Taxol scientific update |
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Eur J Cancer. 2008 Aug 6.
Aravantinos G, Fountzilas G, Bamias A, Grimani I, Rizos S, Kalofonos HP, Skarlos DV, Economopoulos T, Kosmidis PA, Stathopoulos GP, Briasoulis E, Pectasides D, Samantas E, Timotheadou E, Papadimitriou C, Papanikolaou A, Onyenadum A, Papakostas P, Baf
Agii Anargiri Cancer Hospital, Hellenic Cooperative Oncology Group, Hatzikonstanti 18,115 24 Athens, Greece.
Carboplatin and Paclitaxel versus Cisplatin, Paclitaxel and Doxorubicin for first-line chemotherapy of Advanced Ovarian Cancer: A Hellenic Cooperative Oncology Group (HeCOG) study.
INTRODUCTION: The combination of Carboplatin and Paclitaxel is considered the standard of care as initial chemotherapy for Advanced Ovarian Cancer (AOC). We compared this regimen with the combination of Cisplatin, Paclitaxel and Doxorubicin. PATIENTS AND METHODS: Patients with AOC were randomised to either six courses of Paclitaxel 175mg/m(2) plus Carboplatin 7AUC or Paclitaxel at the same dose plus Cisplatin 75mg/m(2) plus Doxorubicin 40mg/m(2). RESULTS: Analysis was performed on 451 patients. The treatment groups were well balanced with regard to patient and disease characteristics. Performance status (PS) was better in the anthracycline arm. In terms of severe toxicity, the only significant difference between the two groups was the development of febrile neutropaenia in the anthracycline arm. Overall response rate was similar in both groups. With a median follow-up of 57.5 months, a marginal significance towards improved Progression-Free Survival (PFS) was noted in favour of the anthracycline arm, whilst there was no difference in overall survival. In multivariate analysis the hazard of disease progression at any time was significantly decreased by 25.5% for patients of the anthracycline arm. CONCLUSION: The combination of Cisplatin, Paclitaxel and Doxorubicin demonstrates a marginal PFS improvement, but no additional survival benefit when compared with the standard Carboplatin/Paclitaxel regimen.
Int J Cardiol. 2008 Aug 9.
Shinke T, Geva S, Pendyala L, Jabara R, Li J, Chen JP, Venegoni A, Colley K, Klein R, Chronos N, Robinson K, Hou D.
Saint Joseph's Translational Research Institute/Saint Joseph's Hospital of Atlanta, GA, USA.
Low-dose paclitaxel elution by novel bioerodible sol-gel coating on stents inhibits neointima with low toxicity in porcine coronary arteries.
OBJECTIVES: The present study was designed to evaluate a novel bioerodible sol-gel film coated paclitaxel-eluting stent (sol-gel-PES, 3 mug per stent) in a porcine coronary artery model. BACKGROUND: Although current polymer-based PES decrease restenosis, the permanent polymer and bound drug have raised concerns regarding delayed vessel healing and late stent thrombosis. METHODS: Polymer-based PES (poly-PES, n=8), sol-gel-PES (n=15), bare metal (BMS, n=14), and sol-gel film only (sham, n=12), stents were implanted in 17 juvenile pigs. Animals were terminated 28 days post-implant for angiographic restudy and complete histopathologic and histomorphometric analyses. RESULTS: Angiographic late loss was equally reduced for both poly-PES and sol-gel-PES (0.51+/-0.64 and 0.61+/-0.52 mm, respectively) compared to both BMS and sham (0.98+/-0.74 and 1.25+/-0.72 mm, p<0.05). Similarly beneficial results were observed for histomorphometric parameters of neointimal thickness and area, yielding reductions of in-stent stenosis by 43% and 48% for poly-PES, as well as 31% and 37% for sol-gel-PES, vs. BMS and sham, respectively (p<0.05). Re-endothelialization was complete in all groups. Although the inflammatory cell infiltration and intramural thrombus scores were no different between poly- and sol-gel-PES, medial necrosis was increased for poly-PES (p<0.05 vs. all others). CONCLUSIONS: A novel bioerodible sol-gel film coated with low-dose paclitaxel demonstrates less toxicity to the coronary tunica media, while retaining effective inhibition of neointimal formation at 28 days.
