Life-threatening hypersensitivity pneumonitis induced by docetaxel (taxotere).

4 patients with advanced non-small-cell lung cancer (NSCLC) treated with docetaxel developed life-threatening pneumonitis requiring mechanical ventilation. Docetaxel (30-60 mg x m(-2), according to a different protocol) was infused within one hour with standard premedications. One patient's pneumonitis occurred 5 days after the first dose of docetaxel, and that of the other 3 between the 2nd and 6th cycles. Based on the clinical course, radiological findings of an interstitial pneumonitis, and exclusion of other possible resultant causes, including metastatic cancer, radiation pulmonary injury, infection, or connective tissue disease, hypersensitivity pneumonitis was diagnosed. The patients were treated with hydrocortisone at 1200 mg per day or methylprednisolone at 240 mg per day. Although 3 of the 4 had a partial improvement in lung oxygenation, all patients' conditions of hypersensitivity pneumonitis persisted and were complicated by other events, such as hospital-acquired infection and tension pneumothorax. The presence of this unusual hypersensitivity pneumonitis, which was so severe as to be life-threatening and refractory to high-dose corticosteroid therapy, should be taken into account during docetaxel treatment.     

Current status of Taxotere® (docetaxel) as a new treatment in breast cancer

Summary Therapy for advanced breast cancer has not improved significantly in recent years, remaining strictly palliative in nature and intent. One approach to increase the effectiveness of the treatment is the introduction of active new drugs. Taxotere^® (docetaxel) is a taxoid derivative isolated from the needles of the European yew,Taxus baccata. Taxotere promotes the assembly of microtubules and inhibits their depolymerization. One EORTC Clinical Screening Group (CSG) phase II trial using Taxotere at 100 mg/m², 1 hour infusion without routine premedication for hypersensitivity reactions, in first line chemotherapy, indicates a high anti-tumor activity: 5 complete and 18 partial responses in 32 patients assessable for response (overall response rate 72%, 95% CI 53%–86%). Other studies confirm this activity in first line and second line chemotherapy for advanced disease and in patients who are refractory to anthracycline containing regimens. Grades III and IV neutropenia without major infection, and grades I and II skin toxicity, were frequently observed adverse events. A fluid retention syndrome (chronic cumulative and non life-threatening toxicity) has been noted in patients treated with Taxotere. Methods for controlling fluid retention — dose reduction to 75 mg/m² (which has little effect) or routine premedication from the start of treatment — are currently being studied.Presented by P. Fumoleau at the 16th Annual San Antonio Breast Cancer Symposium, San Antonio TX, November 4, 1993; Mini-symposium on New Agents in Breast Cancer (supported by an educational grant from Rhône-Poulenc Rorer).     

Clinical and electrophysiological features of peripheral neuropathy induced by administration of cisplatin plus paclitaxel-based chemotherapy

The current prospective study sought to trace the incidence and severity of cisplatin plus paclitaxel (DDP+P)-induced neuropathy and to determine its clinical and electrophysiological pattern. Furthermore, it was attempted to describe its evolution by following up the course of peripheral neuropathy (PN) during chemotherapy as well as 3 months after its discontinuation. Thirteen adult patients scheduled to be treated with six courses of cumulative DDP+P-based regimens for a non-myeloid malignancy participated in this study. These patients were clinically and electrophysiologically monitored at baseline, during chemotherapy and 3 months after its discontinuation. The severity of PN was summarized by means of a modified PN score. Evidence of PN was disclosed in nine of the 13 patients (69.2%). The mean PN score for patients that manifested some grade of PN was 17.3 +/- 6.1 (range 9-28). All longitudinal comparisons concerning the motor conduction velocities (MCV) variables failed to reach significance. By contrast, comparisons of the mean changes at baseline and each of the follow-up studies revealed a significant decrease in all sensory action potentials examined. The follow-up evaluation performed 3 months after the discontinuation of chemotherapy showed that the DDP+P-induced neuropathy persists and progresses over time. Our results indicate that the majority of patients treated with a DDP+P-based regimen at full dose intensities would manifest an axonal, predominately sensory PN, of mild to moderate severity, which would persist for several months after the discontinuation of chemotherapy.     

In vitro comparative evaluation of trastuzumab (Herceptin) combined with paclitaxel (Taxol) or docetaxel (Taxotere) in HER2-expressing human breast cancer cell lines.

