OBJECTIVETo evaluate the safety and preliminary efficacy of dose-modified regimen of 5-fluorouracil plus oxaliplatin and irinotecan (mFOLFOXIRI) for patients with advanced colorectal cancer (CRC).

METHODSData of 312 CRC patients confirmed by pathology receiving triplet drug alone or combined with target therapy between October 2012 and December 2016 at the Sixth Affiliated Hospital of Sun Yat-sen University were retrospectively analyzed. CRC patients who had previously completed adjuvant therapy (or neoadjuvant therapy) within 6 months or palliative chemotherapy were excluded, meanwhile those with poor general condition (ECOG score > 2) or grade 2 neuropathy and allergy to oxaliplatin were excluded as well. Regimen of mFOLFOXIRI: oxaliplatin 85 mg/m² dissolved in 5% glucose solution 500 ml by intravenous infusion for 2 h; irinotecan 150 to 165 mg/m² dissolved in 0.9% sodium chloride 250 ml by intravenous infusion for 90 min; following intravenous infusion of leucovorin 400 mg/m² for 2 h, day 1; 5-FU 2800 mg/m², 48-h continuous intravenous infusion; once every 2 weeks. Therapy could be combined with a targeted drug, bevacizumab 5 mg/kg every two weeks; cetuximab 500 mg/m² every two weeks. Side effect was graded using the National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE 4.0.3). The objective response rate was evaluated according to the Response Evaluation Criteria in Solid Tumors (RECIST 1.1) after administering at least four cycles of chemotherapy.

RESULTSThe median age was 52 years (range 16-73) in the whole group; 113 patients (36.2%) had locally advanced CRC, and 199 (63.8%) had metastatic CRC. Most patients (274/312, 87.8%) did not receive any treatment earlier. There were a total of 1651 chemotherapy cycles in the whole group, with a median of 6(1-19) cycles. Of these 1651 cycles, 124 cycles of chemotherapy(7.5%) were dose-adjusted; 176 cycles of chemotherapy(10.7%) were delayed for median 5(3-13) days; 124 cycles(7.5%) required dose decrease. The overall relative dose intensity was >90%; the specific drug dose intensity was 93.6%(2620 mg×m⁻²×d⁻¹) for fluorouracil, 97.8%(83 mg×m⁻²×d⁻¹) for oxaliplatin, and 94.2%(155 mg×m⁻²×d⁻¹) for irinotecan. Twenty-three patients (7 of intestinal perforation, 7 of intestinal obstruction, 1 of grade 4 hematologic toxicity, and 8 of grade 3 fatigue) refused subsequent chemotherapy due to intolerable toxicity. Main grade 3 or 4 adverse events in patients were neutropenia in 69 cases (22.1%), fatigue in 35 cases (11.2%), and anemia in 28 cases (8.9%). Twenty serious adverse events (6.4%) occurred, including 13 patients of febrile neutropenia (4.2%), 7 patients of intestinal perforation (2.2%, 4 patients in upper rectum, 2 in sigmoid colon, and 1 in transverse colon cancer), and 9 of them had subsequent sepsis (2.9%). All the patients with intestinal perforation underwent emergency operation. No treatment-related deaths occurred. In 199 patients with metastatic CRC, because 22 patients did not receive image evaluation, the preliminary efficacy of 177 patients was actually evaluated. A total of 113 objective response events were observed. The overall response rate was 63.8%(113/177), partial response rate was 61.6%(109/177), clinically complete response rate was 2.3%(4/177), stable disease was 29.9% (53/177), progressive disease was 6.2%(11/177), and the disease control rate was 93.8%(166/177). In 127 patients receiving triplet drug, objective response rate was 40.9% for those with less than four cycles and 81.1% for those with more than four cycles (P<0.001).

CONCLUSIONThe mFOLFOXIRI regimen with reduced dose can be safely used in advanced CRC and has achieved promising results in terms of short-term efficacy.

