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Background: Ovarian cancer is a leading cause of death from gynecological cancer in the world and in India. This study aims to evaluate the efficacy and toxicity profile of oral metronomic chemotherapy (MCT) in the form of etoposide, cyclophosphamide, and tamoxifen in recurrent and metastatic ovarian cancer. Methods: This was a retrospective observational study that included those post?treatment patients who had the recurrent or metastatic disease after completion of treatment in 2018 at Regional Cancer Centre, Bikaner, Rajasthan. Forty patients who were unfit for further intensive intravenous chemotherapy were included. The oral MCT constituted etoposide, cyclophosphamide, and tamoxifen. Descriptive statistics and Kaplan?Meier analyses were performed. Progression?free survival (PFS) and overall survival (OS) were assessed. Results: Forty women with a median age of 62 (range: 35?80) years were enrolled in the study to receive oral MCT. The Eastern Cooperative Oncology Group?Performance Status (ECOG?PS) was 0�in 28 patients and 2�in 12 patients. The best clinical response rate post?oral MCT was seen in the first 4 months. Objective response was observed in 24 (60%) of patients in the form of stable disease (19, 47.5%) and partial response (5, 12.5%). Disease progression was observed in 10 (25%) of patients. The median follow?up was 6.4 months (4.5�2 months). The median estimated OS was 6.5 months. The median estimated PFS was 3.7 months. Nineteen (47.5%) patients had grade?I/II mucositis. Grade?III/IV mucositis were observed in 9 (22.5%) patients. Thirty?seven (92.5%) patients died at the end of the study at 1 year. Dose reduction was required in 15 (37.5%) patients. Conclusion: Oral MCT was found to be an effective and well?tolerated regime with good symptomatic control and low?moderate toxicity profile in patients with relapsed and metastatic ovarian cancer. However, 22% of patients showed grade?III/IV thrombocytopenia.
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The morbidity and mortality of non-small cell lung cancer(NSCLC)are among the highest of all malignancies.The mechanisms concerning metronomic chemotherapy include anti-angiogenesis, immune microenvironment regulation, and cytotoxic effects, among others.As an alternative to traditional chemotherapy, metronomic chemotherapy has shown promising outcomes in the treatment of advanced NSCLC.Several clinical trials have explored the application of metronomic chemotherapy in the treatment of advanced NSCLC, either as a monotherapy or in combination with chemotherapy, anti-angiogenic therapy, targeted therapy or immunotherapy.This paper mainly reviews the mechanisms underlying metronomic chemotherapy and its clinical application in advanced NSCLC, in order to provide more evidence for the optimization of NSCLC treatment regimens.
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This study aimed to report the hematological and biochemical changes caused by conventional and metronomic chemotherapies, using vincristine sulfate to treat canine Transmissible Venereal Tumor (TVT). Twelve dogs were selected, six of them for the group receiving conventional chemotherapy (G1), and six dogs for the group receiving metronomic chemotherapy (G2). The G1 group received vincristine sulfate once a week at the dose of 0.75mg/m² until the tumor had disappeared with treatment, and the G2 group was treated with vincristine sulfate three times a week at the dose of 0.25mg/m2 until the tumor had disappeared. Before and after chemotherapy treatment, hematological and biochemical blood tests were performed to evaluate the main alterations caused by both chemotherapeutic models. Dogs undergoing conventional chemotherapy had significant leukocyte changes (p<0.05), causing neutropenia and leukopenia. In dogs undergoing metronomic chemotherapy, leukocytes remained within the reference range. Half of the dogs in group G1 had normochromic, normocytic anemia. The only biochemical alteration observed was the increase of urea in group G2. Thus, metronomic chemotherapy for the treatment of TVT with vincristine sulfate proved to be an excellent method for treatment, with fewer adverse effects, especially in maintaining the leukogram of dogs within normal range and reducing the number of anemia in animals during treatment.(AU)
