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Address for correspondence: Co-editors, PREMA-EU newsletter : Umberto D'Alessandro [udalessandro itg.be and Prince Leopold Institute of Tropical Medicine, Nationalestraat 155, B-2000 Antwerp, Belgium Tel: + 32- 0 ; 3-2476354 ; . Please pass on this newsletter to friends and colleagues; the editors would be delighted to receive comments and new material. If you are interested in receiving the newsletter or collaborate contribute with the PREMA-EU network you can register at the PREMA-EU website : prema-eu . Details on the last page of this newsletter, for example, hcl. When serving as a consultant, to participate in the Company's medical and dental plans. The consulting fee shall not at any time exceed the annual compensation as adjusted, paid to Mr. Panic. Upon Mr. Panic's retirement, the consulting fee shall not be subject to further cost-of-living adjustments. The Company has employment agreements with eleven other key executives which contain "change in control" benefits. Upon a "change in control" of the Company as defined in the contract, the employee shall receive severance benefits equal to three times salary or for the chairman five times salary and other benefits. As of December 31, 2001, the Company's obligation, assuming a change in control had occurred would be $28, 681, 000 for all employment contracts. 12. Business Segments and Geographic Data The Company is a global, research-based pharmaceutical company that develops, manufactures, distributes and sells pharmaceutical, research and diagnostic products. The Company is organized and operates in the Pharmaceuticals group and the Biomedicals group. The Pharmaceuticals group produces and markets a variety of pharmaceutical products worldwide and derives royalty revenues from sales of certain of its products by a third party under a license agreement. The Biomedicals group markets research products and related services, immunodiagnostic reagents and instrumentation, and provides radiation monitoring services. In 2001, the principal markets for the Company's pharmaceutical products were North America, Western Europe including Poland, Hungary and the Czech Republic ; , Russia and Latin America, which represented approximately 20%, 24%, 12% and 15%, respectively, of the Company's revenues for the year. Approximately 62%, 64%, and 64% of the Company's revenues for the years ended December 31, 2001, 2000 and 1999, respectively, were generated from operations outside the United States. The Company's foreign operations are subject to certain risks inherent in conducting business abroad, including possible nationalization or expropriation, price and exchange controls, limitations on foreign participation in local enterprises, health-care regulation, and other restrictive governmental actions. Changes in the relative values of currencies take place from time to time and may materially affect the Company's results of operations. Their effects on the Company's future operations are not predictable. The Company does not currently provide any hedges on its foreign currency exposure and, in certain countries in which the Company operates, no effective hedging programs are available. In 1998, the Company adopted SFAS No. 131, Disclosures about Segments of an Enterprise and Related Information, which requires reporting certain financial information according to the "management approach." This approach requires reporting information regarding operating segments on the basis used internally by management to evaluate segment performance. SFAS No. 131 also requires disclosures about products and services, geographic areas and major customers. The Company is organized into business units on the basis of geographic region. In applying SFAS No. 131, these business units have been aggregated into seven reportable segments based on similar long-term economic characteristics. The accounting policies of the segments are the same as those described in Note 2. The Company evaluates segment performance based on income from operations, which excludes intersegment sales as well as interest income and expense and foreign exchange gains and losses. The Company allocates amortization on the product rights acquired from Roche and SKB among the segments where the related revenues are reported; the unamortized cost of such acquired product rights is included in assets of the North America Pharmaceuticals segment.