BACKGROUND: Trastuzumab (Herceptin) has clinical indication in association with paclitaxel (Taxol) for the treatment of human epidermal growth factor receptor 2 (HER2)-expressing breast cancer. Synergistic interactions have been reported with taxane derivatives in HER2-expressing breast cancer cells. However, no direct comparison of the potential interest in combining trastuzumab with either paclitaxel or docetaxel (Taxotere) has been reported. MATERIALS AND METHODS: The present study was designed to evaluate in a comparative way the interaction of trastuzumab with paclitaxel or docetaxel in HER2-overexpressing human breast cancer cell lines. HER2 expression was documented in MCF-7, MDA-MB453 and SK-BR3 cell lines using immunocytochemistry with purified mouse anti-human monoclonal antibody. Cytotoxicity assays were performed using the sulforhodamine B assay and in vitro interactions between trastuzumab and taxanes were analyzed using the median-effect principle. RESULTS: Trastuzumab cytotoxicity was confirmed to be directly related to HER2 expression level. At the IC(50), the combination of trastuzumab with either paclitaxel or docetaxel led to synergism in all cell lines. However, considering mean values calculated in the IC(30)-IC(70) range of concentrations, trastuzumab interacted additively with docetaxel in SK-BR3 and MDA-MB453 cell lines while additive and synergistic interactions were achieved with paclitaxel in SK-BR3 and MDA-MB453, respectively. On the same basis, trastuzumab yielded synergistic interaction with both taxanes in the MCF-7 cell line. CONCLUSIONS: The present study shows that at least additive interactions are observed when trastuzumab is combined with either paclitaxel or docetaxel in weak to moderate or more than moderate HER2-expressing cells. Some interesting results were achieved in cells displaying weak HER2 expression which could suggest some further potential interest in trastuzumab.     

Sequential or alternating administration of docetaxel (Taxotere) combined with FEC in metastatic breast cancer: a randomised phase II trial

The aim of this study, using a Fleming single-stage design, was to explore the efficacy and safety of Taxotere 100 x mg x m(-2) docetaxel and FEC 75 cyclophosphamide 500 mg x m(-2), fluorouracil 500 x mg x m(-2) and epirubicin 75 mg x m(-2), in alternating and sequential schedules for the first-line treatment of metastatic breast cancer. One hundred and thirty-six women were randomly allocated, to one of three treatment regimens: DTX 100 plus FEC 75, alternated for eight courses (ALT); four courses of DTX 100 followed by four courses of FEC 75 (SEQ T); or four courses of FEC 75 followed by four courses of DTX 100 (SEQ F). One hundred and thirty-one women were evaluable for tumour response. Although the treatment outcome was equivalent in the two sequential arms and the alternating regimen (P=0.110, not significant), the response rate was less encouraging in the SEQ F arm (52.3%) than in the other two arms (71.1% for ALT and 70.5% for SEQ T), in which docetaxel was administered first. Time to progression was similar in the ALT, SEQ T and SEQ F arms (9.5, 9.3 and 10.4 months respectively). Grade 3-4 neutropenia was observed in nearly all patients; febrile neutropenia occurred in 9% (ALT), 16% (SEQ T) and 2% (SEQ F) of patients. Few patients (< or =9%) developed grade 3-4 non-haematological toxicities. Relative dose intensity was 97-99% for all regimens. All treatment regimens were active and well tolerated.     

5-Fluorouracil as protracted continuous intravenous infusion can be added to full-dose docetaxel (Taxotere)-cisplatin in advanced gastric carcinoma: a phase I-II trial.

