Personalized medicine of non-gene-specific chemotherapies for non-small cell lung cancer

Non-small cell lung cancer is recognized as the deadliest cancer across the globe. In some areas, it is more common in women than even breast and cervical cancer. Its rise, vaulted by smoking habits and increasing air pollution, has garnered much attention and resource in the medical field. The first lung cancer treatments were developed more than half a century ago. Unfortunately, many of the earlier chemotherapies often did more harm than good, especially when they were used to treat genetically unsuitable patients. With the introduction of personalized medicine, physicians are increasingly aware of when, how, and in whom, to use certain anti-cancer agents. Drugs such as tyrosine kinase inhibitors, anaplastic lymphoma kinase inhibitors, and monoclonal antibodies possess limited utility because they target specific oncogenic mutations, but other drugs that target mechanisms universal to all cancers do not. In this review, we discuss many of these non-oncogene-targeting anti-cancer agents including DNA replication inhibitors (

Adverse Factors and the Role of Cisplatin and Vinca Alkaloids for Hearing Impairment in Childhood Cancer Patients and Survivors / 임상소아혈액종양

BACKGROUND: Although combined chemotherapy has increased survival rates among children with cancer, such treatments can induce sensorineural hearing loss. Therefore, we aimed to identify risk factors for hearing impairments in patients with childhood cancer.METHODS: Audiograms were obtained from 115 patients with childhood cancer and survivors (age < 20 years). Pure tone audiometry (PTA) was performed at octave intervals within the range of 250-8000 Hz. We evaluated clinical risk factors associated with hearing impairments. Hearing loss was evaluated based on the maximal decibel (dB) loss in any frequency for each ear (RA(max) or LA(max)) and weighted mean dB loss for specific frequencies (RA(avg) or LA(avg)).RESULTS: Forty percent of patients (N=46) exhibited hearing loss >20 dB based on the weighted mean value in either ear. Severe hearing impairments were observed in 56% of patients with brain tumors. Although cisplatin or vinca alkaloids were significant risk factors for hearing impairment, the use of both cisplatin and vinca alkaloids exhibited the highest odds ratio for hearing impairment (P < 0.001, < 0.001 for R/LA(max); P=0.099, 0.039 for R/LA(avg)). Multivariate analysis revealed that the use of both cisplatin and vinca alkaloids was an independent risk factor for hearing impairment based on RA(max), LA(max), and LA(avg) (P < 0.001, < 0.001, 0.039, respectively).CONCLUSION: Our findings indicate that cisplatin and vinca alkaloids exert an additive effect on the risk of hearing impairment in survivors of childhood cancer. Further prospective studies are thus required to determine the most effective chemotherapeutic regimen for reducing ototoxicity.

Adverse Factors and the Role of Cisplatin and Vinca Alkaloids for Hearing Impairment in Childhood Cancer Patients and Survivors / 임상소아혈액종양

BACKGROUND: Although combined chemotherapy has increased survival rates among children with cancer, such treatments can induce sensorineural hearing loss. Therefore, we aimed to identify risk factors for hearing impairments in patients with childhood cancer. METHODS: Audiograms were obtained from 115 patients with childhood cancer and survivors (age 20 dB based on the weighted mean value in either ear. Severe hearing impairments were observed in 56% of patients with brain tumors. Although cisplatin or vinca alkaloids were significant risk factors for hearing impairment, the use of both cisplatin and vinca alkaloids exhibited the highest odds ratio for hearing impairment (P < 0.001, < 0.001 for R/LA(max); P=0.099, 0.039 for R/LA(avg)). Multivariate analysis revealed that the use of both cisplatin and vinca alkaloids was an independent risk factor for hearing impairment based on RA(max), LA(max), and LA(avg) (P < 0.001, < 0.001, 0.039, respectively). CONCLUSION: Our findings indicate that cisplatin and vinca alkaloids exert an additive effect on the risk of hearing impairment in survivors of childhood cancer. Further prospective studies are thus required to determine the most effective chemotherapeutic regimen for reducing ototoxicity.

