Taxol Group Research Articles

A Comparative Analysis on the Efficacy and Safety of Intaxel® and Taxol® in Advanced Metastatic Breast Cancer

Among the presently available cytotoxic drugs, paclitaxel, in combination with doxorubicin and carboplatin, come under the highly active therapy for metastatic breast cancer. Between the two brands of paclitaxel (Intaxel, which is marketed by Fresenius Kabi and Taxol, the original paclitaxel which is manufactured by BMS) the similarity has not been evaluated in clinical trial settings till date. This prospective, controlled, randomized, multicentre, open-label phase IV study was planned to compare the safety and efficacy of Intaxel with Taxol, when they were used in combination with carboplatin or doxorubicin, as a second line treatment for metastatic breast cancer. Fourty nine eligible patients were randomized to receive Intaxel or Taxol with either doxorubicin or carboplatin. The patients who had received a prior anthracycline based chemotherapy were randomized to the paclitaxel/carboplatin arm. The patients were evaluated in three phases i.e. at baseline, during the treatment and at follow up for the tumour response, the time period till the disease progression and the toxicity. The time till the disease progression was assessed by the Kaplan-Meier method. The continuous and categorical variables were assessed by using the ANOVA test and Fisher's exact test, respectively. After 3 cycles, an objective response rate of 55.56% (CR = 3, PR = 7) was noted in the Intaxel group and that of 59.09% (CR = 1, PR = 12) was noted in the Taxol group. After 6 cycles, an objective response rate of 50% was noted in both the groups. No significant difference was observed in the response rate of the two groups after 3 cycles (p > 0.05) and at the end of the treatment (p > 0.05). The patients who received Intaxel had a lower incidence of thrombocytopaenia (p = 0.0146) and neurosensory loss (p = 0.008) as compared to those who received Taxol. The results of this study demonstrated that the safety and efficacy of Intaxel and Taxol are equivalent when they are used in combination with other cytotoxic agents as the second line of treatment for metastatic stage IV breast cancer.

Effects of combining Taxol and cyclooxygenase inhibitors on the angiogenesis and apoptosis in human ovarian cancer xenografts

The present study aimed to investigate the combined effects of Taxol and cyclooxygenase (COX) inhibitors on angiogenesis and cell apoptosis of SKOV-3 human ovarian carcinoma cell xenograft-bearing mice. The experiments were continued for 28 days. Animals were treated with 3 mg/kg SC-560 (a COX-1-selective inhibitor) alone, 100 mg/kg celecoxib (a COX-2-selective inhibitor) alone or SC-560/celecoxib by gavage twice a day, 20 mg/kg Taxol alone intraperitoneally once a week or in combination with SC-560 or celecoxib or SC-560/celecoxib/Taxol for three weeks. The mRNA levels of vascular endothelial growth factor (VEGF) was determined by reverse transcription-polymerase chain reaction (RT-PCR). The microvessel density (MVD) of ovarian carcinoma was determined by immunohistochemistry with anti-CD34 as the label. The apoptotic index was detected by the terminal deoxynucleotidyl transferase-mediated deoxyuridine triphosphate nick end labeling (TUNEL) method. The MVD value and apoptotic index in the SC-560/Taxol group were notably inhibited compared with the Taxol group (P<0.001). Moreover, the VEGF mRNA levels, MVD value and apoptotic index in the SC-560/Taxol group were significantly different from the celecoxib/Taxol group (P<0.05, P<0.05 and P<0.001, respectively). The present study demonstrated that SC-560 enhances the anti-angiogenic and pro-apoptotic effects of Taxol and these effects are better than with celecoxib.