Esta pesquisa teve como objetivo relatar as alterações hematológicas e bioquímicas causadas pelo tratamento quimioterápico convencional e pela quimioterapia metronômica, utilizando-se sulfato de vincristina para o tratamento do tumor venéreo transmissível canino(TVTC). Foram selecionados 12 cães, sendo seis para o grupo que recebeu quimioterapia convencional (G1) e seis cães para o grupo que recebeu quimioterapia metronômica (G2). O grupo G1 recebeu sulfato de vincristina, uma vez por semana, na dose de 0,75mg/m2, até o desaparecimento do tumor e o grupo G2 foi tratado com sulfato de vincristina, três vezes por semana, na dose de 0,25mg/m2, até o desaparecimento do tumor. Antes e após o tratamento quimioterápico foram realizados exames hematológicos e bioquímicos sanguíneos para avaliação das principais alterações causadas pelos dois modelos quimioterápicos. Os cães submetidos à quimioterapia convencional tiveram alterações leucocitárias significativas (p<0,05), causando uma leucopenia por neutropenia enquanto nos cães, submetidos à quimioterapia metronômica, os leucócitos mantiveram-se dentro do intervalo de referência. A metade dos cães do grupo G1 tiveram uma anemia do tipo normocítica normocrômica. A única alteração bioquímica observada foi o aumento da ureia no grupo G2. Desta forma, a quimioterapia metronômica para o tratamento do TVT com sulfato de vincristina, demonstrou ser um excelente método para a cura do animal, com menores reduções de efeitos adversos, sobretudo, na manutenção do leucograma dos cães e na redução de animais com anemia.(AU)
Subject(s)
Animals , Dogs , Venereal Tumors, Veterinary , Vincristine/analogs & derivatives , Biochemistry/methods , Hematologic Tests/veterinary , Anemia , Leukopenia , Neoplasms , Urea , Dogs/blood , Drug TherapyABSTRACT
ABSTRACT: This study aimed to report the hematological and biochemical changes caused by conventional and metronomic chemotherapies, using vincristine sulfate to treat canine Transmissible Venereal Tumor (TVT). Twelve dogs were selected, six of them for the group receiving conventional chemotherapy (G1), and six dogs for the group receiving metronomic chemotherapy (G2). The G1 group received vincristine sulfate once a week at the dose of 0.75mg/m² until the tumor had disappeared with treatment, and the G2 group was treated with vincristine sulfate three times a week at the dose of 0.25mg/m2 until the tumor had disappeared. Before and after chemotherapy treatment, hematological and biochemical blood tests were performed to evaluate the main alterations caused by both chemotherapeutic models. Dogs undergoing conventional chemotherapy had significant leukocyte changes (p 0.05), causing neutropenia and leukopenia. In dogs undergoing metronomic chemotherapy, leukocytes remained within the reference range. Half of the dogs in group G1 had normochromic, normocytic anemia. The only biochemical alteration observed was the increase of urea in group G2. Thus, metronomic chemotherapy for the treatment of TVT with vincristine sulfate proved to be an excellent method for treatment, with fewer adverse effects, especially in maintaining the leukogram of dogs within normal range and reducing the number of anemia in animals during treatment.
RESUMO: Esta pesquisa teve como objetivo relatar as alterações hematológicas e bioquímicas causadas pelo tratamento quimioterápico convencional e pela quimioterapia metronômica, utilizando-se sulfato de vincristina para o tratamento do tumor venéreo transmissível canino(TVTC). Foram selecionados 12 cães, sendo seis para o grupo que recebeu quimioterapia convencional (G1) e seis cães para o grupo que recebeu quimioterapia metronômica (G2). O grupo G1 recebeu sulfato de vincristina, uma vez por semana, na dose de 0,75mg/m2, até o desaparecimento do tumor e o grupo G2 foi tratado com sulfato de vincristina, três vezes por semana, na dose de 0,25mg/m2, até o desaparecimento do tumor. Antes e após o tratamento quimioterápico foram realizados exames hematológicos e bioquímicos sanguíneos para avaliação das principais alterações causadas pelos dois modelos quimioterápicos. Os cães submetidos à quimioterapia convencional tiveram alterações leucocitárias significativas (p 0,05), causando uma leucopenia por neutropenia enquanto nos cães, submetidos à quimioterapia metronômica, os leucócitos mantiveram-se dentro do intervalo de referência. A metade dos cães do grupo G1 tiveram uma anemia do tipo normocítica normocrômica. A única alteração bioquímica observada foi o aumento da ureia no grupo G2. Desta forma, a quimioterapia metronômica para o tratamento do TVT com sulfato de vincristina, demonstrou ser um excelente método para a cura do animal, com menores reduções de efeitos adversos, sobretudo, na manutenção do leucograma dos cães e na redução de animais com anemia.