Salvia miltiorrhizaand ligustrazine combined with vinpocetine in the treatment of patients with cerebral infarction / 国际中医中药杂志

ObjectiveTo evaluate the therapeutic effect of Salvia miltiorrhiza and ligustrazine combined with vinpocetine in patients with cerebral infarction.MethodsAtotal of 206 patients with cerebral infarction were randomly divided into a controlgroup and a combined treatment group according to the random number table, 103 in each group. The control group was treated with aspirin and vinpocetine, the combined treatment group received Salvia miltiorrhiza and ligustrazine injection on the basis of the control group. The serum contents of malondialdehyde (MDA) and nitric oxide (NO), as well as the serum levels of superoxide dismutase (SOD) and nitric oxide synthase (NOS) were detected before and after the treatment. The electroencephalography (EEG) amplitudes and the regional cerebral blood flow (rCBF) were recorded before and after the treatment .ResultsIn the combined treatment group, the serum content of MDA was significantly decreased (151.36 ± 11.36 mmol/Lvs.62.23 ± 4.11 mmol/L;t=74.878,P<0.01), while the serum content of NO (110.31 ± 9.51 mmol/Lvs.154.23 ± 12.21 mmol/L;t=28.801,P<0.05) and the serum levels of SOD (55.52 ± 4.47 U/mlvs.85.39 ± 7.21 U/ml;t=35.735,P<0.05) and NOS (115.21 ± 8.39 mmol/Lvs.190.12 ± 11.29 mmol/L;t=54.049,P<0.01) were significantly increased than before the treatment. The rCBF (39.39 ± 2.45 ml/100 g?minvs. 69.95 ± 4.25 ml/100 g?min;t=32.385,P<0.05) and EEG (62.41% ± 4.58%vs.97.02% ± 9.67%;t=31.012,P<0.05) in the combined treatment group were significantly increased than before the treatment. The total efficiency rate in the combined treatment group was significant higher than that in the control group (88.3% vs. 66.9%;χ2=12.343, P=0.004).ConclusionsSalvia miltiorrhiza and ligustrazine combined with vinpocetine has a beneficial therapeutic effect in patients with cerebral infarction, and it is probably associated withincreasing cerebral blood flow and enhancing antioxidant activity.

Vinpocetine alleviates cerebral ischemia-reperfusion injury in rats by regulation of the expressions of nuclear factor κB p65, peroxisome proliferator-activated receptor γ and cyclooxygenase-2 / 国际脑血管病杂志

Objective To investigate neuroprotective mechanisms of vinpocetine by observing the effects of vinpocetine injection on the expressions of peroxisome proliferators-activated receptor γ(PPARγ),nuclear factor (NF)-κB p65,cyclooxygenase-2 (COX-2) in the ischemic cortex,and infarct volume after focal cerebral ischemia-reperfusion in rats.Methods A focal cerebral ischemia-reperfusion injury model was induced by suture method.The rats were randomly divided into a normal control,a cerebral ischemiareperfusion and a vinpocetine groups.They were also divided into either a day 7 subgroup or a day 14 subgroup (n =6 in each subgroup) according to the reperfusion time.Western blot was used to detect the expression levels of PPARγand NF-κB P65 in the ischemic cortex.Triphenyl tetrazolium staining was used to detect the volume of cerebral infarction.Results Western blot showed that at day 7 and 14 after cerebral ischemia-reperfusion,expression levels of PPARκ (all P＜0.001) and NF-κB p65 (all P＜0.001) in the cerebral ischemia-reperfusion group were significantly higher than those in the sham operation group,the expression levels of PPARκ (all P ＜0.05) in the vinpocetine group were significantly higher than those in the cerebral ischemia-reperfusion group,but the expression levels of NF-κB p65 (all P ＜0.05) were significantly lower than those in the cerebral ischemia-reperfusion group.Reverse transcription polymerase chain reaction showed that COX-2 mRNA expression levels were upregulated significantly at day 7 and 14 after cerebral ischemia-reperfusion compared with the sham operation group (all P ＜ 0.001),the expression levels of COX-2 mRNA in the vinpocetine group were significantly downregulated compared with the cerebral ischemia-reperfusion group (all P＜ 0.05).The infarct volumes at day 7 (134.308± 9.954 mm3vs.185.543 ± 9.100 mm3;q=10.659,P＜0.001) and at day 14 (137.865 ± 9.094 mm3vs.183.210±4.368 mm3;q=11.166,P＜0.001) in the vinpocetine group were significantly less than those in the cerebral ischemia-reperfusion group.Conclusions Vimpocetine significantly reduces infarct vohme after focal cerebral ischemia-reperfusion,its mechanism may be associated with upreguhtion of PPARγexpression and downreguhtion of the expressions of NF-κB p65 and COX-2.

