Neoadjuvant chemotherapy plus radiotherapy is the most common treatment regimen for advanced nasopharyngeal carcinoma(NPC).Whether chronomodulated infusion of chemotherapy can reduce its toxicity is unclear.This study...Neoadjuvant chemotherapy plus radiotherapy is the most common treatment regimen for advanced nasopharyngeal carcinoma(NPC).Whether chronomodulated infusion of chemotherapy can reduce its toxicity is unclear.This study aimed to evaluate the toxic and therapeutic effects of sinusoidal chronomodulated infusion versus flat intermittent infusion of cisplatin(DDP)and 5-fluorouracil(5-FU)followed by radiotherapy in patients with locoregionally advanced NPC.Patients with biopsy-diagnosed untreated stages III and IV NPC(according to the 2002 UICC staging system)were randomized to undergo2 cycles of sinusoidal chronomodulated infusion(Arm A)or flat intermittent constant rate infusion(Arm B)of DDP and 5-FU followed by radical radiotherapy.Using a"MELODIE"multi-channel programmed pump,the patients were given 12-hour continuous infusions of DDP(20 mg/m2)and 5-FU(750 mg/m2)for 5days,repeated every 3 weeks for 2 cycles.DDP was administered from 10:00 am to 10:00 pm,and 5-FU was administered from 10:00 pm to 10:00 am each day.Chronomodulated infusion was performed in Arm A,with the peak deliveries of 5-FU at 4:00 am and DDP at 4:00 pm.The patients in Arm B underwent a constant rate of infusion.Radiotherapy was initiated in the fifth week,and both arms were treated with the same radiotherapy techniques and dose fractions.Between June 2004 and June 2006,125 patients were registered,and 124 were eligible for analysis of response and toxicity.The major toxicity observed during neoadjuvant chemotherapy was neutropenia.The incidence of acute toxicity was similar in both arms.During radiotherapy,the incidence of stomatitis was significantly lower in Arm A than in Arm B(38.1%vs.59.0%,P=0.020).No significant differences were observed for other toxicities.The 1-,3-,and 5-year overall survival rates were 88.9%,82.4%,and 74.8%for Arm A and 91.8%,90.2%,and 82.1%for Arm B.The 1-,3-,and 5-year progression-free survival rates were 91.7%,88.1%,and 85.2%for Arm A and 100%,94.5%,and 86.9%for Arm B.The 1-,3-,and 5-year distant metastasis-free survival rates were 82.5%,79.1%,and 79.1%for Arm A and 90.2%,85.2%,and 81.7%for Arm B.Chronochemotherapy significantly reduced stomatitis but was not superior to standard chemotherapy in terms of hematologic toxicities and therapeutic response.展开更多
Chemotherapy remains an integral component in the treatment of advanced non-small cell lung cancer(NSCLC).However,patients often experience suboptimal treatment outcomes due to their inability to tolerate high doses a...Chemotherapy remains an integral component in the treatment of advanced non-small cell lung cancer(NSCLC).However,patients often experience suboptimal treatment outcomes due to their inability to tolerate high doses and toxicity of chemotherapy.In recent years,a growing body of research has demonstrated a significant correlation between chemotherapy and circadian rhythms,suggesting that the efficacy of chemotherapy may exhibit a temporal dependence associated with the circadian clock.Existing evidence suggests that chronochemotherapy offers the advantages of high efficacy and low toxicity,although the underlying mechanisms remain unclear.Chronochemotherapy is defined as the infusion of chemotherapeutic drugs at the appropriate stage of human biological rhythm.Therefore,optimizing chemotherapy by employing chronochemotherapy for cost-effectiveness and efficiency has become a critical area of research.There is increasing evidence that chronochemotherapy is an effective treatment for NSCLC,offering a novel therapeutic strategy for its management.展开更多
