The modifying potential of capsaicin (CAP) on lesion development was examined in a rat multiorgan carcinogenesis model. Groups 1 and 2 were treated sequentially with diethylnitrosamine (DEN) (100 mg/kg, ip, single dose at commencement), N-methylnitrosourea (MNU) (20 mg/kg, ip, 4 doses at days 2, 5, 8, and 11), and N,N-dibutylnitrosamine (DBN) (0.05% in drinking water during weeks 3 and 4). Group 3 received vehicles without carcinogens during the initiation period. Group 4 served as the untreated control. After this initiating procedure, Groups 2 and 3 were administered a diet containing 0.01% CAP. All surviving animals were killed 20 weeks after the beginning of the experiment and the target organs examined histopathologically. The induction of GST-P+ hepatic foci in rats treated with carcinogens was significantly inhibited by treatment with CAP. CAP treatment significantly decreased the incidence of adenoma of the lung but increased the incidence of papillary or nodular (PN) hyperplasia of the urinary bladder. The tumor incidence of other organs, such as the kidney and thyroid, was not significantly different from the corresponding controls. These results demonstrated that concurrent treatment with CAP not only can inhibit carcinogenesis but can also enhance it depending on the organ. Thus, this wide-spectrum initiation model could be used to confirm organ-specific modification potential and, in addition, demonstrate different modifying effects of CAP on liver, lung, and bladder carcinogenesis.
Animals ; Capsaicin/pharmacology/*toxicity ; Cocarcinogenesis ; Diethylnitrosamine ; Liver Neoplasms, Experimental/chemically induced/prevention & control ; Lung Neoplasms/chemically induced/prevention & control ; Male ; Methylnitrosourea ; Neoplasms, Experimental/*chemically induced/prevention & control ; Nitrosamines ; Rats ; Rats, Inbred F344 ; Urinary Bladder Neoplasms/chemically induced

Asbestos is a carcinogen that causes diseases such as mesothelioma and lung cancer in humans. There was a sharp increase in the use of asbestos in Korea in the 1970s as Korea's economy developed rapidly, and asbestos was only recently banned from use. Despite the ban of its use, previously applied asbestos still causes many problems. A series of asbestos-related events that recently occurred in Korea have caused the general public to become concerned about asbestos. Therefore, it is necessary to take proper action to deal with asbestos-related events, such as mass outbreaks of mesothelioma among residents who lived near asbestos textile factories or asbestos mines. Although there have been no rapid increases in asbestos-related illnesses in Korea to date, such illnesses are expected to increase greatly due to the amount of asbestos used and long latency period. Decreasing the asbestos exposure level to levels as low as possible is the most important step in preventing asbestos-related illnesses in the next few decades. However, there is a lack of specialized facilities for the analysis of asbestos and experts to diagnose and treat asbestos-related illnesses in Korea; therefore, national-level concern and support are required.
Asbestos/*toxicity ; Asbestosis/*epidemiology/etiology/mortality ; Environmental Exposure/prevention & control ; Humans ; Korea ; Lung Neoplasms/*chemically induced ; Mesothelioma/*chemically induced/epidemiology

Biochanin A, an isoflavone compound, is reported to have an inhibitory effect on benzo(a)pyrene [B(a)P] metabolism. We examined the modifying effect of biochanin A on in vivo carcinogenesis using a mouse lung tumor model. As carcinogens, a single subcutaneous injection of 0.5mg of B(a)P was given within 24 hours after birth. The test groups were injected with 0.125mg of biochanin A in 0.1ml DMSO by i.p. 3 times a week for 6 weeks after weaning. All mice were sacrificed at week 9 and the incidence and multiplicity of lung tumors were examined. Concomitant administration of biochanin A showed a significant inhibitory effect on the incidence of tumor-bearing mice (12.5%, P<0.01), as well as the mean number of tumors (0.13, P<0.001), compared with the group treated with B(a)P alone in which the incidence was 57.1% and the mean number was 1.0. These results suggest that biochanin A has inhibitory potential on the development of mouse lung tumor induced by B(a)P.
Animals ; Animals, Newborn ; Anticarcinogenic Agents/*pharmacology ; Benzo(a)pyrene ; Body Weight/drug effects ; Female ; *Genistein ; Incidence ; Isoflavones/*pharmacology ; Lung Neoplasms/chemically induced/*prevention & control ; Mice ; Neoplasms, Multiple Primary/chemically induced/prevention & control ; Survival Analysis

OBJECTIVETo observe the effect of thalidomide in preventing nausea and vomiting induced by emetogenic cisplatin (CDDP) chemotherapy in patients with advanced non-small cell lung cancer.

