No abstract available.
Antineoplastic Combined Chemotherapy Protocols/*therapeutic use ; Camptothecin/*analogs & derivatives/therapeutic use ; Female ; Fluorouracil/therapeutic use ; Humans ; Leucovorin/therapeutic use ; Male ; Organoplatinum Compounds/therapeutic use ; Stomach Neoplasms/*drug therapy

Colorectal cancer is the second most common malignant tumor in China. The FOLFOXIRI regimen, which combines 5-fluorouracil/leucovorin, oxaliplatin, and irinotecan, is a high-intensity and highly effective chemotherapy regimen. However, the original regimen is poorly tolerated in Chinese patients. In order to promote the standardized and rational application of FOLFOXIRI regimen by clinicians in China, "
Antineoplastic Combined Chemotherapy Protocols/therapeutic use* ; Camptothecin/therapeutic use* ; China ; Colorectal Neoplasms/drug therapy* ; Consensus ; Fluorouracil/therapeutic use* ; Humans ; Irinotecan/therapeutic use* ; Leucovorin/therapeutic use* ; Organoplatinum Compounds/therapeutic use* ; Oxaliplatin ; Treatment Outcome

BACKGROUND: The effect of intra-operative chemotherapy (IOC) on the long-term survival of patients with colorectal cancer (CRC) remains unclear. In this study, we evaluated the independent effect of intra-operative infusion of 5-fluorouracil in combination with calcium folinate on the survival of CRC patients following radical resection. METHODS: 1820 patients were recruited, and 1263 received IOC and 557 did not. Clinical and demographic data were collected, including overall survival (OS), clinicopathological features, and treatment strategies. Risk factors for IOC-related deaths were identified using multivariate Cox proportional hazards models. A regression model was developed to analyze the independent effects of IOC. RESULTS: Proportional hazard regression analysis showed that IOC (hazard ratio [HR]=0.53, 95% confidence intervals [CI] [0.43, 0.65], P  < 0.001) was a protective factor for the survival of patients. The mean overall survival time in IOC group was 82.50 (95% CI [80.52, 84.49]) months, and 71.21 (95% CI [67.92, 74.50]) months in non-IOC group. The OS in IOC-treated patients were significantly higher than non-IOC-treated patients ( P  < 0.001, log-rank test). Further analysis revealed that IOC decreased the risk of death in patients with CRC in a non-adjusted model (HR=0.53, 95% CI [0.43, 0.65], P  < 0.001), model 2 (adjusted for age and gender, HR=0.52, 95% CI [0.43, 0.64], P  < 0.001), and model 3 (adjusted for all factors, 95% CI 0.71 [0.55, 0.90], P  = 0.006). The subgroup analysis showed that the HR for the effect of IOC on survival was lower in patients with stage II (HR = 0.46, 95% CI [0.31, 0.67]) or III disease (HR=0.59, 95% CI [0.45, 0.76]), regardless of pre-operative radiotherapy (HR=0.55, 95% CI [0.45, 0.68]) or pre-operative chemotherapy (HR=0.54, 95% CI [0.44, 0.66]). CONCLUSIONS: IOC is an independent factor that influences the survival of CRC patients. It improved the OS of patients with stages II and III CRC after radical surgery. TRIAL REGISTRATION chictr.org.cn, ChiCTR 2100043775.
Humans ; Fluorouracil/therapeutic use* ; Leucovorin/therapeutic use* ; Colorectal Neoplasms/pathology* ; Retrospective Studies ; Antineoplastic Combined Chemotherapy Protocols/therapeutic use* ; Proportional Hazards Models ; Prognosis

