1.Recent Advances in Chemotherapy of Gastric Cancer.
Korean Journal of Medicine 2012;82(4):417-426
Surgery is the best and the only treatment modality for cure if a patient has resectable gastric cancer. The outcome can be improved by a strategy of perioperative (neoadjuvant or adjuvant) chemotherapy or chemoradiotherapy. Whereas, advanced gastric cancer is treated primarily with chemotherapy; however, no chemotherapy regimen has been considered a standard. First-line chemotherapy generally includes fluoropyrimidine and cisplatin, sometimes with the addition of a third drug (epirubicin or docetaxel). In second-line setting, chemotherapy with single-agent irinotecan or docetaxel has emerged as a new standard of care. With improved understanding of the biology of gastric cancer and the identification of key signaling pathways, a number of promising molecularly-targeted agents have been studied that broaden the therapeutic options in the future. Regardless of the extent of disease or treatment modality, a multidisciplinary team approach is always desired since it can provide best treatment options for the patients.
Biology
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Camptothecin
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Chemoradiotherapy
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Cisplatin
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Humans
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Standard of Care
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Stomach Neoplasms
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Taxoids
2.Cisplatin-Induced Encephalopathy With Status Epilepticus.
Na young KIM ; Seong Yoon BAE ; Se Jin LEE
Journal of the Korean Neurological Association 2013;31(2):122-124
A 75-year old man with esophageal cancer presented with mental status change and seizures. He was under cisplatinand developed several times of generalized tonic-clonic seizures. The EEG (electroencephalography) showed triphasic waves and slowed background activity. He was diagnosed with status epilepticus and encephalopathy caused by cisplatin. He was treated with anticonvulsants and cisplatin was replaced by docetaxel. His mentality recovered completely and he had no more seizure. We conclude that physician using cisplatin should be aware of this rare complication.
Anticonvulsants
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Cisplatin
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Electroencephalography
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Esophageal Neoplasms
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Seizures
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Status Epilepticus
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Taxoids
3.Sub-cellular localization and overexpressing analysis of hydroxylase gene TcCYP725A22 of Taxus chinensis.
Weifang LIAO ; Chunhua FU ; Zhiguo LIU ; Lihong MIAO ; Longjiang YU
Chinese Journal of Biotechnology 2019;35(6):1109-1116
The discovery of hydroxylases in the anticancer drug taxol biosynthesis pathway is a hotspot and difficulty in current research. In this study, a new hydroxylase gene TcCYP725A22 (GenBank accession number: MF448646.1) was used to construct a sub-cellular localization vector pCAMIBA1303-TcCYP725A22-EGFP to get the transient expression in onion epidermal cells. Laser confocal microscopy revealed that the protein encoded by this gene was localized in the cell membrane. Furthermore, the recombinant plant expression plasmid pBI121-TcCYP725A22 was constructed. After transient transformation to the Taxus chinensis mediated by Agrobacterium tumefaciens LBA4404, qRT-PCR and LC-MS were utilized to analyze the effects of TcCYP725A22 overexpression on the synthesis of taxol. The results showed that, in the TcCYP725A22 overexpressed cell line, expression levels of most defined hydroxylase genes for taxol biosynthesis were increased, and the yield of taxanes were also increased. It was concluded that the hydroxylase gene TcCYP725A22 is likely involved in the biosynthetic pathway of taxol.
Biosynthetic Pathways
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Mixed Function Oxygenases
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Paclitaxel
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Taxoids
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Taxus
4.Spectrometric analyses of larotaxel and larotaxel liposomes quantification by high performance liquid chromatography.
Xue Qi LI ; Jian Wei LI ; Qiu Hong LI ; Yan YAN ; Jia Lun DUAN ; Yi Nuo CUI ; Zhan Bo SU ; Qian LUO ; Jia Rui XU ; Ya Fei DU ; Gui Ling WANG ; Ying XIE ; Wan Liang LU
Journal of Peking University(Health Sciences) 2019;51(3):467-476
OBJECTIVE:
Larotaxel is a new chemical structure drug, which has not been marketed worldwide. Accordingly, the standard identification and quantification methods for larotaxel remain unclear. The spectrometric analyses were performed for verifying weight molecular formula, molecular weight and chemical structure of larotaxel. Besides, a quantification method was developed for measuring larotaxel in the liposomes.