METHODSThis study was carried out as a prospective, randomized control clinical trial. 61 patients with advanced non-small cell lung cancer were scheduled to receive chemotherapy (gemcitabin 1000 mg/m(2) i.v. gtt d1, 8 and CDDP 75 mg/m(2) i.v. gtt d1, GP regimen). The patients were randomly divided into a treatment and control groups. All patients in both groups received ramosetron 0.3 mg intravenously (i.v.) and metoclopramide 20 mg intramuscularly (i.m.) 30 min prior to chemotherapy to prevent nausea and emesis on day 1. In the treatment group, addition of thalidomide (50 mg p.o. bid) were administered on days 1 to 5 after the start of chemotherapy.

RESULTSAcute nausea was effectively controlled in 74.2% of the patients in the control group and in 90.0% of treatment group. Acute vomiting was effectively controlled in 90.3% of the patients in the control group and in 93.3% of treatment group. No statistically significant differences showed in effective control of acute nausea and vomiting between the 2 groups (P = 0.108; P = 1.000). Delayed nausea was effectively controlled in 19.4% of the patients in control group and in 56.7% in the treatment group. Delayed vomiting was effectively controlled in 48.4% of the patients in control group and 76.7% in treatment group. Statistically there was a significant differences in effective control of delayed nausea and vomiting between the 2 groups (P = 0.003, P = 0.023). Both antiemetic regimens were well tolerated, and no significant difference was observed in adverse events between the 2 groups (P > 0.05).

CONCLUSIONOur results demonstrate that thalidomide is highly effective in controlling delayed nausea and vomiting episodes in patients induced by moderately emetogenic chemotherapy. Moreover, no serious toxic effects are induced by this treatment.

Antiemetics ; therapeutic use ; Antineoplastic Combined Chemotherapy Protocols ; adverse effects ; therapeutic use ; Carcinoma, Non-Small-Cell Lung ; drug therapy ; pathology ; Cisplatin ; administration & dosage ; Deoxycytidine ; administration & dosage ; analogs & derivatives ; Female ; Humans ; Lung Neoplasms ; drug therapy ; pathology ; Male ; Middle Aged ; Nausea ; chemically induced ; prevention & control ; Neoplasm Staging ; Prospective Studies ; Thalidomide ; therapeutic use ; Vomiting ; chemically induced ; prevention & control

OBJECTIVETo observe the efficacy of Shenmai Injection (SI) in preventing and treating adverse reation of chemotherapy on advanced non-small cell lung cancer (NSCLC).

METHODSForty-five patients with NSCLC in III b-IV stage were randomly divided into two groups, the control group treated with chemotherapy alone and the treated group with chemotherapy and SI. The therapeutic efficacy were evaluated after 3 treatment cycles.

RESULTSThere was no significant difference in short-term effect between the two groups (P >0.05), while it showed remarkable difference in Karnofsky scoring and body weight (P < 0.05). The treated group showed a better effect than the control group in reducing adverse reaction, such as decrease of leucocyte and hemoglobin (P < 0.05), while in the aspects of improving thrombocytopenia and the reducing occurrence of nausea/vomitting and alleviating injury of liver and kidney function, it only showed the lower value in the treated group, but with no significant difference as compared with the control group (P >0.05).

CONCLUSIONSI could not raise the efficacy of chemotherapy on NSCLC, but improve the quality of life, raise the body weight of patients and alleviate adverse reaction of chemotherapy as myelosuppression so as to improve the tolerance of organism to chemotherapy.

Aged ; Antineoplastic Combined Chemotherapy Protocols ; adverse effects ; therapeutic use ; Carcinoma, Non-Small-Cell Lung ; drug therapy ; Drug Combinations ; Drugs, Chinese Herbal ; therapeutic use ; Female ; Humans ; Injections, Intravenous ; Leukopenia ; chemically induced ; prevention & control ; Lung Neoplasms ; drug therapy ; Male ; Phytotherapy ; Quality of Life

OBJECTIVEThe efficacies of the selective 5-hydroxytryptamine3 (5-HT3) antagonists--ramosetron (0.3 mg) and granisetron (3 mg) in treating acute chemotherapy-induced digestive system dysunction were compared.

METHODSA total of 111 patients were enrolled in a single-blind, randomised crossover study; with data from 98 were used to assess efficacy and data from 110 to assess the safety profile. Ramosetron or granisetron was given intraveneously 15 min befire chemotherpy.