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Discussion Here we show that the aminosalicylate mesalazine, a weak COX and lipoxygenase inhibitor well known for its low systemic toxicity, reduces cell growth of colon carcinoma cells in vitro. The anti-proliferative effect is presumably mediated through a specific accumulation of cells in mitosis. This represents a novel mechanism which has not been reported for other NSAID so far and which differs significantly from the G1 arrest induced by well-established chemopreventive agents like sulindac sulfide or indomethacin. Mesapazine also increases apoptosis in HT29 cells--presumably through activation of caspases--although to a lesser extent than sulindac sulfide or indomethacin. Mesalaaine reversibly decreases cell proliferation in HT29 cells Mesalazin3 significantly reduced cellular proliferation of HT29 cells in a dose- and time-dependent manner with an ID50 of ~30 mM at 72 Mesalazzine is thus much less potent on a molar basis in reducing cell growth of HT29 cells than other known chemopreventive agents which we demonstrated directly by testing other compounds in parallel. The growth inhibitory concentrations ID50 ; we determined for HT29 cells using the known chemopreventive agents sulindac sulfide, indomethacin and NS-398 were in close range of those reported by others before [~100 M after 72 h for sulindac sulfide 24 ~200 M for indomethacin at 72 h and 82 M for NS398 26 ; ]. Importantly, however, mesalazine concentrations which were effective in vitro closely correspond to concentrations of mesalazine achievable in the bowel in vivo under standard oral mesalazine treatment 27 ; and may even be increased after rectal administration of the compound as has been suggested by recent studies 28 ; . Furthermore, the drug apparently did not irreversibly damage colon epithelial cells as the effect of mesalazine--even at highest concentrations used--was almost fully reversible. This may implicate that mesalazine acts through specific cellular mechanisms. Sources: health and human services commission and texas comptroller of public accounts and clavulanic, for example, bobby mc. A study has been performed comparing the ability of a foam formulation to release the active ingredient betamethasone benzoate ; with ointment, gel, and cream formulations.[5] It was found that the release of betamethasone benzoate from the ointment, gel, and foam formulations was similar, but better than the release from the cream. This was one of the first investigations into the use of foams in dermatology and illustrates the usefulness of this type of formulation. A foam formulation of the superpotent corticosteroid, clobetasol propionate, has demonstrated anti-inflammatory, antipruritic, and vasoconstrictive properties.[9, 11] In patients with moderate to severe scalp psoriasis, topical application of clobetasol propionate foam 0.05% ; twice daily for 2 weeks resulted in significant improvement of all signs and symptoms of the disease compared with placebo and clobetasol propionate solution 0.05% ; . Furthermore, patients who received clobetasol propionate foam demonstrated greater improvement of scaling after 2 weeks of treatment, and after 2 weeks of follow-up. There are only a limited number of reports in the literature concerning the use of foam formulations in other fields of dermatology or nondermatological fields. Nonsteroidal anti-inflammatory and antifungal agents are among the other drug families that have been formulated into foam products, while nonoxynol-9 foam[12] has been used vaginally as a contraceptive, and chlorhexidine gluconate foam has been used as a preoperative application.[13] If one considers that drug delivery to the alimentary canal and mucosae may be classified as `topical' delivery in the classical sense, then one may include rectal foam products in this discussion of dermatological foams. Prednisolone, hydrocortisone, beclomethasone dipropionate, and mesalazine foams have been applied rectally in ulcerative colitis and the treatment of postepisiotomy pain and erythema. A. Fter the publication last August of data attributing 20, 000 cases of breast cancer over the last decade to hormone replacement therapy HRT ; , there were dramatic headlines likening the situation to the thalidomide tragedy. Professor Bruno Muller-Oerlinghausen, chairman of the German Commission on the Safety of Medicines, was reported as saying: "We are talking about a therapy for women that is used to treat disturbances in well-being. And we are talking about . a nave and careless use of a medication that is perceived as natural and optimal and more or less harmless." While other responses to the findings of the Million Women Study, published in the Lancet, were generally more measured, there is a consensus that they add to the growing body of evidence suggesting the need for a major rethink in the way HRT is used in menopause. The Million and rosiglitazone.

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As pathological inflammation. Since the normal intestinal flora vary in capacity to drive mucosal inflammation, some bacteria such as lactobacilli and bifidobacteria with apparent anti-inflammatory activity have been selected as candidates for probiotic treatment of inflammatory bowel disease. The results in treating different models of murine enterocolitis are encouraging but highlight variability in probiotic performance between organisms depending on the experimental model [50-52]. Thus, as yet, there is uncertainty whether a particular probiotic strain would be effective in all patients or even in the same patient at different stages in the clinical course of the disease. Two controlled trials of a nonpathogenic strain of E. coli in ulcerative colitis have suggested efficacy similar to that of mesalazine [53, 54]. In acute Crohn's disease a preliminary open trial found that Lactobacillus salivarius UCC118 was safe and would reduce the requirement for corticosteroids in the majority of patients. European Commission-funded clinical trials assessing wellcharacterized strains of lactobacilli and bifidobacteria in maintenance of remission of Crohn's and ulcerative colitis are currently in progress. Intestinal Contamination Post Surgery Probiotic therapy has been recommended for prevention and treatment of bacterial overgrowth syndromes after intestinal resection and reconstruction. A hyper-response to products of bacterial overgrowth is thought to be the mechanism of inflammation and diarrhea complicating ileoanal pouch reconstructions in ulcerative colitis patients. This may in part be related to genetic susceptibility and the presence of bacteria peculiar to the ulcerative colitis, as pouchitis is rarely seen in the pouches of patients who were operated on for familial polyposis coli [55-57]. That was in the days before we were so careful about human investigation. My throat and sinuses hurt, I realized that the problem was that big old stiff catheter. All I really wanted were the two rings at the end of the catheter. The next morning I went into the lab, took a pair of diagonal cutters and stripped away the polyethylene coating until I was left with the tip of the catheter and the pair of wires. Then I buried the catheter tip in a spoonful of ice cream and swallowed it. My students laugh about this. One doesn't chew ice cream, so the bipolar pair of electrodes caused no problem. I just swallowed it, and down went the pill. That was the first pill electrode. That was the business end of a catheter electrode with a bipolar pair and a pair of wires holding it up. Within a week or two I discovered a source of very thin and flexible stranded stainless steel wire with Teflon insulation and irbesartan.