Objective: To explore the outcome of different treatment strategies in patients with pancreatic cancer with synchronous liver metastasis (sLMPC). Methods: A retrospective analysis of the clinical data and treatment results of 37 patients with sLMPC treated in China-Japan Friendship Hospital was performed from April 2017 to December 2022. A total of 23 males and 14 females were included,with an age(M(IQR)) of 61 (10) years (range: 45 to 74 years). Systemic chemotherapy was carried out after pathological diagnosis. The initial chemotherapy strategy included modified-Folfirinox, albumin paclitaxel combined with Gemcitabine, and Docetaxel+Cisplatin+Fluorouracil or Gemcitabine with S1. The possibility of surgical resection (reaching the standards of surgical intervention) was determined after systemic treatment,and the chemotherapy strategy was changed in the cases of failed initial chemotherapy plans. The Kaplan-Meier method was used to estimate the overall survival time and rate,while Log-rank and Gehan-Breslow-Wilcoxon tests were used to compare the differences of survival curves. Results: The median follow-up time for the 37 sLMPC patients was 39 months,and the median overall survival time was 13 months (range:2 to 64 months) with overall survival rates of 1-,3-,and 5-year of 59.5%,14.7%,and 14.7%,respectively. Of the 37 patients,97.3%(36/37) initially received systemic chemotherapy, 29 completed more than four cycles,resulting in a disease control rate of 69.4% (partial response in 15 cases,stable disease in 10 cases,and progressive disease in 4 cases). In the 24 patients initially planned for conversion surgery,the successful conversion rate was 54.2% (13/24). Among the 13 successfully converted patients,9 underwent surgery and their treatment outcomes were significantly better than those (4 patients) of those who did not undergo surgery (median survival time not reached vs. 13 months,P<0.05). Regarding the 9 patients whose conversion was unsuccessful, no significant differences were observed in median survival time between the surgical group (4 cases) and the non-surgical group (5 cases) (P>0.05). In the allowed-surgery group(n=13),the decreased in pre-surgical CA19-9 levels and the regression of liver metastases were more significant in the successful conversion sub-group than in the ineffective conversion sub-group;however, no significant differences were observed in the changes in primary lesion between the two groups. Conclusion: For highly selective patients with sLMPC who achieve partial response after receiving effective systemic treatment,the adoption of an aggressive surgical treatment strategy can significantly improve survival time;however, surgery dose not provide such survival benefits in patients who do not achieve partial response after systemic chemotherapy.
Male ; Female ; Humans ; Pancreatic Neoplasms/surgery* ; Antineoplastic Combined Chemotherapy Protocols/therapeutic use* ; Retrospective Studies ; Docetaxel/therapeutic use* ; Liver Neoplasms/secondary* ; Fluorouracil ; Leucovorin/therapeutic use*

BACKGROUNDTo compare clinical efficacy and toxicity of irinotecan combined with 5-fluorouracil and leucovorin with those of oxaliplatin combined with 5-fluorouracil and leucovorin as first-line therapy for advanced colorectal cancer.

METHODSLiterature search was performed by keywords "irinotecan", "oxaliplatin" and "colorectal cancer" on all randomized controlled trails reported on irinotecan versus oxaliplatin combined with 5-fluorouracil and leucovorin as first-line therapy for advanced colorectal cancer in MEDLINE, OVID, Springer, Cochrane Controlled Trials Register (CCTR) and CBMdisc (Chinese Biology and Medicine disc) before January 2010. Two authors drew the details of trial design, characteristics of patients, outcomes, and toxicity from the studies included. Data analysis was performed by RevMan 4.2.

RESULTSAccording to the screening criteria, 7 clinical studies with 2095 participants of advanced colorectal cancer were included in this meta analysis. The baseline characteristics of irinotecan group were similar to those of oxaliplatin group. The response rate of oxaliplatin group was higher than that of irinotecan group (relative risk (RR) = 0.82, 95% confidence interval (95%CI) (0.70, 0.96), P = 0.01), and the median overall survival of oxaliplatin group was longer by 2.04 months than that of irinotecan group (95%CI (-3.54, -0.54), P = 0.008). In the comparison of grade 3 - 4 toxicity between the two groups, the incidences of nausea, emesis, diarrhoea and alopecia in irinotecan group were higher than those in oxaliplatin group (RR = 1.94, 95%CI (1.22, 3.09), P = 0.005; 1.71, 95%CI (1.34, 2.18), P < 0.001; 14.56, 95%CI (4.11, 51.66), P < 0.0001), respectively. However, the incidence of neurotoxicity, neutropenia and thrombocytopenia in irinotecan group were lower than those in oxaliplatin group (RR = 0.06, 95%CI (0.03, 0.14), P < 0.00001; 0.70, 95%CI (0.55, 0.91), P = 0.006; 0.18, 95%CI (0.05, 0.61), P = 0.006), respectively.

