Carboplatin

Abstract full text + links pdf 235 k ; inhibition of repair of carboplatin - induced dna damage.

This phase II study of carboplatin in children with progressive low-grade gliomas demonstrates that it is possible to stabilize disease with this agent given in this dosage schedule in a significant majority of patients with acceptable toxicity. The treatment also allowed delay or avoidance of radiotherapy in most patients. Carboplatin was chosen for this study after observation of its improved toxicity profile over its parent analog cisplatin and the preliminary activity seen in children with low-grade glioma.15, 16 The dose and schedule used in this study were based on a phase I trial of carboplatin reported by Gaynon et al.19 Approximately a quarter of patients demonstrated an objective response in the form of CR, PR, or MR in this study, and a higher proportion of patients 85% ; achieved SD for a median time period of almost 2 years. This is comparable to other large studies of carboplatin in children with low-grade gliomas.20, 21 In a Pediatric Oncology Group study of carboplatin given every 4 weeks in young children with progressive optic pathway tumors, 39 78% ; of 50 children had SD or better, although only two patients demonstrated a PR in this study.20 In another large multiinstitutional study of young children with progressive lowgrade gliomas, Packer et al21 administered carboplatin combined with vincristine in children with previously untreated progressive low-grade gliomas. Forty-four 56% ; of 78 patients demonstrated an objective response four CR; 22 PR; and 18 MR ; to treatment, and 73 93% ; of 78 patients had disease stabilization with a 3-year progression-free survival of 68%. The reasons for a lower objective response rate in our study compared with that reported by Packer et al21 are difficult to assess but may be related to difference in patient population, chemotherapy schedule, and response assessment. Nevertheless, the disease stabilization and FFS rates are similar in these two studies. The monthly schedule of carboplatin has several advantages over the weekly schedule in that the toxicity is tolerable, the rate of allergic reaction is lower, and it is more convenient to the patients and families. A randomized trial comparing these two schedules of carboplatin administration should be performed to accurately assess the superiority of one regimen over the other. In our study, patients with diencephalic tumors defined as tumors involving the thalamus, hypothalamus, and basal ganglia ; had a significantly worse FFS and OS compared with those with tumors located at other sites. Such tumors comprise approximately 5% of all low-grade gliomas, 22 are typically large, and difficult to resect because of the presence of important surrounding structures. They are often poorly responsive to chemotherapy as well. A recent Pediatric Oncology Group study also reported poor outcomes in.
1992; 10: 1- alberts ds, et al: improved therapeutic index of carboplatin plus cyclophosphamide versus cisplatin plus cyclophosphamide: final report by the southwest oncology group of a phase iii randomized trial in stages iii and iv ovarian cancer. Valves linear-elliptical, sub-acute; costrn radiate, distant, very short in the middle, and becoming gradually longer towards the extremities, leaving an elongate, lozenge-shaped, centrical blank space. Length, -0024" ; breadth, about -0006"; costre, 15 in -001". Pinnularia plena O'Meara ; may be thus described: --Valves broadly elliptical, subacute; costao radiate, close, becoming longer towards the eentre, leaving an elliptico-lanceolate central blank space. Length, -0024"; breadth, '0012"; costa3 nearly twice as many in same space as in P. semiplena. To complete the comparison, Mr. O'Meara observed that, in. Vera Gorbounova 1 ; , Nadezda Orel 1 ; , Mark Bychkov 1 ; , Alexander Marenich 1 ; , David Naskhletashvili 1 ; 1 ; Cancer Research Center, RAMS, Dept. of Chemotherapy, Moscow, Russia 22 patients with extensive SCLC and 25 patients with advanced NSCLC were treated with Taxotere 75 mg m2 i.v. day 1 + cisplatin 75 mg m2 i.v. day 1 or Taxotere 75 mg m2 i.v. day 1 + carboplatin - AUC 6 i.v. day 1. 