METHODS:
The molecular formula, molecular weight and chemical structure of larotaxel were studied by using mass spectrometry (MS), infra-red (IR), nuclear magnetic resonance (NMR) and ultraviolet-visible (UV-vis) spectrometric techniques. The absorption wavelength of larotaxel was investigated by UV-vis spectrophotometry full-wavelength scanning. Besides, a quantification method was developed by high performance liquid chromatography (HPLC), and then validated by measuring the encapsulation efficacy of larotaxel liposomes.
RESULTS:
The four spectral characteristics of larotaxel were revealed and the corresponding standard spectra were defined. It was confirmed that larotaxel had the structure of tricyclic diterpenoids, with the molecular formula of C45H53NO14, the molecular weight of 831.900 1, and the maximum absorption wavelength of 230 nm. The quantitative method of larotaxel was established by using HPLC with a reversed phase C18 column (5 μm, 250 mm×4.6 mm), a mobile phase of acetonitrile-water (75:25, volume/volume), and a detection wavelength of 230 nm. The validation study exhibited that the established HPLC method was stable, and had a high recovery and precision in the quantitative measurement of larotaxel in liposomes. In addition, a new kind of larotaxel liposomes was also successfully prepared. The particle size of the liposomes was about 105 nm, with an even size distribution. And the encapsulation efficiency of larotaxel in the liposomes was above 80%.
CONCLUSION
The present study offers reference standard spectra of larotaxel, including MS, IR, NMR, and UV-vis, and confirms the molecular formula, molecular weight and chemical structure of larotaxel. Besides, the study develops a rapid HPLC method for quality control of larotaxel liposomes.
Chromatography, High Pressure Liquid
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Liposomes
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Magnetic Resonance Spectroscopy
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Taxoids
5.Neoadjuvant Chemotherapy with Docetaxel and Adriamycin in Breast Cancer; Clincopathologic Factors Influencing to Response Rate.
Dong Won RYU ; Chang Wan JUN ; Chung Han LEE
Journal of Breast Cancer 2008;11(2):89-94
PURPOSE: The objective of this study was to test the efficacy and toxicity of adriamycin plus docetaxel as the primary chemotherapy for women with advanced breast carcinoma, and including those patients with inflammatory breast cancer. Our study also evaluated the clinicopathologic factors influencing the response rate to neoadjuvant chemotherapy. METHODS: Twenty-eight patients who underwent neoadjuvant chemotherapy between 2002 and 2004 were included for this study. The patients were treated with adriamycin (50 mg/m2; intravenous bolus) followed by docetaxel (75 mg/m2; 1-hr intravenous infusion) on the first day of each cycle for an average four cycles. We analysed the response rate to adjuvant chemotherapy by reviewing the post operative pathologic report. Additionally we compared the clincopathologic factors related to the response rate. Statistical analyses were performed with 2-tests and using SPSS 11.0. RESULTS: The mean age at diagnosis was 48.9 yr old (range 29-63 yr). The tumoral response to neoadjuvant chemotherapy was, 3 patients (10.7%) showed a complete response (CR), 21 patients (75%) showed a partial response (PR). and which about lymph node were that 15 patients (75%) have shown responder, 5 patients (25%) have shown non-responder. The overall response rate to neoadjuvant chemotherapy was 85.7%. The preoperative serum-CEA level was influenced the response rate to neoadjuvant chemotherapy (p=0.025). Grade 3 or 4 neutropenia was recorded in 81.9% of the patients (N=59/72). Grade 3 or 4 anemia was recorded in 2.8% of the patients. CONCLUSION: Neoadjuvant chemotherapy with adriamycin plus docetaxel was effective treatment for patients with locally advanced breast cancer. The preoperative serum CEA level colud be the important factor for the neoadjuvant chemotherapy response rate.
Anemia
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Breast
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Breast Neoplasms
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Chemotherapy, Adjuvant
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Doxorubicin
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Female
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Humans
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Inflammatory Breast Neoplasms
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Lymph Nodes
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Neutropenia
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Taxoids
6.Anaplastic Thyroid Carcinoma - a Therapeutic Dilemma.
