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Platinum compounds are crucial chemotherapy drugs for children with solid tumor, and the ototoxicity is one of the dose-limiting toxicities. Platinum-induced hearing loss is detrimental to language learning and social development especially for children. Several clinical trials of drugs against platinum-based ototoxicity have been carried out, the results prompted that sodium thiosulfate, amifostine and N-acetylcysteine potentially reduce the occurrence risk of hearing loss. Without affecting the therapeutic effect, preventive use of antagonists on platinum-based ototoxicity will improve the life quality and treatment compliance of pediatric patients with tumor.
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Objective To analyze the prognostic implications of second-line double drug regimens for advanced non-small cell lung cancer (NSCLC) patients and related factors.Methods Eighty patients with advanced NSCLC who were accepted from January 2014 to December 2016 in our hospital were chosen as the research objects.The patients were randomly divided into two groups using the random number table method,namely single drug group (n =40) and double drug group (n =40).The patients in single drug group were treated with docetaxel or pemetrexed,and the patients in double drug group were treated with docetaxel,pemetrexed,vinorelbine or paclitaxel combined with platinum (cisplatin).The effects of patients in the two groups were compared and the factors affecting the prognosis of the patients were analyzed.Results The remission rate in the double drug group was significantly higher than that in the single drug group (45.0％ vs.20.0％;x2 =4.493,P =0.021).The results of single factor analysis for patients in double drug group showed that pathological type (x2 =7.511,P =0.023),time from first-line treatment to second-line treatment (x2 =6.412,P =0.041),second-line baseline TNM stage (x2 =4.022,P =0.045),second-line cycle number (x2 =5.065,P =0.027),leukopenia (x2 =4.852,P =0.033) and neuron specific enolase (x2 =9.243,P =0.002) were the main prognostic factors of the second-line chemotherapy.The results of multivariate analysis for patients in double drug group showed that time from first-line treatment to second-line treatment (OR =3.511,95 ％ CI:1.486-3.602,P =0.033),second-line baseline TNM stage (OR =1.623,95 ％ CI:1.127-2.119,P =0.027),second-line cycle number (OR =2.208,95 ％ CI:1.589-2.827,P =0.014) and neuron specific enolase (OR =1.960,95％ CI:1.209-2.773,P =0.025) were independent prognostic factors.Conclusion The remission effect of double second-line treatment scheme based on platinum for patients with NSCLC is good,and the time form first-line treatment to second-line treatment,second-line baseline TNM stage,second-line cycle number and neuron specific enolase are independent prognostic factors.
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Platinum compounds are crucial chemotherapy drugs for children with solid tumor, and the ototoxicity is one of the dose-limiting toxicities. Platinum-induced hearing loss is detrimental to language learning and social development especially for children. Several clinical trials of drugs against platinum-based ototoxicity have been carried out, the results prompted that sodium thiosulfate, amifostine and N-acetylcysteine potentially reduce the occurrence risk of hearing loss. Without affecting the therapeutic effect, preventive use of antagonists on platinum-based ototoxicity will improve the life quality and treatment compliance of pediatric patients with tumor.
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Objective To evaluate the therapeutic efficacy and adverse reactions of raltitrexed plus oxaliplatin (RALOX project) and S1 in patients with advanced primary liver cancer.Methods Seventy-one patients with advanced primary liver cancer admitted to 6 cancer centers from July 2013 to July 2015 were divided into 2 groups according to the wishes of the patients and their families:RALOX group (34 patients) and S1 group (37 patients).The therapeutic efficacy such as objective remission rate (ORR),disease control rate (DCR),median overall survival (mOS),median progression free survival (mPFS),one year survival rate (SR),and adverse reactions in these patients were evaluated.Results Thirty-one patients could be evaluated in RALOX group,and 6 patients obtained partial response (PR),10 stable disease (SD) and 15 progressive disease (PD).Thirty-three patients could be evaluated in S1 group,and 3 patients obtained PR,8 patients SD and 22 PD.The ORR,DCR,and one year SR were 19.4％ vs.9.1％,51.6％ vs.33.3％,and 22.6％ vs.12.1％ respectively,and there were no statistically significant differences in the two groups (x2 =1.393,P =0.238;x2 =2.190,P =0.139;x2 =1.229,P =0.268).The mOS and mPFS were 7.2 months vs.6.1 months and 3.4 months vs.2.8 months,and there were statistically significant differences in the two groups (x2 =6.433,P =0.011;x2 =4.078,P =0.043).There was more serious peripheral nerve toxicity (29.0％ vs.3.0％,x2 =6.344,P =0.012) and lighter hand-foot syndrome (9.7％ vs.30.3％,x2 =4.201,P =0.040) in RALOX group than S1 group.But the incidences of other adverse effects were similar in the two groups.Condnsion RALOX project is safe and effective to the patients with advanced primary liver cancer.Compare with S1 project,RALOX project has better curative effects and the majority of adverse reactions are tolerable.The patients have good condition control and survival benefit.