BACKGROUND: A phase I-II multicenter trial was conducted to define the maximum tolerated dose (MTD) according to tolerance and toxicity (primary objective), as well as to describe the clinical activity, in terms of response and survival (secondary objectives), of a combination of 5-fluorouracil (5-FU) in protracted continuous intravenous infusion (p.i.v.) with docetaxel and cisplatin for patients with advanced gastric cancer. PATIENTS AND METHODS: Patients with measurable unresectable and/or metastatic gastric carcinoma, World Health Organization performance status < or =1, normal hematological and renal functions, adequate hepatic function and not pretreated for advanced disease by chemotherapy, received up to eight cycles of a combination of docetaxel on day 1, cisplatin on day 1 and 5-FU p.i.v. on days 1-14 (TCF) every 3 weeks, which was escalated up to the MTD, defined by the occurrence of dose-limiting toxicity in two patients in one dose level. RESULTS: Fifty-two patients were accrued and treated (43 in the phase I part of the trial and nine additional at the recommended dose level). A median of five cycles/patient was given. The recommended dose of TCF was docetaxel 85 mg/m(2) on day 1, cisplatin 75 mg/m(2) on day 1 and 5-FU p.i.v. 300 mg/m(2)/day on days 1-14. Grade > or =3 toxicities were neutropenia 79%, alopecia 46%, fatigue 23%, mucositis 10%, diarrhea 19%, nausea/vomiting 13%, neurological 4% and palmar-plantar 2%. Ten non-fatal febrile neutropenia episodes were recorded in eight patients. There were no treatment-related deaths. Among 41 patients with measurable disease (79%), we observed one complete and 20 partial responses for an overall intent-to-treat response rate of 51% (95% confidence interval 35-67%). Five patients (20%) had stable disease for > or =12 weeks (four cycles). The median overall survival was 9.3 months. CONCLUSIONS: 5-FU p.i.v. at 300 mg/m(2)/day for 2 weeks out of three could be safely added to the docetaxel-cisplatin (TC) combination, but the dose of docetaxel had to be reduced to 75 mg/m(2) in a subsequent phase II trial. This drug regimen seems to be very active in advanced gastric cancer. Comparison with both TC and ECF in a randomized SAKK trial is ongoing.     

Pediatric chemotherapy induced peripheral neuropathy: A systematic review of current knowledge

BackgroundThe dramatic increase in the number of childhood cancer survivors over the last 60 years has made monitoring and minimising long term side effects of cancer treatment increasingly important. Chemotherapy induced peripheral neuropathy (CIPN) has been described with many commonly used chemotherapy agents. This article provides a critical overview of pediatric CIPN, its incidence, clinical manifestations, late effects, and recent advances in understanding of risk factors and pharmacogenomics as well as evaluating current assessment strategies and treatment approaches.MethodsNeurotoxicity data was systematically collated from Medline, Embase and Pubmed and analysed for quality, relevance and originality in three stages prior to inclusion. Quality scoring was done using the QUALSYST assessment tool.ResultsA total of 61 studies met inclusion criteria. Peripheral neuropathy is common and may be long lasting with characteristics specific to each chemotherapy agent. There is significant variability in reported incidence and natural history, related to challenges in clinical assessment and diagnosis. Emerging risk factors for CIPN include treatment factors such as dose, duration and concurrent medication and patient factors such as age and inherited susceptibilities. Recent identification of individual genetic variations has advanced understanding of pathomechanisms and may direct future treatment approaches.ConclusionWhile these studies guide suggestions for current clinical practice, further systematic research with development of strategies for amelioration and prevention of CIPN is necessary. Standardised assessment protocols and objective outcomes measures of CIPN applicable to patients of different ages are critical to enabling the development of novel treatments and facilitation of future clinical trials and treatment individualisation.     

硼替佐米致周围神经病变27例临床分析

目的:分析和研究硼替佐米致周围神经病变（BIPN）的临床特征。方法:以2014年5月至2015年5月于中国医科大学附属盛京医院血液科住院接受硼替佐米治疗的27例多发性骨髓瘤患者为研究对象,统计分析其治疗过程中周围神经病变发生情况。结果:经硼替佐米方案化疗后,40.7%的患者出现了BIPN,其中初治患者4人,复发难治患者7人;3-4级神经毒性占27.3%（3/11）,其中初治患者1人,复发难治患者2人。复发难治组患者11人既往接受过长春新碱、沙利度胺等神经毒性药物化疗,63.6%的患者产生BIPN,其中2人为3-4级神经毒性。既往糖尿病或酗酒患者共7人,BIPN发生率为85.7%。年轻患者（年龄≤60岁）BIPN发生率为27.3%,低于老年患者（50.0%）。停止治疗后再次评价,81.8%患者症状和体征得到改善。结论:高龄、糖尿病、酗酒,接受过长春新碱、沙利度胺等治疗是硼替佐米致周围神经病变发生的主要危险因素。3-4级神经毒性需要减量或停药,BIPN具有剂量依赖性和可逆性,停止治疗后患者症状和体征会有改善。     