Effects of taxol on in-vitro matured bovine oocyte vitrification

The experiment was designed to assess the effectiveness of Taxol on cryopreserving bovine MII oocytes using straws as the carrier system for vitrification. Bovine matured oocytes were vitrified in droplets of cryoprotectants with or without 1 µM Taxol (droplet 1: TCM-199, 10% FBS, 5% FCS, 10% ethylene glycol (EG), 10% dimethyl sulfoxide (DMSO) for 45s; droplet 2: TCM-199, 10% FBS, 5% FCS, 20% ethylene glycol (EG), 20% dimethyl sulfoxide (DMSO), 0.5 M sucrose for 25s) on straws. After thawing, the oocytes were cultured in IVM medium in 2 hours and oocytes were assessed by ratio of survival oocytes (SO) to vitrified oocytes (VO); survival oocytes (SO) to colected oocytes (CO) and the proportion of normal nuclear oocytes (NNO). The results showed that the ratio of SO to VO and SO to CO in Taxol groups were slightly higher (62.74 ± 2.74% vs. 59.81 ± 1.75% and 70.65 ± 2.44% vs. 67.66 ± 2.12%, P &lt; 0.05); the ratio of NNO in both taxol-pretreatment groups and non-taxol-pretreatment groups (control) had no significant difference (78.14 ± 4.01% vs. 77.89 ± 2.13%, P &gt; 0.05). The results of this experiment indicated that taxol pretreatment affects the survival ratio of vitrified bovine oocytes but there was no significant evidence on preventing abnormal nuclear oocytes

Comparison of Effect between Concurrent Radiochemotherapy with Weekly Taxol Versus with Cisplatin and 5-Fu on Medium and Advanced Stage Cervical Cancer

Objective To investigate better chemothrapy method of concurrent chemothrapy and radiotherapy on medium and advanced stage cervical cancer.Methods The 64 cases were randomly drawn from the patients with medium and advanced stage cervial cancer treated by concurrent chemotherapy and radiotherapy and were divided into 2 groups:Cisplatin combined 5-Fu group(32 cases) and Taxol group(32 cases).The curative effective and side effect were observed and compared.Results Effective rate was87.5% and 93.75%in Cisptatin combined 5-Fu group and Taxol group after radiotherapy,respectively,with no significant difference between two groups(P0.05).The three-year survival rates were 58.1% and 62.5% in the two groups respectively,with no significant difference between two groups(P0.05).There was obviously side-effect of digestive tract and kidney damage in Cisplatin combined 5-Fu group compared to Taxol group.While bone marrow inhibition and neurotoxicity were more obvious in Taxol group than those in Cisplatin combined 5-Fu group(P0.05).Conclusion There was no significant difference in effective and three-year survival rate between the two groups.But different chemotherapy programs with different side-effect.We can choose the optimal chemotherapy program individually according the situation of different patients.

The effects of pre and post vitrification taxol treatment on bovine immature oocyte.

Summary The aim of the present study was to find the effects of pre and post vitrification taxol treatment on bovine immature cumulus oocyte complexes (COCs). Bovine ovaries were collected from the local slaughterhouse in a container with 30-37°C physiologic saline and supplemented with antibiotics. The grade A aspirated COCs were assigned to 6 experimental groups; The 1st group was control (n=100) in which the COCs were subjected to in vitro maturation (IVM) in oocyte maturation medium (OMM). The 2nd group was the COCs (n=51) that were exposed to vitrification and warming solutions and then subjected to IVM. The 3rd group was the COCs which were incubated in OMM contained taxol (1 µM, n=51) for 20 min then transferred to IVM. The 4th group was the COCs (n=50) that were vitrified, warmed and transferred to IVM. The 5th group (n=57) was the COCs which were incubated in OMM containing taxol (1 µM for 20 min), vitrified (solutions with 1 µM taxol), warmed and transferred to IVM. The last group was the COCs (n=58) that were vitrified and warmed, then were incubated in maturation medium containing taxol (1 µM for 20) and, finally, were transferred to IVM. The COCs of all groups were incubated in OMM for 24 h under a humified (95%) condition with a temperature of 39°C and 5% CO2. Oocyte maturation was not affected by exposing the COCs to vitrification solution or taxol groups compared to control (P>0.05). Vitrification reduced the oocyte maturation rate compared to control (P<0.05). Taxol treatment (before and after vitrification) did not improve the bovine oocyte maturation rate compared to control (P<0.05). The results have shown no beneficial effect of taxol on vitrification of bovine immature oocytes.