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Background: Head-and-neck cancer is the most common cancer in developing countries of Southeast Asia. Most of the patients present to the hospital in advanced stage and have a poor prognosis. This study aims to evaluate the efficacy and toxicity profile of oral metronomic chemotherapy (MCT) in the form of methotrexate and celecoxib in locally advanced, recurrent and metastatic head-and-neck cancers. Materials and Methods: This was a single-arm retrospective observational study that included posttreatment patients with locally advanced, recurrent and metastatic disease in the year 2016 (January 1, to December 31, 2016). A total of 84 patients warranting palliative chemotherapy but not willing to take intravenous chemotherapy were included in the study. The oral MCT schedule consisted of oral celecoxib (200 mg twice daily) and oral methotrexate (15 mg/m2/week). Response evaluation was done using the Response Evaluation Criteria in Solid Tumors criteria version 1.1, and toxicity profile was assessed using the National Cancer Institute Common Terminology Criteria for Adverse Events version 4.03. Descriptive statistics and Kaplan–Meier analysis were performed. Results: Eighty-four patients, 68 males and 16 females, with a median age of 62 years (range: 35–80 years), were enrolled in the study to receive oral MCT. The Eastern Cooperative Oncology Group performance status was 0–1 in 62 patients and 2–3 in 22 patients. The primary sites of disease were buccal mucosa (18), tongue (22), tonsil (24), lower alveolus (7), hypopharynx (10), and soft palate (3). The best clinical response rate in post oral MCT was seen in the first 4 months (120 days). Objective response was observed in 67% of patients in the form of stable disease (56%) and partial response (11%). Disease progression was observed in 27% of patients. The median follow-up was 192 (6.4 months) days. The median estimated overall survival was 195 (6.5 months) days. The median estimated progression-free survival was 110 (3.6 months) days. Symptomatic relief with respect to pain was reported in about 75% of patients. Eighteen (21%) patients had Grade I–II mucosal reactions. Grade III–IV mucosal reactions were observed in five (6%) patients. Seventy-eight (93%) patients died at the end of the study at 1 year. Dose reduction was required in 15 (18%) patients. Conclusion: Oral MCT using celecoxib and methotrexate is an effective, economical, and well-tolerated regimen with good pain control and low toxicity profile in patients with locally advanced, recurrent and metastatic head-and-neck cancer.