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Objective To investigate the efficacy and safety of patients with malignant pleural effusion treated with injecting endostar combined with platinum complexes into pleural cavity.Methods Cochrane systematic review methods were used in the data selection,and data were selected from the PubMed,Embase,Cochrane Library,China National Knowledge Infrastructure (CNKI),WanFang,and VIP database to get all clinical controlled trials.The retrieval time was August 2014.The objects of these randomized controlled trials were malignant pleural effusion patients.Endostar combination with platinum complexes was used for the experimental group.Platinum complexes alone were used for the control group.The efficacy and adverse effects of two groups were compared.The quality of included trials was evaluated by two reviewers independently.The software RevMan 5.3 was used for meta-analyses.Results Nine trials with 488 patients were included according to the including criterion.All trials were randomized controlled trials,one of them had B level in quality and eight had C level.Meta analysis results were as follows:there was significant difference in overall effective rate (OR =3.52,95％ CI =2.37 ～ 5.22),Karnofsky (KPS) score changes rate (OR =2.64,95％ CI =1.67 ～ 4.19),between endostar combination with platinum complexes and platinum complexes alone group.The incidences of severe leucopenia (OR =1.0,95％ CI =0.62 ～ 1.61) and nausea and vomiting (OR =0.77,95％ CI =0.43 ～ 1.38) were similar in the endostar combination with platinum complexes group compared to those in the platinum complexes alone group.Conclusions In the treatment of malignant pleural effusion,injecting endostar in combination with platinum complexes into pleural cavity improves the effective rate without obviously raised side effects.Owing to the small sample size and poor quality of included trials,more well-designed double-blinded randomized controlled trials should be performed.
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Objective To analyze non -small cell lung cancer patients with platinum -based chemotherapy excision repair cross -complementing 1 (ERCC1)and breast cancer susceptibility gene 1 (BRCA1 )gene polymor-phism,to examine the correlation of ERCC1 and BRCA1 gene polymorphism and non -small cell lung cancer platinum chemotherapy drugs sensitivity and chemotherapy prognosis.Methods 140 cases of non -small cell lung cancer were selected as subjects of this study.All patients were given platnum -based chemotherapy,peripheral blood ERCC1 and BRCA1 genes polymorphism were determined.The distribution of ERCC1 Asn118Asn genotype and BRCA1 Ser1613Gly genotype was observed.The relationship between different genotypes and the effect of chemotherapy and survival time after chemotherapy was compared.Results The proportions of ERCC1 Asn118Asn TT genotype,CT genotype and CC genotype were 5.7%,30.7% and 63.6%.The proportions of BRCA1 Ser1613Gly GG genotype,AG genotype and AA genotype were 8.6%,52.9% and 38.6%.In 140 patients,completely cured,partial response,stable disease and progressive disease patients were 0 case,33 cases,61 cases and 46 cases,the proportions were 0.0%, 23.6%,43.6% and 32.9%,the chemotherapy effective rate was 33.8%.ERCC1 Asn118Asn genotype was signifi-cantly correlated with the effect of non -small cell lung cancer chemotherapy (χ2 =4.416,P <0.05 ).BRCA1 Ser1613Gly genotype was significantly correlated with the effect of non -small cell lung cancer chemotherapy (χ2 =13.256,P <0.05).By Cox regression analysis and Log -rank test analysis,the average survival time of BRCA1 Ser1613Gly gene CC genotype non -small cell lung cancer after chemotherapy was longer than the CT +TT genotype (OR =2.946,χ2 =5.136,P <0.05).The average survival time of BRCA1 Ser1613Gly gene AA genotype non -small cell lung cancer after chemotherapy was shorter than the AG +GG genotype (OR =3.124,χ2 =5.136,P <0.05).Conclusion ERCC1 Asn118Asn genotype and BRCA1 Ser1613Gly genotype was significantly correlated with non -small cell lung cancer platinum -based chemosensitivity and chemotherapy prognosis.
