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PubMed2005

Combination of immunosuppressive agents in treatment of steroid-resistant minimal change disease and primary focal segmental glomerulosclerosis.

BACKGROUND: Minimal change disease (MCD) and focal segmental glomerulosclerosis (FSGS) are the most prevalent histopathological lesions in idiopathic nephrotic syndrome (INS). The latter is associated with high morbidity and mortality due to symptomatic anasarca, bacterial infections, venous and arterial thromboembolism, and potential progression to end-stage renal disease in the case of FSGS. Traditionally, most patients are treated with corticosteroids, cyclophosphamide (CTX) or calcineurin-inhibitors (C-I). Unfortunately, many patients become steroid or C-I dependent, with the inherent risk of long-term side effects, or are resistant to both. The aim of this paper is to report on our experience with a new protocol of a combination of immunosuppressive agents added sequentially to improve the response of steroid and C-I refractory or resistant-INS and to minimize the long-term side-effects of single-agent treatment. METHODS: Twenty-one patients with corticosteroid-resistant and C-I refractory INS (6 with MCD and 15 with FSGS) were treated prospectively over 6 and a half years. Our protocol consisted of an initial regimen of C-I followed by the addition of mycophenolate mofetil (MMF) and then by monthly intravenous CTX for 3 consecutive months. Dose reduction of C-I or/and MMF was attempted afterwards at 4-months intervals. Patients who remained refractory to the previously mentioned protocol were treated with an additional course of pulse Solu-Medrol given for 3 days followed by oral corticosteroids tapered over 6 months in addition to a second course of intravenous CTX given for 3 consecutive months. RESULTS: With the initial regimen, two patients with MCD, remained in complete remission (CR) without any therapy after the course of CTX. Fifteen patients had variable response to C-I and MMF, but they achieved CR after CTX and their initial dosage of C-I and MMF were reduced to nearly one half. The remaining four patients had refractory form of FSGS even after the initial regimen, yet responded with CR to the additional course of steroid/CTX. However, no success with dose-reduction, in C-I and MMF, was achieved in the latter four patients. CONCLUSION: Our study represents the first clinical trial with prospective and adequate follow-up of combination therapy of immunosuppressive agents in INS. This method is effective and safe for treatment of patients who are refractory to the conventional single-agent therapy.

Adolescent↗

PubMed2005

Survey of depot antipsychotic prescribing in southern Adelaide.

OBJECTIVE: Depot antipsychotic medication (DAP) is widely used in the treatment of schizophrenia and related disorders. The objectives of this study were to (i) determine whether DAP was being prescribed in accordance with established guidelines in terms of dose, interval of administration and indications; and (ii) assess the quality of the assessment and documentation of tardive dyskinesia (TD) as well as blood glucose and lipid abnormalities. METHODS: The survey was carried out between April and June 2003 at all three public hospital affiliated community mental health centres located in the southern region of Adelaide. Data were extracted from three sources: depot prescription charts, community mental health service case notes and hospital case notes. RESULTS: Two hundred and sixty-one patients were receiving DAP. The majority (89%) had a diagnosis of schizophrenia or schizoaffective disorder. The DAP prescribed most frequently was zuclopenthixol decanoate (57%) at a modal dose of 200 mg and a modal administration interval of 2 weeks. Fifty-three per cent of patients had at least one dose reduction during the course of treatment. Four per cent of patients had a case note documented diagnosis of TD. Fifty-seven per cent of patients had at least one blood glucose test in the past year, with nearly half showing high results. Forty-seven per cent of patients had at least one lipid study in the past year, with more than half having high total cholesterol and 22% having high triglycerides. CONCLUSION: The results of this study indicate that DAP is being used mostly for the treatment of schizophrenia and related disorders, which is in agreement with established evidence-based guidelines. The finding of at least one documented attempt at DAP dose reduction or extension of interval of administration in approximately half of the patients receiving DAP is encouraging and may have an impact on reducing the likelihood of TD. A formal TD surveillance programme using a screening tool such as the Abnormal Involuntary Movement Scale is recommended. In addition, more frequent evaluation of blood glucose and lipid levels is needed.

Adult↗

PubMed2005

Influence of sex on toxicity and treatment outcome in small-cell lung cancer.

PURPOSE: Female sex has been shown consistently to be a favorable prognostic factor in small-cell lung cancer (SCLC). Studies have shown that women with other tumor types experience greater treatment toxicity, but there have been few studies of sex-related toxicity in SCLC. PATIENTS AND METHODS: This was a sex-based retrospective analysis of four SCLC trials conducted by the National Cancer Institute of Canada Clinical Trials Group between 1987 and 1999. The 1,006 patients (648 males and 358 females) received similar chemotherapy consisting of cyclophosphamide-doxorubicin-vincristine and etoposide-cisplatin. Toxicities examined included myelosuppression, stomatitis, vomiting, and infection. Other end points included dose reductions and omissions, response, and survival. RESULTS: Women experienced significantly more hematologic toxicity than men (grade 3 and 4 anemia, 16.3% v 7.6%, respectively, P < .001; grade 3 and 4 leukopenia, 80.4% v 69.2%, respectively, P = .0001). However, toxic death rates were similar for men and women (1.5% v 1.1%, respectively, P = .58). Women also had significantly more stomatitis and vomiting of all grades. Despite increased toxicity, 76% of females versus 73.4% of males received all six treatment cycles (P = .38), but 52% of females versus 43.4% of males had treatment delayed for 2 weeks or more (P = .022). Only 31.8% of females and 28.2% of males had at least one cycle of chemotherapy dose reduction (P = .23). The overall response rate was 80.3% for females and 66.9% for males (P < .0001), and the median survival time was 1.31 years for females compared with only 0.91 year for males (P < .0001). CONCLUSION: Women experience more chemotherapy-related toxicity in the treatment of SCLC, but they also have increased response rates and survival.