In Vivo Anti-Tumor Activity of Polypeptide HM-3 Modified by Different Polyethylene Glycols (PEG)

HM-3, designed by our laboratory, is a polypeptide composed of 18 amino acids. Pharmacodynamic studies in vivo and in vitro indicated that HM-3 could inhibit endothelial cell migration and angiogenesis, thereby inhibiting tumor growth. However, the half-life of HM-3 is short. In this study, we modified HM-3 with different polyethylene glycols (PEG) in order to reduce the plasma clearance rate, extend the half-life in the body, maintain a high concentration of HM-3 in the blood and increase the therapeutic efficiency. HM-3 was modified with four different types of PEG with different molecular weights (ALD-mPEG5k, ALD-mPEG10k, SC-mPEG10k and SC-mPEG20k), resulting in four modified products (ALD-mPEG5k-HM-3, ALD-mPEG10k-HM-3, SC-mPEG10k-HM-3 and SC-mPEG20k-HM-3, respectively). Anti-tumor activity of these four modified HM-3 was determined in BALB/c mice with Taxol as a positive control and normal saline as a negative control. Tumor weight inhibition rates of mice treated with Taxol, HM-3, ALD-mPEG5k-HM-3, ALD-mPEG10k-HM-3, SC-mPEG10k-HM-3 and SC-mPEG20k-HM-3 were 44.50%, 43.92%, 37.95%, 31.64%, 20.27% and 50.23%, respectively. Tumor inhibition rates in the Taxol, HM-3 and SC-mPEG20k-HM-3 groups were significantly higher than that in the negative control group. The efficiency of tumor inhibition in the SC-mPEG20k-HM-3 group (drug treatment frequency: once per two days) was better than that in the HM-3 group (drug treatment frequency: twice per day). In addition, tumor inhibition rate in the SC-mPEG20k-HM-3 group was higher than that in the taxol group. We conclude that SC-mPEG20k-HM-3 had a low plasma clearance rate and long half-life, resulting in high anti-tumor therapeutic efficacy in vivo. Therefore, SC-mPEG20k-HM-3 could be potentially developed as new anti-tumor drugs.

Abstract 1654: Evaluation of combination of low doses of chemotherapy and anti-stathmin therapy in mammary tumors

Abstract AIM: Stathmin, a founding member of a family of microtubule-destabilizing proteins, is expressed at high levels in breast cancer (BC) and provides an attractive target for BC therapy. We previously showed that stathmin inhibition could suppress the malignant phenotype of BC cells in vitro and in vivo. Here, we tested whether the therapeutic efficacy of stathmin inhibition could be further enhanced by combining it with standard chemotherapeutic agents in vivo. METHODS: We used a bicistronic adenoviral (Ad) vector that coexpresses green fluorescent protein (GFP) and a ribozyme (Rz) that targets human stathmin mRNA. Thirty-five female nude mice were injected orthotopically in the mammary fat pad of two of the mammary glands (# 4), each with 5×10e6 MDA-MB-231 cells/gland. We initiated treatment after the mice developed tumors of 0.3-0.4 cm in size. Mice bearing established MDA-MB-231 xenografts were divided into 7 groups of 5 mice each. Group I was injected with PBS alone. Groups 2, 3 &amp; 4 were injected with control Ad.GFP (1×10e8 vp/injection). At the same time, adriamycin (5 mg/kg/injection) &amp; taxol (5 mg/kg/injection) was co-administered in groups 3 &amp; 4 respectively. Similarly groups 5, 6 &amp; 7 were injected with Ad.Rz.GFP (1×10e8 vp/injection) anti-stathmin adenovirus. Groups 6 &amp; 7 were also given adriamycin &amp; taxol respectively at the same doses. The adenovirus &amp; the drugs were administered at subtherapeutic doses that were selected based on dose response experiments. All drugs were injected i.p. &amp; the adenoviruses were injected intratumorally once a week for a total of 3 injections. Changes in tumor growth were monitored in the different groups for another 6-8 weeks. RESULTS: Tumors in animals injected with PBS (group 1) or the control Ad.GFP (group 2) continued to grow to larger sizes. The growth of the tumors in animals treated with low doses of drugs alone (groups 3 &amp; 4) or Ad.Rz.GFP alone (group 5) was only modestly slowed compared to control groups. When animals were treated with a combination of low doses of anti-stathmin therapy &amp; adriamycin (group 6), the rate of tumor growth was much slower than animals treated with drug alone or anti-stathmin Rz alone. Interestingly, when animals were treated with a combination of low doses of anti-stathmin therapy &amp; taxol (group 7), tumor regression (greater than or equal to 40%) was observed in 60% of the tumors &amp; 40% of the tumors were stabilized. Although inhibition of tumor growth was observed in both the combination treatment groups compared to groups treated with single agent alone, combination of anti-stathmin therapy &amp; taxol had a more profound inhibition of tumorigenicity, since both agents target the same microtubule pathway. In contrast, the activity of adriamycin does not result from direct interactions with microtubules &amp; the mitotic spindle. These findings are highly relevant for the treatment of BC, since taxol is one of the most active chemotherapeutic agents used in BC care. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 102nd Annual Meeting of the American Association for Cancer Research; 2011 Apr 2-6; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2011;71(8 Suppl):Abstract nr 1654. doi:10.1158/1538-7445.AM2011-1654