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OBJECTIVE: To investigate the presence of cranial neuropathy in patients with platinum-analogue chemotherapy using electrodiagnostic evaluations. METHODS: Thirty-nine patients whose chemotherapy was completed within a month and 40 control subjects were enrolled in the study. Electrodiagnostic evaluation was performed using sensory and motor nerve conduction studies and blink reflex studies, in addition to the two-point discrimination test. RESULTS: The chemotherapy group had significantly longer latencies of bilateral R1 responses (left p<0.001; right p<0.001) and greater distance in two-point discrimination (p<0.001) compared to the control group. In the subgroup with peripheral polyneuropathy, the left R1 (p=0.01), both R2i (left p=0.02; right p=0.03) and the left R2c (p=0.02) were prolonged relative to those without the polyneuropathy, and both R1 (left p<0.001; right p<0.001), R2i (left p=0.01; right p=0.03), and the left R2c (p=0.01) were prolonged relative to the controls. On the other hand, the subgroup without the polyneuropathy showed only prolongation of both R1 (left p=0.006; right p<0.001) relative to the controls. CONCLUSION: In the present study, comparison of blink reflex and two-point discrimination showed the likelihood of subclinical cranial neuropathy following platinum-analogue chemotherapy. Cranial neuropathy caused by platinum agents was more profound in patients with peripheral polyneuropathy and may be dependent on the cumulative dose of the drug. The blink reflex may be of value in detecting subclinical cranial neuropathy in patients undergoing platinum-analogue chemotherapy.
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Humans , Blinking , Cranial Nerve Diseases , Cranial Nerves , Discrimination, Psychological , Drug Therapy , Hand , Neural Conduction , Platinum , Platinum Compounds , PolyneuropathiesABSTRACT
Background: The aim of the present study was to monitor and analyze the pattern of occurrence of adverse drug reactions (ADRs) to commonly used platinum compounds in MNJ Cancer Hospital, Hyderabad. Methods: Cancer patients, who received platinum compounds as chemotherapy regimen, were monitored for adverse reactions. Cancer patients belonging to either gender and of all ages, who were receiving platinum compounds under any standard regimen, were included for the study. Cases that were unlikely, conditional or unaccessible under World Health Organization (WHO)-Uppsala Monitoring Centre causality criteria were excluded from the study. The ADRs were recorded in Central Drugs Standard Control Organization forms. Causality was assessed by the WHO Causality Assessment Scale and Naranjo’s Algorithm. Preventability and severity of ADRs were assessed by modifi ed Schumock and Thornton scale, modifi ed Hartwig and Siegel scale, respectively. Results: Among 100 patients, 78 developed ADRs to platinum compounds. The reactions observed were vomiting, diarrhea, abnormal renal function tests, myelosuppression, anemia, thrombocytopenia, alopecia, and constipation. The WHO Causality Assessment Scale indicated 64.6% “possible” and 35.4% “probably,” but no “certain” reactions. Naranjo’s Algorithm showed 59.4% “possible” 40.6% “probable” reactions. 48% reactions were “defi nitely preventable” 16% were “probably preventable” and 36% were “not preventable.” Modifi ed Hartwig and Siegel Scale of severity assessment showed that 12% reactions were “mild” 69% were “moderate” and 19% were severe. Conclusion: Platinum compounds have high potential for adverse effects. There is a need to improve the management of adverse effects. This study also emphasizes the need to improve pharmacovigilance awareness among physicians in order to improve the pharmacovigilance in India.
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The purpose of this review of the literature was to describe the relationship between use of platinum-based antineoplastics and development of acute pancreatitis in patients with cancer. A literature search was conducted using PubMed, Science Direct and Google scholar databases for articles published from 1985 to 2014. The headings and/or text words (platinum compounds), (acute pancreatitis-induced by platinum compounds), and (cisplatin, carboplatin, and oxaliplatin) were entered, and the search was limited to articles describing case reports in adults with cancer. A total of 12 cases were reported between 1985 and 2012; including three platinum compounds; cisplatin, carboplatin, and oxaliplatin. In conclusion, it is highly recommended to include baseline assessment for acute pancreatitis risk factors and to consider acute pancreatitis in the differential diagnosis of abdominal pain in patients who have received platinum-based chemotherapy.