RESULTSThe ability of ramosetron to prevent emesis, nausea and anorexia was similar to granisetron during the first 6 h following the administration of chemotherapy, ciplatin or doxorubicin. However, during the first 24 h after chemotherapy, significant differences between ramosetron and granisetron appeared: emetic episode (P = 0.068), nausea (P = 0.006), and anorexia (P = 0.048) remained lower in ramosetron-treated patients. The safety profile of ramosetron was similar to that of granisetron and adverse events in both groups were generally mild and transient.

CONCLUSIONRamosetron is more potent and longer-lasting than granisetron in preventing chemotherapy-induced digestive disturbances.

Adolescent ; Adult ; Aged ; Anorexia ; chemically induced ; drug therapy ; Antiemetics ; therapeutic use ; Antineoplastic Agents ; adverse effects ; Benzimidazoles ; therapeutic use ; Cisplatin ; adverse effects ; Cross-Over Studies ; Doxorubicin ; adverse effects ; Female ; Granisetron ; therapeutic use ; Humans ; Lung Neoplasms ; drug therapy ; Male ; Middle Aged ; Nausea ; chemically induced ; prevention & control ; Serotonin Antagonists ; therapeutic use ; Single-Blind Method ; Vomiting, Anticipatory ; etiology ; prevention & control

OBJECTIVETo explore the efficacy of pegylated recombinant human granulocyte colony-stimulating factor (PEG-rhG-CSF) in the prophylaxis of chemotherapy-induced neutropenia.

METHODSPatients with previously untreated non-small cell lung cancer or breast cancer and with normal bone marrow function were eligible for the trial. In the phase I trial, patients were to treated with two cycles of paclitaxel/carboplatin chemotherapy every 21 days. In cycle 1, if absolute neutrophil count (ANC) dropped below 1.0 x 10(9)/ L with fever and/or ANC dropped below 0.5 x 10(9)/L, rhG-CSF 150 microg/d was administrated until WBC > or = 10 x 10(9)/L or ANC > or = 5.0 x 10(9)/L. In cycle 2, patients were to receive a single injection of PEG-rhG-CSF (30, 60, 100, or 200 microg/kg) 48 hours after chemotherapy. Pharmacodynamic analyses were performed.

RESULTSAll the 16 patients enrolled (4 in each group) were eligible for efficacy evaluation. In cycle 1, 7 patients received rhG-CSF administration because of grade 4 neutropenia, while in cycle 2, there was only 1 episode of grade 4 neutropenia, which were in the 30 microg/kg group. In cycle 1, the mean ANC nadir of 1.37 x 10(9)/L occurred on day 13 in the 9 patients who received no rhG-CSF administration. In cycle 2, the mean ANC nadirs were 0.77 x 10(9)/L, 4.54 x 10(9)/L, 3.00 x 10(9)/L, and 5.56 x 10(9)/L, respectively, in 30, 60, 100, or 200 microg/kg group. The nadirs of the first two groups occurred on day 8 of cycle 2, while those of the other two groups appeared on day 7. After PEG-rhG-CSF administration, two mean ANC peaks were observed. The first one ranging from 20.87 x 10(9)/L to 33.61 x 10(9)/L in the 4 groups appeared on day 3 to day 4. In the 30 microg/ kg group, the mean ANC reached the second peak at 5.03 x 10(9)/L on day 14. The second peaks on day 10 in the other groups were 12.42 x 10(9)/L, 11.59 x 10(9)/L, and 18.92 x 10(9)/L, respectively. Pharmacodynamic analyses showed sustained serum concentrations of PEG-rhG-CSF during the period of neutropenia.

CONCLUSIONSPEG-rhG-CSF administration may decrease the incidence of grade 4 neutopenia and result in earlier and higher nadir ANCs. PEG-rhG-CSF has a potential of once-per-cycle administration. The ANC and serum concentration of PEG-rhG-CSF are consistent with neutrophil receptor-mediated clearance.

Adolescent ; Adult ; Aged ; Antineoplastic Combined Chemotherapy Protocols ; adverse effects ; therapeutic use ; Breast Neoplasms ; drug therapy ; Carboplatin ; administration & dosage ; adverse effects ; Carcinoma, Non-Small-Cell Lung ; drug therapy ; Female ; Granulocyte Colony-Stimulating Factor ; biosynthesis ; pharmacology ; therapeutic use ; Humans ; Lung Neoplasms ; drug therapy ; Male ; Middle Aged ; Neutropenia ; chemically induced ; prevention & control ; Paclitaxel ; administration & dosage ; adverse effects ; Recombinant Proteins

OBJECTIVETo assess the efficacy and safety of recombinant human thrombopoietin (rhTPO) on chemotherapy-induced thrombocytopenia in patients with solid tumor.

