OBJECTIVETo evaluate the effects and safety of OXA-LV5FU2 regimen for patients with advanced/metastatic gastric cancer.

METHODSOXA 100 mg/m(2) i.v. 2hr d1, LV200 mg/m(2) i.v. 2hr followed by 5-Fu 400 mg/m(2) i.v. bolus and 5-Fu 600 mg/m(2) i.v. 22hr d1, 2 were given, and repeated every 2 weeks. Efficacy was evaluated at 4 cycles (8 weeks).

RESULTSForty three patients have been entered into the study. Patients with primary tumor resected or non-resected were 17 and 26. The evaluable lesions were 26 primary lesions, 22 lymph node metastases, 12 liver metastases, 1 pancreas metastasis and 2 soft tissue metastases. Forty patients were evaluable for clinical response. Four patients achieved CR (10.0%), 13 PR (32.5%), ORR 42.5% (95% CI 27.2 - 57.8), 17 SD (42.5%) and 6 PD (15.0%). Overall response rate (ORR) for chemotherapy naive (1(st) line) and pretreated (2(nd) line) patients were 50.0% (14/28) and 25.0% (3/12), respectively. Median time to progress (mTTP) was 5 months and median overall survival (mOS) was 8 months. Forty-three patients were evaluable for toxicity, with Grade 3, 4 WHO toxicity of neutropenia in 7 patients (16.3%), thrombocytopenia in 3 patients (7.0%), nausea/vomiting in 1 patient (2.3%). There were no Grade 3, 4 peripheral neuropathy toxicity or any deaths during treatment.

CONCLUSIONOXA-LV5FU2 is a high response regimen for advanced gastric cancer with mild toxicity, which can be practiced safely.

Adult ; Aged ; Antineoplastic Combined Chemotherapy Protocols ; therapeutic use ; Female ; Fluorouracil ; administration & dosage ; Humans ; Leucovorin ; administration & dosage ; Male ; Middle Aged ; Organoplatinum Compounds ; administration & dosage ; Stomach Neoplasms ; drug therapy

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

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

BACKGROUND: Irinotecan, in combination with 5-fluorouracil (5-FU) and a high dose of leucovorin (LV), known as FOLFIRI regimen, has shown activity in recurrent or metastatic colorectal cancer. Therefore, we evaluated the efficacy and safety of irinotecan, 5-FU and a low dose of LV (modified FOLFIRI) as a first line of therapy for patients with relapsed or metastatic colorectal cancer. METHODS: Between January 2002 and October 2004, 44 patients with histologically confirmed recurrent or metastatic colorectal cancer were enrolled. The chemotherapy regimen schedule consisted of 180 mg/m2 of irinotecan being administered intravenously (i.v) on Day 1, 400 mg/m2 of 5-FU via i.v bolus with 600 mg/m2 of continuous infusion for 22 hrs on both Day 1 and 2, and 20 mg/m2 of leucovorin on both Day 1 and 2, repeated every two weeks. RESULTS: The overall response rate was 47.8%. Of the 40 evaluated patients, one had CR (2.3%) and 20 had PR (46.5%). Toxicities were mild and easily manageable. Three patients experienced 23 episodes of Grade 3/4 leukopenia., Only one patient developed Grade 3/4 diarrhea. None experienced Grade 3/4 thrombocytopenia. CONCLUSION: Modified FOLFIRI with a low dose of LV is an effective and tolerable regimen for patients with recurrent or metastatic colorectal cancer.
Neoplasm Recurrence, Local/*drug therapy ; Neoplasm Metastasis/*drug therapy ; Middle Aged ; Male ; Leucovorin/administration & dosage ; Humans ; Fluorouracil/administration & dosage ; Female ; Disease Progression ; Colorectal Neoplasms/*drug therapy/pathology ; Camptothecin/administration & dosage/analogs & derivatives ; Antineoplastic Combined Chemotherapy Protocols/*administration & dosage ; Aged ; Adult

OBJECTIVEThe combination of oxaliplatin (L-OHP), 5-fluorouracil (5-Fu) and folinic acid (FA), being one of the effective regimens for advanced gastric cancer, is used in form of chronomodulated chemotherapy for advanced gastric cancer to investigate its efficacy and safety.

METHODSTwenty-six patients received a 4-day chronomodulated infusion of L-OHP, 5-Fu and FA. L-OHP (25 mg.m(-2).d(-1)) infused from 10:00 am to 22:00 pm, and followed by 5-Fu (600 mg.m(-2).d(-1)) and FA (300 mg.m(-2).d(-1)) from 22:00 pm to 10:00 am for 4 days using a multichannel programmable pump, every 2 weeks as an cycle for at least 2 cycles.