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Objective To observe the efficacy,toxic side effects, survival time and quality of life (QOL) of vinorelbine and vinorelbine plus carboplatin in elderly patients with stage Ⅲ b/Ⅳ non-small cell lung cancer(NSCLC).Methods Eighty patients aged 65 years or over with stage Ⅲ b/Ⅳ non-small cell lung cancer were randomly divided into two groups.One group was treated with vinorelbine (vinorelbine 25 mg/m2 iv d1,8, repeated every 21 days), the other group was treated with vinorelbine plus carboplatin(vinorelbine 25 mg/m2 iv at day 1 and 8 and earboplatin AUC5 iv at day 1, repeated every 21 days).Results The response rate(RR), median survival time(MST) and 1-year survival rate were 35.0%, 9.0 months and 35.0% in vinorelbine group and were 42.5%, 10.0 months and 37.5% in vinorelbine plus carboplatin group respectively.There was no significant difference between two groups(χ2 =0.296,P=0.586).The incidences of Ⅲ-Ⅳ degree granulocytopenia (χ2 =7.168,P=0.014), Ⅲ-Ⅳ degree thrombocytopenia (χ2 = 5.165,P=0.048)and Ⅲ-Ⅳ degree nausea and vomiting (χ2 =6.275, P =0.025) were significantly higher in the combined chemotherapy group than in the vinorelbine treatment group.The scores of lung cancer symptom scale (LCSS) of appetite loss(χ2 =2.600,P=0.011), fatigue(χ2 =3.169,P=0.002) and pain(χ2 =2.257,P=0.027) were more higher in the vinorelbine treatment group than in the combined chemotherapy group.Conclusions Vinorelbine regimen is effective, well tolerated and more favorable for the elderly NSCLC patients.
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Objective To investigate the side effects of a new supramolecular drug-platinum compound CCP on the cardiovascular system,respiratory system and neuropsychological system of healthy rat.Methods After abdominal anaesthesia with 4.0 ml/kg of 10%chloral hydrate.the rats were injected with10,20,40 ms/ks CCP respectively,and then the life indexes,including blood pressure,heart rate,electrocardiogram,respiratory rate and depth were recorded through single femoral and tracheal intubations and so to non-anaesthesia rats.Glucose injection was chosen as negative control and carboplatin(15 mg/kg)as positive control.Results After venous injection with CCP,glucose injection and carboplatin as the dosages as above respectively,the blood pressures of the tested rats are from(57.8±14.1)mm Hg to(86.2±8.1)mm Hg,heart rates are from(250.9±95.4)times/min to(356.7±47.7)times/min,respiratory rates are from(59.3±17.7)times/min to(95.7±26.0)times/min.No obvious changes of blood pressure,heart rate and respiration were observed after drug injection,t values are(0.02～1.96),(P＞0.05).Once of sporadically ventrieular premature beat was recorded in one rat of CCP and earboplatin groups and it is not dosage-dependent.There is no side effect of 40 ms/ks CCP in neuropsychological system and daily activity of non-anaesthesia rats.Conclusion CCP injection is safe in rat and there is no obvious change observed in the cardiovascular system,respiratory system,neuropsyehological system of healthy rat.
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Objective To evaluate the efficacy and safety of platinum-based chemotherapy in elderly patients with advanced non-small cell lung cancer(NSCLC). Methods Clinical data of forty-one elderly patients (≥70 years) with advanced NSCLC who were treated by platinum-based chemotherapy were analyzed retrospectively. Results Among the 41 patients, 18 (43.9%) patientswere treated with vinorelbine, 9 (22.0%) patients with gemcitabine, 7 (17.1%) patients with paclitaxel and docetaxel respectively. The overall response rate was 19.5%. The median time to progression (MTTP) was 5.8 months, and 1-year survival rate was 65.8% with a median survival time (MST) of 14.2 months. No significant statistical differences were found among the four regimens. The major side effect was bone marrow suppression. Three patients withdrew chemotherapy after one cycle due to grade Ⅲ-Ⅳ myelosuppression. There was no death associated with chemotherapy. Conclusions The platinum-based combined chemotherapy is effective and well-tolerated in elderly patients with advanced NSCLC.
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Background: Chemotherapy improves survival in advanced gastric cancer. However the most active combinations have a high level of toxicity that limits their use. Aim: To assess the response, toxicity and survival of patients with advanced gastric cancer, treated with oxaliplatin plus 5-fluorouracil/leucovorin (FOLFOX-4 chemotherapy). Material and methods: Patients with stage IVgastric cancer, according to the American Joint Committee on Cancer or with relapsed disease and functional capacity 0-2 of the South West Oncology Group, were included. FOLFOX-4 chemotherapy was used as first or second line treatment. The response to treatment and survival were assessed. Results: Between 2003 and 2006, 29 patients (median age 52.5 years, 69 percent males) were treated. FOLFOX-4 was given as first line treatment in 65 percent patients and as second line in 35 percent. There was a complete response in 4.6 percent, partial response in 68 percent, stable disease in 20.6 percent and progression in 6.8 percent. Toxicity was observed in 51 percent of patients, that was hematological and non hematological grade 3/4 in 14 percent. Median survival was 12.5 months. Conclusions: FOLFOX-4 chemotherapy was active in advanced gastric cancer and had a low level of toxicity.