METHODSIn this randomized crossover self-controlled multi-center clinical trial, 154 patients with solid tumor were randomly divided into two groups (group A 77 cases and group B 77 cases). All patients were given the same two cycles of chemotherapy. In group A, the first cycle was treated cycle, in which patients were given rhTPO, while the second cycle was non-treated cycle as a control. In group B, the first cycle was non-treated cycle as a control, while the second cycle was treated cycle. RhTPO 1.0 microg/(kg x d) was administered subcutaneously 6-24 hours after chemotherapy for the longest 14 days. Laboratory tests included complete blood counts, urinalysis, serum chemistry, coagulant test, chest radiography, and electrocardiogram. Serum samples were screened for anti-rhTPO antibodies.

RESULTSIn both group A and group B, platelet decrease and duration had no significant difference between the treated cycle and non-treated cycle. Platelet count was higher in the treated cycle, than in the non-treated cycle: [minimal mean platelet count (64.4 +/- 45.4) x 10(9) cells/L and (52.4 +/- 30.9) x 10(9) cells/L (P=0.000), maximal mean platelet count (263.9 +/- 142.5) x 10(9) cells/L and (148.9 +/- 67.7) x 10(9) cells/L (P=0.000)]. Duration of thrombocytopenia was shorter in the treated cycle than in the non-treated cycle [days with platelet count < 50 x 10(9) cells/L, (2.5 +/- 3.9) and (3.7 +/- 5.7) (P=0.04); days with platelet count recovered > or = 75 x 10(9) cells/L, (10.3 +/- 8.7) and (14.0 +/- 8.9) (P=0.000), and days with platelet count recovered > or = 100 x 10(9) cells/L, (15.9 +/- 10.5) and (21.1 +/- 9.5) (P=0.000)]. The need for platelet transfusion was not significantly reduced in treated cycle. The effects of rhTPO on WBC, Hb, hepatic function, renal function, and coagulant function were not found. Transient low-titer non-neutralizing antibody was developed in one patient. Therapy with rhTPO was tolerated by all patients. Mild side effects were observed in individual patients, including fever, dizziness, and chill. Conclusion Administration of rhTPO after chemotherapy can significantly reduce the degree and duration of thrombocytopenia and promote platelet recovery. Therapy with rhTPO seems to be safe.

Adolescent ; Adult ; Aged ; Antineoplastic Agents ; adverse effects ; Cross-Over Studies ; Female ; Humans ; Lung Neoplasms ; blood ; drug therapy ; Male ; Middle Aged ; Neoplasms ; blood ; drug therapy ; Platelet Count ; Recombinant Proteins ; administration & dosage ; therapeutic use ; Thrombocytopenia ; chemically induced ; drug therapy ; prevention & control ; Thrombopoietin ; therapeutic use

OBJECTIVEThis phase II clinical trial was designed to evaluate the efficacy and toxicity of recombinant human interleukin-11 (rhIL-11) derivative manufactured in China in the prevention and treatment of chemotherapy-induced thrombocytopenia in cancer patients.

METHODSA total of 100 cancer patients with chemotherapy-induced thrombocytopenia (< or = 75 x 10(9)/L) were studied by self-cross control. Ninty-one of them received 2 cycles of chemotherapy. In the first cycle (control cycle) the patients received chemotherapy only, while in the second cycle (treatment cycle), the patients were given subcutaneous injection of rhIL-11 derivative (40 microg.kg(-1).d(-1)) once daily after chemotherapy for 10 consecutive days or more until platelet count reached > or = 300 x 10(9)/L.

RESULTS1. The patients with platelet count of < or = 75 x 10(9)/L was 89/89 in the control cycle and 44/89 in the treatment cycle (P = 0.00). The recovery time to the normal platelet count was 1-47 days (median 9 days) in the control cycle, and 1-18 days (median 5.5 days) in treatment cycle (P = 0.00). 2. Patients with platelet count of < or = 50 x 10(9)/L was 56/89 in the control cycle and 20/89 in the treatment cycle (P = 0.00). The recovery time to normal platelet count was 1-31 days (median 9 days) in the control cycle and 3-13 days (median 6 days) in the treatment cycle (P = 0.05). 3. The median nadir platelet count was 44 x 10(9)/L (range: 10 x 10(9)/L-75 x 10(9)/L) in the control cycle, and 83 x 10(9)/L (range: 10 x 10(9)/L-310 x 10(9)/L) in the treatment cycle (P = 0.00). The time of recovery to the normal platelet count was 1-31 days (median 6 days) in the control cycle, and 0-13 days (median 2 days) in the treatment cycle (P = 0.00). 4. Nine of 89 evaluable patients required platelet transfusion in the control cycle versus 1 of 89 patients in treatment cycle (P = 0.01), and the total platelet transfusion was 10 times in the control cycle versus once in the treatment cycle (P = 0.01). 5. The major adverse events associated with rhIL-11 derivative were: headache, fatigue, myalgia/arthralgia, edema and palpitation, etc.