Adolescent ; Adult ; Aged ; Antineoplastic Combined Chemotherapy Protocols ; administration & dosage ; therapeutic use ; Camptothecin ; administration & dosage ; analogs & derivatives ; Colorectal Neoplasms ; drug therapy ; Fluorouracil ; administration & dosage ; Humans ; Leucovorin ; administration & dosage ; Middle Aged ; Organoplatinum Compounds ; administration & dosage ; Retrospective Studies ; Treatment Outcome ; Young Adult

OBJECTIVETo explore the feasibility, safety and efficacy of intraoperative regional infusion chemotherapy by celiac trunk in advanced gastric cancer patients.

METHODSOne hundred and twenty-six patients with advanced gastric cancer(stageII(-III() were screened from database of Gastrointestinal Surgery Department of Taizhou People's Hospital between January 2008 and December 2010 who underwent R0 resection and D2 lymphadenectomy, received postoperative chemotherapy(XELOX or FOLFOX), and had complete follow-up data. They were divided into infusion chemotherapy group (65 cases) and control group (61 cases) according to regional infusion chemotherapy or not (fluorine 1 000 mg and cisplatin 60 mg). The side effects of chemotherapy, parameters related to the operation, long-term survival and relapse rate were compared between the two groups.

RESULTSThe baseline data between the two groups were comparable(all P>0.05). Postoperative III( and IIII( adverse reaction of chemotherapy was not significantly different between the two groups (P>0.05). The time of postoperative intestinal function recovery [(67.9±14.8) hours vs. (68.9±15.0) hours, t=-0.380, P=0.705), volume of postoperative 1-week drainage [(66.1±17.1) ml vs.(61.9±18.2) ml, t=1.478, P=0.142], recent morbidity of complications[55.4%(36/65) vs. 49.2%(30/61), χ=0.256, P=0.613], and the long-term morbidity of complications [16.9% (11/65) vs. 14.8% (9/61), χ=0.111, P=0.739] were all not significantly different between the two groups. The 3-year survival rate and 3-year relapse-free survival rate in infusion chemotherapy group were significantly higher than those in control group(58.4% vs. 37.7%, χ=5.382, P=0.020; 58.4% vs. 34.4%, χ=6.636, P=0.010).

CONCLUSIONRegional infusion chemotherapy by celiac trunk during operation for advanced gastric cancer patients is safe and feasible, and can reduce the risk of local recurrence and improve survival rate.

Antineoplastic Combined Chemotherapy Protocols ; therapeutic use ; Celiac Artery ; Chemotherapy, Cancer, Regional Perfusion ; adverse effects ; methods ; mortality ; Cisplatin ; administration & dosage ; adverse effects ; therapeutic use ; Deoxycytidine ; analogs & derivatives ; therapeutic use ; Disease-Free Survival ; Fluorine ; administration & dosage ; adverse effects ; therapeutic use ; Fluorouracil ; analogs & derivatives ; therapeutic use ; Gastrectomy ; Humans ; Leucovorin ; therapeutic use ; Lymph Node Excision ; Neoplasm Recurrence, Local ; prevention & control ; Organoplatinum Compounds ; therapeutic use ; Postoperative Complications ; Recovery of Function ; Stomach Neoplasms ; drug therapy ; mortality ; surgery ; Survival Rate

OBJECTIVETo explore efficacy and safety of modified FOLFIRINOX (mFOLFIRINOX) regimen by dose attenuation in locally advanced pancreatic cancer (LAPC) and metastatic pancreatic cancer(MPC).

METHODSBetween April 2014 and October 2015, 35 patients with LAPC (n=18) or MPC (n=17) were treated with mFOLFIRINOX regimen (irinotecan 135 mg/m(2), oxaliplatin 68 mg/m(2), 5-FU 2 400 mg/m(2), no bolus of 5-FU, leucovorin 400 mg/m(2)) in the Second Affiliated Hospital of Zhejiang University School of Medicine. The primary end point was progression free survival. The second end points were overall survival, objective response rate, adverse effects, surgical resection rate for LAPC.