47 patients were evaluable for response, 204 curses were evaluable for toxicity. SCLC: Overall response rate was 59, 0% 13 22 ; : 2 complete responses 9, 0% ; and 11 partial responses 50, 0% ; . The median of survival was 10.25 months. In case of objective response the median of survival was 12.0 months and in the group of patients without response - 5.0 months. The median duration of response was 5.5 months. 1-year survival was 41 %. NSCLC: Overall response rate was 32, 0% 8 25 ; : 1 complete response 4, 0% ; and 7 partial responses 28, 0% ; . Stabilisation 4 months - 32, 0% 8 25 ; . The main toxicity of chemotherapy with Taxotere + cisplatin carboplatin was hematological N. of curses - 204 ; : neutropenia G3 G4 - 32, 8%; anemia G3 G4 - 2, 9%. Conclusion: the preliminary results suggest that the combination with Taxotere + cisplatin carboplatin is an active and well tolerated regimen in extensive SCLC and advanced NCSLC. Make on our planet, it is imperative for anyone interested in protecting our children and our environment to do whatever possible to support, protect, and promote breastfeeding 12 ; . References and carmustine. Jacques Demy "Of all the New Wave directors who once professed their joy in cinema, " David Thomson wrote, "Demy has remained the most faithful to the delights of sight and sound and to the romance of movie iconography." His first feature, Lola 1961 ; , starring Anouk Aime as a cabaret singer who must choose among several lovers. The film's stylish camerawork and buoyant romantic flavor would characterize much of Demy's work. It was The Umbrellas of Cherbourg 1964 ; , a romance between a garage mechanic and a shop-girl, that melted audiences' hearts. All of the actors' dialogue was sung, and the lavish photography and sets reflected Demy's fondness for the Hollywood musical; the film won the Grand Prix at Cannes and earned Oscar nominations for Demy's screenplay and the beautiful score by Demy and Michel Legrand. Michel Legrand studied at the Paris Conservatory at the age of eleven and later became a well known singer, pianist, songwriter, and conductor in the jazz and pop music field. He began writing film scores in the early 1950s and gained fame for his work with directors like Agnes Varda Cleo From 5 to 7 1961 ; , Jean-Luc Godard A Woman Is a Woman 1961; My Life to Live 1962; Band of Outsiders 1964 ; , and especially Jacques Demy, with whom he collaborated on Lola 1961 ; , Bay of Angels 1962 ; , and the unforgettable musical The Umbrellas of Cherbourg 1964 ; , which earned him Oscar nominations for Best Score and the song "I Will Wait For You." He was Oscar-nominated for songs from Rochefort, The Thomas Crown Affair 1968, "The Windmills of Your Mind" ; , Pieces of Dreams 1970 ; , and Best Friends 1982 ; and won twice: for Best Original Score, with The Summer of `42 1971 and Best Original Song Score, with the Barbra Streisand psuedo-musical Yentl 1983 ; . His theme for the TV movie Brian's Song 1970 ; became extremely popular. Sheldon Harnick Mr. Harnick's musical theatre career began in the 1950s with songs e.g. "The Boston Beguine, " "Merry Little Minuet" ; in revues on and Off-B'way. In 1957 he teamed with Jerry Bock to create the scores for a number of memorable musicals including Fiorello Tony Award, Pulitzer Prize ; , She Loves Me Grammy ; , Fiddler on the Roof Tony ; , The Rothschilds and The Apple Tree. He has contributed songs to the films The Heartbreak Kid, Blame It on Rio Cy Coleman ; and Aaron's Magic Village Legrand ; . In the world of opera, he has provided librettos for Jack Beeson's Cyrano, Dr. Heidegger's Fountain of Youth and Captain Jinks of the Horse Marines, Henry Mollicone's Coyote Tales and Thomas Z. Shepard's Love in Two Countries. In 2003, TRTC performed Mr. Harnick's translation of Peter Brooke's The Tragedy of Carmen, also directed by Jonathan Fox. Mr. Harnick has won two Tony Awards, two Grammy Awards, three gold records and a platinum record. Jonathan Fox Director ; directed Two River Theatre Company's productions of Abigail's Party, The Tragedy of Carmen, Salome, Old Wicked Songs, A Delicate Balance, La Bte, Light Up the Sky, Blood Wedding, Hedda Gabler, The Illusion, Betrayal, Machinal, and The Beauty Queen of Leenane. He has directed in San Francisco, New York, Philadelphia and Germany, including the German premiere of Mud at the Horizon Theatre in Cologne. He is a recipient of an Alexander von Humboldt Foundation fellowship for research in Germany. Jonathan is Two River Theatre Company's Artistic Director.

