Oromucosal cytokine therapy allows large amounts of cytokines to be administered with improved outcome and without dose limiting toxicity. Orally administered cytokines exert their effects by a novel two pronged mechanism of action. Firstly, specific populations of immuno-competent effector cells are activated in the oral cavity and migrate to the site of virus replication. Secondly, chemokines produced in the lymphoid tissue of the oral cavity enter the peripheral circulation and redirect activated lymphocytes to eliminate virus infected cells. Oromucosal IFN therapy constitutes an alternative and improved means of therapy for diseases such as chronic viral hepatitis which are currently treated parenterally with IFN alpha. The oral route also has obvious advantages for ease of administration and improved patient compliance. Furthermore, the availability of a well tolerated form of IFN therapy will also allow Type I IFNs to be used for the treatment of diseases such as upper respiratory tract virus infections, for which parenteral IFN therapy is currently precluded due to unacceptable toxicity.
Administration, Oral ; Animals ; Antineoplastic Agents/administration & dosage ; Antiviral Agents/*administration & dosage/adverse effects/pharmacology ; Hepatitis, Viral, Human/drug therapy ; Human ; Interferon-alpha/*administration & dosage/adverse effects/pharmacology

OBJECTIVETo observe the efficacy and safety of chemotherapy regimens oxaliplatin combined with capecitabine (CAPOX) or oxaliplatin combined with tegafur, gimeracil and oteracil potassium capsules (S-1)(SOX), and to investigate the value of expression of thymidine phosphorylase (TP) and dihydropyrimidine dehydrogenase (DPD) proteins in tumor tissue for predicting the efficacy of CAPOX and SOX regimens in advanced gastric cancer patients.

METHODSA total of 107 newly-diagnosed, stage Ⅲc/Ⅳ gastric cancer patients (no surgical indication, ECOG performance scores 0-2 and expected survival time ≥3 months) were recruited with 101 patients evaluated. The patients were randomly divided into two groups. One was study group in which the patients received CAPOX regimen. The other was control group received SOX regimen. Each patient received four cycles, at least two cycles chemotherapy every three weeks and followed up until death or lost. Tumor biopsies were obtained by gastroscopy for immunohistochemical examination of the expression of TP and DPD proteins before chemotherapy. Response rate (ORR), overall survival (OS) and time to tumor progression (TTP) of the patients were assessed.

RESULTSThe objective response rate (ORR) of the study and control groups was 49.0% (5/51) vs. 46.0% (23/50), respectively (P>0.05). The overall survival (OS) was 357.36±24.69 days in the study group and 349.87±22.63 days in the control group, and the time-to-progression (TTP) was 216.75±19.32 days in the study group and 220.54±18.47 days in the control group (P>0.05 for both). Stratified analysis showed that the ORR of TP-positive patients in the study group was significantly higher than that in the control group (72.0 % vs. 41.7 %, P=0.032). There was no significant difference in ORR between the TP-negative patients in the study and control groups (26.9% vs. 50.0%, P=0.087), while the ORR of DPD-positive patients in the control group was significantly higher than that of the study group (51.9% vs. 34.6%, P=0.046). There was no significant difference in the ORR between DPD-negative patients in the study and control groups (64.0% vs. 39.1%, P=0.084). The follow-up showed that the OS (378.42±22.56 days) and TTP (271.77±24.92 days) in the TP-positive patients of the study group were significantly longer than those of the control group (OS: 326.57±19.84 days, and TTP: 229.13±22.68 days)( P<0.05). The OS was 371.25±23.97 days and TTP was 264.66±21.36 days in the DPD-positive patients of control group, significantly longer than those of the study group (OS: 334.73±21.47days, and TTP: 208.58±20.70 days) (P<0.05). But there was no significant difference in the OS and TTP between the TP- and DPD-negative patients in the two groups (P>0.05). In respect of adverse events, both the rates of hematological and non-hematological toxicities were low and similar between the two groups (P>0.05), and well-tolerated by the patients.

CONCLUSIONSBoth CAPOX and SOX regimens are effective chemotherapeutic protocols in treatment of patients with advanced gastric cancer. The expression levels of TP and DPD in tumor tissue can be used as a predictive factor for the efficacy of capecitabine or tegafur, gimeracil and oteracil potassium capsules combined with oxaliplatin regimens. CAPOX chemotherapy regimen is more suitable for the TP-positive gastric cancer patients, and SOX regimen is more suitable for the DPS-positive gastric cancer patients.

