紫杉类联合蒽环治疗乳腺癌临床疗效观察

目的探讨乳腺癌患者术前给予紫杉类联合蒽环方案与EC方案治疗的效果。方法选取海口市第三人民医院2011年1月~2012年12月间住院的90例乳腺癌患者为研究对象,按照随机数字法分为A组和B组,A组给予紫杉类联合蒽环方案治疗,B组给予EC方案(表阿霉素+环磷酰胺)治疗,观察两组的治疗效果。结果两组的临床效果比较,A组的临床有效率为82.2%,B组的有效率为71.1%,A组的有效率高于B组,两组有效率比较,差异无统计学意义(χ2=0.46,P>0.05)。A组和B组的胃肠道反应和肝脏毒性以及白细胞减少发生率比较差异无统计学意义(χ2=0.19~0.33,P>0.05);A组化疗后病例化疗反应分级(MP分级)达到4~5级比例为71.1%,B组化疗后MP分级达到4~5级比例为20.0%,A组化疗后MP分级达到4~5级比例明显高于B组,差异有统计学意义(χ2=0.19~0.33,P<0.05)。结论紫杉类联合蒽环方案对乳腺癌患者术前给予治疗的敏感性优于EC方案,不良反应少,患者比较容易接受。     

Carboplatin plus paclitaxel in the treatment of advanced or recurrent endometrial carcinoma

Purpose To evaluate the efficacy and safety of the combination of carboplatin plus paclitaxel in patients with advanced, metastatic and recurrent endometrial cancer. Methods Medical records were retrospectively reviewed to identify endometrial cancer patients treated in the Gynecologic Cancer Program of the Cleveland Clinic with carboplatin/paclitaxel who had both a histologic diagnosis of endometrial adenocarcinoma and either measurable (CT scan, physical examination) or evaluable (CA-125 criteria) disease. Results From 1994 to 2003, 22 individuals (median age 65 years) meeting the above noted criteria received a total of 23 courses of carboplatin (AUC 4–6)/paclitaxel (135–175 mg/m2) administered on a 21-day schedule (median six cycles/patient). The overall response rate was 87% (20/23). The most common toxicity was hematologic. Five patients required dose reductions due to excessive toxicity (three hematologic, one gastrointestinal, one fatigue). There were no treatment related deaths. With a median follow-up of 42 months, 13 patients have died of progressive cancer, while four currently have no evidence of disease at the time of last follow-up. Conclusions The combination of carboplatin plus paclitaxel demonstrates substantial biological activity in endometrial adenocarcinoma. The safety and efficacy of this regimen makes it an attractive option for first-line chemotherapy in patients with advanced or recurrent endometrial carcinoma.     

Initial Biopsy Gleason Score as a Predictive Marker for Survival Benefit in Patients with Castration-resistant Prostate Cancer Treated with Docetaxel: Data from the TAX327 Study

Background

Since 2004, docetaxel has been the standard first-line systemic therapy for patients with metastatic castration-resistant prostate cancer (mCRPC). With abiraterone recently becoming available in the predocetaxel setting, it is warranted to identify subgroups of patients who may obtain the greatest benefit from docetaxel and particularly qualify for receiving docetaxel as first-line treatment for mCRPC.

Objective

We aimed to identify factors that could characterize subgroups of patients who obtain the greatest benefit from the use of docetaxel.

Design, setting, and participants

TAX327 was multinational, randomized, phase 3 study that was conducted from 2000 to 2002 in 1006 men with mCRPC.

Intervention

Patients were randomized to receive docetaxel every 3 wk (D3), weekly docetaxel (D1), or mitoxantrone every 3 wk (M3), each with prednisone.

Outcome measurements and statistical analysis

We investigated whether patients with poorly differentiated tumors (Gleason score ≥7) at diagnosis had greater benefit from D3 compared with M3 than patients with better differentiated tumors (Gleason score ≤6). Using a Cox model, we compared overall survival (OS) between the treatment groups within each subgroup of Gleason score.

Results and limitations

The TAX 327 data showed that the OS benefit of D3 versus M3 was greater in patients with high-grade tumors (median OS: 18.9 vs 14.5 mo; p = 0.009) than in patients with low-grade tumors (median OS: 21.6 vs 20.7 mo; p = 0.674). Limitations of a retrospective analysis apply.

Conclusions

The survival benefit obtained with docetaxel is most pronounced in patients with high-Gleason-score tumors (Gleason ≥7). In a time of shifting paradigms in mCRPC, with abiraterone becoming available prior to docetaxel chemotherapy, Gleason score may help in selecting patients who obtain the greatest benefit from docetaxel as first-line treatment for mCRPC. Prospective validation of these findings is warranted.     

Patient and practice impact of capecitabine compared to taxanes in first-/second-line chemotherapy for metastatic breast cancer

Background  Oral chemotherapy regimens have emerged as comparably effective to intravenous regimens with the potential for less resource utilization, fewer treatment side effects and a better quality-of-life outcome. The objective of this retrospective chart review was to examine these issues among patients who received single-agent taxane therapy vs. single-agent capecitabine for first- or second-line treatment of metastatic breast cancer (MBC) Methods  Data from the medical charts of 61 patients who received single-agent capecitabine, docetaxel, or paclitaxel therapy were supplemented with data from the 38-item Patient Care Monitor (PCM) survey of symptom burden and quality of life, prospectively collected during chemotherapy. The endpoints were PCM index scores, hospitalization during treatment, and the number of clinic visits during treatment. Results  The sample was 75% Caucasian, 16% African–American, with a mean age of 59.4 years. Taxane-treated patients had more clinic visits than capecitabine patients, were more likely to have been hospitalized during treatment, and had worse treatment side effects. Controlling for depression, infusion-treated patients reported greater acute distress at the start of therapy than those on oral medication. Conclusion  Capecitabine for MBC was associated with a more favorable outcome regarding treatment side effects and quality of life, with reduced resource burden to patients and providers. Physicians may have differentially selected patients with greater depressive symptoms for capecitabine therapy. This work was supported in part by funding from Roche.     