Chemometric analysis of metabolism disorders in blood plasma of S180 and H22 tumor‐bearing mice by high performance liquid chromatography‐diode array detection

AbstractThe aim of this paper is to characterize metabolism disorders in Kunming mice induced by S180 and H22 tumor cells. Metabolic fingerprint based on high performance liquid chromatography‐diode array detector (HPLC‐DAD) was developed to map the disturbed metabolic responses. In vivo testing of the antitumor activity of paclitaxel (Taxol) was carried out by inhibiting the growth of S180 and H22 tumor cells. Based on 27 common peaks, principal component analysis (PCA) and partial least squares‐discriminant analysis (PLS‐DA) were used to distinguish the abnormal from control and to find significant endogenous compounds (SECs) which have significant contributions to classification. The tumor growth inhibition ratios (TIRs) of Taxol groups were used to validate the predictive accuracies of the PLS‐DA models. The predictive accuracies of PLS‐DA models for S180 and H22 tumor model groups were 97.6 and 100%, respectively. Nine (S180) and seven (H22) SECs were discovered, including uric acid and cytidine. In addition, the correlations between relative tumor weights (RTWs) and chromatographic data for the SECs were significant (p &lt; 0.05). Investigations on the stability and precision of the established metabolic fingerprints demonstrate that the experiment is well controlled and reliable. This work shows that the platform of HPLC‐DAD coupled with chemometric methods provides a promising method for the study of metabolism disorders induced by tumor cells. Copyright © 2011 John Wiley &amp; Sons, Ltd.

Effcet-site EC50 for etomidate by target-controlled infusion at loss of consciousness in breast cancer patients who accepted adjuvant chemotherapy

Objective To determine the Effcet-site EC50 of etomidate to cause loss of consciousness in patients who accepted adjuvant chemotherapy. Methods According to the therapeutic before their operation,ninety breast cancer patients undergoing elective operations were allocated to 3 groups:non-adjuvant chemotherapy group (group Ⅰ ,n=30),Taxol group (group Ⅱ ,n=30),Adriamycine+Cyclophosphamide+5-Fu group (group Ⅲ ,n=30). TCI etomidate was given byup and down method for 10 min in each group. The ration of two close effect-site concentrations was 1.25. Record the state of consciousness of each patient.Results The EC50 in non-adjuvant chemotherapy group was 0.58 mg/L,the 95% confidence level was 0.53 mg/L～0.63 mg/L. The EC50 in Taxol group was 0.34 mg/L,the 95% confidence level was 0.32 mg/L～0.37 mg/L. The EC50 in non-adjuvant chemotherapy group was0.35μg/ml,the 95% confidence level was0.32 mg/L～0.39 mg/L.Conclusion The EC50 of etomidate to cause loss of consciousness in adjuvant chemotherapy group is low than control group. Key words: Etomidate,TCI; Unconsciousness; EC50

Combined Chemo-immunotherapy as a Prospective Strategy To Combat Cancer: A Nanoparticle Based Approach

The prime objective of this study was to develop a combined chemo-immunotherapeutic formulation which could directly kill cancer cells as well as activate the immunosuppressed tumor microenvironment to mount a robust antitumor immune response. Paclitaxel (PTX) and SP-LPS (nontoxic derivative of lipopolysaccharide) were selected as anticancer drug and immunostimulant respectively. Poly(lactic-co-glycolic acid) (PLGA) based PTX and SP-LPS containing nanoparticles (TLNP) were prepared by the double-emulsion method (w/o/w) and characterized in terms of size, zeta potential and transmission electron microscopy (TEM). The release behavior of PTX and SP-LPS from the TLNP exhibited a biphasic pattern characterized by an initial burst followed by slow continuous release. In vitro anticancer activity of TLNP was found to be higher compared to PTX when studied in a tumor cell-splenocyte coculture system. TLNP activated murine monocytes induced the secretion of various proinflammatory cytokines. After iv administration of TLNP in tumor bearing C57BL/6 mice, the amount of PTX in the tumor mass was found to be higher in TLNP treated mice as compared to commercial Taxol group at all time points studied. In vitro studies suggest that nanoparticles containing PTX and SP-LPS have both direct cytotoxicity and immunostimulatory activity. Hence this might have potential as a chemo-immunotherapeutic formulation against cancer with advantage over present day chemotherapy with Taxol, in terms of tumor targeting, less toxicity and immunostimulation.