Antineoplastic Agents ; adverse effects ; therapeutic use ; Antineoplastic Combined Chemotherapy Protocols ; adverse effects ; therapeutic use ; Capecitabine ; administration & dosage ; adverse effects ; Capsules ; Dihydrouracil Dehydrogenase (NADP) ; metabolism ; Disease Progression ; Humans ; Neoplasm Proteins ; metabolism ; Organoplatinum Compounds ; administration & dosage ; adverse effects ; Oxonic Acid ; administration & dosage ; adverse effects ; Pyridines ; administration & dosage ; adverse effects ; Stomach Neoplasms ; drug therapy ; metabolism ; mortality ; pathology ; Tegafur ; administration & dosage ; adverse effects ; Thymidine Phosphorylase ; metabolism

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 evaluate the safety and efficacy of gemcitabine combined with S-1 in the treatment of advanced pancreatic cancer.

METHODSA retrospective analysis of the clinical data of 49 patients with advanced pancreatic cancer, who did not receive radiotherapy and chemotherapy, were divided into two groups: the study group (25 cases), and control group (24 cases). Patients in the study group received gemcitabine 1 000 mg/m² via intravenous drip at the first and 8th days, and received S-1 80 mg/m², morning and evening (twice a day) for the first 14 days, and 21 days as a treatment cycle of chemotherapy.The control group was given GEMOX regimen: Gemcitabine 1 000 mg/m² via intravenous drip at the first and 8 days, and oxaliplatin 130 mg/m² via intravenous drip at the first day, and 21 d for a treatment cycle of chemotherapy. The efficacy and adverse reactions in patients of the study and control groups were observed and compared.

RESULTSThe efficiency of the study group was 32.0% and disease control rate was 72.0%. The efficiency of the control group was 25.0% and disease control rate was 58.3%. The differences between the two groups were statistically not significant (P > 0.05 for all). The clinical benefit rate in the study group and control group were 80.0% and 50.0%, respectively, showing a significant difference (P < 0.05). The median survival time was 9.7 months in patients of the study group and 9.0 months in the control group, with a significant difference (P < 0.05). The drug toxicity was well tolerated in both groups, and no chemotherapy-related death occurred. The major adverse reactions were myelosuppression and digestive tract reactions, and the adverse reactions in the study group were lower than those in the control group.

CONCLUSIONSGemcitabine combined with S-1 is effective and safe in the treatment of advanced pancreatic cancer, with less side effects, and can be tolerated by the patients.

Antineoplastic Agents ; adverse effects ; therapeutic use ; Antineoplastic Combined Chemotherapy Protocols ; administration & dosage ; adverse effects ; therapeutic use ; Deoxycytidine ; administration & dosage ; adverse effects ; analogs & derivatives ; Drug Administration Schedule ; Drug Combinations ; Humans ; Organoplatinum Compounds ; administration & dosage ; adverse effects ; Oxonic Acid ; administration & dosage ; adverse effects ; Pancreatic Neoplasms ; drug therapy ; pathology ; Retrospective Studies ; Tegafur ; administration & dosage ; adverse effects

AIMTo evaluate the hypersensitivity reaction of the blank paclitaxel microemulsion and study the O/W paclitaxel microemulsion's pharmacokinetics in rats.

METHODSAn alternative paclitaxel microemulsion was prepared with small particle size. The hypersensitivity reaction of the blank microemulsion was investigated in guinea pigs. In pharmacokinetic study, 5 rats were given i.v. Taxol or paclitaxel microemulsion. Blood samples were collected at 0, 0.25, 0.5, 1, 2, 4, 6, 8, 10, 12, 14 h and the concentration of paclitaxel in plasma was determined by HPLC method. The data obtained were processed using 3P87 program.

RESULTSThe mean size of the microemulsion is 17.2 nm. The preparation of blank microemulsion did not show any hypersensitivity, while the injection of commercial product showed significant hypersensitivity. The concentration-time curve of paclitaxel microemulsion and commercial injection (Taxol) fitted a two-compartment model. The K10, K12, K21 and AUC of paclitaxel microemulsion were 0.571.h-1, 1.441.h-1, 3.081.h-1 and 34.98 mg.h.L-1. Those of commercial injection were 1.291.h-1, 1.271.h-1, 0.511.h-1 and 21.85 mg.h.L-1.

CONCLUSIONThe blank paclitaxel preparation of micoemulsion reduced the hypersensitivity in guinea pigs compared with the blank commercial injection. The paclitaxel microemulsion has relatively longer circulating time in rats.