Hepatotoxic effects of vincristine: An experimental study on albino rats.

Vincristine (VCR) is an established drug of choice in treatment of some myelomas, lymphomas and leukemias. Hepatotoxicity is a lesser studied side effect of the drug. Samples of blood and other tissues were collected for morphological, biochemical and histopathological evaluation 2 and 24 hours after single intravenous administration of 1.0 mg/kg of VCR to male Albino Wistar rats. VCR produced weight loss; and elevated serum alkaline phosphatase (515.20±356.22, P<0.05), SGPT (192.00±102.62, P<0.05), and SGOT (574.20±292.16, P<0.05) even after 24 hours of drug administration. Though these changes were most severe during the first 2 hours of VCR administration, they also persisted till 24 hours, which may suggest a possibility of an enterohepatic circulation of the drug or its metabolites. This was complemented with morphological disruption in hepatocytes on light and electron microscopy including Scanning Electron Microscopy and Transmission Electron Microscopy.

The clinical study of combined chemotherapy with vinorelbine plus platinum drugs in patients aged ≥70 years and with advanced non-small cell lung cancer / 中华老年医学杂志

Objective To investigated the efficacy and toxic effects of combined chemotherapy of vinorelbine plus cisplatin or carboplatin in patients aged ≥ 70 years and with non-small cell lung cancer (NSCLC).Methods One hundred patients with lung cancer aged ≥70 years were enrolled in the study.Fifty patients in chemotherapy group were assigned to receive vinorelbine 25 mg/m2 at the first day and the fifth day plus cisplatin 60-70 mg/m2 or carboplatin 250 mg/m2 at the second day.All treatments were repeated every 3 or 4 weeks.Another fifty patients aged ≥ 70 years were taken as control group, not receiving treatment.The primary endpoint was survival.Results Forty-five patients were evaluable for response and the partial remission rate was 35.6% (16/45).One year survival rate was 37.8% and median survival time was 9.75 months in chemotherapy group.The median survival time was 4.0 months for patients in control group.All 50 patients in chemotherapy group were evaluable for toxic side effects.WHO grade Ⅲ incidences of leucopoenia, neutropenia and anemia were 38.0%, 52.0% and 2.2%, respectively.Grade IV incidence of neutropenia was 35.5%.WHO grade Ⅲ incidences of fatigue, constipation and vomit were 22.0%, 8.0% and 14.8%,respectively.Five patients failed to complete the treatment due to side effects.Conclusions Combined chemotherapy of vinorelbine plus platinum drugs is effective and tolerated in patients aged over 70 years with advanced NSCLC.Even patients with stable clinical effects shows benefit of survival time.

A Phase II Study of Vinorelbine, Mitomycin C and Cisplatin Chemotherapy for Advanced Non-Small Cell Lung Cancer

BACKGROUND: This prospective phase II trial was performed to determine the efficacy and toxicity of mitomycin C, vinorelbine and cisplatin combination chemotherapy for patients with previously untreated stage IIIB or IV non-small cell lung cancer (NSCLC). METHODS: Between January 1999 and April 2001, 30 patients with chemotherapy- naive stage IIIB or IV NSCLC were entered into this study. Mitomycin C at a dose of 7 mg/m2, vinorelbine at a dose of 25 mg/m2 and cisplatin at a dose of 75 mg/m2 on day 1 and vinorelbine at a dose of 25 mg/m2 on day 8 were administered. This regimen was repeated every 4 weeks. RESULTS: 29 patients out of 30 patients were assessable. Among the assessable patients, 15 (51.7%) patients had a partial response. The median duration of response and survival was 22 weeks and 39 weeks, respectively. Grade 3 or 4 leukopenia and thrombocytopenia were observed in 28.3% and 4.7% of all the cycles, respectively. Nausea and vomiting of grade 3 occurred only in 2.4% of all the cycles. CONCLUSION: The regimen of mitomycin C, vinorelbine and cisplatin for non-small cell lung cancer is active against advanced NSCLC with tolerable toxicities.