Metastatic eccrine porocarcinoma: Response to docetaxel (Taxotere) chemotherapy

Background:Eccrine porocarcinoma is an uncommon neoplasm of theintra-epidermal sweat gland duct. Patients and methods:A case of eccrine porocarcinoma in a femalerenal transplant patient aged 45 years is described with a review of pertinentliterature. Results:The primary tumour was highly pleomorphic. In placeslarge and small cells merged and focally the former component infiltrated theepidermis in a manner akin to Pagets disease of the breast. Themajority of the tumour was high grade; using the modified Bloom and Richardsongrading system, usually applied to mammary ductal carcinomas, the tumourgraded as 3. Metastatic disease developed nine months following primarysurgical treatment. The metastatic eccrine porocarcinoma was resistant toepirubicin but responded to docetaxel chemotherapy. Conclusions:There are no data to support the use of adjuvanttherapy in the management of eccrine porocarcinoma. The use of the modifiedBloom and Richardson grading system may define cases at high risk of relapsein which adjuvant therapy might be considered. Metastatic eccrineporocarcinoma has proven resistant to many chemotherapeutic agents. We reportthe first use of docetaxel in the management of this disease. The treatmentwas well tolerated and resulted in marked symptomatic and radiologicalresponses. Treatment with docetaxel should be considered in future cases ofthis rare tumour.     

Docetaxel (Taxotere)-cisplatin (TC): an effective drug combination in gastric carcinoma. Swiss Group for Clinical Cancer Research (SAKK), and the European Institute of Oncology (EIO).

Purpose:A multi-centric trial was performed to explore theclinical activity, in terms of response and toxicity (primary objectives),duration of response and survival (secondary objectives), of docetaxel withcisplatin in advanced gastric cancer (AGC). Patients and methods:Patients with measurable unresectable and/ormetastatic gastric carcinoma, performance status 1, normal hematological,hepatic and renal functions and not pretreated for advanced disease bychemotherapy received up to eight cycles of TC (docetaxel 85 mg/m²d1, cisplatin 75 mg/m² d1) q3w. Dose escalation to 100mg/m² was performed in five patients and was discontinued forexcessive toxicity. Results:Forty-eight patients were accrued. A median of 5cycles/patient was given. We observed 2 complete and 25 partial responses foran overall intent to treat response rate of 56% (95% CI:41%–71%). Twelve patients had stable disease for 9weeks (3 cycles). The median time to progression and overall survival were 6.6and 9 months, respectively. Grade 3 toxicities were neutropenia81%, anemia 32%, thrombocytopenia 4%, alopecia36%, fatigue 9%, mucositis 9%, diarrhea 6%,nausea/vomiting 4%, neurologic 2%, and one anaphylaxisprecluding treatment administration. We recorded nine episodes of non-fatalfebrile neutropenia in eight patients, two of them with docetaxel at 100mg/m². There were no direct treatment-related deaths. Conclusions:TC is active in AGC with a high response rate in amulticentric trial. Despite its hematotoxicity, this regimen is well toleratedand can be recycled as originally planned in 78% of the cases. Theseresults may serve as basis for further developments of docetaxel containingregimens in this disease.     

Risk-reduction and treatment of chemotherapy-induced peripheral neuropathy

Introduction: Chemotherapy-induced peripheral neuropathy (CIPN), a common adverse effect of several chemotherapeutic agents, has a significant impact on quality of life and may even compromise treatment efficacy, requiring chemotherapy dose reduction or discontinuation. CIPN is predominantly related with sensory rather than motor symptoms and the most common related cytotoxic agents are platinum compounds, taxanes and vinca alkaloids. CIPN symptoms may resolve after treatment cessation, but they can also be permanent and continue for years.

Areas covered: We present an overview of CIPN pathophysiology, clinical assessment, prevention and treatment identified through a Pubmed search.

Expert commentary: No substantial progress has been made in the last few years within the field of prevention and/or treatment of CIPN, in spite of remarkable efforts. Continuous research could expand our knowledge about chemotherapeutic-specific neuropathic pathways and eventually lead to the conception of innovative and targeted agents for the prevention and/or treatment of this debilitating chemotherapy adverse effect.     

Schwann cell autophagy induced by SAHA, 17-AAG, or clonazepam can reduce bortezomib-induced peripheral neuropathy

Background:

The proteasome inhibitor bortezomib has improved the survival of patients with multiple myeloma but bortezomib-induced peripheral neuropathy (BiPN) has emerged as a serious potential complication of this therapy. Animal studies suggest that bortezomib predominantly causes pathological changes in Schwann cells. A tractable system to evaluate combination drugs for use with bortezomib is essential to enable continuing clinical benefit from this drug.