CONCLUSIONSBoth irinotecan and oxaliplatin combined with 5-fluorouracil and leucovorin were effective in the first-line therapy of advanced colorectal cancer. However, the combined regimen of oxaliplatin plus 5-fluorouracil and leucovorin is more excellent. Irinotecan tended to result in more gastrointestinal tract reactions than oxaliplatin did, but the myelosuppression and neurotoxicity were more frequent in oxaliplatin regimen than irinotecan regimen.

Antineoplastic Agents ; therapeutic use ; Antineoplastic Combined Chemotherapy Protocols ; Camptothecin ; analogs & derivatives ; therapeutic use ; Colorectal Neoplasms ; drug therapy ; Fluorouracil ; therapeutic use ; Humans ; Leucovorin ; therapeutic use ; Organoplatinum Compounds ; therapeutic use ; Treatment Outcome

OBJECTIVETo compare the therapeutic effect and toxicity of chemotherapy, used alone or in combined with Shenqi Fuzheng Injection (SFI), for the treatment of advanced colorectal carcinoma (ACRC).

METHODSOne hundred and fifty-two patients with ACRC were equally randomized by digital table, to the treated group, treated by chemotherapy of FOLFOX regimen combined with SFI, and the control group treated by FOLFOX regimen alone. The therapeutic effect and adverse reaction of the treatment in patients were assessed.

RESULTSThe effective rate (CR +PR) was 63.2% (48/76) in the treated group and 46.1% (35/76) in the control group, showing significant difference between the two groups (P < 0.05). The median survival time in the two groups was 31 weeks and 28 weeks respectively. CD4/CD8 ratio was significantly increased in the treated group (1.56 +/- 0.21, 1.64 +/- 0.28, P < 0.05), but significantly decreased in the control group (1.58 +/- 0.22, 1.46 +/- 0.33, P < 0.01). Quality of life in the former group was higher than that in the latter group (P < 0.05). Times/case of nausea, vomiting, leukopenia occurring in the control group was more than those in the treated group A (P < 0.05).

CONCLUSIONBy combining with SFI, some adverse reactions of chemotherapy (such as nausea, vomiting, leukopenia) and its influence on patients' immunity could be alleviated in treating ACRC, which might enhance the efficacy of chemotherapy, and improve the quality of life and prolong the median survival time in patients.

Antineoplastic Combined Chemotherapy Protocols ; therapeutic use ; Colorectal Neoplasms ; drug therapy ; Drugs, Chinese Herbal ; therapeutic use ; Fluorouracil ; therapeutic use ; Humans ; Leucovorin ; therapeutic use ; Organoplatinum Compounds ; therapeutic use ; Quality of Life ; Survival Rate

OBJECTIVETo investigate the association of CD133 expression in rectal cancer tissues with neoadjuvant chemoradiotherapy (nCRT) and tumor regression grading (TRG) after nCRT.