Journal of Korean Thyroid Association 2012;5(2):132-137
Anaplastic thyroid carcinoma (ATC) is a rare type of malignancy of thyroid follicular cell origin. It is one of the most aggressive human cancers, and typically associated with a fatal prognosis. Most patients are presenting as locally advanced and systemically disseminated disease. A single mode of therapy, whether it is surgery, chemotherapy, or radiotherapy, fails to afford significantly favorable outcomes. While multimodality approaches may enhance the treatment response to a small degree, such implementations of these modalities are often impractical as many patients are of old age and are unable to tolerate the intensity of treatments. As in many other types of carcinomas, radical resection may be the mainstay of therapy for ATC, but surgery itself is seldom possible for this condition. Even with aggressive surgical therapy for those invasive ATCs, there is no evidence of decreased recurrence rates, while only the post-surgical morbidity rates increase. One chemotherapeutic agent that seems to demonstrate some effect against ATC is adriamycin, which is more effective when administered in combination, and is also known to act synergistically with radiotherapy. A commonly employed treatment modality is the combination therapy of adriamycin and cisplatin administration with hyperfractionated radiation therapy. Other chemotherapeutic agents proven to be effective are taxanes such as paclitaxel and docetaxel. Despite of disappointing result of conventional radiotherapy, however, hyperfractionated radiation therapy and combined chemotherapy has been suggested to improve survival rates by some institutions, while others disagree. The dismal results of conventional treatments for ATCs have stimulated the investigation for new therapeutic methods with improved outcome. There have been a number of trials of new materials or therapeutic methods. In recent studies, some trials were partially successful or promising in vitro or in vivo. The examples of these trials are; redifferentiation therapies, molecular targeted therapies, and some other miscellaneous methods. Although the observations may suggest that some of the methods may have a therapeutic effect on ATCs, or may act as an adjunct to other primary treatment modality, the efficacy and safety have not been ascertained yet in human trials, and further confirmation through in-depth studies are required.
Cisplatin
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Doxorubicin
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Humans
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Molecular Targeted Therapy
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Paclitaxel
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Prognosis
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Recurrence
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Survival Rate
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Taxoids
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Thyroid Gland
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Thyroid Neoplasms
7.Docetaxel-induced nail toxicity: a case of severe onycholysis and topic review.
Chi-Pan LAU ; Pun HUI ; Tak-Cheung CHAN
Chinese Medical Journal 2011;124(16):2559-2560
Docetaxel is a commonly-used anti-cancer chemotherapeutic agent given its efficacy in a large variety of solid tumors. It is associated with various adverse effects one of which is nail toxicity. We report a case of severe onycholysis as a result of treatment with docetaxel in a patient who suffered from metastatic nasopharyngeal carcinoma. The case report will be followed by a discussion on the possible mechanism and preventive strategies for taxane-induced nail toxicity.
Adult
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Female
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Humans
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Nails
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drug effects
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pathology
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Onycholysis
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chemically induced
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Taxoids
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adverse effects
8.The evidence for adjuvant taxanes in early breast cancer.
Journal of Breast Cancer 2006;9(3):172-183
Adjuvant chemotherapy plays an important role in improving disease free and overall survival in women with high-risk early stage breast cancer. While more than seventy thousand women have enrolled in taxane-based adjuvant chemotherapy studies, interim and final results are available from several of these randomized phase III adjuvant studies. In this review, we will summarize the design and outcomes from the reported trials, and draw conclusions about the role adjuvant taxanes now play in the standard management of operable breast cancer. In aggregate, these studies show that adjuvant taxanes can improve important clinical outcomes beyond those achieved with anthracycline-based chemotherapy, without imparting prohibitive acute or chronic toxicities. Important questions are being addressed in ongoing adjuvant trials, including comparisons of combination to sequential therapy, direct comparisons between paclitaxel and docetaxel, and how to safely integrate targeted therapies into these highly active adjuvant regimens.
Breast Neoplasms*
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Breast*
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Chemotherapy, Adjuvant
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Drug Therapy
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Female
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Humans
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Paclitaxel
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Taxoids*
9.Survival benefit of taxane plus platinum in recurrent ovarian cancer with non-clear cell, non-mucinous histology.