Taxane-based mono- or combination therapy for managing metastatic breast cancer (MBC) in routine practice: a multinational prospective observational study

Abstract

Objectives:

Taxanes are standard for first-line chemotherapy of metastatic breast cancer (MBC), but indications for single-agent versus combination treatment remain controversial. This non-interventional study in 12 different countries explored treatment patterns and progression-free survival (PFS) in routine practice.     

New taxanes from the seeds of Taxus mairei

Two new taxoid metabolites were isolated from the methanol extract of the Taxus mairei seeds. Their structures were established as 2α-hydroxy-9α,10β,13α-triacetoxy-5α-cinnamoyloxytaxa-11-en-4β,20-epoxide (1) and 2′-acetyl taxol (2) on the basis of spectral analysis.     

Taxanes: Promising Anti-Cancer Drugs

Taxanes are amongst the most promising antitumor agents available at hand today, of increasing importancein Asia given that cancer is now one of the major public health problems which needs to be dealt urgently forthe benefit of affected patients. Several ongoing experimental and clinical trials have supported the fact thateven with their side effects and poor solubilities, taxanes are still the first lines of treatment chosen for breast,ovary, lung and other metastatic cancers. Prolonging the life of cancer patients is the main aim of all researchers,scientists, pharmaceutical companies and clinicians; therefore this review emphasizes the mechanisms of actionof taxanes and how they can play an important role in palliative treatment if not applied for curative purposes,hence being considered a boon for cancer management.     

Weekly taxane–anthracycline combination regimen versus tri-weekly anthracycline-based regimen for the treatment of locally advanced breast cancer: a randomized controlled trial

Background: Extensive studies have confirmed the efficacy of taxanes in combination with anthracycline-basedchemotherapy on breast cancer. However, few studies have assessed the efficacy of weekly taxane–anthracyclineregimens on locally advanced breast cancer. This study was to compare the efficacy and safety of a weekly taxane–anthracycline regimen with those of tri-weekly anthracycline-based regimen in patients with locally advanced breastcancer.Methods: Patients with locally advanced breast cancer were randomized to receive 4–6 cycles of neoadjuvant chemotherapywith tri-weekly 5-fluorouracil–epirubicin–cyclophosphamide (FEC) regimen or weekly paclitaxel–epirubicin(PE) regimen. The primary endpoint was the pathologic complete response (pCR) rate. Other endpoints included theclinical tumor response, breast-conserving surgery rate, and adverse events.Results: Between March 2010 and September 2013, 293 patients were randomized to the FEC (n = 151) and PE(n = 142) arms. The overall clinical response rate was significantly higher in the PE arm than in the FEC arm (76.06% vs.59.95%, P = 0.001). Consistently, the post-chemotherapy pathologic T and N stages were significantly lower in the PEarm than in the FEC arm (P < 0.001). However, the pCR rate was similar in the two arms (10.61% vs. 12.31%, P = 0.665).Overall, 36 (27.27%) patients in the FEC arm and 6 (35.28%) in the PE arm were qualified for breast-conserving surgery.Most adverse events were comparable in both arms, with more severe neutropenia in the PE arm than in the FEC arm(11.97% vs. 5.96%, P = 0.031).Conclusions: In patients with locally advanced breast cancer, weekly PE was not superior to FEC in terms of pCR.However, weekly PE has a higher response rate and superior down-staging effects. On this account, the PE regimenmay be considered an alternative option for locally advanced breast cancer. Long-term follow-up data are needed toconfirm the efficacy of this regimen on locally advanced breast cancer.     

Olesoxime prevents microtubule-targeting drug neurotoxicity: Selective preservation of EB comets in differentiated neuronal cells

Microtubule-targeting agents (MTAs), anticancer drugs widely used in the clinic, often induce peripheral neuropathy, a main dose-limiting side effect. The mechanism for this neurotoxicity remains poorly understood and there are still no approved therapies for neuropathies triggered by MTAs. Olesoxime (cholest-4-en-3-one, oxime; TRO19622) has shown marked neuroprotective properties in animals treated with paclitaxel and vincristine. The purpose of this study was to investigate its mechanism of neuroprotection against MTA neurotoxicity by using rat and human differentiated neuronal cells. We first showed that olesoxime prevented neurite shrinkage induced by MTAs in differentiated PC-12 and SK-N-SH neuroblastoma cell lines by up to 90%. This neuroprotective effect was correlated with enhanced EB1 accumulation at microtubule plus-ends, increased growth cone microtubule growing rate (20%) and decreased microtubule attenuation duration (54%). The effects of olesoxime on EB comets were specific for differentiated neuronal cells and were not seen either in proliferating neuroblastoma cells, glioblastoma cells or primary endothelial cells. Importantly, olesoxime did not alter MTA cytotoxic properties in a wide range of MTA-sensitive tumor cells, a prerequisite for future clinical application. Finally, olesoxime also counteracted MTA inhibition of microtubule-dependent mitochondria trafficking. These results provide additional insight into the neuroprotective properties of olesoxime, highlighting a role for microtubule dynamics in preservation of neurite architecture and axoplasmic transport, which are both disturbed by MTAs. The neuron-specific protective properties of olesoxime support its further development to treat MTA-induced neuropathy.