OBJECTIVETo explore the correlation between UGT1A1 (*28, *60 and * 93) polymorphism and the adverse reactions in small cell lung cancer patients after irinotecan chemotherapy.

METHODSClinical data of 58 small cell lung cancer patients in extensive stage treated in our hospital were retrospectively analyzed. Polymerase chain reaction was used to amplify the UTG, and direct sequencing was performed to determine the UGT polymorphism. The adverse reactions ≥ grade 3 after irinotecan chemotherapy in patients with different UGT genotype were analyzed.

RESULTSAmongthe 58 patients with extensive stage small cell lung cancer, there were 45 (77.6%) cases of wild type UGT1A1*28, 40 (69.0%) cases of wild type UGT1A1* 93, 38 (65.5%) cases of wild type UGT1A1*60, 18 cases of mutation in UGT1A1* 93 and 20 cases of mutation in UGT1A1*60. In UGT1A1 promoter position 28, there were 8 (13.8%) cases of TA5 mutation and 5 (8.6%) cases of TA7 mutation. Among the patients with TA5 mutation, 5 cases had ≥ grade 3 diarrhea, 3 cases had ≥ grade 3 leucopenia and 3 cases had ≥ grade 3 neutropenia, while among the patients with UGT1A1 * 93 mutation, 7 cases had ≥ grade 3 diarrhea, 6 cases had ≥ grade 3 leucopenia and 4 cases had ≥ grade 3 neutropenia.

CONCLUSIONSTA5 and UGT1A1* 93 mutation increase the risk of diarrhea and ≥ grade 3 leukopenia and neutropenia, however, wild type UGT1A1 (*28, * 93, *60) and mutant UGT1A1*60 do not increase those risks. Further prospective study in a larger number of patients is needed to clarify the association between UGT1A1*28, UGT1A1* 93 and UGT1A1*60 polymorphism and adverse reactions of irinotecan, and to help clinicians in choosing a better therapeutic modality for personalized chemotherapy to improve curative effect and reduce adverse reactions.

Antineoplastic Agents, Phytogenic ; adverse effects ; Camptothecin ; adverse effects ; analogs & derivatives ; Diarrhea ; Genotype ; Glucuronosyltransferase ; genetics ; metabolism ; Humans ; Neutropenia ; Polymorphism, Genetic ; Promoter Regions, Genetic ; Prospective Studies ; Retrospective Studies ; Small Cell Lung Carcinoma ; drug therapy ; genetics

OBJECTIVETo explore the effect of Shengjiang Xiexin Decoction (SXD) on the intestinal mucosal and functional cells of rats after irinotecan (CPT-11) chemotherapy.

METHODSTotally 24 healthy Sprague-Dawley (SD) male rats were divided into three groups, the normal control group, the CPT-11 group, the SXD combined CPT-11 group according to random digit table, 8 in each group. CPT-11 was injected at the daily dose of 150 mg/kg to rats in the CPT-11 group and the SXD combined CPT-11 group from the caudal vein on the 4th day, once daily for 2 successive days to duplicate delayed diarrhea model. Equal volume of normal saline was injected to rats in the normal control group from the caudal vein. SXD at 2 g/mL (10 g/kg body weight) was administered to rats in the SXD combined CPT-11 group by gastrogavage for 9 successive days. Deionized water was administered to rats in the CPT-11 group and the normal control group. Diarrhea was observed at 48, 60, 72, 84, 96, and 108 h to calculate the incidence rate of diarrhea. Meanwhile, scoring for diarrhea was performed by referring methods of Akinobu Kurita. Rats were killed on day 10, ileum, cecum, and colon tissues were collected and fixed in 10% formalin solution. HE staining was performed. Intestinal mucosa injuries were graded under light microscope according to the criterion of Chiu's score. The expressions of goblet cells and Paneth cells were observed by PAS stain. Enteroendocrine cells were observed by immunohistochemical CgA staining. Positive cells were counted and cumulative optical density (IOD) analyzed by Image-Pro-Plus 6.0.