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Fast Metabolizers are generally not at risk for adverse side effects. Since the drug is cleared quickly, the relief they receive may be limited to a few hours, but they are for the most part not in danger of adverse side effects. The opposite is true for the Slow Metabolizers. The drug slowly builds up and can reach toxic levels. In some cases, there is a high level of the drug in the blood when the second dose is administered, sending the drug level even higher. While this variation in metabolic rate is an issue with many of the NSAIDs, it is clearly not the only problem. Dogs with compromised kidneys, livers, heart problems or preexisting gastro- intestinal ulceration are at risk, even if they are Fast Metabolizers and avodart. Good luck -kelli ar1977 member # 9246 posted september 13, 2007 last cycle i wasn't ttc because i had a cyct so they had me on birth control pills, for example, colitis mesalazine.

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Mesalazine 5-aminosalicylic acid ; is an anti-inflammatory agent structurally related to the salicylates. Results Mesakazine inhibits proliferation of colon cancer cells First, we evaluated the effect of mesalazine on the proliferation of colon cancer cells in vitro in direct comparison with other known chemopreventive NSAID. We chose the colon carcinoma cell line HT29 because it is among the most widely used cell lines for in vitro analyses of potential chemopreventive agents. HT29 cells were treated with increasing concentrations of mesalazine, sulindac sulfide, indomethacin all non-selective COX inhibitors ; or NS-398 a selective COX-2 inhibitor ; for 72 h and cell proliferation was measured with a colorimetric assay. In pilot experiments, this assay was validated by standard cell counting experiments see Materials and methods ; . Mesalazine doses of 20 mM significantly reduced proliferation of HT29 cells compared with controls P 0.0081 ; whereas mesalazine concentrations of 30 mM reduced OD values of HT29 cells by 50% ID50 ; compared with untreated controls Figure 1A ; . The ID50 for indomethacin was 400 M Figure and abacavir. DATE OF ADMISSION TO LABOUR DELIVERY ROOM Date of admission to the Labour and Delivery Room in apparent labour and delivered before discharged from the unit. Found on the `PARTOGRAM' or the `PROGRESS NOTES' or `MATERNAL ADMISSION ASSESSMENT'. Use the following format: `YYYYMMDD'. In the case of an in-patient induction with oxytocin or prostaglandin, record the date that the drug was initiated. In the case of an out-patient induction with prostaglandin, record the date of admission to the LDR in apparent labour In the case of an inpatient induction with prostaglandin followed by oxytocin, record the time the oxytocin was initiated. In the case of an induction using Artificial Rupture of Membranes only, record the date the membranes were ruptured in an attempt to induce labour If date of admission to LDR is unknown, leave `LDR Date' blank, and code `9' in the field immediately following!
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REFERENCES 1. Top 50 pharmaceutical companies of 1999. Pharmaceutical Executive 2000 April; 20 4 ; : 72. 2. Maitland A. Under the skin. Sir William Castell: Amersham's main continuity man. The Financial Times 2002 September 25; Inside Track: 11. 3. Fortune 500 Top Performing Industries 2002. Fortune online ; . : fortune500 Accessed 17 February 2003. 4. Laing R. Pharmaceutical company profits and salaries listings. Proceedings of the International AIDS Conference; 2000 July 11; Durban, South Africa. : actupny reports durban-licensing Accessed 17 February 2003.

