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

In this work, we developed PEO-PPO-PEO micelles loaded with irinotecan hydrochloride (CPT-11) using breast cancer resistance protein (BCRP) inhibitory material PEO20-PPO70-PEO20, and studied its mechanism of decreasing CPT-11 induced delayed diarrhea and intestinal toxicity. BCRP-overexpressing MDCKII (MDCKII/BCRP) cells were used to evaluate the effect of PEO20-PPO70-PEO20 and PEO-PPO-PEO micelles on transmembrane transport of CPT-11 in vitro. The biliary excretion, delayed diarrhea and intestinal damage of CPT-11 loaded PEO-PPO-PEO micelles of rats were investigated. The results showed that the obtained micelles could decrease the biliary excretion of CPT-11, ameliorate delayed diarrhea and intestinal toxicity of rats through inhibiting BCRP-mediated CPT-11 efflux. PEO-PPO-PEO micelles were promising carriers to reduce intestinal toxicity of CPTs.
ATP Binding Cassette Transporter, Sub-Family G, Member 2 ; ATP-Binding Cassette Transporters ; metabolism ; Animals ; Antineoplastic Agents, Phytogenic ; administration & dosage ; adverse effects ; pharmacokinetics ; Bile ; secretion ; Biological Transport ; Camptothecin ; administration & dosage ; adverse effects ; analogs & derivatives ; pharmacokinetics ; Cells, Cultured ; Diarrhea ; chemically induced ; drug therapy ; Dogs ; Drug Carriers ; Intestines ; drug effects ; Madin Darby Canine Kidney Cells ; Male ; Micelles ; Neoplasm Proteins ; metabolism ; Polyethylene Glycols ; administration & dosage ; chemistry ; Propylene Glycols ; administration & dosage ; chemistry ; Rats ; Rats, Sprague-Dawley

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

OBJECTIVETo evaluate the efficacy and safety of intravesical instillation with gemcitabine after first-line intravesical chemotherapy failure, including mitomycin (MMC), epirubicin (EPB) and camptothecin (CPT), in the treatment of non-muscle-invasive bladder cancer (NMIBC).

METHODSFrom June 2007 to October 2008, 72 patients with NMIBC, who had tumor recurrence within one year of first-line intravesical chemotherapy, were assigned to 3 groups (24 cases each). Group A received intravesical gemcitabine in a dose of 1000 mg, Group B received 2000 mg gemcitabine, and Group C received original intravesical chemotherapy. The time of reccurrence and adverse effects were recorded.

RESULTSThe 2-year tumor free survival rates of the 3 groups were 66.7%, 75.0% and 45.8%, respectively. The 2-year TFS rate of the patients who received gemcitabine was 70.8%, significantly higher than 45.8% of the patients treated by original chemotherapy. There was one case with renal function impairement in the groups A and B, respectively. There was no significant difference between the rates of low urinary tract symptoms in the 3 groups. No severe hematological side effects were observed in this study.

CONCLUSIONThe intravescal chemotherapy with gemcitabine in patients with recurrent bladder tumor after first-line intravesical chemotherapy is effective and well tolerated, however, renal function should be routinely assessed.

Administration, Intravesical ; Adult ; Aged ; Antibiotics, Antineoplastic ; therapeutic use ; Antimetabolites, Antineoplastic ; administration & dosage ; adverse effects ; therapeutic use ; Antineoplastic Agents, Phytogenic ; therapeutic use ; Camptothecin ; therapeutic use ; Deoxycytidine ; administration & dosage ; adverse effects ; analogs & derivatives ; therapeutic use ; Disease-Free Survival ; Dose-Response Relationship, Drug ; Epirubicin ; therapeutic use ; Female ; Follow-Up Studies ; Humans ; Male ; Middle Aged ; Mitomycin ; therapeutic use ; Neoplasm Invasiveness ; Neoplasm Recurrence, Local ; Urinary Bladder Neoplasms ; drug therapy ; pathology

