Productions of Taxol and Related Taxanes by Cell Suspension Cultures of Taxus yunnanensis

A high taxol yield cell line of Taxus yunnanensis Cheng et L. K. Fu keeps a high taxol_producing level after successive subcultures for more than eight years. In this study, eight taxanes were isolated from the suspension cell cultures of this cell line. Based on NMR and MS analyses, and comparison with literature data and standards, their structures were determined to be 2α,5α,10β_triacetoxy_14β_propionyloxy_4(20),11_taxadiene (1), 2α,5α,10β_triacetoxy_14β_(2′_methyl)_butyryloxy_4(20),11_taxadiene (2), 2α,5α,10β_14β_tetra_acetoxy_4 (20),11_taxadiene (3, taxuyunnanine C), 2α,5α,10β_triacetoxy_14β_(2′_methyl_3′_hydroxy)_butyryloxy_4(20),11_taxadiene (4, yunnanxane) and its 3′_epimer (5), baccatin Ⅳ (6), baccatin Ⅲ (7) and taxol (8), respectively. Among those compounds, 3, 5, 6 and 7 were reported to be isolated from the suspension cell cultures of T. yunnanensis for the first time. TLC and HPLC analyses indicated that the chemical constituents of the culture solution were similar to those of cultured cells. Moreover, the highest taxol content of this cell line reached 0.3% and the cell line could be applied for a large_scale culture.

Unfavorable Pathological Complete Response Rate of Neoadjuvant Chemotherapy Epirubicin plus Taxanes for Locally Advanced Triple-negative Breast Cancer

Anthracycline-Taxane chemotherapy is widely used in neoadjuvant treatment for breast cancers. However, there is limited data reported in patients with triple negative breast cancer （TNBC）. Here, we evaluated the pathologic responses and survival of neoadjuvant epirubicin and taxanes chemotherapy in patients with locally advanced TNBC to provide some useful information for clinical practice. A total of 43 patients with locally advanced TNBC were enrolled in this study. Patients were administered with epirubicin 75 mg/m^2 plus paclitaxel 175 mg/m^2 or docetaxel 75 mg/m^2 every 3 weeks for at least 2 cycles. The primary endpoint was pathologic complete response （pCR）, which was defined as no residual invasive cancer, or only carcinoma in situ in both the excised breast and axillary lymph node, while relapse-free survival （RFS） and overall survival （OS） were secondary endpoints. Thirty-nine （90.7%） patients were at clinical stages II B-IIIC. Thirty-seven （86%） completed 4-6 cycles of preop- erative chemotherapy, and objective response rate （ORR） was 81.4% （35/43）. Forty-two patients un- derwent radical surgery subsequently. The pCR rate was 14.3% （6/42）. The most common adverse events in neoadjuvant chemotherapy were nausea/vomiting （88.4%, 38/43） and neutropenia （88.4%）. After a median follow-up period of 34.0 months, 3-year RFS and OS rate was 53.6% and 80.1%, respectively. All events of recurrence and death occurred in non-pCR patients, in whom the 3-year RFS and OS rates were 44.3% and 76.6%, respectively. This study suggest that neoadjuvant chemotherapy with epirubicin plus taxanes has a relatively low pCR rate and high early recurrence risk in locally ad- vanced TNBC, which indicates the necessity for more efficacious treatment. Further study is needed to validate these results.

A New Deoxygenation Method for Taxanes Using Hypophosphorous Acid

An efficient and practical radical chain deoxygenation method by phosphorus centered radicals generated from hypophosphorous acid was developed in the synthesis of analogues of paclitaxel.

Role of taxanes in pancreatic cancer

Pancreatic cancer is one of the most deadly cancers and is characterized by a poor prognosis. Single agent gemcitabine, despite its limited activity and modest impact on disease outcome, is considered as the standard therapy in pancreatic cancer. Most of the combination regimens used in the treatment of this disease, also including the targeted agents, did not improve the outcome of patients. Also, taxanes have been tested as single agent and in combination chemotherapy, both in first line and as salvage chemotherapy, as another possible option for treating pancreatic cancer. The inclusion of taxanes in combination with gemcitabine as upfront therapy obtained promising results. Accordingly, taxanes, and above all, new generation taxanes, appear to be suitable candidates for further testing to assess their role against pancreatic cancer in various clinical settings.