RESULTSAmong 35 patients, 6 patients (17.1%) who dropped out and received less than 2 cycles were excluded for response analysis. Among the other 29 patients, 9 patients had grade 3 or 4 adverse effects. No patients ceased treatment due to adverse effects. The 29 patients received 5 (2-13) cycles were evaluated by efficacy and found partial remission in 16 cases, stable disease in 10 cases, progression disease in 3 cases. Response rate was 55.2%. Nine patients with LAPC accomplished surgery after neoadjuvant treatment without perioperative complication and death, and 6 patients accepted R0 resection.

CONCLUSIONSThe mFOLFIRINOX regimen used in the study is well-tolerated in Chinese population with high treatment efficacy on patients with LAPC and MPC. Further investigation of efficacy and adverse effects on more advanced pancreatic cancer patients is necessary.

Antineoplastic Combined Chemotherapy Protocols ; Camptothecin ; administration & dosage ; analogs & derivatives ; Disease Progression ; Disease-Free Survival ; Fluorouracil ; administration & dosage ; Humans ; Leucovorin ; administration & dosage ; Neoadjuvant Therapy ; Organoplatinum Compounds ; administration & dosage ; Pancreatic Neoplasms ; drug therapy ; Tertiary Care Centers ; Treatment Outcome

Gastric cancer frequently disseminates to the liver, lung, and bone via hematogeneous, lymphatic, or peritoneal routes. However, gastric adenocarcinoma that metastasize to the colon and that shows typical linea platisca pattern on colonofiberscopy has rarely been reported. Recently, the authors experience a case of advanced gastric cancer with colonic metastases in a 55-year-old female patient. Multiple colonic lymphoid hyperplasias were detected on colonofiberscopy and biopsy revealed metastatic gastric cancer to the colonic wall. She was treated with mFOLFOX (5-FU, oxaliplatin, leucovorin) and has achieved stable disease status without disease progression. Herein, we report a rare case of signet ring-cell gastric cancer which metastasized to the colon in the form of multiple colonic lymphoid hyperplasias.
Antineoplastic Combined Chemotherapy Protocols/therapeutic use ; Colonic Neoplasms/*diagnosis/secondary ; Colonoscopy ; Female ; Fluorouracil/administration & dosage ; Gastroscopy ; Humans ; Hyperplasia/diagnosis ; Leucovorin/administration & dosage ; Middle Aged ; Organoplatinum Compounds/administration & dosage ; Positron-Emission Tomography ; Stomach Neoplasms/*diagnosis/drug therapy ; Tomography, X-Ray Computed

Primary colorectal choriocarcinoma is a rare neoplasm. Only 19 cases have been reported worldwide, most of which involved adenocarcinomas. The prognosis is usually poor, and the standard therapy for this tumor has not been established. A 61-year-old woman presented with constipation and lower abdominal discomfort. She was diagnosed with primary adenocarcinoma with focal choriocarcinomatous differentiation in the sigmoid colon and liver metastasis. Because the serum beta-human chorionic gonadotropin level was not significantly elevated, and because only focal choriocarcinomatous differentiation was diagnosed, we selected the chemotherapy regimen that is used for the treatment of metastatic colorectal adenocarcinoma. The patient survived for 13 months after the initial diagnosis. This is the first case in Korea to assess the suppressive effects of the standard chemotherapy for colorectal adenocarcinoma against coexisting colorectal choriocarcinoma and adenocarcinoma.
Adenocarcinoma/*diagnosis/drug therapy/pathology ; Antineoplastic Agents/administration & dosage ; Antineoplastic Combined Chemotherapy Protocols/therapeutic use ; CA-19-9 Antigen/analysis ; Chorionic Gonadotropin, beta Subunit, Human/blood ; Colon, Sigmoid/pathology ; Colonic Neoplasms/*diagnosis/drug therapy/pathology ; Colonoscopy ; Constipation/etiology ; Female ; Fluorouracil/therapeutic use ; Humans ; Leucovorin/therapeutic use ; Liver Neoplasms/secondary ; Middle Aged ; Organoplatinum Compounds/therapeutic use ; Prognosis ; Tomography, X-Ray Computed

OBJECTIVETo analyze the characteristics of recurrence in gastric cancer patients after radical gastrectomy and adjuvant chemotherapy.