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Skinner, M. H.; Kuan H. Y.; Pan, A.; Sathirakul, K.; Knadler, M. P.; Gonzales, C. R.; Yeo, K. P.; Reddy, S.; Lim, M.; Ayan-Oshodi, M.; Wise, S. D. Clin. Pharmacol. Ther. 2003, 73, 170. Steiner, E.; Spina, E. Clin. Pharmacol. Ther. 1987, 42, 278. O'Reilly, R. A.; Goulart, D. A.; Kunze, K. L.; Neal, J.; Gibaldi, M.; Eddy, A. C.; Trager, W. F. Pharmacol. Ther. 1992, 6, 656. Kim, M. J.; Nafziger, A. N.; Kashuba, A. D.; Kirchheiner, J.; Bauer, S.; Gaedigk, A.; Bertino, J.S. Eur. J. Clin. Pharmacol. 2006, 62, 431. O'Reilly, R.A. N. Engl. J. Med. 1976, 295, 354. Ouellet, D.; Bramson, C.; Roman, D.; Remmers, A.E.; Randinitis, E.; Milton, A.; Gardner, M. Br. J. Clin. Pharmacol. 2006, published on line at : blackwell-synergy toc bcp 0 0. Chung, E.; Nafziger, A. N.; Kazierad, D. J.; Bertino, J. S. Clin. Pharmacol. Ther. 2006, 79, 350. Persson, K. P.; Ekehed, S.; Otter, C.; Lutz, E. S.; McPheat, J.; Masimirembwa, C. M.; Andersson, T. B. Pharm. Res. 2006, 23, 56. Shitara, Y.; Sato, H.; Sugiyama, Y. Ann. Rev. Pharmacol. Toxicol. 2005, 45, 689. Mizuno, N.; Niwa, T.; Yotsumoto, Y. Pharmacol. Rev. 2003, 55, 425. Kusuhara, H.; Sugiyama, Y. In Drug-Drug Interactions Rodrigues A.D., Ed.; Marcel Dekker, New York, 2002, pp. 123-188. Zhang, L.; Strong, J. M.; Qiu, W.; Lesko, L. J.; Huang, S. M. Mol. Pharmaceut. 2006, 3, 62. Court, M. H. Methods Enzymol. 2005, 400, 104. Baranczewski, P.; Kallin, A.; Andersson, A.; Hagigi, S.; Aberg, M.; Postlind, H.; Mankowitz, L. Assay Drug Dev. Technol. 2004, 2, 345. Uchaipichat, V.; Mackenzie, P. I.; Elliot, D. J.; Miners, J. O. Drug Metab. Dispos. 2006, 34, 449. Thomson micromedex, greenwood village, co drug facts and comparisons on-line.

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The Child with Bipolar Disorder Weaning after Infant Demise Pediatric Acute Care Medical Surgical Nurses "Who we are and how we grow" Eating Disorders in Adolescents Adoption and Breastfeeding Kid's Bill of Rights Beware of the Higher Risk and Implications of Celiac Disease in Children with Type 1 Diabetes Pressure Ulcers in Pediatrics; How does your Practice Measure up?.
Patients and Methods: Patients with progressive, recurrent, or metastatic adenoid cystic carcinoma ACC ; immunohistochemically expressing at least 1 EGFR and or 2 erbB2 were treated with lapatinib 1, 500 mg daily, in a two-stage cohort. Patients with non-ACC MSGTs were treated as a separate single-stage cohort. Results: Of 62 patients screened, 29 of 33 88% ; ACC and 28 of 29 97% ; non-ACC patients expressed EGFR and or erbB2. Forty patients with progressive disease were enrolled onto the study. Among 19 assessable ACC patients, there were no objective responses, 15 patients 79% ; had stable disease SD ; , nine patients 47% ; had SD 6 months, and four patients 21% ; had progressive disease PD ; . For 17 assessable non-ACC patients, there were no objective responses, eight patients 47% ; had SD, four patients 24% ; had SD 6 months, and nine patients 53% ; had PD. The most frequent adverse events were grade 1 to 2 diarrhea, fatigue, and rash. Eight paired tumor biopsies for correlative studies were procured; results did not correlate with clinical outcome. Conclusion: Although no responses were observed, lapatinib was well tolerated, with prolonged tumor stabilization of 6 months in 36% 95% CI, 21% to 54% ; of assessable patients. The antitumor effects of lapatinib in MGSTs appear mainly cytostatic, hence evaluation of other molecular targeted agents, or combinations with lapatinib, may be considered. Continued efforts should be made to gain better understanding into the biology of this heterogeneous group of malignancies. J Clin Oncol 25: 3978-3984. 2007 by American Society of Clinical Oncology, for instance, pentasa.