Methods:

Rat schwannoma cells were pretreated with vincristine (VCR), histone deacetylase inhibitors, anticonvulsants, or a heat-shock protein 90 (HSP90) inhibitor. To then monitor aggresome formation as a result of proteasome inhibition and the activation of chaperone-mediated autophagy (CMA), we performed double-labelling immunofluorescent analyses of a cellular aggregation-prone protein marker.

Results:

Aggresome formation was interrupted by VCR, whereas combination treatments with bortezomib involving suberoylanilide hydroxamic acid, 17-allylamino-17-demethoxy-geldanamycin, or clonazepam appear to facilitate the disposal of unfolded proteins via CMA, inducing HSP70 and lysosome-associated membrane protein type 2A (LAMP-2A).

Conclusions:

This schwannoma model can be used to test BiPN-reducing drugs. The present data suggest that aggresome formation in Schwann cells is a possible mechanism of BiPN, and drugs that induce HSP70 or LAMP-2A have the potential to alleviate this complication. Combination clinical trials are warranted to confirm the relevance of these observations.     

S-phase specificity of cell killing by docetaxel (Taxotere) in synchronised HeLa cells.

Cell viability following short (1 h) contact with paclitaxel or docetaxel was assayed using synchronised HeLa cells. Docetaxel proved almost totally lethal against S-phase cells. Its toxicity was only partial against cells in mitosis, and declined to a minimum with progression to G1. For paclitaxel, cytotoxicity increased with progression through S and G2, peaked at the time of mitosis, and decreased thereafter. Maximum resistance to paclitaxel was in early S. Although lethal, brief exposure to docetaxel in S-phase did not delay progression through S and G2. Gross damage was detectable immediately after mitosis, with dysfunction in cytokinesis and accumulation of multinucleated, non-viable cells. Arrest of cells at prometaphase required continuous contact with lethal amounts of docetaxel or reintroduction of drug shortly before mitosis following pulse-chase treatment in mid-S-phase. Paclitaxel at moderate doses presumably acts mostly via damage to the mitotic spindle. In contrast, the available data suggest that docetaxel primarily targets centrosome organisation, leading to abortive mitosis and cell death.     

Rasch-built Overall Disability Scale for patients with chemotherapy-induced peripheral neuropathy (CIPN-R-ODS)

Chemotherapy-induced peripheral neuropathy (CIPN) is a common neurological side-effect of cancer treatment and may lead to declines in patients’ daily functioning and quality of life. To date, there are no modern clinimetrically well-evaluated outcome measures available to assess disability in CIPN patients. The objective of the study was to develop an interval-weighted scale to capture activity limitations and participation restrictions in CIPN patients using the Rasch methodology and to determine its validity and reliability properties. A preliminary Rasch-built Overall Disability Scale (pre-R-ODS) comprising 146 items was assessed twice (interval: 2–3 weeks; test–retest reliability) in 281 CIPN patients with a stable clinical condition. The obtained data were subjected to Rasch analyses to determine whether model expectations would be met, and if necessarily, adaptations were made to obtain proper model fit (internal validity). External validity was obtained by correlating the CIPN-R-ODS with the National Cancer Institute-Common Toxicity Criteria (NCI-CTC) neuropathy scales and the Pain-Intensity Numeric-Rating-Scale (PI-NRS).The preliminary R-ODS did not meet Rasch model’s expectations. Items displaying misfit statistics, disordered thresholds, item bias or local dependency were systematically removed. The final CIPN-R-ODS consisting of 28 items fulfilled all the model’s expectations with proper validity and reliability, and was unidimensional.The final CIPN-R-ODS is a Rasch-built disease-specific, interval measure suitable to detect disability in CIPN patients and bypasses the shortcomings of classical test theory ordinal-based measures. Its use is recommended in future clinical trials in CIPN.     

