OBJECTIVETo evaluate the short-term efficacy and toxicity of endostar in combination with XELIRI as the second-line treatment for advanced colorectal cancer.

METHODSTwenty-one patients with advanced colorectal cancer were treated with intravenous infusion of endostar (15 mg/day for 14 consecutive days) and irinotecan (250 mg/m(2), single dose on the first day), and oral administration of capecitabine (1.0 mg/m(2), twice daily for 14 days), and the treatment cycle was repeated every 21 days. The efficacy and toxicity of the treatments were evaluated according to RECIST and NCI-CTCAE3.0 standard, respectively.

RESULTSThe overall response rate was 9.5% in these patients, with a median time to progression (mTTP) of 3.9 months. The main adverse effects associated with the treatment included leucopenia, nausea/vomiting and peripheral neuritis.

CONCLUSIONEndostar combined with XELIRI is effective and safe as the second-line treatment for advanced colorectal cancer, and further clinical investigation is warranted.

Adult ; Aged ; Antineoplastic Combined Chemotherapy Protocols ; adverse effects ; therapeutic use ; Camptothecin ; administration & dosage ; adverse effects ; analogs & derivatives ; Capecitabine ; Colorectal Neoplasms ; drug therapy ; secondary ; Deoxycytidine ; administration & dosage ; adverse effects ; analogs & derivatives ; Endostatins ; administration & dosage ; adverse effects ; genetics ; Female ; Fluorouracil ; administration & dosage ; adverse effects ; analogs & derivatives ; Humans ; Male ; Middle Aged ; Recombinant Proteins ; administration & dosage ; adverse effects

OBJECTIVETo evaluate the efficacy and adverse effects of irinotecan combined with cisplatin in the treatment of advanced non-small cell lung cancer (NSCLC).

METHODSFifteen patients (10 males and 5 females) aged from 32 to 58 years (median age of 47 years) with KPS>70 and the diagnosis of advanced NSCLC by pathology or cytology were treated with cisplatin 80 mg/m(2) plus irinotecan 60 mg/m(2) by intravenous infusion on 1, 8, 15 days, and the treatment was repeated every 4 weeks. After treatment for at least 2 cycles, the therapeutic effects and adverse drug reactions were evaluated.

RESULTSOf all the cases, PR was achieved in 4 (26.7%), SD in 9 (60%), and PD in 2 (13.3%), with an overall response rate of 26.7%. The median survival time was 11 months and 1-year survival rate was 46.7% (7/15). The main toxicities were delayed diarrhea and granulocytopenia.

CONCLUSIONIrinotecan plus cisplatin is an effective and tolerable treatment for advanced NSCLC with low incidence of adverse effects.

Adult ; Antineoplastic Combined Chemotherapy Protocols ; adverse effects ; therapeutic use ; Camptothecin ; administration & dosage ; adverse effects ; analogs & derivatives ; Carcinoma, Non-Small-Cell Lung ; drug therapy ; Cisplatin ; administration & dosage ; adverse effects ; Female ; Humans ; Lung Neoplasms ; drug therapy ; Male ; Middle Aged

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

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

We have evaluated the efficacy and safety of cetuximab plus FOLFIRI for irinotecan and oxaliplatin-refractory colorectal cancers. From September 2004 to February 2006, 31 patients with metastatic colorectal cancer were treated with cetuximab (400 mg/m2 intravenously [IV] over 2 hr on day 1 followed by weekly 1-hr infusions of 250 mg/m2) plus bi-weekly FOLFIRI (irinotecan 150 mg/m2 IV over 90 min, and leucovorin 100 mg/m2 IV over 2 hr, followed by 5-FU 400 mg/m2 IV bolus on day 1, and followed by 5-FU 2,400 mg/m2 by continuous IV over 46 hrs). Patients received a median of four cycles (range: 1-23). Eight (25.8%) patients had confirmed partial responses and 10 (32.2%) had stable disease. After a median follow-up of 13.2 months for surviving patients, the median time to progression was 2.9 months, the median duration of response was 5.4 months, and the median overall survival was 10.9 months. Skin toxicity was observed in 25 patients (80.4%) including grade 3 in 6 patients (19.4%). Other common non-hematologic toxicities of all grades were mucositis (32.3%), asthenia (22.6%), diarrhea (12.9%), and paronychial cracking (12.9%). The combination of cetuximab with FOLFIRI was effective and tolerable in colorectal cancer patients heavily pretreated with a number of chemotherapy regimens.
Adult ; Aged ; Antibodies, Monoclonal/*administration & dosage/adverse effects ; Antineoplastic Agents/*administration & dosage/adverse effects ; Antineoplastic Combined Chemotherapy Protocols/*administration & dosage/adverse ; Camptothecin/administration & dosage/adverse effects/analogs & derivatives ; Colorectal Neoplasms/*drug therapy/secondary ; Drug Resistance, Neoplasm ; Female ; Fluorouracil/administration & dosage/adverse effects ; Humans ; Leucovorin/administration & dosage/adverse effects ; Male ; Middle Aged ; Organoplatinum Compounds/pharmacology ; Prognosis ; Receptor, Epidermal Growth Factor/antagonists & inhibitors ; Safety

