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 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

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

The paper reported an investigation of the pharmacokinetics of SN-38 (7-ethyl-10-hydroxy-camptothecin) in rats and the tissue distribution in mice after injection of irinotecan hydrochloride nanoparticles (CPT-11) via tail veins. An LC-MS/MS method was established to determine the concentrations of SN-38 in whole blood of rats and in different tissues of mice. The pharmacokinetics and tissue distribution of SN-38 were compared after the intravenous injection of CPT-11 NPs and CPT-11 solution. Compared with irinotecan solution, the elimination half-life of SN-38 was prolonged from 2.17 h to 2.67 h after the intravenous injection of CPT-11 NPs, but its AUC had little change. After the injection of CPT-11 NPs in mice, over time, the concentrations of CPT-11-metabolized SN-38 in CPT-11 NPs were significantly higher in the whole blood, colon and lungs than those in CPT-11 solution, followed by in the spleen and liver, but those in the heart and brain had no change. However, the amount of SN-38 in the kidneys was reduced with time. CPT-11 NPs could prolong SN-38's (one of its metabolites) blood circulation time in rats and significantly increased the concentration of CPT-11-metabolized SN-38 in the whole blood, colon and lungs of mice. CPT-11 NPs made SN-38 efficiently target-bind to the colon and lungs of mice.
Animals ; Antineoplastic Agents, Phytogenic ; pharmacokinetics ; Camptothecin ; analogs & derivatives ; pharmacokinetics ; Chromatography, Liquid ; Colon ; metabolism ; Half-Life ; Injections, Intravenous ; Lung ; metabolism ; Mice ; Nanoparticles ; administration & dosage ; Rats ; Tandem Mass Spectrometry ; Tissue Distribution

OBJECTIVETo evaluate the efficacy and safety of trastuzumab combined with chemotherapy in the treatment for HER-2-positive chemo-refractory advanced gastric or gastro-esophageal junction adenocarcinoma.

METHODSTwenty consecutive cases of chemo-refractory advanced gastric or gastro-esophageal junction adenocarcinoma treated in Peking University Cancer Hospital between 2009 June and 2013 August were included in this study. The patients with adenocarcinoma were previously confirmed and were eligible if their tumor showed overexpression of HER-2+++ by immunohistochemistry or HER-2 gene amplification-positive by FISH, and if they failed to at least one previous chemotherapy. Response and toxicities were evaluated with RECIST 1.0 and CTC AE 3.0 criteria.

RESULTSThe twenty patients received trastuzumab plus second- or later-line chemotherapy, consisting of nine platinum with fluoropyrimidines, five paclitaxel with fluoropyrimidines, three fluoropyrimidines monotherapy, two irinotecan monotherapy, and one docetaxel monotherapy. In these 20 cases, 3 PR (15.0%) and 10 SD (50.0%) were achieved, with a disease control rate of 65.0%. The median PFS was 6.1 months (95%CI 3.0-9.2) and median OS was 11.1 months (95%CI 8.4-13.7). The median cycle number of Trastuzumab administration was 6.5. The patients treated with Trastuzumab ≥ 6 times had a median OS of 13.8 months, significantly longer than that of 9.5 months in the patients treated <6 times (P < 0.001). The patients treated with Trastuzumab ≥ 6 times had a median PFS of 7.8 months, significantly longer than that of 3.7 months in patients treated <6 times (P = 0.029). Among the 20 cases, loss of appetite (13 cases of grade 1-2), neutropenia (12 cases of grade 1-2 and 3 cases of grade 3-4) and fatigue (9 cases of grade 1-2 and 3 cases of grade 3-4) were the most frequent adverse events. No cardiac events including asymptomatic decreases in LVEF ≥ 10% and no treatment-related death were recorded.

CONCLUSIONSCombination of trastuzumab with chemotherapy is effective and safe in patients with HER2-positive advanced chemo-refractory gastric or gastro-esophageal junction adenocarninoma. However, prospective studies are warranted to further confirm its efficacy and safety.

Adenocarcinoma ; drug therapy ; metabolism ; secondary ; surgery ; Adult ; Aged ; Anorexia ; chemically induced ; Antibodies, Monoclonal, Humanized ; administration & dosage ; adverse effects ; Antineoplastic Combined Chemotherapy Protocols ; adverse effects ; therapeutic use ; Camptothecin ; administration & dosage ; adverse effects ; analogs & derivatives ; Cisplatin ; administration & dosage ; adverse effects ; Disease Progression ; Disease-Free Survival ; Drug Resistance, Neoplasm ; Esophagogastric Junction ; Fatigue ; chemically induced ; Female ; Follow-Up Studies ; Humans ; Liver Neoplasms ; drug therapy ; secondary ; Male ; Middle Aged ; Neutropenia ; chemically induced ; Paclitaxel ; administration & dosage ; adverse effects ; Pyrimidines ; administration & dosage ; adverse effects ; Receptor, ErbB-2 ; metabolism ; Remission Induction ; Retrospective Studies ; Stomach Neoplasms ; drug therapy ; metabolism ; secondary ; surgery ; Survival Rate ; Trastuzumab