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Introduction: Metronomic chemotherapy (MC) is an emerging therapeutic option in clinical oncology and it may prove usefulat least in metastatic head and neck squamous cell carcinoma (HNSCC) patients. To develop rational therapeutic strategies,it is important to identify molecular targets that are linked to the pathogenesis of HNSCC.Aim: The aim of the study was to assess the effect of oral MC on changes in quality of life (QOL) in advanced/recurrent HNSCCpatients.Materials and Methods: Patients with advanced, metastatic, and recurrent HNSCC patients who are not amenable to localtreatment with surgery, radiotherapy, and chemotherapy were included in the study. QOL assessed with the European organizationfor research and treatment of cancer (EORTC) QLQ-C30 and QLQ-H&N 35 questionnaires.Results: In this study, 50 patients were included, 37 patients (74%) become pain-free at the end of 6 months. A decreasedpain grade was observed in another 13 patients (26%). Mean QLQ-C 30 score at the time of presentation was 68.67, 75.35at 2 months, 81.26 at 4 months, and 85.38 at the end of 6 months. Mean QLQ-H&N 35 score at the time of presentation was61.53, 72.16 at 2 months, 76.43 at 4 months, and 81.69 at the end of 6 months. In subgroup analysis, both QLQ-C30 andQLQ-H&N 35 significantly correlated with disease progression.Conclusion: The use of oral metronomic therapy with methotrexate and celecoxib significantly improves the QOL and improvespain control in patients with advanced/recurrent HNSCC
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Introduction: Metronomic chemotherapy (MC) is an emerging therapeutic option in clinical oncology and it may prove usefulat least in metastatic HNSCC patients. To develop rational therapeutic strategies, it is important to identify molecular targetsthat are linked to the pathogenesis of HNSCC.Aim: This study aims to assess the efficacy and toxicity of oral MC with methotrexate and celecoxib in the treatment of advanced/recurrent HNSCC.Methods: Patients who received MC for advanced/recurrent HNSCC were analyzed. The combination of weekly oral methotrexate5 mg twice daily for 2 days/week and oral celecoxib 200 mg twice daily was offered as MC. The efficacy was noted in terms ofclinical benefit rate (CBR), pain control, changes in quality of life (QOL), and median time to progression (TTP).Results: A total of 50 patients were included in this study. At the end of 6 months, 4 patients (8%) had partial response (PR), 28patients (56%) had stable disease (SD), and 18 patients (36%) had progressive disease. The CBR (complete response+PR+SD)was 64% at 6 months. The median TTP was 8 weeks. At the end of 6 months, 60% of patients were pain free. The most common(>20% of patients) treatment-related adverse events were nausea (22%), vomiting (22%), and mucositis (20%). 6 patients (12%)developed anorexia and 3 patients (6%) developed fatigue. Mean QOL scores were improved with this MC.Conclusion: Oral MC with methotrexate and celecoxib for patients with advanced/recurrent HNSCC was effective, well tolerated,provides good pain control, and improves QOL with least toxicity profile.
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Metronomic chemotherapy is a brand-new and multi-target chemotherapy strategy.Totally different from the traditional chemotherapy,metronomic chemotherapy can exert synergistic and durable anti-tumor effects via multiple mechanisms,including cytotoxic effect,anti-angiogenesis,immune regulation and so on.Single and combined therapy modes of metronomic oral vinorelbine have good curative effects and safeties for the treatment of advanced non-small cell lung cancer.With the in-depth understanding of metronomic chemotherapy,it will certainly become an important treatment mode for advanced non-small cell lung cancer.
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Background: It is expected that about 65,000 new patients will be diagnosed with head and neck cancer in 2017 in the United States. Patients with recurrent or advanced or metastatic head and neck do not have good survival due to aggressive and recurrent nature of this cancer. Moreover, cumulative and residual toxicities from previous and ongoing treatments significantly impede quality of remaining part of their life. Currently available chemotherapeutic regimens for this group are derived from the treatments used for the potentially curable disease. These regimens and associated toxicity are obviously not the best matches for the treatment with palliative intent. We here present a retrospective study where we used dose-adjusted chemotherapy specifically for palliative treatment this sub-group of head and neck cancer patients. Methods: Study population was identified from the University of Florida, and IRB approval was obtained. We used currently available and approved chemotherapeutic agents (including Taxols, Platins, 5-Fluorouracil and Epidermal Growth Factor Receptor inhibitors) for treatment of head and neck cancer but dose-adjusted at approximate 50% dose of currently recommended doses. We then gave personalized doses for a prolonged period by titrating doses based on response and tolerability of each patient. Data was collected for treatment, response, side effects, and outcomes. KM analysis was performed for survival data. Results: Total of 32 patients were included in this study with a median age of 65.2 years and a median follow-up of 10.1 months. 