhibit VEGF expression through its immunomodulatory activity,thereby improve the efficiency on NB in coordination with cyclophosphamide.

Immune enhancement effect of an herb complex extract through the activation of natural killer cells and the regulation of cytokine levels in a cyclophosphamide-induced immunosuppression rat model

Objective: To investigate the effects of a herb complex extract(HCE) prepared from Cornus officinalis Sieb. Et Zucc., Eriobotrya japonica Lindley, and olive leaves on immune response of mouse spleen NK cells in vitro and in vivo analysis. Methods: The activity of natural killer(NK) cells was measured in splenocytes and YAC-1 cells. Mice were immunosuppressed using cyclophosphamide(5 mg/kg body weight). Three different doses of HCE(200, 400, and 800 mg/kg body weight) and red ginseng extract(800 mg/kg body weight) which was used as standard immunomodulatory herb were administered orally for 4 weeks. The body weight, dietary, water intake, organs(liver, thymus, and spleen) weight, completed blood count, and cytokines(tumor necrosis factor alpha, interferon gamma, and interleukin-2) production was measured. Results: At the maximum concentration of HCE, the activity of NK cells was increased by 48.5%. HCE increased liver, spleen, and thymus weights without altering numbers of white blood cells, lymphocytes, and neutrophils in a cyclophosphamide-induced immunosuppression rat model. However, HCE recovered the inhibited cytokine expression; HCE(800 mg/kg) increased cytokines levels. The results indicate the immune enhancement potential of this HCE. Conclusion: The HCE enhances immunity by increasing NK cell activity, regulating cytokine levels, and maintaining spleen weight. Therefore, it may be used as a potential immunity enhancer.

Sesamol Alleviates the Cytotoxic Effect of Cyclophosphamide on Normal Human Lung WI-38 Cells via Suppressing RAGE/NF-κB/Autophagy Signaling

Cyclophosphamide(CYL)is a chemotherapeutic medication commonly used in managing various malignancies like breast cancer or leukemia.Though,CYL has been documented to induce lung toxicity.Mechanism of CYL toxicity is through oxidative stress and the release of damage-associated molecular patterns(DAMPs).Sesamol(SES)is a natural antioxidant isolated from Sesamum indicum and its effect against CYL-induced lung toxicity is not studied yet.This study aims to inves-tigate whether SES could prevent any deleterious effects induced by CYL on lung using normal human lung cells,WI-38 cell line,without suppressing its efficacy.Cells were pretreated with SES and/or CYL for 24 h,then cell viability was estimated by MTS and trypan blue assays.The mode of cell death was determined by AO/EB staining.Additionally,caspase-3 level,oxidative stress,and inflammatory markers were evaluated by colorimetric and ELISA techniques.qRT-PCR was performed to evaluate RAGE,NF-κB,and Beclin-1 mRNA-expression.CYL-treated WI-38 cells developed a significantly increased cell death with enhanced oxidative and RAGE/NF-κb/Autophagy signaling,which were all attenuated after pretreatment with SES.Thus,we concluded that SES offered a protective role against CYL-induced lung injury via suppressing oxidative stress and RAGE/NF-κB/Autophagy signaling,which is a natural safe therapeutic option against CYL toxicities.

Nephroprotective effect of Murraya koenigii on Cyclophosphamide induced nephrotoxicity in rats

Objective: To evaluate the nephroprotective effect of defatted mehtanolic extract and aqueous extract of Murraya koenigii against Cyclophosphamide drug. Methods: Nephrotoxicity was induced by Cyclophosphamide in 7 d at 150 mg/kg body weight through intraperitoneal route in rat model. Nephroprotective activity of Murraya koenigii(M. koenigii) extract(100 mg/kg and 200 mg/kg in intraperitoneal route) was measured, including nephrological source, oxidative stress parameters like superoxide dismutase, glutathione, the lipid peroxide and in vivo assay like blood urea nitrogen, creatinine were determined and analyzed by One way analysis of variance followed by Tukey's test. Results: The study result showed that important phytochemicals such as carbohydrates, flavonoids, tannin, alkaloids, glycosides, protein and steroids were found to be present in the extract of M. koenigii. The renal function markers like blood urea nitrogen and ceatinine level were found to be decreased significantly by M. koenigii extract treatment. A significant difference was found to be at P<0.01. Conclusions: The present study reveals the protective role of M. koenigii extract against Cyclophosphamide induced nephrotoxicity.