METHODSRadical resected rectal cancer specimens and clinicopathological data of 105 patients, including 60 men and 45 women with median age of 59 years, diagnosed as locally advanced rectal cancer in Peking Union Medical College Hospital from January 2008 to December 2014 were collected retrospectively. Thirty-nine and 66 cases were histologically classified as good-moderate and poor differentiation respectively. Sixty-eight and 37 cases were clinically graded as stage I(-II( and III(-IIII( in preoperative assessment respectively. NCRT was administered in 61 cases before surgery (nCRT group). The nCRT consisted of preoperative pelvic radiotherapy using 50 Gy (2 Gy once, for 25 sessions) with FOLFOX regimen (5-fluorouracil plus oxaliplatin) for 2-3 cycles or XELOX regimen (capecitabine plus oxaliplatin) for 2 cycles. Patients underwent surgery after 6 courses of nCRT, and then received the same previous chemotherapy regimen. In nCRT group, biopsy specimens before nCRT were obtained in 45 cases. Forty-four cases received surgery alone without nCRT (surgery alone group). CD133 expression was tested by immunohistochemical Envision two-step methods. The histological TRG evaluation was performed in the nCRT group. TRG score 0-2 was defined as insensitivity to nCRT, whereas TRG score 3-4 was defined as sensitivity. CD133 expression in rectal cancer samples before and after nCRT was compared. Association of CD133 expression with TRG after nCRT was examined.

RESULTSNo significant differences of baseline parameters were found between nCRT group and surgery alone group (all P>0.05). The positive rate of CD133 in nCRT group was 70.4%(43/61,) which was significantly higher than that in surgery alone group (47.7%, 21/44)(χ(2)=5.566, P=0.018) and that in biopsy samples before nCRT group (44.4%, 20/45)(χ(2)=7.287, P=0.007). Twenty-two cases (36.1%, 22/61) in nCRT group had TRG score of 3-4 . Among these 22 cases, 11 cases were negative CD133, and constituted 61.1% (11/18) of all CD133-low expression cases in nCRT group, whereas the other 11 cases were positive CD133, and constituted 25.6%(11/43) of all CD133-high expression cases in nCRT group (χ(2)=6.974, P=0.008).

CONCLUSIONThe CD133 expression up-regulates markedly in rectal cancer after nCRT and nCRT may have potential positive modulation on CD133 expression. CD133-positive cancer reveals lower response to nCRT, suggesting CD133 may be a potential target for improving efficacy of nCRT in rectal cancer.

AC133 Antigen ; metabolism ; Antineoplastic Combined Chemotherapy Protocols ; therapeutic use ; Chemoradiotherapy ; Deoxycytidine ; analogs & derivatives ; therapeutic use ; Female ; Fluorouracil ; analogs & derivatives ; therapeutic use ; Humans ; Leucovorin ; therapeutic use ; Male ; Middle Aged ; Neoadjuvant Therapy ; Neoplasm Staging ; Organoplatinum Compounds ; therapeutic use ; Rectal Neoplasms ; metabolism ; therapy

OBJECTIVETo observe the effect of modified Sijunzi Decoction (SJZD) on immune function in patients with colorectal cancer undergoing chemotherapy (CM) with FOLFOX4 protocol (oxaliplatin + calcium folinate + 5-fluorouracil).

METHODSForty-five patients with colorectal cancer were randomly assigned to two groups, the 22 in the control group treated with CM alone and the 23 in the treated group treated with CM plus SJZD. The therapeutic course for both groups was 2 chemotherapy cycles. Immunologic indices, including T-lymphocyte subgroup and NK cell proportion were detected before and after treatment using immunofluorescence stain and flow cytometry. Meantime, patients' quality of life (QOL) was scaled by KPS scoring, body mass was weighed, side and toxic effects of chemotherapy were recorded.

RESULTSCompared with pre-treatment, CD4 and CD4/CD8 significantly decreased after treatment in the control group (P < 0.05), while in the treated group, CD3, CD4 and CD4/CD8 increased significantly (P < 0.05). In addition, CD4 and CD4/CD8 were much higher in the treated group than in the control group (P < 0.05). Compared with the control group, the treated group had stabilized KPS score and body weight, and reduced chemotherapeutic toxicity shown as higher level of leucocyte amount, less symptoms of nausea and vomiting (P < 0.05).

CONCLUSIONSJZD could improve the immune function and QOL of colorectal cancer patients undergoing FOLFOX4, and reduce the side effects of CM.