62.5% (n = 20) had locally advanced disease and rest had metastatic disease. 37.5% (n = 12) had new disease while rest had recurrent cancer. Of 32 patients, 14 patients received TPF based while 18 patients received PFE based chemotherapy. Total of 270 chemotherapy cycles were delivered among these 32 patients. They received a median of 9 cycles (range 314) over a median of 6.2 months (range 1.821.1). With this treatment approach, we noted median progression-free survival of 14.0 months and median overall survival of 15.7 months. Notable grade 3 toxicities were generalized fatigue in 12.5% (n = 4), nausea/vomiting in 6.3% (n = 2), diarrhea in in 6.3% (n = 2), mouth soreness in 6.3% (n = 2), rash in 3.1% (n = 1), neutropenia in 18% (n = 6) and anemia in 15.6% (n = 5) while notable grade 4 toxicities were neutropenia and anaphylaxis in 3.1% (n = 1) patient each (AU)
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Humans , Male , Female , Palliative Care , Recurrence , Carcinoma, Squamous Cell/therapy , Drug Therapy , Administration, Metronomic , Head and Neck Neoplasms/drug therapy , Antineoplastic AgentsABSTRACT
Objective To investigate the clinical efficacy of capecitabine metronomic chemotherapy in the maintenance of elderly patients with metastatic breast cancer. Methods Fifty-six patients with metastatic breast cancer treated in Jiangsu Shengze Hospital from April 2014 to April 2017 were randomly divided into two groups according to random number table method: metronomic chemotherapy group (n = 28) and conventional chemotherapy group (n = 28). The patients in the metronomic chemotherapy group were treated with capecitabine 500 mg, 2 times/d and continuous oral administration. The conventional chemotherapy group received capecitabine 1 250 mg, 2 times/d for 14 days, rested for 7 days, 21 days was a course of treatment.After two courses,the clinical efficacy,toxicity and quality of life were evaluated. Results There were no significant differences in RR and DCR between the metronomic chemotherapy group and conventional chemotherapy group (RR: 39.3 % vs. 42.8 %, DCR: 89.3 % vs. 85.7 %, both P > 0.05). The median progression-free survival (PFS) time in the metronomic chemotherapy group was 5.8 months (95 % CI 3.23-7.44, P= 0.764) and median overall survival (OS) time was 7.9 months (95 % CI 4.15-7.95, P=0.519). The median PFS time in the conventional chemotherapy group was 7.2 months (95 % CI 3.32-6.33, P=0.835), median OS time was 10.3 months (95 % CI 4.08-7.37, P=0.463). There was no significant difference between the two groups (both P> 0.05). The incidences of hand-foot syndrome, myelosuppression and digestive tract reaction in conventional chemotherapy group were higher than those in metronomic chemotherapy group, there were significant differences between the two groups (all P < 0.05). No Ⅲ-Ⅳ level adverse reactions were found in the metronomic chemotherapy group. The overall rate of improvement of the quality of life in the metronomic chemotherapy group was significantly higher than that in the conventional chemotherapy group (92.9 % vs. 78.8 %, χ 2= 7.629, P < 0.05). Conclusion The clinical efficacy of capecitabine metronomic chemotherapy in the maintenance of elderly patients with metastatic breast cancer is similar to conventional dose maintenance therapy,but it can not only reduce the side effects, but also improve the quality of life of patients.
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Primary liver cancer,particularly hepatocellular carcinoma(HCC),is a common type of digestive tumor in China.The majority of HCC patients is diagnosed with advanced stage and thus cannot be treated with surgery and local treatment.Systemic therapy is considered to be the main treatment of advanced HCC.The effect of traditional cytotoxic drug chemotherapy on advanced HCC is not evident.Although sorafenib,a molecular-targeted drug,has survival benefits,this drug is expensive and has low objective effective rate of only 2%-3%. Metronomic chemotherapy has received increasing attention because it targets tumor angiogenesis for the treatment of advanced metastatic cancer.This article aimed to review the progress of metronomic chemotherapy in advanced HCC treatment.
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Primary liver cancer,particularly hepatocellular carcinoma(HCC),is a common type of digestive tumor in China.The majority of HCC patients is diagnosed with advanced stage and thus cannot be treated with surgery and local treatment.Systemic therapy is considered to be the main treatment of advanced HCC.The effect of traditional cytotoxic drug chemotherapy on advanced HCC is not evident.Although sorafenib,a molecular-targeted drug,has survival benefits,this drug is expensive and has low objective effective rate of only 2%-3%. Metronomic chemotherapy has received increasing attention because it targets tumor angiogenesis for the treatment of advanced metastatic cancer.This article aimed to review the progress of metronomic chemotherapy in advanced HCC treatment.