多西他赛所致少见不良反应及其防治

多西他赛作为目前临床应用最为广泛的抗肿瘤药物之一,在对多种实体瘤有较高有效率的同时,经常伴随着一些不良反应的发生。较常见的如骨髓抑制、过敏反应、消化道反应、乏力、脱发、外周神经损害等。而当临床医师面对一些较少见的不良反应,如泪溢、液体潴留、皮肤毒性、鼻衄等时,及时作出正确诊断并对症处理则会有一定的难度。现通过查阅文献对这些少见不良反应的特点、处理及预防进行归纳和总结并作一综述,以期为临床合理应用多西他赛、减少或治疗相关不良反应提供参考。     

泰索帝每周方案治疗晚期乳腺癌及非小细胞肺癌临床疗效观察

目的 :观察泰索帝 (Taxotere)每周用药方案治疗晚期乳腺癌及非小细胞肺癌的临床疗效和毒性反应。方法 :泰索帝 2 5mg m2 ,d1、d8、d15,静脉滴入 1h ,每次给药前 30min予地塞米松 10mg静脉推注。乳腺癌联合吡喃阿霉素 4 0mg m2 ,d2 ,静脉推注 ;非小细胞肺癌联合卡铂 30 0mg m2 ,d2 ,静脉滴入。2 8d为 1个周期。治疗 2个周期。结果 :乳腺癌 5例 ,PR 2例 ,NC 3例 ,有效率 4 0 .0 % ;非小细胞肺癌11例 ,CR 1例 ,PR 3例 ,NC 5例 ,PD 2例 ,有效率 36 4 %。全组 16例 ,有效 6例 ,总有效率 37 5 %。毒性反应主要为白细胞减少 ,但无Ⅳ度者。非血液毒性为乏力、恶心及脱发。结论 :泰索帝每周给药方案与每 3周给药方案相比疗效基本相同且具有良好的耐受性 ,骨髓抑制轻微     

硼替佐米所致周围神经病变的研究进展

蛋白酶体抑制剂硼替佐米已被用于多种肿瘤的治疗,其最大的毒副作用为周围神经病变,限制了其临床应用.文章简述了硼替佐米所致周围神经病变（BIPN）的病因、危险因素、病理机制、临床表现和分级、检测及评估方法,并介绍了BIPN的防治方法.     

多发性骨髓瘤周围神经病变临床特征分析

目的探讨多发性骨髓瘤周围神经病变(MMPN)患者的临床和神经电生理异常表现。方法回顾性分析2010年3月至2018年6月山西省人民医院诊断的35例MMPN患者的临床资料。所有患者均进行神经电生理检测,包括神经传导速度(NCV)及皮肤交感反应(SSR)。结果 MMPN患者最常见周围神经受累的表现为感觉异常(25例,71%),包括根性疼痛(3例,9%)、双下肢或上肢痛觉减弱(18例,51%)、运动障碍(15例,43%)、双下肢膝反射或踝反射减低或消失(13例,37%)以及自主神经障碍症状(20例,57%)。感觉神经传导速度(SCV)异常和(或)运动神经传导速度(MCV)异常共29例(83%)。上肢NCV异常13例,上肢潜伏期延长5例,波幅降低10例;下肢NCV异常8例,下肢潜伏期延长6例,波幅降低4例。SSR检查发现17例(49%)异常。仅上肢SSR异常8例,上肢潜伏期延长2例,波幅降低7例,波形消失1例;仅下肢SSR异常6例,下肢潜伏期延长1例,波幅降低4例,波形消失2例;上下肢SSR均异常3例。结论 MM最常见的周围神经系统损害表现为"袜子和手套样"分布的感觉减退,自主神经也可累及;NCV检查是诊断MMPN的一种基本方法,SSR对于检测MMPN自主神经障碍有重要作用。     

Managing the neurotoxicity of paclitaxel (Taxol) and docetaxel (Taxotere) with neurotrophic factors

Paclitaxel and the related compound docetaxel are diterpine alkaloids (taxoids) that have demonstrated significant efficacy against a variety of different tumors, including carcinomas of the ovary, breast, head and neck, and lung (1-5). Paclitaxel was originally isolated from the bark of the Pacific yew tree, Taxus brevifolia, during a screening program looking for natural antitumor agents sponsored by the National Cancer Institute in 1971 (6). Before 1993, paclitaxel was referred to as taxol. The Bristol-Myers Squibb Company (Princeton, NJ) registered the name Taxol®, and the generic name paclitaxel was approved. Paclitaxel binds to tubulin and promotes microtubule polymerization (7,8). In tissue culture, paclitaxel causes abnormal bundles of microtubules to form throughout the cytoplasm, disrupting normal cell functions such as proliferation (8). Docetaxel has a similar mechanism of action in that it also binds to the β-subunit of tubulin, inducing polymerization, but may be more potent than paclitaxel (9).