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

PURPOSE: To investigate chemosensitivity with an adenosine triphosphate-based chemotherapy response assay in patients with epithelial ovarian or peritoneal cancer according to tumor histology, grade, and disease status. MATERIALS AND METHODS: One hundred specimens were collected during primary or secondary debulking from 67 patients with primary ovarian cancer, 24 patients with recurrent ovarian cancer, 5 patients with primary peritoneal cancer, and 4 patients with recurrent peritoneal cancer; samples were collected between August 2006 and June 2009. Tumor cells were isolated and cultured for 48 hours in media containing chemotherapy. The chemosensitivity index (CI) was calculated as 300 minus the sum of the cell death rate at 0.2x, 1x, and 5x drug concentrations, and the CI values were compared. RESULTS: CI values were obtained from 93 of 100 patients. The most active agents against primary disease were ifosfamide and paclitaxel. For primary serous adenocarcinoma, paclitaxel and irinotecan were the most active, followed by ifosfamide. For clear cell carcinoma, ifosfamide was the most active, followed by paclitaxel and irinotecan. Although not statistically significant, the CIs of cisplatin, carboplatin, paclitaxel, and docetaxel decreased as tumor grade increased. In 14 cases of recurrent disease, paclitaxel was the most active, followed by ifosfamide and cisplatin. CONCLUSION: Ifosfamide and paclitaxel were the most active drugs for primary and recurrent disease. Therefore, we recommend further clinical studies to confirm the efficacy of paclitaxel, ifosfamide, and cisplatin combination chemotherapy for recurrent and primary ovarian cancer.
Adenocarcinoma, Clear Cell/*drug therapy/metabolism/pathology ; Adenosine Triphosphate/*metabolism ; Adult ; Aged ; Antineoplastic Combined Chemotherapy Protocols/*therapeutic use ; Camptothecin/administration & dosage/analogs & derivatives ; Carboplatin/therapeutic use ; Cisplatin/administration & dosage ; Drug Resistance, Neoplasm ; Drug Screening Assays, Antitumor/methods ; Female ; Humans ; Ifosfamide/administration & dosage ; Middle Aged ; Neoplasm Recurrence, Local/*drug therapy ; Neoplasms, Glandular and Epithelial/*drug therapy/metabolism/pathology ; Ovarian Neoplasms/*drug therapy/metabolism/pathology ; Paclitaxel/therapeutic use ; Peritoneal Neoplasms/*drug therapy/metabolism/pathology ; Predictive Value of Tests ; Sensitivity and Specificity ; Taxoids/administration & dosage

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

To investigate the pharmacokinetics of irinotecan hydrochloride (CPT-11) in rats and the tissue distribution of CPT-11 in mice after injection of irinotecan hydrochloride nanoparticles (CPT-11 NPs) via tail veins, separately, a LC-MS/MS method was established to determine the concentration of CPT-11 in whole blood of rats and in different tissues of mice. The pharmacokinetics and tissue distribution of CPT-11 were compared after the intravenous injection of CPT-11 NPs and CPT-11 solution. Compared with CPT-11 solution, the elimination half-life of CPT-11 was prolonged from 2.28 h to 3.95 h after the intravenous injection of CPT-11 NPs, and its AUC was 1.47 times than that of CPT-11 solution. After the injection of CPT-11 NPs in mice, the concentrations of CPT-11 loaded in CPT-11 NPs were significantly higher in the whole blood, colon and lungs than those in CPT-11 solution, but lower in the spleen, liver, kidney and heart, but the least in brain. CPT-11 NPs could improve CPT-11 's AUC, and help CPT-11 to reach long circulation activity.
Animals ; Antineoplastic Agents, Phytogenic ; administration & dosage ; blood ; pharmacokinetics ; Area Under Curve ; Camptothecin ; administration & dosage ; analogs & derivatives ; blood ; pharmacokinetics ; Chromatography, High Pressure Liquid ; Female ; Injections, Intravenous ; Male ; Mice ; Nanoparticles ; Random Allocation ; Rats ; Rats, Sprague-Dawley ; Spectrometry, Mass, Electrospray Ionization ; Tissue Distribution

This study plans to prepare lipid bilayer-coated mesoporous silica nanoparticles (LMSNs) which are pH sensitive with core-shell structure to improve the tumor cell lethality of antitumor drug. The lipid coated mesoporous silica nanoparticles loaded with irinotecan (CPT-11) (CPT-11-LMSNs) were prepared by hot water-film hydration method, and the characterized its morphology, particle size and release in vitro. Meanwhile, the intracellular uptake and cell toxicity of CPT-11-LMSNs and intracellular accumulation of CPT-11 were evaluated on human breast carcinoma cell line (MCF-7). The results indicated that the mean diameter of the spherical LMSNs was (120.27 +/- 5.91) nm. The slow release in simulated normal physiological conditions and a rapid release under simulated intracellular condition demonstrated the pH sensitivity of CPT-11-MSNs in vitro. Moreover, the CPT-11-LMSN could improve the intracellular CPT-11 cumulant 2.1 times and reduce half maximal inhibitory concentration (IC50) values of CPT-11 1.4 times compared with CPT-11-MSNs, demonstrating a stronger cell lethality.
Antineoplastic Agents, Phytogenic ; administration & dosage ; pharmacology ; Camptothecin ; administration & dosage ; analogs & derivatives ; pharmacology ; Cell Proliferation ; drug effects ; Drug Carriers ; Humans ; Hydrogen-Ion Concentration ; Lipid Bilayers ; administration & dosage ; chemistry ; MCF-7 Cells ; Nanoparticles ; Particle Size ; Porosity ; Silicon Dioxide ; administration & dosage ; chemistry