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Objective To explore the clinical efficiency and safety of radiofrequency ablation combined with Tegafur,Gimeracil and Oteracil Porassium Capsules( S-1 capsules) for hepatocellular carcinoma.Methods Sixty HCC patients included in this study were underwent initial radiofrequency ablation and then they were di-vided into RFA+S-1 group and RFA control group according to the metronomic chemotherapy either with S-1 or not.The local tumor control and disease free survival outcome between the two groups were compared.Results Follow-up observation showed that the total control rate after 9 months′treatment was 93.3%in RFA+S-1 group vs.73.4%in RFA control group(P=0.038).During the 18 months of follow up,the median time for dis-ease free survival was 16.25 months in RFA+S-1 group vs.12.25 months in RFA control group( P<0.001) . One-year progression free survival rate in RFA group was 53.3%,which was significantly lower than the RFA+S-1 group(83.3%)(P=0.012).The major complication rate was 13.3%.No procedu rerelated death or severe complications occurred.Conclusion Metronomic chemotherapy with S-1 following initial radiofrequency ablation delays tumor progression and prolongs overall survival of patients with HCC tumors.
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Neoadjuvant chemotherapy has practical and theoretical advantages over adjuvant chemotherapy strategy in breast cancer (BC) management. Moreover, metronomic delivery has a more favorable toxicity profile. The present study examined the feasibility of neoadjuvant metronomic chemotherapy in two cohorts [HER2+ (TraQme) and HER2− (TAME)] of locally advanced BC. Twenty patients were prospectively enrolled (TraQme, n=9; TAME, n=11). Both cohorts received weekly paclitaxel at 100 mg/m2 during 8 weeks followed by weekly doxorubicin at 24 mg/m2 for 9 weeks in combination with oral cyclophosphamide at 100 mg/day (fixed dose). The HER2+ cohort received weekly trastuzumab. The study was interrupted because of safety issues. Thirty-six percent of patients in the TAME cohort and all patients from the TraQme cohort had stage III BC. Of note, 33% from the TraQme cohort and 66% from the TAME cohort displayed hormone receptor positivity in tumor tissue. The pathological complete response rates were 55% and 18% among patients enrolled in the TraQme and TAME cohorts, respectively. Patients in the TraQme cohort had more advanced BC stages at diagnosis, higher-grade pathological classification, and more tumors lacking hormone receptor expression, compared to the TAME cohort. The toxicity profile was also different. Two patients in the TraQme cohort developed pneumonitis, and in the TAME cohort we observed more hematological toxicity and hand-foot syndrome. The neoadjuvant metronomic chemotherapy regimen evaluated in this trial was highly effective in achieving a tumor response, especially in the HER2+ cohort. Pneumonitis was a serious, unexpected adverse event observed in this group. Further larger and randomized trials are warranted to evaluate the association between metronomic chemotherapy and trastuzumab treatment.
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Humans , Decontamination/methods , Geobacillus stearothermophilus/drug effects , Hydrogen Peroxide/administration & dosage , Infection Control/methodsABSTRACT
Objective: To investigate the influence of maximum-tolerated dose chemotherapy with cisplatin (MTD-DDP) and low-dose metronomic chemotherapy with DDP (LDM-DDP) on human ovarian carcinoma xenograft tumor in nude mice and the expression of aldehyde dehydrogenase 1 (ALDH1) in xenograft tumor. Methods: Murine subcutaneous xenograft tumors of human epithelial ovarian cancer SKOV3 cells were established in nude mice and treated with MTD-DDP and LDM-DDP, respectively. The growth of xenograft tumor was observed. The xenograft tumor primary cells were established. ALDH1-positive cells were obtained by fluorescence-activated cell sorting. The abilities of colony formation and tumorigenicity of ALDH1-positive cells in vitro and in vivo were detected by colony formation assay and tumor formation in nude mice, respectively. The expression levels of Ki-67, breast cancer resistant protein (BCRP) and CD133 in ALDH1-positive cells were detected by Western blotting. Results: The growth of xenograft tumor in nude mice was inhibited by MTD-DDP and LDMDDP, and this inhibition effect was significant in LDM-DDP group (P < 0.001). The proportion of ALDH1-positive cells in xenograft tumor primary cells was lower in MTD-DDP group and higher in LDM-DDP group as compared with that in the control group (0.9% NaCl solution) (both P < 0.001). The abilities of colony formation and tumorigenicity of ALDH1-positive cells were higher than those of ALDH1-negative cells (both P < 0.001). The expression level of Ki-67 was lower but the expression levels of BCRP and CD133 were higher in ALDH1-positive cells than those in ALDH1-negative cells (all P < 0.001). Conclusion: LDM-DDP can effectively inhibit the growth of human ovarian carcinoma xenograft tumors in nude mice and reduce the proportion of ALDH1-positive cells.