Taxol inhibits stretch-induced electrophysiological alterations in isolated rat hearts with acute myocardial infarction

Mechanosensitive channels have been determined to work as transducers of mechanoelectric feedback in the heart, which is associated with the generation of arrhythmias. Recent studies have investigated the role of the cytoskeleton in ion channels control. This study explored the ability of taxol to inhibit stretch-induced electrophysiological alterations in the ischemic myocardium. Thirty-two Wistar rats were randomly divided into four groups: normal control group (n=9), taxol group (n=7), myocardial infarction (MI) group (n=9), and MI+taxol group (n=7). After Langendorff perfusion, the isolated hearts were stretched for 5 s by balloon inflation to 0.2 or 0.3 mL. The effects of stretching on 90% monophasic action potential duration (MAPD(90)), premature ventricular beats (PVB), and ventricular tachycardia (VT) were observed for 30 s. Stretching increased MAPD(90) in both the normal control and MI groups, but MAPD(90) increased more in the MI group for the same degree of stretch. Taxol (5 mumol L(-1)) had no effect on MAPD(90) under baseline, unstretched conditions, but MAPD(90) in the taxol group was slightly increased after stretching compared with the normal control group (P>0.05). However, taxol reduced MAPD(90) in infarcted myocardium (P<0.05 at DeltaV=0.3 mL). The incidences of PVB and VT in the MI group were higher than in the normal control group (both P<0.01). Taxol had no effect on the occurrence of arrhythmias in normal myocardium, but it inhibited PVB and VT in infarcted hearts (both P<0.01). Thus changes in MAPD and the occurrence of arrhythmias caused by mechanical stretching of the myocardium could be inhibited by taxol in isolated rat hearts during AMI, indicating the involvement of tubulin in mechanoelectric feedback in AMI.

Paclitaxel ameliorates fibrosis in hepatic stellate cellsviainhibition of TGF-β/Smad activity

To investigated if paclitaxel can attenuate hepatic fibrosis in rat hepatic stellate cells (RHSCs). RHSCs were cultured in vitro and randomly assigned to four groups: normal control group (treated only with Dulbecco's Modified Eagle's Medium), Taxol group (200 nmol/L paclitaxel was added to the cell culture), transforming growth factor (TGF)-beta group (5 ng/mL recombinant human TGF-beta1 was added to the cell culture), and TGF-beta + Taxol group. TGF-beta signaling cascade and status of various extracellular matrix proteins were evaluated by real time reverse transcriptase polymerase chain reaction and Western blotting. The paclitaxel treatment markedly suppressed Smad2/3 phosphorylation. This was associated with attenuated expression of collagen I and III and fibronectin in RHSCs. These data indicate that 200 nmol/L paclitaxel ameliorates hepatic fibrosis via modulating TGF-beta signaling, and that paclitaxel may have some therapeutic value in humans with hepatic fibrosis.

The protective effect of beta-1,3-D-glucan on taxol-induced hepatotoxicity: a histopathological and stereological study

The present study was undertaken to determine the histopathological and quantitative effects of the antineoplastic agent, taxol, on the liver. The protective effects of the strong antioxidant, β-1,3-D-glucan, against liver damage induced by taxol were also investigated. Mice were divided into four main treatment groups: control, taxol, β-1,3-D-glucan, and taxol+β-1,3-D-glucan. Each group was further subdivided into six subgroups, according to time of sacrifice (6, 12, 24, and 48 hours and 7 and 14 days). After the experiments, quantitative and histopathological changes in liver were examined by light microscopy and modern stereological systems. Stereological results indicated that the portal triad area of the taxol group was significantly reduced, compared to the controls at 12 hours, whereas in the taxol plus β-glucan and β-glucan groups, the means were similar to those of the controls. There was no statistically significant difference in the numerical density of hepatocytes with time between the control and other groups. The histopathological results indicated an increased, time-dependent degeneration and necrosis of the liver tissues in mice in the taxol group. Regenerative changes in livers of mice in the taxol plus β-glucan group were observed, when compared with those of the taxol group. Stereological and histopathological results suggest that β-glucan may reduce taxol-induced hepatic damage by blocking the change in the portal area and suppressing processes leading to necrosis.