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

Agranulocytosis ; chemically induced ; Antineoplastic Agents, Phytogenic ; administration & dosage ; adverse effects ; Antineoplastic Combined Chemotherapy Protocols ; adverse effects ; therapeutic use ; Camptothecin ; administration & dosage ; adverse effects ; analogs & derivatives ; therapeutic use ; Colorectal Neoplasms ; drug therapy ; pathology ; Diarrhea ; chemically induced ; Drug Resistance, Neoplasm ; Fluorouracil ; adverse effects ; therapeutic use ; Humans ; Leucovorin ; adverse effects ; therapeutic use ; Neoplasm Staging ; Survival Analysis

OBJECTIVETo observe and compare the response rate and toxicity of irinotecan or oxaliplatin combined with capecitabine in the treatment of advanced gastric cancer.

METHODSSixty-three patients with advanced gastric cancer were randomly divided into two groups. The CPT-11 + CAP group consisted of 32 patients who received irinotecan plus capecitabine: CPT-11 100 mg/m(2) was injected in 90 minutes on d 1, 8;capecitabine 2000 mg/m(2), bid, with the first dose in the evening of day 1 and last dose the morning of day 15, repeated for every 21 days. The L-OHP + CAP group consisted of 31 patients who received oxaliplatin plus capecitabine: oxaliplatin 100 mg/m(2) on day 1, capecitabine 2000 mg/m(2), bid, with the first dose in the evening of day 1 and last dose the morning of day 15, repeated for every 21 days. Two or more cycle chemotherapy was completed in each group.

RESULTSIn the CPT-11 + CAP group, no patient achieved complete response and 13 patients achieved partia1 response. The overall response rate was 40.6% (13/32), and the median progression-free survival time was 6.3 months. In the L-OHP + CAP group, no patient achieved complete response and 12 patients achieved partial response. The overall response rate was 38.7% (12/31), and the median progression-free survival time was 6.1 months. There was no significant difference between them (P > 0.05). The most common toxicities were gastrointestinal reaction, peripheral neuropathy and myelosuppression in the two groups. Patients in CPT-11 + CAP group experienced more III/IV diarrhea (28.1%/3.2%, P = 0.018). On the contrary, the rate of III/IV neurotoxicity in the group B was higher (25.8%/3.1%, P = 0.027). No chemotherapy-related death occurred.

CONCLUSIONThe therapeutic effects of irinotecan or oxaliplatin combined with capecitabine in the treatment of advanced gastric cancer are good and comparable, and their toxicities are tolerable.

Adenocarcinoma ; drug therapy ; pathology ; secondary ; Adult ; Aged ; Agranulocytosis ; chemically induced ; Antineoplastic Combined Chemotherapy Protocols ; adverse effects ; therapeutic use ; Camptothecin ; administration & dosage ; adverse effects ; analogs & derivatives ; Capecitabine ; Deoxycytidine ; administration & dosage ; adverse effects ; analogs & derivatives ; Diarrhea ; chemically induced ; Disease-Free Survival ; Female ; Fluorouracil ; administration & dosage ; adverse effects ; analogs & derivatives ; Humans ; Liver Neoplasms ; drug therapy ; secondary ; Lymphatic Metastasis ; Male ; Middle Aged ; Neoplasm Staging ; Neuritis ; chemically induced ; Organoplatinum Compounds ; administration & dosage ; adverse effects ; Ovarian Neoplasms ; drug therapy ; secondary ; Remission Induction ; Stomach Neoplasms ; drug therapy ; pathology ; Young Adult

OBJECTIVETo evaluate the efficacy and toxicity of campto (CPT-11) monotherapy or combined with 5Fu + leucovorin (CF) in advanced large intestinal cancer.

METHODS186 such patients were divided into campto monotherapy group and CPT-11 plus 5Fu + CF [De Gramont (DGM) or Mayo protocal] groups. The mean dose of CPT-11 was 270 mg/m(2) alone in the monotherapy group and 150 mg/m(2) in the combination group. Campto was given as iv infusion in no less than 30-minutes.

RESULTS186 patients were eligible for response evaluation. The response rates were 27.9% in the monotherapy group, 32.7% in CPT-11 + DGM and 27.3% in CPT-11 + Mayo group. For 55 untreated patients, the response rates of monotherapy, Campto + DGM and Campto + Mayo regime groups were 33.3%, 28.9% and 50.0%. For 131 treated patients, they were 26.4%, 34.8% and 22.2%, respectively. The toxicities of the whole group were 16.0% cholinergic syndrome, 51.9% delayed diarrhea and 19.8% leucopenia. There were 2 treatment-related deaths.

CONCLUSIONThe efficacy and toxicities of campto are similar as compared with the reports by other investigators.

Adult ; Aged ; Aged, 80 and over ; Antineoplastic Combined Chemotherapy Protocols ; therapeutic use ; Bone Marrow ; drug effects ; Camptothecin ; adverse effects ; analogs & derivatives ; therapeutic use ; Female ; Humans ; Intestinal Neoplasms ; drug therapy ; Male ; Middle Aged