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OBJECTIVE: The purpose of this study was to evaluate the clinical efficacy of continuous low-dose temozolomide (TMZ) chemotherapy for recurrent and TMZ-refractory glioblastoma multiforme (GBM) and to study the relationship between its efficacy and microvessel density within the tumor. METHODS: Thirty patients who had recurrent GBM following Stupp's regimen received TMZ daily at 50 mg/m2/day until tumor progression between 2007 and 2013. The median duration of continuous low-dose TMZ administration was 8 weeks (range, 2-64). RESULTS: The median progression-free survival (PFS) of continuous low-dose TMZ therapy was 2 months (range, 0.5-16). At 6 months, PFS was 20%. The median overall survival (OS) from the start of this therapy to death was 6 months (95% CI : 5.1-6.9). Microvessel density of recurrent tumor tissues obtained by reoperation of 17 patients was 22.7+/-24.1/mm2 (mean+/-standard deviation), and this was lower than that of the initial tumor (61.4+/-32.7/mm2) (p-value=0.001). It suggests that standard TMZ-chemoradiotherapy reduces the microvessel density within GBM and that recurrences develop in tumor cells with low metabolic burden. The efficacy of continuous low-dose TMZ could not be expected in recurrent GBM cells in poor angiogenic environments. CONCLUSION: The efficacy of continuous low-dose TMZ chemotherapy is marginal. This study suggests the need to develop further treatment strategies for recurrent and TMZ-refractory GBM.
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Humans , Disease-Free Survival , Drug Therapy , Glioblastoma , Microvessels , Recurrence , ReoperationABSTRACT
Objective:This study aimed to observe the synergistic effect of a new tumor vaccine combined with metronomic che-motherapy in vivo on breast cancer. This study was also conducted to investigate the mechanism of this combination. Methods:Balb/c mice inoculated with 4T1 mouse breast cancer cell were used as tumor models. High-mobility group nucleosome-binding protein 1 (HMGN1) gene was used to transfect 4T1 cell lines as cancer vaccines. After 4T1 cell was inoculated, the mice were randomized into four groups:normal saline (NS);metronomic gemcitabine (GEM) alone;cancer vaccine alone;and combination therapy group. Tumor growth and potential toxicities of these regimens were observed. The Foxp3 expression of regulatory T cells (Tregs) was detected by western blot and immunohistochemical staining. The microvessel density (MVD) of the tumor was also detected by immunohistochemi-cal staining. Results:The tumor volume of the mice was significantly lower in the combination group than in the MET group or cancer vaccine group (P<0.05). This result exhibited a higher significant difference than the tumor volume of the mice in the NS group (P<0.01). Foxp3 expression was significantly lower in the mice treated with GEM (combination or MET group). MVD was significantly lower in these two groups than in the cancer vaccine group or NS group (P<0.05). Furthermore, adverse reactions slightly occurred in each group. Conclusion: The combination of cancer vaccines and metronomic GEM is a very active and well-tolerated regimen for breast cancer in mice.