Clin Cancer Res. 2008 Aug 15;14(16):5108-15.
Milenic DE, Garmestani K, Brady ED, Baidoo KE, Albert PS, Wong KJ, Flynn J, Brechbiel MW.Milenic DE, Garmestani K, Brady ED, Baidoo KE, Albert PS, Wong KJ, Flynn J, Brechbiel MW.
Authors' Affiliations: Radioimmune and Inorganic Chemistry Section, Radiation Oncology Branch, and Molecular Imaging Program, Center for Cancer Research, National Cancer Institute, NIH.
Multimodality therapy: potentiation of high linear energy transfer radiation with Paclitaxel for the treatment of disseminated peritoneal disease.
PURPOSE: Studies herein explore paclitaxel enhancement of the therapeutic efficacy of alpha-particle-targeted radiation therapy. EXPERIMENTAL DESIGN: Athymic mice bearing 3 day i.p. LS-174T xenografts were treated with 300 or 600 mug paclitaxel at 24 h before, concurrently, or 24 h after [(213)Bi] or [(212)Pb]trastuzumab. RESULTS: Paclitaxel (300 or 600 mug) followed 24 h later with [(213)Bi]trastuzumab (500 muCi) provided no therapeutic enhancement. Paclitaxel (300 mug) administered concurrently with [(213)Bi]trastuzumab or [(213)Bi]HuIgG resulted in median survival of 93 and 37 days, respectively; no difference was observed with 600 mug paclitaxel. Mice receiving just [(213)Bi]trastuzumab or [(213)Bi]HuIgG or left untreated had a median survival of 31, 21, and 15 days, respectively, 23 days for just either paclitaxel dose alone. Paclitaxel (300 or 600 mug) given 24 h after [(213)Bi]trastuzumab increased median survival to 100 and 135 days, respectively. The greatest improvement in median survival (198 days) was obtained with two weekly doses of paclitaxel (600 mug) followed by [(213)Bi]trastuzumab. Studies were also conducted investigating paclitaxel administered 24 h before, concurrently, or 24 h after [(212)Pb]trastuzumab (10 muCi). The 300 mug paclitaxel 24 h before radioimmunotherapy (RIT) failed to provide benefit, whereas 600 mug extended the median survival from 44 to 171 days. CONCLUSIONS: These results suggest that regimens combining chemotherapeutics and high linear energy transfer (LET) RIT may have tremendous potential in the management and treatment of cancer patients. Dose dependency and administration order appear to be critical factors requiring careful investigation.
Gan To Kagaku Ryoho. 2008 Aug;35(8):1379-82.
Fukuda N, Sugiyama Y, Wada J, Niki M, Nomoto T.
Dept. of Surgery, Mizonokuchi Hospital, Teikyo University School of Medicine.
[A case of advanced gastric cancer successfully treated with s-1 and Paclitaxel followed by curative resection.] [Article in Japanese]
A 59-year-old man diagnosed with Stage IV advanced gastric cancer due to pancreatic invasion(T4)and splenic hilum lymph node metastasis(N3)was initially treated with neoadjuvant chemotherapy using S-1 and CDDP. However, it was discontinued because the tumor marker increased after 1 course. Instead of S-1 and CDDP, S-1 and paclitaxel were then administered. After 4 courses, CT scan revealed reduced tumor size and the disappearance of splenic hilum lymph node swelling that indicated PR of the chemotherapy. Moreover, serum CEA was remarkably decreased to 77 ng/mL from 1,092 ng/mL. He could undergo subtotal gastrectomy(Billroth II)with lymph node dissection(D2)and cholecystectomy. Histopathological examination revealed Stage II(pT2(SS), pN1, CY0, ly1, v2)advanced gastric cancer that showed good effect of S-1 and paclitaxel. At this writing(October 2007), the patient has remained free of disease for more than 1 year and 6 months with good nutrition. Neoadjuvant chemotherapy using S-1 and paclitaxel for advanced gastric cancer seems to have been effective.
J Clin Oncol. 2008 Aug 20;26(24):3950-7.