Adapted from: The State of New York Department of Health: Antonia C. Novello, M.D., M.P.H., Dr. P.H. Commissioner of Health and carteolol. Quality of Life In 5 of the analysed studies, the impact of paclitaxel platinum-containing regimens on quality of life was evaluated. There were no significant differences for overall QoL. Gatzemeier et al. 2000 A combination of paclitaxel plus low dose cisplatin was compared with high-dose cisplatin monotherapy in 414 patients with stage IIIB or IV NSCLC. There was no significant improvement in survival in the paclitaxel cisplatin arm vs. the high-dose cisplatin arm; however, the combination produced a better clinical response, resulting in an increased time to progression. Smit et al. 2003 Paclitaxel cisplatin control arm ; was compared with paclitaxel gemcitabine and cisplatin gemcitabine in 480 patients with NSCLC. Cisplatin gemcitabine and paclitaxel gemcitabine did not increase overall survival vs. paclitaxel cisplatin and there was shorter progression-free survival in the paclitaxel gemcitabine group versus the paclitaxel cisplatin group. Comella et al. 2001 A cisplatin-containing triplet regimen of paclitaxel cisplatin gemcitabine n 114 patients ; was compared with cisplatin gemcitabine n 122 ; and a triplet of cisplatin gemcitabine vinorelbine n 117 ; in 354 patients with NSCLC. The triplet regimens paclitaxel cisplatin plus gemcitabine and cisplatin gemcitabine vinorelbine were associated with improved outcome Rosell et al. 2002 A paclitaxel carboplatin combination was compared with a paclitaxel cisplatin combination in a total of 618 patients with stage IIIB or IV NSCLC. Paclitaxel carboplatin yielded a similar response rate to paclitaxel cisplatin; however, median survival was significantly longer with paclitaxel cisplatin. Discussion of Efficacy In the pivotal BMS trials paclitaxel cisplatin produced improvements in response compared to teniposide cisplatin and etoposide cisplatin ; , survival and progression-free survival compared to etoposide cisplatin ; in patients with advanced NSCLC. These data led to paclitaxel cisplatin becoming the new reference regimen. Although survival benefits with paclitaxel cisplatin in advanced are.
Consistent with this, the frequency of CAV appeared to be greater in the pre-ganciclovir era, suggesting a benefit of antiviral prophylaxis in reducing the incidence of CAV 24 ; . We have reported that heart transplant recipients receiving more aggressive anti-CMV prophylaxis exhibit reduced acute rejection and CAV 14 ; and our work has suggested an important role for the preexisting CMV-specific CD4 T cell response in suppressing viral infection that predisposes to acute rejection and CAV 22 and caverject. 0 The patient is the measure of all things when it comes to developing a therapy. Active substances therefore need to be processed in such a way that they are easy to use for the patient, safe and painless. Along with the efficacy of a therapy, these are the very aspects that improve a patient's quality of life. Betaferon is a good example. The antiMS drug has become more patient-friendly in two ways: while it used to be necessary to keep Betaferon in a refrigerator, it can now be stored at room temperature. This enables patients to travel to distant countries or undertake extended hikes and other important activities without taking any additional measures. Schering's second innovation is also designed to provide greater independence for patients: the Betaject and Betaject light for patients with a less advanced disease ; injectomats have been developed to administer exactly the right dose of the substance to the desired site at exactly the right speed. This makes independent administration of the drug considerably easier for many patients. At the same time, skin irritations and other undesired effects are reduced by more than half. As a consequence, patients are more willing to continue with their therapy. The ACT Action for Choices in Treatment ; Program also aims to improve therapy and quality of life. It is based on the model called mental representation. Developed by leading psychologists in the mid-1980s, this model describes how patients produce a picture of their disease. In other words, their perception of the disease is the central focus their feelings and thoughts about MS, their knowledge of the disease and how they perceive and describe their symptoms. This information helps the person with MS make decisions together with his or her physician about how to handle everyday problems or to choose alternatives in daily life and about individualized treatment. A questionnaire is used to monitor the decisions at regular intervals, which may result in dropping less successful approaches. The patient may also recognize that his or her thoughts and opinions have changed and so too the attitude towards a particular treatment.