Objective:To validate the safety and efficacy of chronochemotherapy for locoregionally advanced nasopharyngeal carcinoma(NPC).Methods:Participants for this phase II randomized controlled trial were recruited from the ...Objective:To validate the safety and efficacy of chronochemotherapy for locoregionally advanced nasopharyngeal carcinoma(NPC).Methods:Participants for this phase II randomized controlled trial were recruited from the Department of Head and Neck Oncology at the Affiliated Cancer Hospital of Guizhou Medical University.Patients enrolled(128 in total,112 in the final analysis)between April 1,2017,and February 28,2018,were randomly divided into the chronochemotherapy and conventional chemotherapy groups.In the chronochemotherapy group,docetaxel was intravenously administered between 3:30 a.m.and 4:30 a.m.on day 1,followed by intravenous administration of cisplatin between 10:00 a.m.and 10:00 p.m.from day 1to day 5.In addition,5-fluorouracil was administered through a continuous intravenous pump between 10:00 p.m.and 10:00 a.m.(2nd day)from day 1 to day 5.In the conventional chemotherapy group,docetaxel(on day 1),cisplatin(on day 2),and 5-fluorouracil(from day 1 to day 5,120 h in total)were administered without time-specific constraints.Both groups underwent intensitymodulated radiation therapy with 6-MV X-rays.The gross target volume(GTV)comprised the nasopharyngeal GTV and cervical lymph node GTV.The primary endpoint was immune function,quantified by measuring dendritic cell and lymphocyte subsets,whereas the secondary endpoints were therapeutic efficacy and incidence of adverse events.Pearson Chi-square test was applied to compare total events between the groups,Mann-Whitney U test was used to compare the DC subsets and toxicities,and Wilcoxon signed-rank test was used to compare the continuous variables between the two groups.Results:Chronochemotherapy preserved immune function,as evidenced by elevated levels of myeloid dendritic cells(P=0.394)and higher CD4/CD8 ratio(P?0.781).No significant difference in overall response rate,measured as the sum of complete and partial response rates,was observed between the groups(P=0.711).A reduction in the incidence of vomiting(P=0.002),stomatitis(P=0.028),and mucositis(P=0.028)was observed in the chronochemotherapy group.Leukopenia incidence rate was 83.3% and 92.3% in the chronochemotherapy and conventional chemotherapy groups,respectively(P=0.232).Conclusions:In patients with locoregionally advanced NPC,the overall response rate of chronochemotherapy is comparable to that of conventional chemotherapy;however,chronochemotherapy shows fewer adverse events.展开更多
基金supported by a grant from the Principal Research Program of Clinical Disciplines of State Health Ministry(No.321)
文摘Neoadjuvant chemotherapy plus radiotherapy is the most common treatment regimen for advanced nasopharyngeal carcinoma(NPC).Whether chronomodulated infusion of chemotherapy can reduce its toxicity is unclear.This study aimed to evaluate the toxic and therapeutic effects of sinusoidal chronomodulated infusion versus flat intermittent infusion of cisplatin(DDP)and 5-fluorouracil(5-FU)followed by radiotherapy in patients with locoregionally advanced NPC.Patients with biopsy-diagnosed untreated stages III and IV NPC(according to the 2002 UICC staging system)were randomized to undergo2 cycles of sinusoidal chronomodulated infusion(Arm A)or flat intermittent constant rate infusion(Arm B)of DDP and 5-FU followed by radical radiotherapy.Using a"MELODIE"multi-channel programmed pump,the patients were given 12-hour continuous infusions of DDP(20 mg/m2)and 5-FU(750 mg/m2)for 5days,repeated every 3 weeks for 2 cycles.DDP was administered from 10:00 am to 10:00 pm,and 5-FU was administered from 10:00 pm to 10:00 am each day.Chronomodulated infusion was performed in Arm A,with the peak deliveries of 5-FU at 4:00 am and DDP at 4:00 pm.The patients in Arm B underwent a constant rate of infusion.Radiotherapy was initiated in the fifth week,and both arms were treated with the same radiotherapy techniques and dose fractions.Between June 2004 and June 2006,125 patients were registered,and 124 were eligible for analysis of response and toxicity.The major toxicity observed during neoadjuvant chemotherapy was neutropenia.The incidence of acute toxicity was similar in both arms.During radiotherapy,the incidence of stomatitis was significantly lower in Arm A than in Arm B(38.1%vs.59.0%,P=0.020).No significant differences were observed for other toxicities.The 1-,3-,and 5-year overall survival rates were 88.9%,82.4%,and 74.8%for Arm A and 91.8%,90.2%,and 82.1%for Arm B.The 1-,3-,and 5-year progression-free survival rates were 91.7%,88.1%,and 85.2%for Arm A and 100%,94.5%,and 86.9%for Arm B.The 1-,3-,and 5-year distant metastasis-free survival rates were 82.5%,79.1%,and 79.1%for Arm A and 90.2%,85.2%,and 81.7%for Arm B.Chronochemotherapy significantly reduced stomatitis but was not superior to standard chemotherapy in terms of hematologic toxicities and therapeutic response.