Albain KS, Nag SM, Calderillo-Ruiz G, Jordaan JP, Llombart AC, Pluzanska A, Rolski J, Melemed AS, Reyes-Vidal JM, Sekhon JS, Simms L, O'Shaughnessy J.
Loyola University Chicago Stritch School of Medicine, Cardinal Bernardin Cancer Center, 2160 S First Ave, Maywood, IL 60153, USA.
Gemcitabine plus Paclitaxel versus Paclitaxel monotherapy in patients with metastatic breast cancer and prior anthracycline treatment.
PURPOSE: The objective of this phase III global study was to compare the efficacy of gemcitabine plus paclitaxel (GT) versus paclitaxel in patients with advanced breast cancer. It was designed as a pivotal study for the approval of G for a breast cancer treatment indication. PATIENTS AND METHODS: Patients who relapsed after adjuvant anthracyclines were randomly assigned to gemcitabine,1,250 mg/m(2) days 1 and 8 plus paclitaxel, 175 mg/m(2) on day 1; or, to paclitaxel at same dose on day 1 (both arms administered every 21 days, unblinded). The primary end point was overall survival (OS) and secondary end points were time to progression (TTP), response rate (RR), progression-free survival, response duration, and toxicity. This final OS analysis was planned at 380 deaths. RESULTS: A total of 266 patients were randomly assigned to GT and 263 to paclitaxel. Median survival on GT was 18.6 months versus 15.8 months on paclitaxel (log-rank P = . 0489), with an adjusted Cox hazard ratio of 0.78 (95% CI, 0.64 to 0.96; P = .0187). The TTP was longer (6.14 v 3.98 months; log-rank P = .0002) and the RR was better (41.4% v 26.2%; P = .0002) on GT. There was more grade 3 to 4 neutropenia on GT and grade 2 to 4 fatigue and neuropathy were slightly more prevalent on GT. CONCLUSION: This phase III study documents a role for gemcitabine in advanced breast cancer after anthracycline-based adjuvant therapy. The results establish GT as a reasonable choice for women who require cytoreduction with manageable toxicities and validate ongoing testing of GT in the adjuvant setting.
Neoplasia. 2008 Sep;10(9):964-72.
Park DC, Yeo SG, Wilson MR, Yerbury JJ, Kwong J, Welch WR, Choi YK, Birrer MJ, Mok SC, Wong KK.
Department of Obstetrics and Gynecology, Saint Vincent's Hospital, The Catholic University of Korea, Suwon, Republic of Korea.
Clusterin interacts with Paclitaxel and confer Paclitaxel resistance in ovarian cancer.
Optimal debulking followed by chemotherapy is the standard treatment of managing late-stage ovarian cancer, but chemoresistance is still a major problem. In this study, we compared expression profiles of primary tumor tissue from five long-term (>8 years) and five short-term (<2 years) ovarian cancer survivors and identified clusterin as one of the genes that were significantly up-regulated in short-term survivors. We then evaluated the prognostic significance of clusterin and its possible correlation with chemoresistance in ovarian cancer by immunohistostaining of clusterin in 62 tumor samples from patients with stage III, high-grade serous ovarian cancer. After adjusting for debulking status and age, Cox regression analyses showed that high levels of clusterin expression correlate with poor survival (hazard ratio, 1.07; 95% confidence interval, 1.002-1.443; P = .04). We also investigated clusterin in paclitaxel resistance by modulating the endogenous clusterin expression in ovarian cancer cells and treating the cells with purified clusterin. Results indicate that high-clusterin-expressing ovarian cancer cells are more resistant to paclitaxel. Moreover, exposing ovarian cancer cells to exogenous clusterin increases cells' resistance to paclitaxel. Finally, using size exclusion chromatography and fluorescently labeled paclitaxel, we demonstrated that clusterin binds to paclitaxel. In summary, our findings suggest that high levels of clusterin expression increase paclitaxel resistance in ovarian cancer cells by physically binding to paclitaxel, which may prevent paclitaxel from interacting with microtubules to induce apoptosis. Thus, clusterin is a potential therapeutic target for enhancing chemoresponsiveness in patients with a high-level clusterin expression.
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Drug category:Anti-cancer drugs
 Taxol scientific update
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