Cyclophosphamide abrogates the expansion of CD4^(+)Foxp3^(+) regulatory T cells and enhances the efficacy of bleomycin in the treatment of mouse B16-F10 melanomas

Objective:Promotion of the proliferative expansion of CD4^(+)Foxp3^(+)regulatory T cells(Tregs)is one of the side effects that limits the use of bleomycin(BLM)in the treatment of tumors.In this study,we examined the hypothesis that cyclophosphamide(CY),a chemotherapeutic agent with the capacity to eliminate tumor infiltrating Tregs,abrogated BLM-induced expansion of Tregs and consequently resulted in a better anti-tumor effect.Methods:The in vitro effects of BLM,with or without mafosfamide(MAF,the active metabolite of CY),on both TGF-β-induced differentiation of Tregs(iTregs),and TNF-induced expansion of naturally occurring Tregs(nTregs)were assessed.The in vivo effect of low doses of BLM and CY on tumor-infiltrating Tregs,as well as on the growth of mouse B16-F10 melanomas,was also studied.Results:In vitro treatment with BLM promoted the differentiation of iTregs,as well as TNF-induced expansion of nTregs.These effects of BLM were completely abrogated by MAF.Furthermore,in the mouse B16-F10 melanoma model,treatment with low doses of BLM increased the number of tumor-infiltrating Tregs,and this effect of BLM was also abrogated by CY.Importantly,combination therapy with low doses of BLM and CY showed synergistic anti-tumor effects.Conclusions:CY abrogated the effect of BLM on the expansion of Tregs.The combination of these 2 chemotherapeutic agents may represent a safer and more effective therapy in the treatment of cancer patients,and thus merits future clinical evaluation.

Study on the Antitumor Effects of Low-energy Laser Irradiation Combined with Cyclophosphamide

Systematic experiments about the antitumor effects of low energy laser irradiation combined with the traditional antitumor medicine of cyclophosphamide were conducted using the experimental model of mouse S180 ascites sarcoma.The three groups of tumor bearing mice were irradiated upon the inner corners with the dosages of 11 00,14 67 and 22 00 J·cm -2 LELI respectively,and injected with CYT intraperitoneally to observe the changes of the survival time,the ascites growth speed,and the kinetic changes of immune functions.The survival times of the three groups of CYT/LELI combination were obviously longer than those of the tumor and CYT control groups.Correspondingly,the amounts of ascites,tumor cells densities and total tumor cells in CYT/LELI groups decreased significantly,while the death ratio of the tumor cells increased.Comparatively,the group of 22 00 J·cm -2 LELI combined with CYT showed the most ideal antitumor effects,and the life prolongation ratio was up to 53 20%.

Cyclophosphamide and Etoposide as a Salvage Treatment in Metastatic Osteosarcoma Patients

Background and Objective: Osteosarcoma is a rare bone cancer with approximately 30% - 35% of patients who will relapse either systemically or locally, with the lung being the commonest site of relapse. The objective of this trial was to evaluate the efficacy of cyclophosphamide and etoposide, in treatment of metastatic osteosarcoma patients progressed after one or more chemotherapy lines, with the progression free survival and treatment response as the primary endpoints, while the secondary endpoints were overall survival and treatment toxicity. Patients and Methods: Twenty seven metastatic osteosarcoma patients were enrolled into this trial and received cyclophosphamide and etoposide chemotherapy. Cyclophosphamide was given at a dose of 500 mg/m2 per day, I.V for 5 days and etoposide (100 mg/m2 per day I.V for 5 days). Response was assessed after 3 cycles according to Response Evaluation Criteria in Solid Tumors (RECIST) version 1.1. Chemotherapy Toxicity was graded according to the Common Terminology Criteria for Adverse Events (CTCAE). Results: The median overall survival time and progression-free survival were 12 months and 8 months, respectively. Four patients (14.8%) achieved partial response;14 patients (51.9%) had stationary disease (SD);and 9 (33.3%) expressed tumor progression. Hematologic toxicity was the main toxicity. None of the patients had G4 or life threatening toxicities. Conclusion: The combination of cyclophosphamide and etoposide represents an efficient and tolerable treatment option for patients with metastatic osteosarcoma.

Acupuncture enhances anticancer effects of cyclophosphamide on 4T1 tumors via suppression of angiogenesis in BALB/c mice

Objective:Acupuncture is considered an important part of the alternative medical treatment of tumors.However,it is still unclear whether acupuncture has a direct effect on inhibition of tumor growth.The purpose of this study was to evaluate the effects of acupuncture treatment on tumors in BALB/c mice that were or were not administered cyclophosphamide.Methods:A 4T1 breast carcinoma mouse model for this study was established.When the mice developed 5 mm × 5 mm visible subcutaneous tumors,they were subjected to acupuncture and/or cyclophosphamide (CTX) treatment for 15 days.Results:Acupuncture and CTX treatment both reduced the size of the solid tumors.When used in conjunction,the tumor size reduction was even more obvious.Hematoxylin and eosin staining showed that acupuncture had a significant effect on induction of tumor cell necrosis and inhibition of angiogenesis.Immunohistochemistry showed that the expression of CD34 and matrix metalloproteinase-9 (MMP-9),which were related to angiogenesis,decreased after treatment with either acupuncture or CTX.However,when the two treatments were used in conjunction,they showed a synergistic effect on inhibiting the expression of CD34.However,the synergistic effect was not observed onMvMP-9 expression.Conclusion:Acupuncture plays an important role in improving the effect of chemotherapy by inhibiting angiogenesis.