基金supported by the National Natural Science Foundation of China(No.82302640)Guangzhou Science and Technology Plan Project(grant No.2023A04J1129)Guangdong Medical Scientific Research(grant No.B2023038&A2024619).
文摘Chemotherapy remains an integral component in the treatment of advanced non-small cell lung cancer(NSCLC).However,patients often experience suboptimal treatment outcomes due to their inability to tolerate high doses and toxicity of chemotherapy.In recent years,a growing body of research has demonstrated a significant correlation between chemotherapy and circadian rhythms,suggesting that the efficacy of chemotherapy may exhibit a temporal dependence associated with the circadian clock.Existing evidence suggests that chronochemotherapy offers the advantages of high efficacy and low toxicity,although the underlying mechanisms remain unclear.Chronochemotherapy is defined as the infusion of chemotherapeutic drugs at the appropriate stage of human biological rhythm.Therefore,optimizing chemotherapy by employing chronochemotherapy for cost-effectiveness and efficiency has become a critical area of research.There is increasing evidence that chronochemotherapy is an effective treatment for NSCLC,offering a novel therapeutic strategy for its management.
基金supported by Guizhou Provincial Department of Sci-ence and Technology Cooperation Program Project,China(No.LH20157379).
文摘Objective:To validate the safety and efficacy of chronochemotherapy for locoregionally advanced nasopharyngeal carcinoma(NPC).Methods:Participants for this phase II randomized controlled trial were recruited from the Department of Head and Neck Oncology at the Affiliated Cancer Hospital of Guizhou Medical University.Patients enrolled(128 in total,112 in the final analysis)between April 1,2017,and February 28,2018,were randomly divided into the chronochemotherapy and conventional chemotherapy groups.In the chronochemotherapy group,docetaxel was intravenously administered between 3:30 a.m.and 4:30 a.m.on day 1,followed by intravenous administration of cisplatin between 10:00 a.m.and 10:00 p.m.from day 1to day 5.In addition,5-fluorouracil was administered through a continuous intravenous pump between 10:00 p.m.and 10:00 a.m.(2nd day)from day 1 to day 5.In the conventional chemotherapy group,docetaxel(on day 1),cisplatin(on day 2),and 5-fluorouracil(from day 1 to day 5,120 h in total)were administered without time-specific constraints.Both groups underwent intensitymodulated radiation therapy with 6-MV X-rays.The gross target volume(GTV)comprised the nasopharyngeal GTV and cervical lymph node GTV.The primary endpoint was immune function,quantified by measuring dendritic cell and lymphocyte subsets,whereas the secondary endpoints were therapeutic efficacy and incidence of adverse events.Pearson Chi-square test was applied to compare total events between the groups,Mann-Whitney U test was used to compare the DC subsets and toxicities,and Wilcoxon signed-rank test was used to compare the continuous variables between the two groups.Results:Chronochemotherapy preserved immune function,as evidenced by elevated levels of myeloid dendritic cells(P=0.394)and higher CD4/CD8 ratio(P?0.781).No significant difference in overall response rate,measured as the sum of complete and partial response rates,was observed between the groups(P=0.711).A reduction in the incidence of vomiting(P=0.002),stomatitis(P=0.028),and mucositis(P=0.028)was observed in the chronochemotherapy group.Leukopenia incidence rate was 83.3% and 92.3% in the chronochemotherapy and conventional chemotherapy groups,respectively(P=0.232).Conclusions:In patients with locoregionally advanced NPC,the overall response rate of chronochemotherapy is comparable to that of conventional chemotherapy;however,chronochemotherapy shows fewer adverse events.