TAXAYUNTIN A,B,C AND D----FOUR NEW TETRACYCLIC TAXANES FROM TAXUS YUNNANENSIS

Four new taxane diterpenoids were isolated from the bark of Taxus yunnanensis.Their structures were elucidated as the new skeleton with 5/7/6/4 membered rings by spectral analysis and 2D NMR shift correlation experiments.

NEW TAXANES FROM TAXUS CHINENSIS.2

Tow new taxane diterpenes were isolated from the leaves and stems of Taxus chinensis.Thcir structures were established as 2-deacctyl-5-decinnamatetaxagifine and taxagifinc Ⅲ on the basis of spectroscopic analysis.

Optic Nerve Metastasis from Breast Carcinoma after Treatment with Taxanes

Introduction: The incidence of ocular metastasis from Breast Carcinoma is only between 5% - 30%, mainly located in choroid, but the location in optic nerve is even more infrequent. We present a rare case that combined both locations sequentially in the same eye. Methods: Case report. Results: A 58-year-old woman with advanced breast cancer was referred with a choroidal metastasis in her right eye which responded well to systemic Taxol and Avastin. Afterwards, she developed an optic nerve metastasis in the same eye when she was under the treatment, so it was changed to Docetaxel. Unfortunately the patient didn’t respond to this treatment and died. Conclusions: Choroidal metastasis secondary to breast cancer generally responds well to radiotherapy. Even so, in cases that a great deterioration of visual acuity is expected after radiation, chemotherapy like taxanes is an alternative to preserve vision with complete tumor regression. Nevertheless, the presentation of a second metastasis in optic nerve can be indicative of inadequate treatment of metastatic disease or complication of the treatment, or both.

Pseudocirrhosis after the Use of Taxanes and Bevacizumab in Metastatic Breast Cancer： Case Reports

Currently, multiple lines of cytotoxic chemotherapy for treatment of metastatic breast cancer are available, and Taxanes, used as monotherapy or in combination with anti-angiogenic drugs, such as Bevacizumab, are one of the most used schemes in clinical practice. These drugs have different side effects and the liver is one of the most affected organs. The objective of this paper is to report three cases of metastatic breast cancer with positive expression of hormone receptors and without amplification of HER-2 protein that were treated with Taxane and Bevacizumab, developed pseudocirrosis probably caused by these drugs and died due to liver failure. It can be drawn from the study that liver failure, as a pseudocirrhosis evolution, is an unusual but lethal event that may occur during the treatment of metastatic breast cancer with Taxanes and Bevacizumab. This warns the importance of diagnostic suspicion of this pathology.

Adjuvant Taxanes in Breast Cancer: A Critical Re-appraisal

Purpose: Several studies have reported a positive impact for taxanes in adjuvant breast cancer (BC) treatment in terms of reduced recurrence and mortality. However the impact of the magnitude on overall survival (OS) remains partially controversial. Methods: We examined the impact of taxane-containing adjuvant therapy for patients with early BC on OS, based on the number of deaths and on the calculated number of patients who need to be treated with taxanes to avoid one death (NNT). We classified patients in three different groups according to whether taxanes were administered concurrently or sequentially, and whether all treatment arms had the same or different duration. Results: 1) Taxanes in combination therapy: 8258 patients (4373 with taxanes and 3885 without taxanes), with 723 OS events. Overall survival for taxane-treated patients was 92.7% versus 89.6% for patients not receiving taxanes. NNT was 33. 2) Sequential treatment of unequal duration in the treatment arms: 14,228 patients (7970 with taxanes and 6256 without). Overall survival in taxane-treated patients was 86% compared with 83.2% for patients not receiving taxanes. NNT was 44. 3) Sequential treatment and similar duration in treatment arms: 9511 women (5093 with taxanes and 4418 without). Overall survival in patients treated with taxanes was 87% versus 85% in patients not receiving taxanes. NNT was 50. When the results of all these trials were considered together, the NNT stands at 43 patients. Conclusion: Taxanes afford a modest increase in overall survival in BC patients regardless of how they are given. Translational trials may well help to improve patient selection in the future.