Chemoprotective activity of aqueous leaf extract of Acalypha wilkesiana against cyclophosphamide-induced toxicity in rats

Objective:To investigate the protective effect of aqueous leaf extract of Acalypha(A.)wilkesiana Muell.Arg(Euphorbiaceae)against cyclophosphamide-induced toxicity in albino rats.Methods:Twenty male albino rats were randomly divided into five groups of four animals each.The control group(Ⅰ)was fed with pellets and distilled water,while group Ⅱ was orally administered with only 20 mg/kg cyclophosphamide.Groups Ⅲ,Ⅳ and Ⅴ were coadministered with 20 mg/kg body weight cyclophosphamide and 110,220 and 440 mg/kg body weight A.wilkesiana leaf extract,respectively,for 7 d.After treatment,liver and kidney function biomarkers,haematological parameters,liver antioxidants,and mitochondrial membrane permeability transition pore opening were investigated.Results:A.wilkesiana leaf extract significantly reduced(P<0.05)cyclophosphamide-induced increase in plasma aspartate aminotransferase,alanine aminotransferase,creatinine,uric acid and urea.It increased superoxide dismutase,catalase,glutathione-S-transferase activities and reduced glutathione levels.It also increased packed cell volume count,hemoglobin concentration and white blood cell count while inhibiting the induction of mitochondrial swelling.Conclusions:This study demonstrates that aqueous extract of A.wilkesiana leaf protected tissues against cyclophosphamide-induced oxidative damage.

EFFICIENT ACTIVATION OF ANTITUMOR IMMUNITY BY IL-6 GENE-MODIFIED LEUKEMIA VACCINE IN COMBINATION WITH LOW DOSE CYCLOPHOSPHAMIDE AND LOW DOSEIL-2

Objective: To investigate the antitumor effect of the IL 6 gene modified erythroleukemia cells combined with low dose cyclophosphamide (Cy) and low dose IL 2 Methods: Mice inoculated with FBL 3 IL 6 in combination with low dose IL 2 and low dose cyclophosphamide (Cy) Results: Mice received combined therapy of FBL 3 IL 6, IL 2 and Cy developed tumors most slowly and survived much longer when compared with mice in control groups, with 5 out of 8 leukemia bearing mice being tumor free 100 days after the combined treatment To further explain the mechanism of the antitumor effects by the combined therapy It was found that combined therapy with low dose Cy, low dose IL 2 and FBL 3 IL 6 achieved maximal cytotoxic effects of nature killer cells and specific cytotoxic T lymphocytes, increased production IL 2, TNF and GM CSF from spleen lymphocytes in tumor bearing mice Vaccination with the FBL3 IL 6 also enhanced the cytotoxic activity of the peritoneal macrophages The results demonstrated that administration of low dose Cy and low dose IL 2 in combination with IL 6 gene modified leukemia vaccine could elicit potent anti leukemia effects, and the mechanisms involved in the antitumor process may include the induction of specific and nonspecific antitumor immunity, reversal of T suppressor cells that mediated local immuno suppression in tumor bearing mice Conclusion: The combined therapy with cytokine gene modified tumor vaccine, low dose of Cy and IL 2 might be a promising approach for the treatment of leukemia

Cyclophosphamide-associated enteritis: A rare association with severe enteritis

Cyclophosphamide is a potent cytotoxic agent used in many clinical settings. The main risks of cyclophosphamide therapy include hematological disorders, infertility, hemorrhagic cystitis and malignancies. Gastrointestinal side effects reported to date are often non-specific and not severe. We present the first case of a fatal small bowel enteritis and pan-colitis which appears to be associated with cyclophosphamide. We aim to raise the readers' awareness of this significant adverse event to facilitate clinical suspicion and early recognition in potential future cases.