1. Ong ST, Vogelzang NJ. Chemotherapy in malignant pleural mesothelioma: A review. J Clin Oncol 1996; 14 3 ; : 1007-17. 2. Solheim OP, Saeter G, Finnanger AM, Stenwig AE. High-dose methotrexate in the treatment of malignant mesothelioma of the pleura. A phase II study. Br J Cancer 1992; 65: 956-60. Chahinian AP, Antman K, Goutsou M et al. Randomized phase II trial of cisplatin with mitomycin or doxorubicin for malignant mesothelioma by the CALGB. J Clin Oncol 1993; 11: 1559-65. Vogelzang NJ, Goustou M, Corson JM et al. Carboplatin in malignant mesothelioma: A phase II study of the CALGB. Cancer Chem Pharm 1990; 27: 239 t2. 5. Vogelzang NJ, Weissman LB, Herndon JE et al. Trimetrexate in malignant mesothelioma: A CALGB phase II study. J Clin Oncol 1994; 12 7 ; : 1436-42. 6. Vogelzang NJ, Herndon JE II, Cirrincione C et al. Dihydro-5azacytidine in malignant mesothelioma: A phase II trial demonstrating activity but with cardiac toxicity. Cancer 1997; 79: 223742. Samuels BL, Herndon JE, Harmon DC et al. Dihydro-5-azacytidine and cisplatin in the treatment of malignant mesothelioma: A phase II study by the Cancer and Leukemia Group B. Cancer 1998; 82: 1578-84. Millard FF, Herndon J, Vogelzang NJ, Green MR. Gemcitabine for malignant mesothelioma MM ; : A phase II study of the Cancer and Leukemia Group B CALGB 9530 ; . Proc Soc Clin Oncol 1997; 16: 1710. Herndon JE, Green MR, Chahinian P et al. Factors predictive of and cefazolin.
19. de Wit R, Roberts JT, Wilkinson P et al. Final analysis demonstrating the equivalence of 3 BEP vs. 4 cycles and the 5 day schedule vs. 3 days per cycle in good prognosis germ cell cancer. An EORTC MRC phase III study. Proc Soc Clin Oncol 2000; 19: 326a Abstr ; . 20. Einhorn LH, Williams SD, Troner M et al. The role of maintenance therapy in disseminated testicular cancer. N Engl J Med 1981; 305: 727731. Bajorin DF, Sarosdy MF, Pfister DG et al. Randomized trial of etoposide and cisplatin versus etoposide and carboplatin in patients with good-risk germ cell tumors: a multiinstitutional study. J Clin Oncol 1993; 11: 598606. Bokemeyer C, Khrmann O, Tischler J et al. A randomized trial of cisplatin, etoposide and bleomycin PEB ; versus carboplatin, etoposide and bleomycin CEB ; for patients with "good-risk" metastatic non-seminomatous germ cell tumors. Ann Oncol 1996; 7: 1015 Horwich A, Sleijfer DT, Foss SD et al. Randomized trial of bleomycin, etoposide, and cisplatin compared with bleomycin, etoposide, and carboplatin in good-prognosis metastatic nonseminomatous germ cell cancer: a multi-institutional Medical Research Council European Organization for Research and Treatment of Cancer trial. J Clin Oncol 1997; 15: 18441852. Bosl GJ, Geller NL, Bajorin D et al. A randomized trial of etoposide + cisplatin versus vinblastine + bleomycin + cisplatin + cyclophosphamide + dactinomycin in patients with good-prognosis germ cell tumors. J Clin Oncol 1988; 6: 12311238. Wozniak AJ, Samson MK, Shah NT et al. A randomized trial of cisplatin, vinblastine and bleomycin versus vinblastine, cisplatin and etoposide in the treatment of advanced germ cell tumors of the testis: a Southwest Oncology Group study. J Clin Oncol 1991; 9: 7076. Levi JA, Raghavan D, Harvey V et al. The importance of bleomycin in combination chemotherapy for good-prognosis germ cell carcinoma. Australasian Germ Cell Trial Group. J Clin Oncol 1993; 11: 13001305. Loehrer PJ, Johnson D, Elson P et al. Importance of bleomycin in favorable-prognosis disseminated germ cell tumors: an Eastern Cooperative Oncology Group trial. J Clin Oncol 1995; 13: 470476. de Wit R, Stoter