RESULTSTwenty-six patients with previously untreated advanced gastric cancer were eligible. Two complete and 13 partial remissions were observed with an overall response rate of 57.7%. Stable disease was observed in 6 patients (23.1%) and progressive disease in five (19.2%). Four of these patients underwent surgery. The median remission time was 3.5 months and time to tumor progression (TTP) was 4.5 months. The median overall survival time was 8 months. A total of 80 cycles were given without any grade 4 toxicity observed, but grade 3 thrombocytopenia (1.3%) and mucositis (1.3%) in one patient, two grade 3 neutropenia (2.5%) and nausea/vomiting (2.5%) in 2.

CONCLUSIONChronomodulated intravenous chemotherapy of oxaliplatin, 5-fluorouracil and folinic acid is effective and safe in the treatment of advanced gastric cancer.

Adenocarcinoma ; drug therapy ; Adult ; Aged ; Antineoplastic Combined Chemotherapy Protocols ; therapeutic use ; Chronotherapy ; Drug Administration Schedule ; Female ; Fluorouracil ; administration & dosage ; Humans ; Leucovorin ; administration & dosage ; Male ; Middle Aged ; Organoplatinum Compounds ; administration & dosage ; Stomach Neoplasms ; drug therapy ; Treatment Outcome

OBJECTIVETo evaluate the clinical efficacy and the toxicity of neoadjuvant chemotherapy with paclitaxel and FOLFOX4 (5-fluorouracil/leucovorin combined and oxaliplatin) regimen for advanced gastric cancer.

METHODSSeventy-eight patients with cTNM stage III or IV (M0) gastric cancer were enrolled and 39 were randomized into the treatment arm (n=39, paclitaxel combined with FOLFOX4 regimen neoadjuvant chemotherapy every two weeks in each cycle) and control group (n=39). Clinical response was evaluated with RECIST criteria after 3 cycles. Patients in experimental group received surgery after 2-4 weeks and postoperative chemotherapy of 3 cycles of the original regimen. When disease progressed, postoperative chemotherapy regimen was changed into ECF regimen. The control group of 39 patients received surgery within 2 weeks and postoperative chemotherapy of 6 cycles of paclitaxel combined with FOLFOX4 regimen.

RESULTSThe clinical response rate was 66.7% in the treatment arm. The R0 resection rate (59.0%) was significantly higher than that in the control group (P=0.025) and the number of lymph node metastasis in the treatment arm(3.23±2.80) was significantly lower than that in the control group (5.79±2.69, P=0.001). There were no significant differences in postoperative complication rate (5.1% vs. 2.6%) and the number of lymph node dissection (19.69±2.95 vs. 20.59±3.22) between the two groups (P>0.05). The median survival time and 2-year survival rate in the treatment arm [(27.10±2.32) months and 59.0%] was significantly higher than that in the control group[(18.20±1.30) months and 28.2%] (P=0.001, P=0.006). Cox regression multivariable analysis showed that tumor differentiation, R0 resection, lymph node metastasis were independent prognostic factors. Adverse reaction of chemotherapy, mainly hematological adverse reactions, and peripheral nerve toxicity, were tolerable. No significant differences were noted between the two groups in adverse reactions (P>0.05).

CONCLUSIONSThe efficacy of paclitaxel combined with FOLFOX4 as neoadjuvant chemotherapy is high. Patients tolerance and compliance are satisfactory. It can improve in patients with advanced gastric cancer the R0 resection rate, reduce lymph node metastasis and improve survival.

Adult ; Aged ; Antineoplastic Combined Chemotherapy Protocols ; Female ; Fluorouracil ; administration & dosage ; Humans ; Leucovorin ; administration & dosage ; Male ; Middle Aged ; Neoadjuvant Therapy ; Neoplasm Staging ; Organoplatinum Compounds ; administration & dosage ; Paclitaxel ; administration & dosage ; Stomach Neoplasms ; drug therapy ; pathology

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

OBJECTIVETo explore the feasibility of short-term neoadjuvant chemotherapy (NACT) in patients with advanced gastric cancer (AGC), and to compare clinical efficacy of short-term neoadjuvant chemotherapy with different ways.

METHODSClinical data of 310 AGC patients treated with one course of NACT using EOF regimen(epirubicin, oxaliplatin and fluorouracil plus calcium folinate) in our hospital from January 2008 to December 2011 were retrospectively analyzes. Efficacy was compared between regional arterial infusion chemotherapy and intravenously chemotherapy.