Cyclophosphamide-associated enteritis presenting with severe protein-losing enteropathy in granulomatosis with polyangiitis:A case report

BACKGROUND Although cyclophosphamide(CPA)is the key drug for the treatment of autoimmune diseases including vasculitides,it has some well-known adverse effects,such as myelosuppression,hemorrhagic cystitis,infertility,and infection.However,CPA-associated severe enteritis is a rare adverse effect,and only one case with a lethal clinical course has been reported.Therefore,the appropriate management of patients with CPA-associated severe enteritis is unclear.CASE SUMMARY We present the case of a 61-year-old woman diagnosed with granulomatosis with polyangiitis based on the presence of symptoms in ear,lung,and,kidney with positive myeloperoxidase-antineutrophil cytoplasmic antibody.She received pulsed methylprednisolone followed by prednisolone 55 mg/d and intravenous CPA at a dose of 500 mg/mo.Ten days after the second course of intravenous CPA,she developed nausea,vomiting,and diarrhea,and was admitted to the hospital.Laboratory testing revealed hypoalbuminemia,suggesting proteinlosing enteropathy.Computed tomography revealed wall thickening of the stomach,small intestine,and colon with contrast enhancement on the lumen side.Antibiotics and immunosuppressive therapy were not effective,and the patient’s enteritis did not improve for>4 mo.Because her condition became seriously exhausted,corticosteroids were tapered and supportive therapies including intravenous hyperalimentation,replenishment of albumin and gamma globulin,plasma exchange,and infection control were continued.These supportive therapies improved her condition,and her enteritis gradually regressed.She was finally discharged 7 mo later.CONCLUSION Immediate discontinuation of CPA and intensive supportive therapy are crucial for the survival of patients with CPA-associated severe enteritis.

Successful treatment of a high-risk nonseminomatous germ cell tumor using etoposide, methotrexate, actinomycin D, cyclophosphamide, and vincristine: A case report

BACKGROUND Choriocarcinoma is an infrequent entity and the most aggressive subtype of germcell tumors.Because of early metastatic spread and rapid disease progression,choriocarcinoma patients display poor prognosis.Although etoposide,methotrexate,actinomycin D,cyclophosphamide,and vincristine(EMA-CO)regimen is widely used to treat gestational trophoblastic tumors in females,its role in treating male choriocarcinoma is seldom reported.CASE SUMMARY A 32-year-old man was diagnosed with burned-out primary germ cell tumors(GCT)with retroperitoneum,liver and lung metastases.Biopsy of the liver revealed pure choriocarcinoma.The patient received bleomycin,etoposide,and cisplatin chemotherapy.After two cycles of treatment,response evaluation revealed the mixed response.EMA-CO regimen was used in the second-line therapy.After eight cycles,the patient showed a potentially resectable state and thus,all residual masses were surgically removed.The patient was completely cured,and 10 years later,he is leading a healthy life without complications.CONCLUSION This paper is the first case of high-risk nonseminomatous GCT in a male patient to be successfully treated with the EMA-CO regimen.The EMA-CO regimen can be used actively in patients with high-risk nonseminomatous GCT.

Modulation of IL-10/IL-10R expression by mafosfamide, a derivative of 4-hydroxycyclophosphamide, in a rat B-cell lymphoma

We have already shown that IL-10 plays an important role in immunosuppression and metastatic dissemination in the rat B-cell lymphoma L-TACB model.It was suggested that the up-regulation of IL10 production and IL-10 receptor(IL-10R)expression would be part of the transition from primary tumor to metastatic phenotype and that IL-10,besides its immunosuppressive activity,may act as a growth factor for metastatic L-TACB cells.The treatment of L-TACB-bearing rats with a single low-dose cyclophosphamide decreased IL-10 production,reverted immunosuppression and induced the immunologic rejection of tumor metastasis without any effect on primary tumor growth.Our current aim was to investigate the effects of cyclophosphamide on the expression of IL-10 and IL-10R on primary and metastatic L-TACB cells.Considering that cyclophosphamide is a prodrug,we used mafosfamide,a compound that yields in vitro the same active metabolites as cyclophosphamide does in vivo.Mafosfamide induced down-regulation of IL-10 production and IL-10R expression on metastatic cells and,concomitantly,inhibited metastatic cell proliferation.We suggest that mafosfamide would inhibit the regulatory loop mediated by the IL-10/IL-10R system and,as a consequence,metastatic cell proliferation.These results may have a considerable impact on the design of new therapies for metastatic lymphomas.

Genotoxic and Cytotoxic Damage by Cyclophosphamide and Adriamycin as a Response to Treatment in Breast Cancer Patients: Pilot Study

The aim of this study was to evaluate the genotoxicity induced by cyclophosphamide-adriamycin treatment in breast cancer patients through the frequencies of Sister Chromatid Exchange (SCE), Replication Index (RI), Mitotic Index (MI) and Cell Proliferation Index (CPI) and to study the possible association between biomarkers of genotoxicity and the early response to treatment. The frequencies were obtained before and immediately after therapy from 17 patients with breast cancer (p < 0.001). Response to treatment was assessed after two years resulting in 12 patients in a state of remission. MI and CPI had high values after treatment in women with active cancers compared to those in a state of remission, however there were not significant differences. Conclusions: It is possible that MI y CPI biomarkers can serve as indicators for early assessment of treatment with cyclophosphamide-adriamycin. It should be noted that these are preliminary results and further study is necessary.