Purpose: Low-dose metronomic chemotherapy is an emergent treatment schedule in which low doses of cytotoxic agents are given orally continuously, with no or short drug-free intervals. In general, it provides better to...Purpose: Low-dose metronomic chemotherapy is an emergent treatment schedule in which low doses of cytotoxic agents are given orally continuously, with no or short drug-free intervals. In general, it provides better tolerance, especially in patients who have been previously exposed to other oncologic treatments, with a favorable cost-effectiveness profile. It is well known that all these low-dose schedules have a favorable safety profile and may provide an adequate tumor control in patients with metastatic breast cancer. However, there are no data in literature reporting the patient’s tolerance and response to subsequent lines of chemotherapy after receiving metronomic regimens. Methods: We retrospectively analyzed 40 patients with metastatic breast cancer treated with low doses of Cyclophosphamide and/or Methotrexate and/or Capecitabine in a single center from June 2009 to April 2014. The following data were collected: age, hormone and epidermal growth factor receptor 2 (HER-2) status, number of lines of chemotherapy prior to and after low-dose metronomic treatment, duration of metronomic treatment, toxicity reason for treatment discontinuation. Duration of low-dose metronomic chemotherapy was also correlated with the variables analyzed and treatment outcomes. Results: The median time on metronomic chemotherapy was 5.4 months. The most frequent drugs administered were cyclophosphamide, methotrexate and capecitabine alone. Asthenia, myelotoxicity, gastrintestinal symptoms and handfoot syndrome were the most commonly recorded treatment related toxicity. Twenty six (65%) patients had the opportunity to receive a classic chemotherapy regimen following metronomic regimen interruption. Although patients who developed toxicity to low-dose metronomic chemotherapy remained less time (<6 months) in subsequent chemotherapy, there was no statistically significant difference among those who received more lines of chemotherapy. Discussion: This is the first report in the literature describing the efficacy of low-dose metronomic regimens and the tolerance to subsequent lines of treatments following a period of metronomic chemotherapy. Most of our patients were able to tolerate conventional chemotherapy regimens administered in full doses. Several patients received as many as three lines of additional chemotherapy for periods that exceeded 6 months of treatment, which suggests that the use of prolonged metronomic treatment does not affect a patient’s ability to tolerate subsequent therapy.展开更多
Background: metronomic chemotherapy is based on antiangiogenic and immunologic mechanisms obtained by the administration of traditional cytotoxic drugs at lower concentration without rest periods. The low dosage induc...Background: metronomic chemotherapy is based on antiangiogenic and immunologic mechanisms obtained by the administration of traditional cytotoxic drugs at lower concentration without rest periods. The low dosage induces fewer or no side effect compared to classic maximum tolerated dose administration (MTD). At present, no treatment related acute leukaemia was reported in cyclophosphamide-based metronomic chemotherapy (CMC). Case: We report the case of an 81-year-old man considered as having castration and chemo-refractory metastatic prostate cancer. CMC was started. Objective response was observed in this heavily pre-treated patient with progression free survival lasting more than 30 months. No toxicity was observed in this period and his autonomy was maintained. Finally, our patient developed a chemotherapy-induced acute myeloid leukaemia at 36th month of CMC. Conclusion: Even CMC is a well-tolerated treatment;secondary acute leukaemia is related to cumulative dose of cyclophosphamide. The benefit and the risk of long-term exposure to cyclophosphamide should be carefully balanced.展开更多
Background:Real-world data of the CM regimen[cyclophosphamide(CTX)plus methotrexate(MTX)]in metronomic pattern for advanced breast cancer is limited to small-sample or retrospective studies.This study was aimed to det...Background:Real-world data of the CM regimen[cyclophosphamide(CTX)plus methotrexate(MTX)]in metronomic pattern for advanced breast cancer is limited to small-sample or retrospective studies.This study was aimed to determine the effectiveness and safety of CM regimen in treating advanced breast cancer and to identify which patients are most likely to benefit from metronomic CM regimen.Methods:Patients with advanced breast cancer who received the metronomic CM regimen at least once between January 2009 and February 2019 in Sun Yat-sen University Cancer Center were included.Clinicopathological characteristics were collected.Overall survival(OS)and progression-free survival(PFS)were assessed using Kaplan-Meier estimates.Characteristics between patients with PFS<6 months and≥6 months were compared using the Chi-square test.Univariate and multivariate Cox regression model was used to estimate the prognostic factors for PFS and OS.Results:A total of 186 patients were included.The median age and follow-up were 49 years and 13.3 months,respectively.Over 50%of the patients were estrogen receptor/progesterone receptor-positive,and 60.8%had been heavily treated(≥3 lines).The objective response rate was 3.8%,the disease control rate at 12 weeks was 41.4%,and the clinical benefit rate at 24 weeks was 31.2%(58/186).The