Animals ; Antineoplastic Agents, Phytogenic ; administration & dosage ; adverse effects ; pharmacokinetics ; Drug Hypersensitivity ; etiology ; Emulsions ; Female ; Guinea Pigs ; Injections, Intravenous ; Male ; Paclitaxel ; administration & dosage ; adverse effects ; pharmacokinetics ; Rats

OBJECTIVES: To determine the effectiveness and toxicity when levamisole was added to the adjuvant combination chemotherapy in patients with operable gastric cancer. METHODS: After en bloc resection of gastric cancer without gross or microscopic evidence of residual disease from April 1991 to December 1992, 100 patients were randomized to 6 months of 5-fluorouracil 1,000 mg/m2/day administered as continuous infusion for 5 days, cisplatin 60 mg/m2/day as intravenous infusion for 1 day with or without levamisole (50 mg every eight hours P.O for a period of three days every 2 weeks for 6 months). This chemotherapy treatment was begun within 2 to 4 weeks after the surgery. The chemotherapy consisted of discrete 5-day courses administered at 4-weeks intervals. All 100 patients are assessable. RESULTS: The fifty patients were assigned to each treatment group. There was no statistical difference and no bias in the distribution of characteristics of the 100 evaluable patients between the two groups. A total of 274 courses of treatment were given in the levamisole group and 260 courses of treatment in non-levamisole group. Eleven patients in each group did not finish planned 6 courses of treatment mainly due to non-compliance. At median follow up of 39 months, 32 patients relapsed 19 in the levamisole group and 13 in the non-levamisole group (p = 0.284). Twenty five patients died of relapsed diseases, 15 in the levamisole group and 10 in the non-levamisole group. The levamisole group tended to show more risk of overall death rate and recurrence than the non-levamisole group. However, this result was not statistically significant at 3 years. The treatment was well tolerated in both treatment groups. The grade 2-3 toxicities were nausea/ vomiting (levamisole, non-levamisole group; 31.7%, 29.3% of treatment courses respectively), diarrhea (7.6%, 8.4%), mucositis (11.6%, 12.3%), and leukopenia (9.8%, 9.6%). CONCLUSION: Levamisole had negative effects on disease-free survival and overall survival when added to adjuvant combination chemotherapy of cisplatin and 5-fluorouracil in patients with operable gastric cancer. Both treatment arms were generally well tolerated and the toxicity profile was similar with or without levamisole.
Adjuvants, Immunologic/administration & dosage* ; Adult ; Aged ; Antineoplastic Agents, Combined/therapeutic use* ; Antineoplastic Agents, Combined/adverse effects ; Cisplatin/administration & dosage ; Comparative Study ; Female ; Fluorouracil/administration & dosage ; Human ; Levamisole/administration & dosage* ; Male ; Middle Age ; Stomach Neoplasms/mortality ; Stomach Neoplasms/drug therapy*

Antineoplastic Agents ; administration & dosage ; adverse effects ; Arsenicals ; administration & dosage ; adverse effects ; Cerebral Hemorrhage ; chemically induced ; Humans ; Infusions, Intravenous ; Leukemia, Promyelocytic, Acute ; drug therapy ; Leukocytosis ; chemically induced ; Oxides ; administration & dosage ; adverse effects

OBJECTIVETo observe the efficacy of polyethylene glycol conjugated asparaginase (peg-asp) for induction treatment of children with newly diagnosed acute lymphoblastic leukemia (ALL).

METHODA total of 268 newly diagnosed children with ALL enrolled in CCLG-2008 from January, 2010 to August, 2012 were analyzed. Patients received either native Escherichia coli asparaginase or pegaspargase along with multiagent chemotherapy during remission induction treatment. Status of bone marrow aspiration was assessed on day 15, day 33 (M1, M2, M3).

RESULTOf the 268 patients stratified, 37.3% (n = 100) were SR, 32.1% (n = 86) were IR, and 31.6% (n = 82) were HR; 159 patients received native Escherichia coli asparaginase and 109 patients received pegaspargase. Characteristics of two groups in age, sex, blood count at diagnosis, immunophenotype and response to prednisolone had no significant difference (P > 0.05). Bone marrow status on day 15 in pegaspargase group was M1 in 70 (64.2%) cases, M2 in 23 (21.1%) and M3 in 16 (14.7%), while in native Escherichia coli asparaginase group, M1 in 112 (70.4%) cases, M2 in 21 (13.2%) and M3 in 26 (16.4%), respectively (χ(2) = 2.938, P = 0.230). Bone marrow status on day 33 was M1 in 105 (96.3%), M2 in 3 (2.8%) and M3 in 1 (0.9%) in pegaspargase group, while it was M1 in 154 (96.9%) cases, M2 in 5 (3.1%) and M3 in native Escherichia coli asparaginase group, respectively (χ(2) = 1.494, P = 0.474).