Novel self-assembling PEG-p-(CL-co-TMC) polymeric micelles as safe and effective delivery system for Paclitaxel

Paclitaxel (PTX) is an effective anti-cancer drug currently used to treat a wide variety of cancers. Unfortunately, nonaqueous vehicle containing Cremophor EL is associated with serious clinical side effects. This work aimed to evaluate the ability of polymeric micelles to (i) solubilize PTX without Cremophor EL and to be used as a (ii) safe and (iii) effective delivery system for PTX. Hence, we developed novel self-assembling poly(ethyleneglycol)(750)-block-poly(epsilon-caprolactone-co-trimethylenecarbonate) (PEG-p-(CL-co-TMC)) polymeric micelles which form micelles spontaneously in aqueous solution. The solubility of PTX increased up to three orders of magnitude. The PTX-loaded micelles showed a slow release of PTX with no burst effect. The HeLa cells viability assessed by the MTT test was lower for PTX-loaded micelles than for Taxol (IC(50) 10.6 vs. 17.6 microg/ml). When solubilized in micelles, PTX induced apoptosis comparable with Taxol. The maximum tolerated doses (MTD) of PTX-loaded micelles and Taxol in mice were 80 mg/kg and 13.5mg/kg, respectively, after intraperitoneal administration; and 45 mg/kg and 13.5mg/kg, respectively, after intravenous administration. Similar anti-tumor efficacy of PTX-loaded micelles and Taxol was observed at the dose of 13.5mg/kg on TLT-tumor-bearing mice, while the body weight loss was only observed in Taxol group. However, as higher dose was tolerated (80 mg/kg - IP), a higher growth delay was induced with PTX-loaded micelles. These results demonstrated that PTX-loaded self-assembling micelles present a similar anti-tumor efficacy as Taxol, but significantly reduced the toxicity allowing the increase in the dose for better therapeutic response.

Mitochondrial behaviors in the vitrified mouse oocyte and its parthenogenetic embryo: effect of Taxol pretreatment and relationship to competence

To investigate the effect of Taxol pretreatment on mitochondrial behaviors in vitrified mouse mature oocytes and their parthenogenetic embryos. Experimental animal study. University research laboratory and state key laboratory. Sexually mature female Kunming white strain mice. Taxol before vitrification group (Tax). Oocytes were pretreated with M(2) containing 1 mmol/L Taxol for 2 minutes at 37C and then vitrified-warmed using the OPS vitrification procedure. Both ED solution and EDFS30 solution contained 1 mmol/L Taxol. Mitochondrial behaviors examined by fluorescence microscopy technology and fluorescence recovery after photobleaching (FRAP) technology. In the control group, mitochondria were homogeneously distributed, in slow movement in oocytes, and perinuclearly distributed in 42.6% (n = 115) of their parthenogenetic two-cell embryos. Mitochondria from the toxicity group showed similar localization and movement to those of the control group, but not in the vitrification group. The perinuclear mitochondrial localization pattern of two-cell embryos was statistically significantly lower in both the toxicity (27.2%) and vitrification groups (19.8%) than in the control group. After parthenogenetic activation, the blastocyst formation rate of oocytes in the treated groups (28.1 to 48.6%) was statistically significantly lower than that of control (61.2%), but the rate of Taxol group (47.9%) was statistically significantly higher than that in the vitrification group (28.1%). Taxol pretreatment before vitrification helps to reduce the mitochondrial disturbance induced by vitrification in oocytes and their parthenogenetic early-stage embryo.