G, Kaye SB et al. Importance of bleomycin in combination chemotherapy for good-prognosis testicular nonseminoma: a randomized study of the European Organization for Research and Treatment of Cancer Genitourinary Tract Cancer Cooperative Group. J Clin Oncol 1997; 15: 18371843. Culine S, Kerbrat P, Bouzy J et al. Are 3 cycles of bleomycin, etoposide and cisplatin 3 BEP ; or 4 cycles of etoposide and cisplatin 4 EP ; equivalent regimens for patients pts ; with good-risk metastatic non seminomatous germ cell tumors NSGCT ; ? Preliminary results of a randomized trial. Proc Soc Clin Oncol 1999; 18: 309a Abstr ; . 30. Bajorin DF, Bosl GJ. Bleomycin in germ cell tumor therapy: not all regimens are created equal. J Clin Oncol 1997; 15: 17171719. Cvitkovic E. Bleomycin in nonseminomatous germ-cell tumors: cure rate versus morbidity. J Clin Oncol 1998; 16: 799800. Harrison JH Jr, Lazo JS. High dose continuous infusion of bleomycin in mice: a new model for drug-induced pulmonary fibrosis. J Pharmacol Exp Ther 1987; 243: 11851194. Vogelzang NJ. Continuous infusion chemotherapy: a critical review. J Clin Oncol 1984; 2: 12891304. Jensen JL, Goel R, Venner PM. The effect of corticosteroid administration on bleomycin lung toxicity. Cancer 1990; 65: 12911297.
GS-thiyl radical besides GSSG see Ref. 23 ; , and these glutathionylating species may react preferentially at a site s ; different from Cys90, which is modified by GSSG. Normally, mitochondria produce 0.6 1.0 nmol of H2O2 min mg of protein, accounting for 2% oxygen uptake, under the conditions of state 4 respiration 61 ; . Physiologically, it is likely that intrinsic S-glutathionylation of SQR is an early consequence of mitochondrial oxidative stress. This S-glutathionylation may serve to protect the 70-kDa subunit of SQR from oxidative damage. Similar observation of enhanced activity resulted from S-glutathionylation was also reported in the case of complex I 62 ; and sarcoendoplasmic reticulum calcium ATPase 63 ; . Therefore, intrinsic S-glutathionylation of SQR should play the protective role against oxidative stress under normal physiological conditions. Eaton et al. 64 ; have reported reperfusion of increased S-thiolation of a number of cardiac proteins by 3-fold by loading biotinylated cysteine into the ischemic rat heart. It seems paradoxical that deglutathionylation of SQR was detected under the conditions of oxidative stress. However, other examples undergoing deglutathionylation under similar conditions of oxidative challenge were also observed in the proteins of actin and caspase-3 65, 66 ; . Superoxide Production Mediated by SQR--The generation of superoxide by FADH2 autooxidation has been reported. However, until now there has been no direct evidence supported by EPR. Our detection of the DEPMPO OOH adduct by EPR provided a direct measurement of SQR-mediated superoxide generation. The inhibitory effect of TTFA on the detected DEPMPO OOH indicated that FADH2 autooxidation partially . contributed to the SQR-mediated O2 generation 43% under experimental conditions here, see Fig. 8D ; . The production of . O2 SQR was minimized under the conditions of enzyme turnover in the presence of Q2 Fig. 8E ; . Based on the x-ray crystal structure 67 ; , Cys90 Cys47 in the mature protein ; is located within the part of the N-terminal -barrel subdomain Ala10Ans61 in the mature protein ; of the large FAD-binding domain residues 10 273 and residues 361 445 in mature protein ; . Specifically, Cys90 is situated in the hydrophilic pocket with the structure of -sheet turnhelix turn-sheet-turn-loop ; , suggesting this