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BACKGROUND: Metronomics is defined by the combination of metronomic chemotherapy and drug repositioning. Since off‑patent chemotherapeutic drugs can be used and given the low toxicity profile of this approach, metronomics appears to be an invaluable alternative to bring affordable targeted therapies in low‑income countries. OBJECTIVE: The aim of this study was to report on the preliminary efficacy and safety of a metronomic vincristine/cyclophosphamide/methotrexate/ valproic acid regimen given to children with refractory cancer of various tumor types or with a very advanced disease. MATERIALS AND METHODS: This prospective, single‑center study evaluated the use of a metronomics protocol, consisting of a first cycle of weekly vincristine 1.5 mg/m2 (days: 1, 8, 15 and 22), daily cyclophosphamide 25 mg/m2 (days: 1‑21), twice weekly methotrexate 15 mg/m² (days: 21‑42) and daily valproic acid (30 mg/kg/d) followed by a 1‑week break. For the following cycles, vincristine was administrated only at week 1 and 5 of the cycle. This treatment was proposed to children with refractory disease and patients who were not eligible for the protocols available in the hospital. Adverse events were determined through laboratory analyses and investigator observations. RESULTS: From January 2010 to January 2011, 7 children (mean age: 5.4 ± 3 years old) were treated. Most frequent diagnosis was retinoblastoma. Two partial responses were observed in patients with neuroblastoma and retinoblastoma. These two patients are alive with stable disease at last follow‑up (6 and 26 months, respectively) after stopping treatment. CONCLUSION: Metronomics allows treating patients with advanced or refractory or relapsing disease and the introduction of targeted treatments in low‑income countries. The potential of metronomics in children and young adults living in middle‑ and low‑income countries warrants further larger studies.
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Administration, Metronomic , Adolescent , Antineoplastic Combined Chemotherapy Protocols/therapeutic use , Child , Child, Preschool , Cyclophosphamide/administration & dosage , Cyclophosphamide/adverse effects , Developing Countries , Female , Humans , Male , Mali , Methotrexate/administration & dosage , Methotrexate/adverse effects , Neoplasms/drug therapy , Pilot Projects , Poverty , Valproic Acid/administration & dosage , Valproic Acid/adverse effects , Vincristine/administration & dosage , Vincristine/adverse effects , Young AdultABSTRACT
BACKGROUND: Metronomic chemotherapy (MCT) with cyclophosphamide (Cy) and celecoxib (Cel) has therapeutic efficacy and low toxicity profile in advanced breast cancer patients (ABCP), but no reliable biomarkers of response have been found yet that allow patient selection for treatment. AIM: To investigate the potential role as biomarkers of pro‑ and antiangiogenic parameters and evaluate their response in ABCP receiving metronomic Cy 50 mg p.o./day + Cel 400 mg p.o./day. MATERIALS AND METHODS: Serum levels of vascular endothelial growth factor‑C (VEGF‑C), soluble VEGF receptors 2 and 3 (sVEGFR‑2, sVEGFR‑3), were measured at different time points in 13/15 patients included in a phase II trial of MCT with Cy+Cel. RESULTS: Serum levels of sVEGFR‑2 and sVEGFR‑3 increased significantly during treatment (P = 0.0392; P = 0.0066, respectively). VEGF‑C showed no significant modifications. Previous determinations of VEGF and TSP‑1 in the same patients were utilized. VEGF/sVEGFR‑2, VEGF/TSP‑1, and VEGF‑C/sVEGFR‑3 ratios decreased significantly along the treatment (P = 0.0092; P = 0.0072; P = 0.0141, respectively). Nonsignificant variations were observed for VEGF‑C/sVEGFR‑2 ratio. Baseline values of VEGF/sVEGFR‑2 and VEGF/TSP‑1 ratios were associated with time to progression (TTP) (P = 0.0407; P = 0.0394, respectively) meanwhile baseline VEGF was marginally significant (P = 0.0716). Patients with values lower than the 50th percentile for both ratios showed longer TTP. CONCLUSIONS: We have identified the baseline VEGF/sVEGFR‑2 and VEGF/TSP‑1 ratios as potential biomarkers of response in ABCP treated metronomically with Cy+Cel. This finding warrants its confirmation in a higher number of patients.