Carcinosarcoma of the ovary

The objective of this study was to evaluate the treatment and outcome in patients with ovarian carcinosarcoma. The Tumor Board Registry was reviewed for patients with ovarian carcinosarcoma treated at our institution from June 1993 to December 2004. The medical records were retrospectively analyzed with emphasis on cytoreduction, cytotoxic regimens, progression-free interval, and survival. Twenty-two patients were identified. All but two presented with advanced stage disease. The median survival for the entire cohort was 38 months. Median survival was 46 months for 18 optimally debulked (&lt;1 cm) patients and 27 months for four suboptimally debulked (&gt;1 cm) patients. Six patients were treated with optimal cytoreduction and adjuvant cisplatin (40 mg/m2× 1 day) and ifosfamide (1200 mg/m2/day × 4 days) every 28 days. Median progression-free interval in the cisplatin and ifosfamide group was 13 months, and median survival was 51 months. The combination of carboplatin (AUC 5) and taxol (175 mg/m2) every 21 days was administered to four patients as first-line chemotherapy following optimal cytoreduction. In the carboplatin and taxol group, median progression-free interval was 6 months and median survival was 38 months. The difference in survival between the cisplatin and ifosfamide group and the carboplatin and taxol group was not statistically significant (P= 0.48). In conclusion, patients with ovarian carcinosarcoma usually present with advanced stage disease. Treatment consists of optimal cytoreduction and chemotherapy. The most effective cytotoxic regimen remains to be determined. First-line cisplatin and ifosfamide or carboplatin and taxol can achieve survival rates observed in epithelial ovarian cancer.

Carcinosarcoma of the ovary

The objective of this study was to evaluate the treatment and outcome in patients with ovarian carcinosarcoma. The Tumor Board Registry was reviewed for patients with ovarian carcinosarcoma treated at our institution from June 1993 to December 2004. The medical records were retrospectively analyzed with emphasis on cytoreduction, cytotoxic regimens, progression-free interval, and survival. Twenty-two patients were identified. All but two presented with advanced stage disease. The median survival for the entire cohort was 38 months. Median survival was 46 months for 18 optimally debulked (<1 cm) patients and 27 months for four suboptimally debulked (>1 cm) patients. Six patients were treated with optimal cytoreduction and adjuvant cisplatin (40 mg/m(2)x 1 day) and ifosfamide (1200 mg/m(2)/day x 4 days) every 28 days. Median progression-free interval in the cisplatin and ifosfamide group was 13 months, and median survival was 51 months. The combination of carboplatin (AUC 5) and taxol (175 mg/m(2)) every 21 days was administered to four patients as first-line chemotherapy following optimal cytoreduction. In the carboplatin and taxol group, median progression-free interval was 6 months and median survival was 38 months. The difference in survival between the cisplatin and ifosfamide group and the carboplatin and taxol group was not statistically significant (P= 0.48). In conclusion, patients with ovarian carcinosarcoma usually present with advanced stage disease. Treatment consists of optimal cytoreduction and chemotherapy. The most effective cytotoxic regimen remains to be determined. First-line cisplatin and ifosfamide or carboplatin and taxol can achieve survival rates observed in epithelial ovarian cancer.

Antitumor Activity of Hydrophilic Paclitaxel Copolymer Prodrug Using Locoregional Delivery in Human Orthotopic Non–Small Cell Lung Cancer Xenograft Models

Paclitaxel (Taxol) has demonstrated clinical activity in non-small-cell lung cancer (NSCLC), but its use has not led to marked improvements in survival. This ineffectiveness can in part be attributed to inadequate delivery of effective drug levels to the lung via systemic administration and to drug resistance mechanisms. Locoregional drug administration and the use of drug copolymers are possible approaches to address these issues. In this study, we evaluated the activity of a poly(L-glutamic acid)-paclitaxel (PGA-TXL) formulation administered by intratracheal injection to mice bearing orthotopic human NSCLC tumors (H460, H358). H460 cells were found to be sensitive to paclitaxel and PGA-TXL in vitro, in a time- and concentration-dependent manner. In preliminary acute toxicity studies, PGA-TXL administered by intratracheal injection was found to be much less toxic than paclitaxel, as anticipated. Mice into which H460 cells had been implanted by intratracheal injection were given single-dose intratracheal treatments with paclitaxel (1.2 or 2.4 mg/kg) or with PGA-TXL (15 mg/kg, paclitaxel equivalents) 1 week later. When the mice were sacrificed at up to 65 days after tumor implantation, they were evaluated grossly for tumor at bronchial, neck, and lung sites. Control mice had tumors in 60% of all three sites, and all of the control mice had tumors in at least one site. The low- and high-dose Taxol groups had fewer incidences at these three sites (27-33%) and 60-80% of these mice had tumors in at least one site. The PGA-TXL mice displayed a low (13%) incidence at these sites, and only 40% had detectable tumors. In a subsequent survival study with the intratracheal H358 model, control mice had a mean life span of 95 days, whereas both the intratracheal Taxol (2.5 mg/kg, every 7th day for three doses) and the intratracheal PGA-TXL (20 mg/kg, paclitaxel equivalents, every 7th day for three doses) groups had improved survival (mean life spans: 133.5 and 136.5 days, respectively). In pilot studies intended to compare the feasibility of the development of paclitaxel aerosols suitable for clinical application, based either on Cremophor solutions or on PGA backbones, only the latter gave acceptable particle size distributions and flow rates. These results encourage the development and application of Cremophor-free copolymer formulations of paclitaxel for locoregional treatment (e.g., as aerosol) of endobronchial malignant diseases.