Ing that time, and no results were obtained with antibiotics. On admission, the patient was in good general condition, obese weighing 101.5 kg and measuring 185 cm at the age of 15 years and 6 months ; . Physical examination revealed no abnormalities. Mild CU, involving the whole intestine, was diagnosed on the basis of colonoscopy Figure 5 ; . Treatment with mesakazine and metronidazole was instituted. Despite periodic bloody stools, the boy gained 3 kg. Control colonoscopy performed 4 months later revealed persistent inflammatory lesions, restricted to the distal segment of the descending colon, sigmoid and rectum. Hydrocortisone enemas were added to the therapy with a good result and hydroxyzine. Kathy hitchens, phar the author is a medical writer based in the indianapolis area.

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Compared with delayed-release mesalazinw MES ; Green et al.[34] Kruis et al.[35] 12 6 BAL 3 MES 1.2f BAL 3 BAL 6 MES 1.5f Compared with sulfasalazine SUL ; McIntyre et al.[32] Balsalazide dosage comparison Giaffer et al.[31] Green et al.[33] a b c BAL 2 BAL 4 BAL 3 BAL 6 All but one[32] were multicentre trials. Primary outcomes and intent-to-treat analysis, unless stated otherwise. Four patients in the delayed-release MES group were lost to follow-up immediately after randomisation; statistical analysis included only treated patients. No recurrence of moderate or severe symptoms. Three-month results. Delayed-release formulation 1.6 g day recommended ; .[36] Clinical as well as endoscopic remission. No recurrence of previous symptoms. No recurrence of clinical symptoms and sigmoidoscopic or histological abnormalities. 65 68 54 BAL 2 SUL 2 41 38. Whitmore-Jewett Stages: stage A is clinically undetectable tumor confined to the gland and is an incidental finding at prostate surgery. A1: well-differentiated with focal involvement A2: moderately or poorly differentiated or involves multiple foci in the gland stage B is tumor confined to the prostate gland. BO: non-palpable, PSA-detected B1: single nodule in one lobe of the prostate B2: more extensive involvement of one lobe or involvement of both lobes stage C is a tumor clinically localized to the periprostatic area but extending through the prostatic capsule; seminal vesicles may be involved. C1: clinical extracapsular extension C2: extracapsular tumor producing bladder outlet or ureteral obstruction stage D is metastatic disease. DO: clinically localized disease prostate only ; but persistently elevated enzymatic serum acid phosphatase Dl: regional lymph nodes only D2: distant lymph nodes, metastases to bone or visceral organs D3: D2 prostate cancer patients who relapse after adequate endocrine therapy stem cell: cell that has the ability to divide for indefinite periods in culture and to give rise to specialized cells; the ultimate stem cell might be a fertilized egg capable of producing the entire organism stenosis: abnormal narrowing of a bodily canal or passageway stent: a tube used by a surgeon to drain fluids step-section histopathology: the sectioning of diseased tissues into ordered slices used for microscopic analysis stepper: a motor especially an electric motor ; that moves or rotates in small discrete steps steroid: any one of the hormones made in the outer layer of the adrenal glands adrenal cortex ; stratified: In an analysis of data, a particular clinical or pathologic feature s ; is used as the basis for comparison, e.g. clinical stage, pathologic stage, PSA, Gleason score stress incontinence: passing a small amount of urine when coughing, lifting, etc. stricture: scarring as a result of a procedure or an injury that constricts the flow of a fluid; for example, a urethral stricture would restrict the flow of urine through the urethra stroma: the supporting tissue of an organ stromal BPH: a non-cancerous cause of prostate enlargement BPH ; within the connective tissue framework of the prostate. Conversely, mesalazine with a eudragit-l-coating salofalk ; releases mesalazine exposed to a ph level of 6 to 5, limiting its action to the mid small intestine and onwards, whereas a similar formulation with eudragit-s-coating asacol ; , releases when exposed to ph levels of 7, corresponding approximately to the last part of the small intestine. Involvement of CMV, and both CMV pp65 and antiCMV immunoglobulin Ig ; M were absent. The dosage of prednisolone was decreased to 15 mg daily and that of mesalazine was increased to 1600 mg twice daily. Ganciclovir was given intravenously for 4 weeks. Acolonic biopsy was performed 1 month later and showed the absence of inclusion bodies; however, there were still signs of active UC. Gradual symptomatic improvement was observed subsequently. In October 1997, the patient was well and asymptomatic, and was passing normal stool once or twice daily. Prednisolone treatment was gradually terminated and only mesalazine is currently being given.
