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 ; Cisplatin ; Electroencephalography ; Esophageal Neoplasms ; Seizures ; Status Epilepticus ; Taxoids

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 ; Camptothecin ; Chemoradiotherapy ; Cisplatin ; Humans ; Standard of Care ; Stomach Neoplasms ; Taxoids

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 ; Mixed Function Oxygenases ; Paclitaxel ; Taxoids ; Taxus

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 ; Liposomes ; Magnetic Resonance Spectroscopy ; Taxoids

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 ; Doxorubicin ; Humans ; Molecular Targeted Therapy ; Paclitaxel ; Prognosis ; Recurrence ; Survival Rate ; Taxoids ; Thyroid Gland ; Thyroid Neoplasms

The fragmentation pathways of two taxanes drugs have been studied in positive ion mode by Q-TOF with the advantages of high mass accuracy and high resolution analysis. The [M+H] + ions were observed by ESI-MS, from which the molecular weights were obtained. Using the protonated pseudo-molecular ions [M+H]+ as internal reference compounds, the accurate mass and element composition of the fragment ions were determined. The collision induced dissociation (CID) data of the [M+H] ions provided fragmentation pathways of related compounds. Results showed that the major cleavage pathways of paclitaxel and docetaxel were the same that the cleavage of C-O bond between the side chain and taxol skeleton easily occurred, then stripping of the functional groups on the parent ring. Some common fragments were formed, such as m/z 105.033 7, 291.137 3, 309.148 5, 327.159 7, 387.181 2 and 509.217 4, which would provide a basis for future qualitative and quantitative analysis of taxanes in vitro and in vivo.
Paclitaxel ; chemistry ; Peptide Fragments ; chemistry ; Spectrometry, Mass, Electrospray Ionization ; methods ; Taxoids ; chemistry

Acetates ; metabolism ; Animals ; Antineoplastic Agents, Phytogenic ; metabolism ; pharmacokinetics ; Biotransformation ; Diterpenes ; metabolism ; Paclitaxel ; metabolism ; Taxoids ; metabolism ; pharmacokinetics

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 ; Drug Therapy, Combination ; Humans ; Mucins ; Ovarian Neoplasms* ; Platinum* ; Prognosis ; Taxoids

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 ; Female ; Humans ; Nails ; drug effects ; pathology ; Onycholysis ; chemically induced ; Taxoids ; adverse effects

PURPOSE: Breast cancer is heterogeneous disease and the response to chemotherapeutic agents is also heterogeneous from patient to patient. Chemotherapy response assay is in vitro test that is performed to evaluate the degree of tumor growth inhibition by chemotherapy drugs. In this study, we performed the chemotherapy response assay using adenosine triphosphate (ATP-CRA) in breast cancer patients and assessed the clinical availability. METHODS: Sixty five breast cancer patients were enrolled in this study. Cancer cells were evenly divided and treated with commonly used chemotherapeutic drugs in breast cancer (doxorubicin, epirubicin, 5-fluorouracil, paclitaxel, docetaxel, vinorelbine, and gemcitabine). To verify in vitro ATP-CRA indirectly, we analyzed the correlation between cell death rate (CDR) of doxorubicin and epirubicin, and between doxorubicin and paclitaxel. We also analyzed the mean CDR of doxorubicin, epirubicin and paclitaxel by HER2 status. RESULTS: We could successfully perform the ATP-CRA in 60 patients (95.2%). In all cases, we can get the results within 7 days. The range of CDR was very wide, from 0 to more than 50%, except gemcitabine. Epirubicin showed the highest mean CDR (39.9%) and doxorubicin, paclitaxel in order. According to the chemosensitivity index, paclitaxel is the most frequently first-ranked and doxorubicin, epirubicin in order. Correlation coefficient between the cell death rate of doxorubicin and epirubicin is 0.4210 and 0.1299 between paclitaxel and doxorubicin. In HER2 positive group, mean CDR of paclitaxel, epirubicin and doxorubicin was higher than in HER2 negative group, even though epirubicin and doxorubicin were not statistically significant (p=0.018, p=0.114, p=0.311, respectively). CONCLUSION: ATP-CRA showed heterogeneous results in individual patients. ATP-CRA was successful and can be performed within short time period. According to our in vitro study, it showed similar results with in vivo study but for the clinical use, the prospective randomized controlled trial should be preceded.
Adenosine Triphosphate ; Breast ; Breast Neoplasms ; Cell Death ; Deoxycytidine ; Doxorubicin ; Epirubicin ; Fluorouracil ; Humans ; Paclitaxel ; Polyphosphates ; Taxoids ; Vinblastine