METHODSThe clinicopathological data of 110 gastric cancer patients who developed recurrence or second primary malignancies after radical gastrectomy and adjuvant chemotherapy with FOLFOX4 regimen or docetaxel plus FOLFOX4 regimen were analyzed retrospectively.

RESULTSThe median time to recurrence was 13.9 months (range, 1.7 to 63.1 months), and the median overall survival was 27.4 months (range, 6.9 to 90.7 months) in the whole group. The median survival time after recurrence was 10.1 months (range, 0.3 to 73.9 months). 82 (74.5%) patients had recurrence within 2 years after gastrectomy. The modes of surgical procedure and lymph node dissection influenced significantly on the time to recurrence (P<0.05 for both). Among the 110 patients with recurrence, 46 (41.8%) patients had peritoneal metastases, 33 (30.0%) had hematogenous metastases and 32 (29.1%) had locoregional lymph node metastases. Single, double, triple and quatro recurrences were observed at the first time of relapse in 78 (70.9%), 21(19.1%), 9(8.2%) and 2 cases (1.8%), respectively. Patients who developed simultaneous quatro recurrence had the poorest prognosis with a median overall survival of 15.2 months, significantly shorter than that of patients with single recurrence (31.8 months, P=0.003). Patients with peritoneal recurrence died most quickly ( mean 5.6 months), and patients with surgical field recurrence alone survived longest (mean 17.1 months).

CONCLUSIONSPeritoneal, hematogenous and locoregional lymph node metastases are the most frequent recurrences after radical gastrectomy and adjuvant chemotherapy in patients with gastric cancer. Single recurrence occurred in most patients at the first relapse. Combination with other adjuvant treatments should be considered besides adjuvant chemotherapy in gastric cancer patients after radical gastrectomy.

Antineoplastic Combined Chemotherapy Protocols ; administration & dosage ; therapeutic use ; Chemotherapy, Adjuvant ; Fluorouracil ; administration & dosage ; Gastrectomy ; methods ; Humans ; Leucovorin ; administration & dosage ; Lymph Node Excision ; Lymphatic Metastasis ; Neoplasm Recurrence, Local ; mortality ; Neoplasms, Second Primary ; Organoplatinum Compounds ; administration & dosage ; Prognosis ; Retrospective Studies ; Stomach Neoplasms ; mortality ; therapy ; Taxoids ; administration & dosage ; Time Factors

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

No abstract available.
Angiogenesis Inhibitors/administration & dosage ; Antineoplastic Combined Chemotherapy Protocols/therapeutic use ; Bevacizumab/administration & dosage ; Camptothecin/analogs & derivatives/therapeutic use ; Colonic Neoplasms/*diagnosis/drug therapy/pathology ; Colonoscopy ; Female ; Fluorouracil/therapeutic use ; Humans ; Leucovorin/therapeutic use ; Liver Neoplasms/drug therapy/pathology/secondary ; Lung Neoplasms/drug therapy/pathology/secondary ; Middle Aged ; Positron-Emission Tomography ; Tomography, X-Ray Computed