RESULTSAll the 310 AGC patients completed one course of NACT and none was interrupted by adverse events. Postoperative pathological remission rate was 33.9% (105/310) and 5 patients (1.6%) had complete pathological remission. The pathologic response rate in the regional arterial infusion chemotherapy group was higher than that in the intravenously chemotherapy group(42.4% vs. 23.6%, P = 0.001). Multivariate analysis revealed that chemotherapy method(HR=1.827, 95% CI:1.006-3.316, P = 0.048) was associated with significantly higher pathologic response.

CONCLUSIONSPathological response rate is quite low following short-term NACT. Regional arterial infusion chemotherapy with short-term NACT can improve the pathological response rate of advanced gastric cancer.

Antineoplastic Combined Chemotherapy Protocols ; administration & dosage ; therapeutic use ; Epirubicin ; Fluorouracil ; Humans ; Infusions, Intra-Arterial ; Leucovorin ; Neoadjuvant Therapy ; Organoplatinum Compounds ; Remission Induction ; Retrospective Studies ; Stomach Neoplasms ; drug therapy

BACKGROUND/AIMS: Limited options remain for patients with metastatic colorectal cancer (CRC) after failure of standard systemic chemotherapy. Readministration of chemotherapeutic agents by hepatic arterial infusion (HAI) has the rationale of providing higher concentrations of chemotherapeutic agents to hepatic metastases. The present study was conducted to evaluate the efficacy and safety of HAI of fluorouracil with leucovorin (HAI 5-FU/LV) for patients with liver metastases from CRC. METHODS: Fourteen patients with liver metastases from CRC who received HAI 5-FU/LV after failure of systemic chemotherapy containing fluorouracil and leucovorin were identified and their medical records were reviewed. RESULTS: Of 10 patients evaluable for response, one partial response, six stable disease, and three progressive disease were reported. Additionally, the overall response and disease control rates were 7% and 50%, respectively. The median time to progression was 4.3 months (range, 2.9 to 5.6), to hepatic progression was 5.8 months (range, 4.7 to 6.9), and to extrahepatic progression was 5.8 months (range, 2.3 to 9.2). No grade 3/4 hematologic toxicities occurred and one case of abdominal pain and two cases of oral mucositis were the only grade 3 nonhematologic toxicities. Catheter-related complications occurred in three patients: one thrombosis, one infection, and one displacement. CONCLUSIONS: HAI 5-FU/LV was well tolerated and showed modest efficacy for patients with liver metastases from refractory CRC. Readministration of previously used chemotherapeutic agents via the hepatic artery could be an effective salvage option and warrants further investigation in a prospective trial.
Adult ; Aged ; Antineoplastic Combined Chemotherapy Protocols/*administration & dosage/adverse effects ; Colorectal Neoplasms/*pathology ; Female ; Fluorouracil/administration & dosage/*therapeutic use ; Humans ; *Infusions, Intra-Arterial ; Leucovorin/administration & dosage/*therapeutic use ; Liver Neoplasms/*drug therapy/mortality/*secondary ; Male ; Middle Aged ; *Salvage Therapy

The objectives of the present study were to evaluate the efficacy and safety of an outpatient-basis chemotherapy of oxaliplatin, 5-fluorouracil, and leucovorin as the first-line treatment for patients with advanced colorectal cancer. Forty-three histologically confirmed patients with metastatic or recurrent colorectal cancer were enrolled. The chemotherapy consisted of oxaliplatin 85 mg/m2 as a 2-hr infusion on day 1, plus leucovorin 30 mg/m2 over 10 min, followed by bolus 5-fluorouracil 400 mg/m2 and an 8-hr infusion of 5-fluorouracil 600 mg/m2 on days 1 and 2 (modified FOLFOX4), all of which were administered on an outpatient basis every 2 weeks. The median age was 58 yr (range 33-72 yr), and 25 (58.1%) patients had metastatic diseases. Eventually, 39 patients were assessable for efficacy and all assessable for toxicity. Four (9.3%) complete responses and 11 (25.6%) partial responses were confirmed, giving an overall response rate of 34.9% (95% CI; 20.0-49.7%). The median time to progression and median overall survival for all patients was 6.1 months and 17.4 months, respectively. Grade 3/4 neutropenia occurred in 2 patients (4.7%) and febrile neutropenia was observed in 1 patient (2.3%). Modified FOLFOX4, an outpatient-basis regimen, was found to be well-tolerated and effective as the firstline chemotherapy in patients with advanced colorectal cancer.
Adolescent ; Adult ; Aged ; Antineoplastic Combined Chemotherapy Protocols/*therapeutic use ; Colorectal Neoplasms/*drug therapy/pathology ; Female ; Fluorouracil/*administration & dosage ; Humans ; Leucovorin/*administration & dosage ; Male ; Middle Aged ; Neoplasm Metastasis ; Organoplatinum Compounds/*administration & dosage ; Outpatients ; Recurrence