Figure 3 Comparison of patients who were taken on a waiting list for transplantation immediately after referral Transplantation ; and who were initially considered too well Medical therapy ; . Although therapy of heart failure has changes since publication, these results nicely show the progressive nature of heart failure and the need for ongoing reassessment of prognosis in these patients adapted from [30].
Future restrictions in the form of laws, regulations or additional guidelines ; on direct-to-consumer advertising of erectile dysfunction medications could impact us and our competitors; however, the relative impact on each product might be affected by other factors such as length of time on the market or current recognition of the brand. When you present your membership card at a participating pharmacy, you will be required to make a copayment for each prescription based on the type of medication you purchase: For a generic drug on the Humana Drug List, you will make a $10 copayment for a maximum of a 30-day supply. For a brand-name drug on the Humana Drug List, when a generic equivalent is not available, you will make a$25 copayment for a maximum of a 30-day supply. If a generic is available and you elect to purchase the brand-name drug, you must make the generic copayment and be responsible for 100 percent of the difference in cost between the brand-name drug and its generic equivalent. * For a drug that is not on the Humana Drug List you will make a $40 copayment for a maximum of a 30-day supply. If a brand-name drug, not on the Drug List is dispensed when a generic is available, you will make the $40 copayment and be responsible for 100 percent of the difference in cost between the brand-name drug and its generic equivalent. * There are no claim forms to file if you present your membership card with each prescription. * If your physician requires the dispensing of a brand-name drug, you will make the applicable copayment and will not be responsible for any difference in cost between the brand-name and generic drug.

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Patients were randomly asked to participate in the study while attending the gastroenterology outpatient clinic of the University Hospital of Maastricht. Thirty three patients with CD 13 males, 20 females ; were included in the study in April and May 1997. Characteristics of the patient population are given in table 1. CD was diagnosed by clinical findings and a combination of radiology, endoscopy, and histology for which the Lennard-Jones criteria were applied.18 At the time of the study all patients were in clinical remission. Disease activity was measured using the Crohn's disease activity index CDAI ; .19 All patients had small bowel involvement and 13 patients also had inflammation of the colon. In 24 patients an ileal resection had been performed. All patients were using mesalazine 5aminosalicylic acid ; . Four patients were receiving prednisolone or a steroid equivalent.

Table 1 shows the number of patients treated at the various doses. With the exception of one patient at 75 mg m', the same patient after dose-reduction to 60 mg m', and three patients at 175 mg m', all patients who did not complete the prescribed 28 days of treatment went off study because of progressive disease Table 1. Side effects occurred in all ; 48 patients 95% confidence limit, 93% to 1 0 ; The most 0%. common was headache, which occurred in 71% of patients 95% confidence limit, 56% to 81% ; . Dy skin and nausea r vomiting were reported in 31% 95% confidence limit, 20% to 46% ; and 21% 95% confidence limit, 12% to 35% ; , respectively. The majority of side effects were mild or moderate with the exception of one case of hypotension at 75 mg m' and again at 60 mg m'. and one case of severe headache at 110 mg m' ; until a dose of 175 mg m' was reached Table 1 ; . Eight patients began treatment at this dose, of whom two were removed from study because of progressive disease without severe toxicity after two and 10 doses, respectively ; and three because of severe toxicity, leaving three patients who completed 28 days without severe toxicity. The dose-limiting side effects in the three who were removed because of toxicity were joint pain in two and exfoliative rash in one. One of the patients who had severe joint pain at 175 mg m' had therapy resumed at 140 mg m' 5 days later, after recovery from toxicity. The patient completed 28 days at 1 0 mg m2 without further grade 3 to 4 toxicity. 4 After the three patients developed grade 3 to 4 toxicity at 175 mg m', a second cohort four patients ; was treated at 140 mg m'. Although none of the total of eight patients at 140 mg m' seven completing 28 days ; had dose-limiting.

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