RESULTSNo diarrhea occurred in rats of the normal control group at each time point. The incidence rate of diarrhea was 75.0% (6/8) at 48 h, 100.0% (8/8) at 60 h, 100.0% (8/8) at 72 h, 87.5% (7/8) at 84 h, 75.0% (6/8) at 96 h, and 75.0% (6/8) at 108 h in the CPT-11 group. The incidence rate of diarrhea was 25.0% (2/8) at 48 h, 50.0% (4/8) at 60 h, 12.5% (1/8) at 72 h, 0.0% (0/8) at 84 h in the SXD combined CPT-11 group. Compared with the same group at 60 h, scores for diarrhea at 48, 84, 96, and 108 h obviously decreased in the CPT-11 group, and scores for diarrhea at 48, 72, 84, 96, and 108 h obviously decreased in the SXD combined CPT-11 group (P < 0.05, P < 0.01). Compared with the same group at 72 h, scores for diarrhea at 84, 96, and 108 h obviously decreased in the CPT-11 group (P < 0.05, P < 0.01). Compared with the normal control group, scores for diarrhea increased in the CPT-11 group at each time point (P < 0.01); grading of ileum, cecum, and colon mucosal tissues increased (P < 0.05, P < 0.01); expressions of ileum and cecum mucosal epithelial goblet cells obviously decreased (P < 0.05); the number and expressions of ileum and cecum mucosal epithelial Paneth cells increased (P < 0.01). Expressions of ilium endocrine cells increased, while those of cecum and colon endocrine cells decreased in the CPT-11 group (P < 0.01). Compared with the CPT-11 group, scores for diarrhea were obviously lowered (P < 0.05, P < 0.01), grading of ileum, and cecum mucosal tissues decreased (P < 0.05, P < 0.01); expressions of ileum, cecum, and colon mucosal epithelial goblet cells obviously increased (P < 0.05, P < 0.01); the number and expressions of ileum cecum mucosal epithelial Paneth cells increased (P < 0.05); expressions of cecum and colon endocrine cells increased (P < 0.05, P < 0.01) in the SXD combined CPT-11 group.

CONCLUSIONSXD played roles in preventing and treating CPT-11 induced delayed diarrhea by improving CPT-11 chemotherapy induced apoptosis and necrosis of intestinal mucosal and functional cells.

Animals ; Apoptosis ; Camptothecin ; adverse effects ; analogs & derivatives ; Colon ; Diarrhea ; Drug Therapy ; Drugs, Chinese Herbal ; pharmacology ; therapeutic use ; Ileum ; Intestinal Mucosa ; drug effects ; Male ; Rats ; Rats, Sprague-Dawley ; Wound Healing ; drug effects

BACKGROUND/AIMS: The purpose of this study was to investigate the efficacy and safety of irinotecan based FOLFIRI chemotherapy as a second-line treatment after failure of FOLFOX-4 chemotherapy in patients with advanced gastric cancer. METHODS: Fifty-two patients who were pathologically diagnosed with unresectable gastric cancer and received FOLFIRI chemotherapy after failure of FOLFOX-4 chemotherapy between September 2005 and February 2012 were enrolled in this study. Data were collected by retrospectively reviewing the medical records. The response to chemotherapy was assessed every 3 cycles by World Health Organization criteria and long term survival was analyzed. The toxicities were evaluated for every course of chemotherapy according to National Cancer Institution (NCI) toxicity criteria version 3.0. RESULTS: Median age of the patients was 57 years. Median overall survival (OS) and time to progression (TTP) were 7.8 and 5 months, respectively. The number of patients showing complete remission, partial remission, stable disease, and progressive disease were 0 (0.0%), 9 (17.3%), 30 (57.7%), and 13 (25.0%), respectively. The overall response rate was 17.3%. During a total of 345 cycles, anemia worse than NCI toxicity grade 3 occurred in 2.9%, leukopenia in 20.3%, neutropenia in 12.2%, and thrombocytopenia in 1.5%. Patients with less organ involvement by metastasis, less than 34 U/mL of CA 19-9 and good responsiveness to third cycle of second line chemotherapy were associated with longer OS and TTP. CONCLUSIONS: FOLFIRI chemotherapy has a modest efficacy with acceptable toxicities in patients with advanced gastric cancer as a second-line treatment. Further well-controlled studies are needed to elucidate the efficacy of FOLFIRI chemotherapy as second-line treatment in patients with advanced stomach cancer.
Adult ; Aged ; Anemia/etiology ; Antineoplastic Combined Chemotherapy Protocols/adverse effects/*therapeutic use ; Camptothecin/adverse effects/*analogs & derivatives/therapeutic use ; Disease Progression ; Female ; Fluorouracil/adverse effects/therapeutic use ; Humans ; Kaplan-Meier Estimate ; Leucovorin/adverse effects/therapeutic use ; Male ; Middle Aged ; Neoplasm Staging ; Organoplatinum Compounds/adverse effects/therapeutic use ; Retrospective Studies ; Stomach Neoplasms/*drug therapy/mortality/pathology ; Treatment Outcome