Non-platinum-based chemotherapy for treatment of advanced gastric cancer:5-fluorouracil,taxanes,and irinotecan

Despite numerous advances in treatment options,advanced gastric cancer(AGC)remains a major public health issue and the leading cause of cancer-related deaths.Cisplatin is one of the most effective broadspectrum anticancer drugs for AGC and a doublet combination regimen of either cisplatin-based or 5-fluorouracil(5FU)-based chemotherapy is generally used for treatment of patients with AGC.However,there is still no consensus on the best regimen for treating AGC.Recently,various new chemotherapeutic agents,including oral 5FU,taxanes,and irinotecan,have been identified as improving the outcomes for AGC when used as a single agent or in combination with nonplatinum chemotherapy.Nonetheless,it is still unclear whether non-platinum-based chemotherapy is a viable treatment option for patients with AGC.Accordingly,this review focuses on the efficacy and tolerability of non-platinum-based chemotherapy for patients with AGC.

Breakthrough therapy for peritoneal carcinomatosis of gastric cancer:Intraperitoneal chemotherapy with taxanes

The effect of chemotherapy on peritoneal carcinomatosis(PC) of gastric cancer remains unclear.Recently,the intraperitoneal(IP) administration of taxanes [e.g.,paclitaxel(PTX) and docetaxel(DOC)] during the perioperative period has shown promising results.Herein,we summarized the rationale and methodology for using IP chemotherapy with taxanes and reviewed the clinical results.IP administered taxanes remain in the IP space at an extremely high concentration for 48-72 h.The drug directly infiltrates peritoneal metastatic nodules from the surface and then produces antitumor effects,making it ideal for IP chemotherapy.There are two types of perioperative IP chemotherapy with taxanes: neoadjuvant intraperitoneal and systemic chemotherapy and sequential perioperative intraperitoneal chemotherapy(SPIC).In SPIC,patients receive neoadjuvant IP chemotherapy and the same regimen of IP chemotherapy after cytoreductive surgery(CRS) until disease progression.Usually,a taxane dissolved in 500-1000 m L of saline at ordinary temperature is administered through an IP access port on an outpatient basis.According to phase Ⅰ?studies,the recommended doses(RD) are as follows: IP DOC,45-60 mg/m2; IP PTX [without intravenous(IV) PTX],80 mg/m2; and IP PTX(with IV PTX),20 mg/m2.Phase Ⅱ studies have reported a median survival time of 14.4-24.6 mo with a 1-year overall survival of 67%-78%.A phase Ⅲ study comparing S-1 in combination with IP and IV PTX to S-1 with IV cisplatin started in 2011.The prognosis of patients who underwent CRS was better than that of those who did not; however,this was partly due to selection bias.Although several phase Ⅱ studies have shown promising results,a randomized controlled study is needed to validate the effectiveness of IP chemotherapy with taxanes for PC of gastric cancer.

A Highly Regioselective Deacetylation of Taxanes

A highly regioselective O-deacetylation of taxanes at C-5 position was accomplished by treatment with t-BuOK and a possible mechanism was proposed.

Reduction of 1-Deoxy-13-oxotaxanes

Reduction of 1-deoxy-13-oxotaxanes has been studied under different reaction conditions. Some interesting reactions were reported.

Paclitaxel for second-line treatment of squamous cell carcinoma of the head and neck:A multicenter retrospective Italian study

BACKGROUND Squamous cell carcinoma of the head and neck(SCCHN)accounts for 3%of all malignant tumors in Italy.Immune checkpoint inhibitors combined with chemotherapy is first-line treatment for SCCHN;however,second-line treatment options are limited.Taxanes are widely used for combination therapy of SCCHN,as clinical trials have shown their efficacy in patients with this disease,partic ularly in patients with prior therapy.AIM To perform a multicenter retrospective study on the efficacy and safety of weekly paclitaxel for SCCHN.METHODS All patients were previously treated with at least one systemic therapy regimen,which included platinum-based therapy in the vast majority.No patient received prior immunotherapy.RESULTS Median progression-free survival(mPFS)was 3.4 months and median overall survival(mOS)was 6.5 months.Subgroup analysis was performed according to three principal prognostic factors:Smoking,alcohol consumption,and body mass index.Analysis demonstrated reduced survival,both mOS and mPFS,in the unfavorable prognostic groups,with the biggest deltas observed in mOS.CONCLUSION Weekly paclitaxel provided favorable survival and disease control rates,with low severe adverse events.Paclitaxel is a safe and valid therapeutic option for patients with SCCHN who received prior therapy.