median PFS was 4.0 months[95%confidence interval(CI):3.6-4.7 months],the median duration of clinical benefit was 9.5 months(95%CI:8.2-10.8 months),and the median OS was 26.8 months(95%CI:20.9-37.7 months).Multivariate analysis for PFS revealed the CM regimen as maintenance therapy and no liver metastasis as favorable prognostic factors.Furthermore,patients without liver metastasis were more likely to have a PFS over 6 months than those with liver involvement(P=0.022).Liver,lymph node,and brain metastases were unfavorable prognostic factors for OS.The CM regimen was well-tolerated without newly reported adverse events.Conclusions:The CM regimen was effective in selected patients.In clinical practice,it would be better used as maintenance therapy and in patients without liver metastasis.Further follow-up investigation should be performed to examine its effect when used in combination with other treatments and determine predictive biomarkers.展开更多
For centuries,therapeutic cancer vaccines have been developed and tried clinically.Way back in the late 19th century,the Father of Immunotherapy,William Coley had discovered that bacterial toxins were effective for in...For centuries,therapeutic cancer vaccines have been developed and tried clinically.Way back in the late 19th century,the Father of Immunotherapy,William Coley had discovered that bacterial toxins were effective for inoperable sarcomas.In the 1970s,the Bacillus Calmette-Guérin(BCG)vaccine was repurposed,e.g.,for advanced melanomas.Then,therapeutic cancer vaccines based on tumorassociated antigens(found on the surfaces of cancer cells)were tried clinically but apparently have not made a really significant clinical impact.For repurposed pathogen vaccines,only the BCG vaccine was approved in 1989 for local application to treat nonmuscle-invading bladder cancers.Although the mildly toxic vaccine adjuvants deliberately added to conventional pathogen vaccines are appropriate for seasonal applications,when repurposed for continual oncology usage,toxicity may be problematic.In 2010,even with the approval of sipuleucel-T as the very first cancer vaccine(dendritic cell)developed for designated prostate cancers,it has also not made a really significant clinical impact.Perhaps more"user friendly"cancer vaccines should be explored.As from approximately 30 years ago,the safety and effectiveness of mRNA vaccination for oncology had already been studied,the current coronavirus disease 2019 pandemic,though disastrous,has given such progressively advancing technology a kickstart.For oncology,other virtues of mRNA vaccines seem advantageous,e.g.,rapid and versatile development,convenient modular design,and entirely cell-free synthesis,are being progressively recognized.Moreover,mRNAs encoding various oncology antigens for vaccination may also be tested with the combination of relatively non-toxic modalities of oncology treatments,e.g.,metformin or metronomic(low-dose,prolonged administration)chemotherapy.Admittedly,robust clinical data obtained through good quality clinical trials are mandatory.展开更多
文摘Purpose: Low-dose metronomic chemotherapy is an emergent treatment schedule in which low doses of cytotoxic agents are given orally continuously, with no or short drug-free intervals. In general, it provides better tolerance, especially in patients who have been previously exposed to other oncologic treatments, with a favorable cost-effectiveness profile. It is well known that all these low-dose schedules have a favorable safety profile and may provide an adequate tumor control in patients with metastatic breast cancer. However, there are no data in literature reporting the patient’s tolerance and response to subsequent lines of chemotherapy after receiving metronomic regimens. Methods: We retrospectively analyzed 40 patients with metastatic breast cancer treated with low doses of Cyclophosphamide and/or Methotrexate and/or Capecitabine in a single center from June 2009 to April 2014. The following data were collected: age, hormone and epidermal growth factor receptor 2 (HER-2) status, number of lines of chemotherapy prior to and after low-dose metronomic treatment, duration of metronomic treatment, toxicity reason for treatment discontinuation. Duration of low-dose metronomic chemotherapy was also correlated with the variables analyzed and treatment outcomes. Results: The median time on metronomic chemotherapy was 5.4 months. The most frequent drugs administered were cyclophosphamide, methotrexate and capecitabine alone. Asthenia, myelotoxicity, gastrintestinal symptoms and handfoot syndrome were the most commonly recorded treatment related toxicity. Twenty six (65%) patients had the opportunity to receive a classic chemotherapy regimen following metronomic regimen interruption. Although patients who developed toxicity to low-dose metronomic chemotherapy remained less time (<6 months) in subsequent chemotherapy, there was no statistically significant difference among those who received more lines of chemotherapy. Discussion: This is the first report in the literature describing the efficacy of low-dose metronomic regimens and the tolerance to subsequent lines of treatments following a period of metronomic chemotherapy. Most of our patients were able to tolerate conventional chemotherapy regimens administered in full doses. Several patients received as many as three lines of additional chemotherapy for periods that exceeded 6 months of treatment, which suggests that the use of prolonged metronomic treatment does not affect a patient’s ability to tolerate subsequent therapy.