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

Previous studies reported that oxaliplatin is associated with sinusoidal obstruction syndrome. However few reports on oxaliplatin induced liver fibrosis are found in the literature. Furthermore pathogenesis of liver fibrosis is not well known. We report a case of 45-yr-old Korean man in whom liver fibrosis with splenomegaly developed after 12 cycles of oxaliplatin based adjuvant chemotherapy for colon cancer (T4N2M0). Thorough history taking and serological examination revealed no evidence of chronic liver disease. Restaging CT scans demonstrated a good response to chemotherapy. Five month after chemotherapy, he underwent right hepatectomy due to isolated metastatic lesion. The liver parenchyma showed diffuse sinusoidal dilatation and centrilobular vein fibrosis with necrosis without steatosis. We could conclude that splenomegaly was due to perisinusoidal liver fibrosis and liver cell necrosis induced portal hypertension by oxaliplatin. In addition, to investigate the pathogenesis of liver fibrosis, immunohistochemical stains such as CD31 and alpha-smooth muscle actin (alpha-SMA) were conducted with control group. The immunohistochemical stains for CD31 and alpha-SMA were positive along the sinusoidal space in the patient, while negative in the control group. Chemotherapy with oxaliplatin induces liver fibrosis which should be kept in mind as a serious complication.
Actins/metabolism ; Antigens, CD31/metabolism ; Antineoplastic Combined Chemotherapy Protocols/*therapeutic use ; Camptothecin/*analogs & derivatives/therapeutic use ; Chemotherapy, Adjuvant ; Colonic Neoplasms/*drug therapy ; Fluorouracil/therapeutic use ; Humans ; Hypertension, Portal/etiology ; Immunohistochemistry ; Leucovorin/therapeutic use ; Liver Cirrhosis/*diagnosis/etiology/pathology ; Liver Neoplasms/secondary/surgery ; Male ; Middle Aged ; Organoplatinum Compounds/*administration & dosage/adverse effects/therapeutic use ; Splenomegaly/*diagnosis/etiology ; Thrombocytopenia/etiology ; Tomography, X-Ray Computed

Anticonvulsants ; adverse effects ; Aryl Hydrocarbon Hydroxylases ; genetics ; Asian Continental Ancestry Group ; genetics ; Camptothecin ; analogs & derivatives ; metabolism ; Carbamazepine ; adverse effects ; Cytochrome P-450 CYP2C19 ; Glucuronosyltransferase ; genetics ; HLA-A Antigens ; genetics ; HLA-B Antigens ; genetics ; Humans ; Platelet Aggregation Inhibitors ; metabolism ; Stevens-Johnson Syndrome ; genetics ; Ticlopidine ; analogs & derivatives ; metabolism ; Topoisomerase I Inhibitors ; metabolism

Antineoplastic Agents, Phytogenic ; adverse effects ; therapeutic use ; Camptothecin ; adverse effects ; analogs & derivatives ; therapeutic use ; Colorectal Neoplasms ; drug therapy ; genetics ; Diarrhea ; chemically induced ; Glucuronosyltransferase ; genetics ; Humans ; Neutropenia ; chemically induced ; Polymorphism, Single Nucleotide

Antineoplastic Agents, Phytogenic ; therapeutic use ; Camptothecin ; adverse effects ; analogs & derivatives ; therapeutic use ; Child ; Child, Preschool ; Female ; Hepatoblastoma ; drug therapy ; Humans ; Liver Neoplasms ; drug therapy ; Male ; Neoplasm Recurrence, Local ; drug therapy

OBJECTIVETo assess the efficacy and safety of bevacizumab (BEV) plus chemotherapeutic agents in the treatment of metastatic colorectal cancer (mCRC).

METHODSSeventy-seven mCRC patients received BEV plus 5-Fu type, oxaliplatin or irinotecan-based chemotherapy. The clinical efficacy and bevacizumab-related adverse reactions were observed. The efficacy assessment was conducted after at least 2 cycles of BEV therapy. The adverse reactions were recorded in each therapy cycle. Among the 77 cases, 64 patients had finished the efficacy assessment. The adverse reactions in all patients were assessed.

RESULTSThe overall response rate (ORR) of BEV plus chemotherapy regimen was 18.75% (12/64), and the disease control rate (DCR) was 75.0% (48/64). In 27 patients who received the regimen as first-line treatment, the ORR reached 37.0% (10/27), while the DCR was 85.2%. Four patients with potentially resectable lesions became resectable after the regimen and received R0 resection of the liver metastases successfully. Twenty-five patients who received the regimen as second line therapy had poor result with ORR 8.0% and DCR 76.0%. Hypertension was observed in 12 cases, with 8 cases of grade 1, 3 cases of grade 2, 1 case of grade 3. Various bleedings occurred in 24/77 cases (31.2%), all were of grade 1-2, including 17 cases of epistaxis, grade 1 hemorrhoid bleeding in one case, hematuria in 3 case (2 of grade 1, 1 of grade 2), GI bleeding in 2 cases, hemoptysis in 1 case (grade 2), and proteinuria in 4 cases (grade 1). Intestinal perforation occurred in 1 case (0.3%). In two patients who had incomplete intestinal obstruction history appeared exacerbated intestinal obstruction symptoms after the application of BEV plus CPT11 regimen.