Concurrent chemoradiotherapy comparison of taxanes and platinum versus 5-fluorouracil and platinum in nasopharyngeal carcinoma treatment

Background Nasopharyngeal carcinoma （NPC） is a squamous-cell carcinoma especially prevailing among the natives of southern China.The regimen of concurrent chemoradiotherapy （CCRT） that include platinum and 5-fluorouracil （5-FU）is considered to be the standard treatment for NPC.However,its clinical use is limited by its toxicity.Our purpose was to evaluate the efficacy and safety of the regimen of CCRT with taxanes and platinum versus the regimen of CCRT with 5-FU and platinum in NPC treatment.Methods Medline,the Cochrane library,and the Chinese medical literature database were searched for eligible studies.Meta-analysis was performed using Review Manager （Version 5.2）.Results Six random controlled trials （RCTs） including 514 patients met our criteria.Meta-analysis showed that the regimen of CCRT with taxanes and platinum had an improved significant difference in complete remission （CR） and less incidence rate in adverse reactions such as gastrointestinal impairment grades Ⅲll-Ⅳ,liver and kidney impairment grades Ⅰ-Ⅱ,and radiodermatitis grades Ⅲ-Ⅳ versus the conventional regimen of CCRT with 5-FU and platinum,while the long-term effectiveness rate of overall survival,Iocoregional failure-free survival,or distant metastasis failure-free survival between the two groups was therapeutic equivalence.Conclusions The regimen of CCRT with taxanes and platinum in NPC therapy may be more efficient and safe compared to the conventional modality of 5-FU and platinum in CCRT.However,we need more high-quality studies of multi-center and randomized double-blind clinical trials to further compare,analyze,and confirm the findings.

Probing the new strategy for the oral formulations of taxanes:changing the method with the situation

The first-generation taxanes(including paclitaxel and docetaxel)are widely used for the treatment of various cancers in clinical settings.In the past decade,a series of new-generation taxanes have been developed which are effective in the inhibition of tumor resistance.However,intravenous(i.v.)infusion is still the only route of administration,and may result in serious adverse reactions with respect to the utilization of Cremophor EL or Tween-80 as solvent.Besides,the dosing schedule is also limited.Therefore,oral administration of taxanes is urgently needed to avoid the adverse reactionss and increase dosing frequency.In this review,we first outlined the discovery and development of taxane-based anticancer agents.Furthermore,we summarized the research progress on the oral formulations of taxanes and proposed some thoughts on the future development of oral taxane formulations.

The magnitude of benefit from adding taxanes to anthracyclines in the adjuvant settings of breast cancer:discussion of large trials and meta-analyses

The taxanes family of chemotherapy,which includes paclitaxel and docetaxel,has been incorporated in the adjuvant breast cancer treatments since 1990s.Sequential and concurrent use of taxanes was investigated with anthracyclines in many adjuvant early breast cancer randomized clinical trials.Results from taxanes trials showed inconsistent benefits.However,several meta-analyses showed significant survival benefit of adding taxanes.In this review article,data were collected and summarized from eleven large randomized trials and three meta-analyses to show and discuss the magnitude of benefit of taxanes-anthracyclines combination compared to anthracyclines only adjuvant regimens in early breast cancer.This article aims at providing the oncologists with a well-organized,inclusive and updated evidence.

Necrotizing fasciitis as a complication of taxanes: a case report

Necrotizing fasciitis is a rare complication of chemotherapy,however,few reports were published as a specific complication of taxanes.We are reporting this rare complication of a lady who was treated with taxanes as an adjuvant therapy for her breast cancer who was referred to us from the medical department and turned out to be necrotizing fasciitis in her right thigh.We are also presenting the literature review of this type of complication.

Impact of taxanes on androgen receptor signaling

The development and progression of metastatic castration-resistant prostate cancer is the major challenge in the treatment of advanced prostate cancer. The androgen receptor signaling pathway remains active in metastatic castration-resistant prostate cancer. Docetaxel and cabazitaxel are the first- and second-line chemotherapy, respectively, for patients with metastatic castration-resistant prostate cancer. These two taxanes, in general, function by (i) inhibiting mitosis and inducing apoptosis and (ii) preventing microtubule-dependent cargo trafficking. In prostate cancer, taxanes have been reported to inhibit the nuclear translocation and activity of the androgen receptor. However, whether this is attainable or not clinically remains controversial. In this review, we will provide a comprehensive view of the effects of taxanes on androgen receptor signaling in prostate cancer.

TAXANES FROM Taxus chinensis

In our preivous study, five new taxane diterpenes were extracted from the air-dried stems and leaves of Taxus chinensis (Pilgre) Rehd, collected in Xiaolong mountains of Gansu Province, China. In this note, we wish to report the structures of other four minor taxane diterpenes (Fig. 1).