CONCLUSIONrhIL-11 derivative can be safely and effectively used for the prevention and treatment for chemotherapy-induced thrombocytopenia.

Adult ; Aged ; Antineoplastic Combined Chemotherapy Protocols ; adverse effects ; therapeutic use ; Breast Neoplasms ; drug therapy ; China ; Female ; Humans ; Injections, Subcutaneous ; Interleukin-11 ; administration & dosage ; adverse effects ; Lung Neoplasms ; drug therapy ; Lymphoma ; drug therapy ; Male ; Middle Aged ; Platelet Count ; Recombinant Proteins ; administration & dosage ; adverse effects ; Thrombocytopenia ; chemically induced ; drug therapy ; prevention & control

OBJECTIVETo explore the safety and efficacy of pegylated recombinant human granulocyte colony-stimulating factor (PEG-rhG-CSF) in preventing chemotherapy-induced neutropenia in patients with breast cancer and non-small cell lung cancer (NSCLC), and to provide the basis for clinical application.

METHODSAccording to the principle of open-label, randomized, parallel-group controlled clinical trial, all patients were randomized by 1∶1∶1 into three groups to receive PEG-rhG-CSF 100 μg/kg, PEG-rhG-CSF 6 mg, or rhG-CSF 5 μg/kg, respectively. The patients with breast cancer received two chemotherapy cycles, and the NSCLC patients received 1-2 cycles of chemotherapy according to their condition. All patients were treated with the combination chemotherapy of TAC (docetaxel+ epirubicin+ cyclophosphamide) or TA (docetaxel+ epirubicin), or the chemotherapy of docetaxel combined with carboplatin, with a 21 day cycle.

RESULTSThe duration of grade 3-4 neutropenia in the PEG-rhG-CSF 100 μg/kg and PEG-rhG-CSF 6 mg groups were similar with that in the rhG-CSF 5 μg/kg group (P>0.05 for all). The incidence rate of grade 3-4 neutropenia in the PEG-rhG-CSF 100 μg/kg group, PEG-rhG-CSF 6 mg group, and G-CSF 5 μg/kg group were 69.7%, 68.4%, and 69.5%, respectively, with a non-significant difference among the three groups (P=0.963). The incidence rate of febrile neutropenia in the PEG-rhG-CSF 100 μg/kg group, PEG-rhG-CSF 6 mg group and G-CSF 5 μg/kg group were 6.1%, 6.4%, and 5.5%, respectively, showing no significant difference among them (P=0.935). The incidence rate of adverse events in the PEG-rhG-CSF 100 μg/kg group, PEG-rhG-CSF 6 mg group and G-CSF 5 μg / kg group were 6.7%, 4.1%, and 5.5%, respectively, showing a non-significant difference among them (P=0.581).

CONCLUSIONSIn patients with breast cancer and non-small cell lung cancer (NSCLC) undergoing TAC/TA chemotherapy, a single 100 μg/kg injection or a single fixed 6 mg dose of PEG-rhG-CSF at 48 hours after chemotherapy show definite therapeutic effect with a low incidence of adverse events and mild adverse reactions. Compared with the continuous daily injection of rhG-CSF 5 μg/kg/d, a single 100 μg/kg injection or a single fixed 6 mg dose of PEG-rhG-CSF has similar effect and is more advantageous in preventing chemotherapy-induced neutropenia.

Antineoplastic Agents ; adverse effects ; therapeutic use ; Antineoplastic Combined Chemotherapy Protocols ; Breast Neoplasms ; drug therapy ; Carboplatin ; administration & dosage ; adverse effects ; Carcinoma, Non-Small-Cell Lung ; drug therapy ; Cyclophosphamide ; administration & dosage ; adverse effects ; Epirubicin ; administration & dosage ; adverse effects ; Female ; Granulocyte Colony-Stimulating Factor ; therapeutic use ; Humans ; Incidence ; Induction Chemotherapy ; Lung Neoplasms ; drug therapy ; Neutropenia ; chemically induced ; epidemiology ; prevention & control ; Polyethylene Glycols ; Recombinant Proteins ; administration & dosage ; Taxoids ; administration & dosage ; adverse effects