CONCLUSIONSBEV plus chemotherapy regimen as first-line treatment can improve the ORR and DCR of mCRC patients. When it was used as second- or later-line therapy, it may display satisfied DCR, although with a poor efficacy. The bevacizumab-related toxicity is mild and can be well tolerated.

Adult ; Aged ; Angiogenesis Inhibitors ; adverse effects ; therapeutic use ; Antibodies, Monoclonal, Humanized ; adverse effects ; therapeutic use ; Antineoplastic Combined Chemotherapy Protocols ; adverse effects ; therapeutic use ; Bevacizumab ; Camptothecin ; adverse effects ; analogs & derivatives ; therapeutic use ; Colonic Neoplasms ; drug therapy ; pathology ; Deoxycytidine ; adverse effects ; analogs & derivatives ; therapeutic use ; Disease-Free Survival ; Female ; Fluorouracil ; adverse effects ; analogs & derivatives ; therapeutic use ; Follow-Up Studies ; Hemorrhage ; chemically induced ; Humans ; Hypertension ; chemically induced ; Leucovorin ; adverse effects ; therapeutic use ; Liver Neoplasms ; drug therapy ; secondary ; Lung Neoplasms ; drug therapy ; secondary ; Male ; Middle Aged ; Neoplasm Staging ; Organoplatinum Compounds ; adverse effects ; therapeutic use ; Proteinuria ; chemically induced ; Rectal Neoplasms ; drug therapy ; pathology ; Remission Induction ; Young Adult

OBJECTIVETo prospectively evaluate the efficacy and toxicity of irinotecan plus cisplatin (IP regimen) compared with gemcitabine plus cisplatin (GP regimen) as a first-line treatment for advanced non-small cell lung cancer (NSCLC).

METHODSA total of 63 patients were randomly assigned to two regimens. IP Group (31 patients): irinotecan 100 mg/m(2), iv, d1 and d8; cisplatin 25 mg/m(2), iv, d1 to d3, and 3 weeks a cycle. GP Group (32 patients): gemcitabine 1000 mg/m(2), d1 and d8; cisplatin 25 mg/m(2), iv, d1 to d3, and 3 weeks a cycle. All the patients at least received two cycles of therapy. The response rate (RR), disease control rate (DCR), median time to tumor progression (TTP), median survival time (MST), l-year survival rate, and side effects were observed.

RESULTSAmong the 31 cases of IP group, 8 patients had PR, 17 patients had SD and 6 patients had PD. The RR and DCR were 25.8% (8/31) and 80.6% (25/31), respectively. The TTP was 6.7 months, MST was 11.2 months and the 1-year survival rate was 45.2% (14/31). Among 32 cases in the GP group, 11 patients had PR, 18 patients had SD and 3 patients had PD. The RR and DCR were 34.4% (11/32) and 90.6% (29/32), respectively. The TTP was 6.5 months, MST was 11.0 months and the 1-year survival rate was 43.7% (14/32). The main side effects of the two groups included hematologic toxicities, digestive tract reaction and hair loss. The incidence of diarrhea in the IP group was significantly higher than that in the GP group (P < 0.05), but the incidence of thrombocytopenia in the GP group was significantly higher than that in the IP group (P < 0.01).

CONCLUSIONSOur findings demonstrate that the two regimens have similar efficacy as a first-line treatment for advanced NSCLC. The major toxicities of the two regimens are well tolerable.

Adult ; Aged ; Antineoplastic Combined Chemotherapy Protocols ; adverse effects ; therapeutic use ; Camptothecin ; administration & dosage ; analogs & derivatives ; Carcinoma, Non-Small-Cell Lung ; drug therapy ; pathology ; Cisplatin ; administration & dosage ; Deoxycytidine ; administration & dosage ; analogs & derivatives ; Diarrhea ; chemically induced ; Disease Progression ; Female ; Humans ; Lung Neoplasms ; drug therapy ; pathology ; Male ; Middle Aged ; Neoplasm Staging ; Prospective Studies ; Remission Induction ; Survival Rate ; Thrombocytopenia ; chemically induced