Hiroaki KAJIYAMA ; Kiyosumi SHIBATA ; Mika MIZUNO ; Tomokazu UMEZU ; Shiro SUZUKI ; Ryuichiro SEKIYA ; Kaoru NIIMI ; Hiroko MITSUI ; Eiko YAMAMOTO ; Michiyasu KAWAI ; Tetsuro NAGASAKA ; Fumitaka KIKKAWA
Journal of Gynecologic Oncology 2014;25(1):43-50
OBJECTIVE: This study was conducted to examine the effects of front-line chemotherapy on overall survival (OS) and postrecurrence survival (PRS) of patients with recurrent ovarian cancer, when stratifying the histologic type. METHODS: Five hundred and seventy-four patients with recurrent ovarian cancer with sufficient clinical information, including front-line chemotherapy, were analyzed. The pathologic slides were evaluated by central pathologic review. The patients were divided into two groups: group A (n=261), who underwent taxane plus platinum, and group B (n=313), who underwent conventional platinum-based chemotherapy without taxanes. RESULTS: The median age was 54 years (range, 14 to 89 years). Group A had significantly better median OS (45.0 months vs. 30.3 months, p<0.001) and PRS (23.0 months vs. 13.0 months, p<0.001) compared to group B. The OS and PRS were similar between the groups in patients with clear cell or mucinous histology. In contrast, among patients with non-clear cell, non-mucinous histologies, the OS and PRS of group A were significantly better than those of group B (OS, p<0.001; PRS, p<0.001). Multivariable analyses revealed that, among patients with non-clear cell, non-mucinous histologies, chemotherapy including taxane and platinum was an independent predictor of favorable survival outcomes. Conversely, in patients with clear cell or mucinous histology, taxane-including platinum-based combination chemotherapy did not improve the OS and PRS compared to a conventional platinum-based regimen which did not include taxanes. CONCLUSION: Since the emergence of taxane plus platinum, the prognosis of patients with recurrent ovarian cancer has improved. However, we here demonstrate that this improvement is limited to patients with non-clear cell, non-mucinous histologies.
Drug Therapy
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Drug Therapy, Combination
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Humans
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Mucins
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Ovarian Neoplasms*
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Platinum*
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Prognosis
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Taxoids
10.A Phase II Study of Leucovorin, 5-FU and Docetaxel Combination Chemotherapy in Patients with Inoperable or Postoperative Relapsed Gastric Cancer.
Kwang Sun LEE ; Ha Yeon LEE ; Eun Kyung PARK ; Joung Soon JANG ; Sang Jae LEE
Cancer Research and Treatment 2008;40(1):11-15
PURPOSE: To estimate the effect and toxicity of bimonthly low-dose leucovorin (LV) and fluorouracil (5-FU) bolus plus continuous infusion(LV5FU2) with docetaxel combination chemotheraphy in patients with inoperable or postoperative relapsed gastric cancer. MATERIALS AND METHODS: Total 27 patients are enrolled in this study. LV 20 mg/m2 (bolus), 5FU 400 mg/m2 (bolus), 5-FU 600 mg/m2 (24-hour continuous infusion) on day 1, 2, 15, and 16, docetaxel 60 mg/m2 (1-hour infusion) on day 15 every 4 weeks. RESULTS: Total of 141 cycles were administered and response rate were 36.8% with 2 complete response (10.5%) and 5 partial response (26.3%) in 19 evaluable patients. The median response duration is 8.1 months (95% CI, 4.0~12.1). The median progression-free survival time is 6.7 months (95% CI, 5.0~8.5) and the median overall survival time is 11.9 months (95% CI, 4.8~19.1). The grade 3-4 toxcity of neutropenia (24.8%) and anemia (11.3%), neutropenic fever (2.8%) is observed. The grade 1 toxcity of injection site reaction is observed all patients and the grade 1-2 toxcity of alopecia is observed 60%. CONCLUSIONS: LV5FU2 with docetaxel combination chemotheraphy is effective and tolerable in patients with inoperable or postoperative relapsed gastric cancer.
Alopecia
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Anemia
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Disease-Free Survival
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Drug Therapy, Combination
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Fever
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Fluorouracil
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Humans
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Leucovorin
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Neutropenia
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Stomach Neoplasms
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Taxoids