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

The efficacy and safety of bevacizumab with modified irinotecan, leucovorin bolus, and 5-fluorouracil intravenous infusion (mIFL) in the first-line treatment of metastatic colorectal cancer (mCRC) has not been well evaluated in randomized clinical trials in Chinese patients. We conducted a phrase III trial in which patients with previously untreated mCRC were randomized 2:1 to the mIFL [irinotecan (125 mg/m(2)), leucovorin (20 mg/m(2)) bolus, and 5-fluorouracil intravenous infusion (500 mg/m(2)) weekly for four weeks every six weeks] plus bevacizumab (5 mg/kg every two weeks) group and the mIFL group, respectively. Co-primary objectives were progression-free survival (PFS) and 6-month PFS rate. In total, 214 patients were enrolled. Our results showed that addition of bevacizumab to mIFL significantly improved median PFS (4.2 months in the mIFL group vs. 8.3 months in the bevacizumab plus mIFL group, P < 0.001), 6-month PFS rate (25.0% vs. 62.6%, P < 0.001), median overall survival (13.4 months vs. 18.7 months, P = 0.014), and response rate (17% vs. 35%, P = 0.013). Grades 3 and 4 adverse events included diarrhea (21% in the mIFL group and 26% in the bevacizumab plus mIFL group) and neutropenia (19% in the mIFL group and 33% in the bevacizumab plus mIFL group). No wound-healing complications or congestive heart failure occurred. Our results suggested that bevacizumab plus mIFL is effective and well tolerated as first-line treatment for Chinese patients with mCRC. Clinical benefit and safety profiles were consistent with those observed in pivotal phase III trials with mainly Caucasian patients.
Adult ; Aged ; Angiogenesis Inhibitors ; adverse effects ; therapeutic use ; Antibodies, Monoclonal, Humanized ; adverse effects ; therapeutic use ; Antineoplastic Combined Chemotherapy Protocols ; adverse effects ; therapeutic use ; Asian Continental Ancestry Group ; Bevacizumab ; Camptothecin ; administration & dosage ; adverse effects ; analogs & derivatives ; Colorectal Neoplasms ; drug therapy ; pathology ; Diarrhea ; chemically induced ; Disease-Free Survival ; Female ; Fluorouracil ; administration & dosage ; adverse effects ; Humans ; Leucovorin ; administration & dosage ; adverse effects ; Male ; Middle Aged ; Neoplasm Metastasis ; Neutropenia ; chemically induced ; Prospective Studies ; Survival Rate ; Young Adult

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 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 assess the efficacy and safety of bevacizumab plus irinotecan-based regimen for the first line treatment in metastatic colorectal cancer (mCRC) patients, and to investigate the correlation between serum tumor markers including CEA and CA19-9 and response as well as prognosis.

METHODSFrom May 2007 to July 2008, 67 previously untreated mCRC patients received treatment of IFL (n = 25), IFL plus Bevacizumab (n = 20) or FOLFIRI (n = 22). The treatment continued until disease progression or unacceptable toxicity. The data were retrospectively analyzed.

RESULTSAll patients were evaluable for response, survival and toxicity analysis. The objective response rate of IFL, IFL plus Bevacizumab or FOLFIRI regimen groups was 16.0% (4/25), 35.0% (7/20) and 18.2% (4/22), respectively (χ(2) = 6.026, P = 0.049). The median progression-free survival (PFS) of IFL plus bevacizumab group was 7.5 months, significantly improved as compared with 3.7 months in the IFL group and 4 months in FOLFIRI group (χ(2) = 11.97, P = 0.003). Of all 67 cases, the one-year survival rate was 47.0%, two-year survival rate was 27.0%, and the median overall survival (OS) was 13.0 months, with no significant difference among the three treatment groups (χ(2) = 3.42, P = 0.18). The serum CEA and CA19-9 levels were decreased after treatment, but with no significant difference among the three groups (P > 0.05). The common toxicity profiles of IFL and FOLFIRI regimens were diarrhea and neutropenia, while the toxicity related to bevacizumab was consistent with that documented in previous literature, such as hypertension, hemorrhage, cardiac toxicity and delayed wound healing.

CONCLUSIONThe addition of bevacizumab to irinotecan-based regimen significantly improves the response rate and PFS in first-line treatment for patients with mCRC and its toxicity is well tolerated.

Adenocarcinoma ; blood ; drug therapy ; secondary ; Adenocarcinoma, Mucinous ; blood ; drug therapy ; secondary ; Adult ; Aged ; Angiogenesis Inhibitors ; adverse effects ; therapeutic use ; Antibodies, Monoclonal, Humanized ; adverse effects ; therapeutic use ; Antineoplastic Combined Chemotherapy Protocols ; adverse effects ; therapeutic use ; Bevacizumab ; CA-19-9 Antigen ; blood ; Camptothecin ; administration & dosage ; analogs & derivatives ; therapeutic use ; Carcinoembryonic Antigen ; blood ; Colonic Neoplasms ; blood ; drug therapy ; secondary ; Diarrhea ; chemically induced ; Disease-Free Survival ; Female ; Fluorouracil ; administration & dosage ; therapeutic use ; Follow-Up Studies ; Humans ; Hypertension ; chemically induced ; Leucovorin ; therapeutic use ; Male ; Middle Aged ; Neutropenia ; chemically induced ; Rectal Neoplasms ; blood ; drug therapy ; secondary ; Remission Induction ; Retrospective Studies ; Survival Rate ; Young Adult