specific thiol is susceptible to attack by GSSG. The x-ray structure also reveals that Cys90 is near the AMP moiety of FAD 7.7 ; . where the major catalysis of electron transfer and O2 production occurs. As demonstrated by EPR spin trapping, the elec. tron transfer coupled with O2 generation as induced by succinate is partially controlled by reduced FAD cofactor and its FAD-binding protein moiety at the 70-kDa subunit Fig. 8 ; . Therefore, specific S-glutathionylation at Cys90 seems likely to induce a small conformational change near the FAD-binding site, which might marginally increase the efficiency of electron transfer away from FADH2 to the 2Fe-2S moiety S1 center ; , and subsequently decrease the electron leakage under enzyme turnover conditions Figs. 9 and 10 ; . In postischemic injury, deglutathionylation rendered SQR highly susceptible to oxidant stress, presumably because of the and cefprozil.
Water in wells usedasa sourceof water for mixing pesticidesin fruit orchardsinWestVirginia USA ; wasfound tocontain endrin at about I ng litre in 1985 and in 1986. The water in these wells was not used for drinking-water. Endrin had not beenused in the areasince 1970, and the authors cite their results as evidencefor the persistenceof endrin and its capacity to conJaminategroundwater many years after cessationof use Hogmire et al., 1990. U0 is an priori estimation of the initial condition. Therefore the problem is to determine U , V ; minimizing J. The Euler-Lagrange equation, the optimality system O.S ; is deduced : dX F B.V dt X 0 ; Xobs ; 21.3 ; dt X P the adjoint variable, in the dual space of the state variable X Another source of information is provided by the statistics on the fields, it can be plugged in the analysis via the norms which are used in the space of observations and in the space of the initial condition taking into account the matrix of correlations of these fields. For sake of simplicity we won't use this information here. The optimal solution is obtained by carrying out a method of unconstrained optimization BFGS, Quasi or Truncated Newton ; , the direction of descent, depending in the gradient of the cost function which is obtained by solving the adjoint model. This method is presently used by the main meteorological services in the world. It worth to point out that all the available information is contained in the optimality system. Thanks to the variational principle it has been possible to make a link between heterogeneous sources of information : mathematical information the model ; , physical information data ; and statistical information and ceftriaxone. Advanced non-small-cell Jung cancer Chemotherapy. Lung Cancer 1991; 7 Suppl ; : 100S-143S. 6. Ettinger DS. Metastatic non-small cell lung cancer. Lung Cancer 1993; 9 Suppl ; : 69S-79S. 7. Thatcher N, Niven RM, Anderson H. Aggressive versus nonaggressive therapy for metastatic NSCLC. Chest 1996; 109 Suppl ; : 87S-92S. 8. Hardy JR, Noble T, Smith IE. Symptom relief with moderate dose chemotherapy mitomycin C, vinblastine and cisplatin ; in advanced non-small cell lung cancer. Br J Cancer 1989; 60: 764-66. Fernandez C, Resell R, Abad-Esteve A, et al. Quality of life during chemotherapy in non-small cell lung cancer patients. Acta Oncol 1989; 28: 29-33. Cullen MH. Trials with mitomycin, ifosphamide and cisplatin in non-small cell lung cancer. 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Paclitaxel 1-hour ; and carboplatin area under the concentration-time curve 7.5 ; HKMJ Vol 5 No 2 June 1999 185 and carboplatin.

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