Antineoplastic Combined Chemotherapy Protocols ; therapeutic use ; Colorectal Neoplasms ; drug therapy ; immunology ; Drugs, Chinese Herbal ; administration & dosage ; therapeutic use ; Female ; Fluorouracil ; therapeutic use ; Humans ; Leucovorin ; therapeutic use ; Male ; Middle Aged ; Organoplatinum Compounds ; therapeutic use ; Phytotherapy ; Quality of Life

BACKGROUNDHigh-dose methotrexate (HD-MTX) with folinic acid (leucovorin) rescue is the gold standard therapy in the treatment of osteosarcoma. The plasma concentration of MTX is closely related to efficacy and toxicity. There are large individual differences. Many authors have described the pharmacokinetic (PK) profile of MTX regarding osteosarcoma under a variety of circumstances. However, no data concerning Chinese osteosarcoma patient PKs using the nonlinear mixed effects models (NONMEM) have been previously reported. The goals of this study were to establish the population pharmacokinetics (PPK) of HD-MTX treatment in Chinese osteosarcoma patients, and to explore the influence of patient covariates and between-occasion variability on drug disposition.

METHODSAn intravenous HD-MTX solution (10 g/m 2 ) was given 274 times to 148 osteosarcoma patients. MTX plasma concentrations were measured at 0, 6, 12, 24, 48 and 72 h after commencement of the infusion, and the fluorescence polarization immunoassay was used to determine MTX plasma concentrations. The PPK model and parameters were estimated using NONMEM software. The effects of fixed-effect factors were evaluated, and the final regression model was obtained.

RESULTSThe following population parameters were obtained using a two-compartment model: CL1 (clearance of central compartment): (CL1 ) = CL1TV × [1 - θ CL1- MTXNUM × MTXNUM] × [1 - θ CL1- CrCl1 × (CrCl1 - 1.89)] × e ηCL1i (L/h). V1 (central volume): (V1)i = V1TV × e ηV1i (L). CL2 (clearance of peripheral compartment): (CL2)i = CL2TV × [1 - θCL2 - BODY AREA × (body area - 1.62)] × e ηCL2i (L/h). V2 (peripheral compartment): (V2 )i = V2TV × [1 - θ V2-bodyarea × (bodyarea-1.62)] × e ηV2i (L). The PPK parameters (RSD%) were CL1, V1, CL2 and V2 with values of 6.20 L/h (8.48%), 19.6 L (extremely small), 0.0172 L/h (50.9%) and 0.515 L (39.1%), respectively. Creatinine clearance and the number of methotrexate chemotherapy cycles before MTX infusion had a significant effect on the CL1, and body surface area had a significant effect on the CL2 and the V2 (P < 0. 01).

CONCLUSIONSA good fit was derived for the PPK. The model could be used to provide guidance for MTX treatment and reduce adverse effects.

Adolescent ; Adult ; Child ; Female ; Humans ; Infusions, Intravenous ; Leucovorin ; administration & dosage ; therapeutic use ; Male ; Methotrexate ; administration & dosage ; therapeutic use ; Models, Molecular ; Osteosarcoma ; drug therapy ; Young Adult

Oxaliplatin with 5-fluorouracil plus leucovorin (FOLFOX) has become the standard treatment in patients with colorectal cancer. Among known toxicities induced by oxaliplatin, hematological, gastrointestinal and neurological toxicities are common. However, acute pulmonary toxicity associated with oxaliplatin is unusual. One case of interstitial lung disease associated with the FOLFOX protocol is reported here.
Aged ; Antineoplastic Agents/*adverse effects/therapeutic use ; Antineoplastic Combined Chemotherapy Protocols ; Colorectal Neoplasms/drug therapy ; Fluorouracil/*adverse effects/therapeutic use ; Humans ; Leucovorin/*adverse effects/therapeutic use ; Lung Diseases, Interstitial/chemically induced/*etiology/radiography ; Male ; Organoplatinum Compounds/*adverse effects/therapeutic use