CONCLUSIONDomestic pegaspargase of our country can achieve the similar efficacy in induction treatment for ALL patients as compared with native Escherichia coli asparaginase. The drug could be considered as not only the choice for allergic patients but also a first-line alternative for new patients.

Adolescent ; Antineoplastic Agents ; administration & dosage ; adverse effects ; therapeutic use ; Antineoplastic Combined Chemotherapy Protocols ; adverse effects ; therapeutic use ; Asparaginase ; administration & dosage ; adverse effects ; Bone Marrow Cells ; drug effects ; pathology ; Case-Control Studies ; Child ; Child, Preschool ; Female ; Humans ; Infant ; Male ; Polyethylene Glycols ; administration & dosage ; adverse effects ; Precursor Cell Lymphoblastic Leukemia-Lymphoma ; drug therapy ; pathology ; Prednisone ; administration & dosage ; adverse effects ; Remission Induction ; Retrospective Studies ; Treatment Outcome

The benefits of radio-chemotherapy in HIV-negative primary central nervous system (CNS) lymphomas were analyzed in 40 patients, who received radiotherapy to the brain or craniospinal axis with the total dose of 4460-5940 cGy to the primary tumor. Radiotherapy was followed by systemic chemotherapy, mainly with the cyclophosphamide, doxorubicin, vincristine and prednisolone (CHOP) regimen, in 16 of the patients. Follow-up ranged from four to 95 months with a median of 15 months. The relapse rate was 72.5%, and 83% of the relapses occurred within the radiation field. Median survival was 19 months and the two-year survival rate was 41%. Survival was significantly influenced by treatment method and radiation dose when measured by univariate analysis; median survival and the two-year survival rate was 29 months and 63% after radio-chemotherapy, while 13.5 month and 29% after radiotherapy alone (p= 0.027), and 22 months and 49% with doses of 50 Gy or more, but 12.5 months and 13% with doses less than 50 Gy (p=0.009). However, statistical significance was lost in multivariate analysis. These results might suggest the short-term efficacy of radio-chemotherapy, however, cautious observation is needed to confirm long-term effects.
Adolescence ; Adult ; Aged ; Antineoplastic Agents, Combined/therapeutic use* ; Antineoplastic Agents, Combined/adverse effects ; Bleomycin/administration & dosage ; Central Nervous System Neoplasms/therapy* ; Central Nervous System Neoplasms/mortality ; Cyclophosphamide/administration & dosage ; Disease-Free Survival ; Doxorubicin/administration & dosage ; Epirubicin/administration & dosage ; Female ; Human ; Lymphoma/therapy* ; Lymphoma/mortality ; Male ; Mechlorethamine/administration & dosage ; Methotrexate/administration & dosage ; Middle Age ; Neoplasm Recurrence, Local ; Prednisolone/administration & dosage ; Procarbazine/administration & dosage ; Radiotherapy Dosage ; Radiotherapy, Adjuvant/adverse effects ; Survival Rate ; Treatment Failure ; Vincristine/administration & dosage

There has been no standard therapy for patients with metastatic colorectal cancer who have failed to first-line fluorouracil-based treatment. The present study was designed to assess the efficacy and toxicities of a combination of oxaliplatin, 5-fluorouracil (5-FU) and leucovorin in fluoropyrimidine-pretreated patients with metastatic colorectal cancer. Chemotherapy consisted of oxaliplatin 85 mg/m2 on day 1, followed by leucovorin 20 mg/m2 and 5-FU 1,200 mg/m2 on days 1 and 2. Treatment courses were repeated every two weeks. Thirty-nine patients were enrolled in this study. All patients previously received fluoropyrimidine-based chemotherapy. Thirty-one patients were assessable for response and 33 for treatment toxicity. Six patients required dose reduction of 5-FU due to grade III/IV cytopenia. Nausea/vomiting and peripheral neuropathy were common non-hematologic toxicities. Overall response rate was 42.0% including 3 complete response and 10 partial response. The median response duration was 91 days (range, 28-224+). The median duration of progression-free survival was 132 days (range, 40-308). A combination of oxaliplatin, 5-FU, and leucovorin showed high response rate in fluoropyrimidine-pretreated patients with metastatic colorectal cancer, but the duration of response was relatively short. It may be worthwhile to explore its therapeutic potential in the first-line treatment setting.
Adult ; Aged ; Antineoplastic Agents, Combined/therapeutic use* ; Antineoplastic Agents, Combined/adverse effects ; Colorectal Neoplasms/mortality ; Colorectal Neoplasms/drug therapy* ; Disease-Free Survival ; Female ; Fluorouracil/administration & dosage ; Human ; Leucovorin/administration & dosage ; Male ; Middle Age ; Organoplatinum Compounds/administration & dosage