Combined modality radioimmunotherapy with Taxol and 90Y-Lym-1 for Raji lymphoma xenografts.

Despite effective therapies for non-Hodgkin's lymphoma (NHL), the majority of patients are not cured. Radioimmunotherapy (RIT) has shown good results in preclinical and clinical trials even in patients that are non-responsive to standard chemotherapy. To make RIT more effective, agents such as paclitaxel (Taxol), that can enhance radiation effects, are being tested. Nude mice bearing human Burkitt's lymphoma (Raji) xenografts were treated with: 1) 150 or 200 microCi (5.5 or 7.3 MBq) of 90Y-2IT-BAD-Lym-1 alone, 2) 600 micrograms of Taxol alone, 3) 150 or 200 microCi of 90Y-2IT-BAD-Lym-1 plus 600 micrograms of Taxol given 24 hours after RIT, or 4) no treatment. Tumor size, survival, mouse weight and blood counts were monitored to assess efficacy and toxicity. Survival for mice treated in this 84 day trial was: 71% for 90Y-2IT-BAD-Lym-1 (200 microCi) plus Taxol, 29% for Taxol alone, 6% for 90Y-2IT-BAD-Lym-1 (200 microCi) alone and 14% in the untreated group. Average tumor volume in the 90Y-2IT-BAD-Lym-1 (200 microCi) plus Taxol group was reduced by 89 and 99% compared to the RIT alone and Taxol alone groups, respectively. Mice treated with 150 microCi had less toxicity than those treated with 200 microCi of 90Y-2IT-BAD-Lym-1, however, the higher radiation dose, and Taxol, were required for improved survival. Mouse weights and myelotoxicity in the combined modality (RIT plus Taxol) groups were similar to those receiving the same dose of RIT alone. In the Raji tumored nude mouse model, addition of Taxol to 90Y-2IT-BAD-Lym-1, in doses clinically achievable in humans, provided therapeutic synergy without increased or excessive toxicity.

The effect of intermittent-release intraperitoneal chemotherapy on wound healing

OBJECTIVE: Our purpose was to study the effect on wound healing when intraperitoneal chemotherapy was instilled on a daily basis. STUDY DESIGN: Intraperitoneal carboplatin, Taxol, or saline solution was instilled daily into 70 rats after they underwent laparotomy. The animals were killed and analyzed for adhesions. An area measuring 5 × 5 cm including the incision was also harvested for biomechanical testing. The wound thickness was measured, and the Shore Western Materials Testing System (Monrovia, Calif.) was used to test the force required to break the wound, the stress, and the stiffness. RESULTS: Groups of 10 rats received saline solution control, carboplatin 6 mg/kg, 7 mg/kg, 8 mg/kg, or Taxol 2.5 mg/kg, 3.0 mg/kg, or 3.5 mg/kg. The total dose was divided into seven equal amounts, administered daily. No significant adhesions developed in any of the animals. The carboplatin group experienced no significant decrease in wound thickness whereas the higher-dose Taxol group had a significant decrease in thickness from 1.06 mm to 0.72 mm ( p = 0.02). The wound-breaking strength (force) also decreased for the highest-dose Taxol group from 710 gm to 411 gm ( p = 0.02). The wound stiffness was also decreased from 69 gm/mm to 46 gm/mm ( p = 0.01). The other measured parameters for both the Taxol and carboplatin groups were not significantly decreased when compared with those of controls. CONCLUSION: The immediate instillation of divided daily carboplatin did not influence wound strength whereas the use of Taxol on a similar schedule significantly decreased wound strength. (Am J Obstet Gynecol 1997;176:819-25.)