文摘Background: metronomic chemotherapy is based on antiangiogenic and immunologic mechanisms obtained by the administration of traditional cytotoxic drugs at lower concentration without rest periods. The low dosage induces fewer or no side effect compared to classic maximum tolerated dose administration (MTD). At present, no treatment related acute leukaemia was reported in cyclophosphamide-based metronomic chemotherapy (CMC). Case: We report the case of an 81-year-old man considered as having castration and chemo-refractory metastatic prostate cancer. CMC was started. Objective response was observed in this heavily pre-treated patient with progression free survival lasting more than 30 months. No toxicity was observed in this period and his autonomy was maintained. Finally, our patient developed a chemotherapy-induced acute myeloid leukaemia at 36th month of CMC. Conclusion: Even CMC is a well-tolerated treatment;secondary acute leukaemia is related to cumulative dose of cyclophosphamide. The benefit and the risk of long-term exposure to cyclophosphamide should be carefully balanced.
基金Joint Fund of National Natural Science Foundation of China,Grant/Award Number:U1601224Research Data Deposit,Grant/Award Number:RDDA2020001375。
文摘Background:Real-world data of the CM regimen[cyclophosphamide(CTX)plus methotrexate(MTX)]in metronomic pattern for advanced breast cancer is limited to small-sample or retrospective studies.This study was aimed to determine the effectiveness and safety of CM regimen in treating advanced breast cancer and to identify which patients are most likely to benefit from metronomic CM regimen.Methods:Patients with advanced breast cancer who received the metronomic CM regimen at least once between January 2009 and February 2019 in Sun Yat-sen University Cancer Center were included.Clinicopathological characteristics were collected.Overall survival(OS)and progression-free survival(PFS)were assessed using Kaplan-Meier estimates.Characteristics between patients with PFS<6 months and≥6 months were compared using the Chi-square test.Univariate and multivariate Cox regression model was used to estimate the prognostic factors for PFS and OS.Results:A total of 186 patients were included.The median age and follow-up were 49 years and 13.3 months,respectively.Over 50%of the patients were estrogen receptor/progesterone receptor-positive,and 60.8%had been heavily treated(≥3 lines).The objective response rate was 3.8%,the disease control rate at 12 weeks was 41.4%,and the clinical benefit rate at 24 weeks was 31.2%(58/186).The median PFS was 4.0 months[95%confidence interval(CI):3.6-4.7 months],the median duration of clinical benefit was 9.5 months(95%CI:8.2-10.8 months),and the median OS was 26.8 months(95%CI:20.9-37.7 months).Multivariate analysis for PFS revealed the CM regimen as maintenance therapy and no liver metastasis as favorable prognostic factors.Furthermore,patients without liver metastasis were more likely to have a PFS over 6 months than those with liver involvement(P=0.022).Liver,lymph node,and brain metastases were unfavorable prognostic factors for OS.The CM regimen was well-tolerated without newly reported adverse events.Conclusions:The CM regimen was effective in selected patients.In clinical practice,it would be better used as maintenance therapy and in patients without liver metastasis.Further follow-up investigation should be performed to examine its effect when used in combination with other treatments and determine predictive biomarkers.
文摘For centuries,therapeutic cancer vaccines have been developed and tried clinically.Way back in the late 19th century,the Father of Immunotherapy,William Coley had discovered that bacterial toxins were effective for inoperable sarcomas.In the 1970s,the Bacillus Calmette-Guérin(BCG)vaccine was repurposed,e.g.,for advanced melanomas.Then,therapeutic cancer vaccines based on tumorassociated antigens(found on the surfaces of cancer cells)were tried clinically but apparently have not made a really significant clinical impact.For repurposed pathogen vaccines,only the BCG vaccine was approved in 1989 for local application to treat nonmuscle-invading bladder cancers.Although the mildly toxic vaccine adjuvants deliberately added to conventional pathogen vaccines are appropriate for seasonal applications,when repurposed for continual oncology usage,toxicity may be problematic.In 2010,even with the approval of sipuleucel-T as the very first cancer vaccine(dendritic cell)developed for designated prostate cancers,it has also not made a really significant clinical impact.Perhaps more"user friendly"cancer vaccines should be explored.As from approximately 30 years ago,the safety and effectiveness of mRNA vaccination for oncology had already been studied,the current coronavirus disease 2019 pandemic,though disastrous,has given such progressively advancing technology a kickstart.For oncology,other virtues of mRNA vaccines seem advantageous,e.g.,rapid and versatile development,convenient modular design,and entirely cell-free synthesis,are being progressively recognized.Moreover,mRNAs encoding various oncology antigens for vaccination may also be tested with the combination of relatively non-toxic modalities of oncology treatments,e.g.,metformin or metronomic(low-dose,prolonged administration)chemotherapy.Admittedly,robust clinical data obtained through good quality clinical trials are mandatory.