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Female , Humans , Male , Middle Aged , Antineoplastic Combined Chemotherapy Protocols/therapeutic use , Stomach Neoplasms/drug therapy , Antineoplastic Combined Chemotherapy Protocols/administration & dosage , Antineoplastic Combined Chemotherapy Protocols/adverse effects , Fluorouracil/administration & dosage , Fluorouracil/adverse effects , Leucovorin/administration & dosage , Leucovorin/adverse effects , Neoplasm Staging , Organoplatinum Compounds/administration & dosage , Organoplatinum Compounds/adverse effects , Pyridines/administration & dosage , Pyridines/adverse effects , Stomach Neoplasms/mortality , Survival Analysis , Treatment OutcomeABSTRACT
Cisplatin,carpolatin and oxaliplatin are platinum-based drugs that are widely used in cancer chemotherapy. Peripheral neuropathy is major dose-limiting side effect of platinum-based drug. Accordingly, this side effect restrict its clinic application. This review will focus on the research advancement on the mechanism of dorsal root ganglia neurons apoptosis in cellular and molecular biology.
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Heptaplatin is a recently developed platinum derivative. This agent has been reported to have a response rate of 17% as a single agent, and tolerable toxicity in the treatment of advanced gastric cancer. The aim of this study was to evaluate the efficacy and toxicity of a combination of 5-fluorouracil (5-FU) and heptaplatin in patients with advanced gastric cancer. Forty-seven chemotherapy-naive patients with advanced or recurred gastric cancer were recruited. 5-FU was administered over 120 hr by continuous intravenous infusion from day 1 to 5, at a daily dose of 1,000 mg/m2 and heptaplatin was administered over 1 hr by intravenous infusion on day 1 at 400 mg/m2, and this cycle was repeated every 4 weeks. The response rate was 21%, median progression-free survival was 1.9 months (95% CI, 1.6 to 2.2 months). Median overall survival was 6.2 months (95% CI, 4 to 8.4 months) and the 1-yr survival rate was 29% for all patients. The most frequent toxicity was proteinuria. Toxicities were generally mild and reversible. This study demonstrates that the combination of 5-FU/heptaplatin combination is less active but tolerated in patients with advance gastric cancer.
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Adult , Aged , Female , Humans , Male , Middle Aged , Antineoplastic Combined Chemotherapy Protocols/therapeutic use , Disease-Free Survival , Fluorouracil/administration & dosage , Follow-Up Studies , Malonates/administration & dosage , Organoplatinum Compounds/administration & dosage , Stomach Neoplasms/drug therapy , Time Factors , Treatment OutcomeABSTRACT
Objective To perform comparative proteomic analysis of human ovarian cancer cell lines for detecting platinum-resistance associated proteins.Methods The total proteins of two sensitive (SKOV3 and A2780)and four resistant(SKOV3/CDDP,SKOV3/CBP,A2780/CDDP and A2780/CBP) human ovarian cancer cell lines were separated by two-dimensional gel electrophoresis(2-DE).The differentially expressed proteins were analyzed using image analysis software,stained with Coomassie Brilliant Blue,then identified using matrix-assisted laser desorption/ionization time-of-flight mass spectrometry(MALDI-TOF-MS)and database searching.The mRNA and protein levels of the differentially expressed protein which was most significant in all of the four resistant cell lines were validated by RT-PCR and western blotting,respectively.Results Five proteins were found to be significant in four cell lines. Annexin A3 and destrin were up-regulated and nicotinamide-adenine dinucleotide phosphate(NADP)- dependent isocitrate dehydrogenase 1 was down-regulated in all the four resistant samples.Glutathione transferase omega 1 had an increased expression in the other three resistant cell lines except for SKOV3/CBP in which its expression was not changed.However,cofilin 1 represented a different trend.In the two resistant sublines of SKOV3,eofilin 1 had a down-regulation,but it had an up-regulation in the cell lines induced from SKOV3.The expression of annexin A3 was up-regulated by 3-20 fold and the results of RT- PCR and western blotting showed complete consistency with that by 2-DE.Conclusions Proteomic techniques are useful to the identification of the resistance-associated proteins in ovarian cancer platinum- resistant cell lines and five candidates have been found.The five differential proteins might become hopeful candidate biomarkers for resistance.