BACKGROUND/AIMS: The incidence of colorectal cancer has been increasing every year in Korea. Irinotecan- or oxaliplatin-based regimens including biologic agents are known to be effective in patients with advanced colorectal cancer. But in practice, FOLFOX (combination of oxaliplatin, 5-fluorouracil, and leucovorin) or FOLFIRI (combination of irinotecan, 5-fluorouracil, and leucovorin) regimens without biologic agents are more commonly used in Korea due to of the high costs of biologic agents. The aim of this study was to evaluate the efficacy and toxicity of FOLFIRI following FOLFOX4 in patients with advanced colorectal cancer. METHODS: A total of 54 patients with advanced colorectal cancer who were treated between May 2005 and May 2013 with FOLFOX4 as first-line chemotherapy and with FOLFIRI as second-line chemotherapy at Kosin University Gospel Hospital (Busan, Korea) were reviewed retrospectively. RESULTS: A total of 54 patients received second-line FOLFIRI chemotherapy. Five patients (9.3%) had a partial response, 29 patients (53.7%) had a stable disease. The median overall survival was 8.90 months and the median time to progression was 4.33 months. Toxicities were tolerable. CONCLUSIONS: In a Korean population, FOLFIRI as second-line chemotherapy is effective and well tolerated in patients with advanced colorectal cancer after failure of FOLFOX4. Although the efficacy of FOLFIRI in this study was lower than that of second-line FOLFIRI with biologic agents, these results can help in the formulation of a treatment strategy for financially troubled patients.
Adult ; Aged ; Aged, 80 and over ; Antineoplastic Combined Chemotherapy Protocols/*therapeutic use ; Camptothecin/administration & dosage/*analogs & derivatives/therapeutic use ; Colorectal Neoplasms/*drug therapy/mortality ; Drug Administration Schedule ; Female ; Fluorouracil/administration & dosage/therapeutic use ; Humans ; Injections, Intravenous ; Leucovorin/administration & dosage/therapeutic use ; Male ; Middle Aged ; Neoplasm Staging ; Organoplatinum Compounds/administration & dosage/therapeutic use ; Republic of Korea ; Retrospective Studies ; Survival Analysis

BACKGROUND/AIMS: Information on prognostic factors for metastatic colorectal cancer is an important basis for planning the treatment and predicting the outcomes of the patients; however, it has not been well established. The aim of this study was to identify factors that predict results of chemotherapy and to establish a plan for treatment of patients whose tumors are inoperable due to metastatic colorectal cancer. METHODS: We conducted a retrospective review of records from 75 patients treated for colorectal cancer in Kosin University Gospel Hospital, from October 2004 to September 2008. Patients with inoperable tumors due to metastasis at the time of diagnosis who were treated with oxaliplatin or irinotecan as the first-line treatment were included in this study. We investigated the factors that might have an effect on overall survival. RESULTS: A total of 75 patients were included in this study. Results of univariate analysis showed that hemoglobin (Hb) > or =10 g/dL at the time of diagnosis, no increase in CEA on the follow-up examination after chemotherapy, chemotherapy plus surgery, and better response to chemotherapy were significant prognostic factors. Results of multivariate analysis showed that Hb > or =10 g/dL at the time of diagnosis (p<0.001), surgery after chemotherapy (p=0.001), and better response to chemotherapy (p=0.014) were significant prognostic factors. CONCLUSIONS: In this study, Hb > or =10 g/dL at the time of diagnosis, surgery after chemotherapy, and better response to chemotherapy were significant prognostic factors for metastatic colorectal cancer.
Adult ; Aged ; Aged, 80 and over ; Antineoplastic Combined Chemotherapy Protocols/*therapeutic use ; Camptothecin/*analogs & derivatives/therapeutic use ; Colorectal Neoplasms/*diagnosis/*drug therapy/mortality/surgery ; Female ; Fluorouracil/administration & dosage/therapeutic use ; Hemoglobins/analysis ; Humans ; Kaplan-Meier Estimate ; Leucovorin/administration & dosage/therapeutic use ; Male ; Middle Aged ; Neoplasm Metastasis ; Odds Ratio ; Organoplatinum Compounds/therapeutic use ; Prognosis ; Retrospective Studies