Antineoplastic Combined Chemotherapy Protocols↗

PubMed2007

Dose-dependent reduction of dietary protein-induced colonocyte DNA damage by resistant starch in rats correlates more highly with caecal butyrate than with other short chain fatty acids.

Previous studies have shown increased levels of colonocyte DNA damage (as measured by the comet assay) and thinning of the colonic mucus layer in rats fed higher dietary protein as casein or red meat with highly digestible starch. Feeding resistant starch (RS) as high amylose maize starch (HAMS) opposed these changes. However, the dietary level of HAMS was relatively high (48% by weight) so this study was conducted to establish whether HAMS had the same effects at lower dietary levels. Adult male rats were fed a diet containing 25% casein with 0%, 10%, 20%, 30% or 40% HAMS for 4 wk. DNA single strand breaks and 8-hydroxyguanosine levels were measured in isolated colonocytes by the comet assay. As expected, comet tail moment was greatest and the mucus barrier thinnest in rats fed 0% HAMS. DNA damage was reduced and the mucus barrier thickened in a logarithmic dose-dependent manner by HAMS. There was no significant difference in 8-hydroxyguanosine between dietary groups. Caecal and fecal short chain fatty acid (SCFA) pools rose with the increased level of dietary HAMS. DNA damage of colonocytes correlated negatively with caecal SCFA but the strongest correlation was with caecal butyrate, which is consistent with the proposed role of this SCFA in promoting a normal cell phenotype. These data show that HAMS prevents protein-induced colonic DNA damage in a dose-dependent manner. Inclusion of 10% HAMS was found to be sufficient to oppose colonocyte DNA damage, and to increase caecal and fecal SCFA pools.

Animals↗

PubMed2004

A phase II trial of gefitinib (Iressa, ZD1839) in stage IV and recurrent renal cell carcinoma.

PURPOSE: The epidermal growth factor receptor (EGFR) is overexpressed in 75 to 90% of renal cell carcinomas and may play a role in tumor initiation and progression. Gefitinib (Iressa, ZD1839) is a potent, selective EGFR-tyrosine kinase inhibitor. This trial was undertaken to assess the efficacy and toxicity of gefitinib in advanced renal cell carcinoma. EXPERIMENTAL DESIGN: Oral gefitinib, 500 mg once daily, was given continuously. A single-dose reduction to 250 mg daily was allowed for toxicity. The primary end point was response rate (defined as complete remission + partial remission + stable disease). Secondary end points were progression-free survival, overall survival, toxicity, and correlation of response with EGFR status. RESULTS: Twenty-one patients were enrolled on this study, and all are evaluable for response and toxicity. Patient characteristics were median age 61 (range, 35-78 years); 17 males, 4 females; median performance status 0 (range 0-2); median number of prior systemic therapies 1 (range, 0-3). The median and mean number of cycles of therapy received was 3 and 4.7 (range, 1-14+). The best response was stable disease in eight patients (38%). Median progression-free survival was 2.7 months. Median overall survival was 8.3 months. The difference in overall survival was significantly different between patients with progressive disease versus stable disease (6.1 months versus 16+ months; Log-Rank test P value < 0.0001). Three patients required a dose reduction, all for grade 3 diarrhea. There was no apparent correlation between EGFR status and stability of disease or progression of disease. CONCLUSIONS: Gefitinib is without significant conventional activity in renal cell carcinoma. The relation of "stable disease" to treatment or to disease-related prognostic heterogeneity remains to be defined.

Adult↗

PubMed1995

Obesity and therapy-related toxicity in patients treated for small-cell lung cancer.

BACKGROUND: Obese individuals have altered pharmacokinetics for many medications when compared with the non-obese. For the oncologist treating an obese cancer patient, these changes in drug disposition may potentially cause increased therapy-related toxicity. As a consequence, oncologists frequently treat obese patients with dose reductions in an effort to decrease chemotherapy toxicity. However, little clinical data exist to either support or refute this policy. PURPOSE: The clinical course of a cohort of patients treated for small-cell lung cancer (SCLC) was evaluated to determine if the obese patients had an increase in therapy-related toxicity. METHODS: The study sample included 262 patients with histologically confirmed SCLC treated in clinical trials from 1977 through 1993. Before 1986, patients with limited stage SCLC were treated with a cyclophosphamide-based regimen with (n = 47) or without (n = 46) chest radiotherapy. Subsequent patients with limited stage disease (n = 54) received etoposide and cisplatin plus twice-daily chest radiotherapy. Patients with extensive stage SCLC were randomly treated with standard-dose (n = 46) or high-dose etoposide plus cisplatin (n = 44); poor-risk patients with extensive stage disease (n = 25) were assigned to standard dose etoposide plus cisplatin. For all patients, actual body weight was used when determining initial doses of chemotherapy. The measure of relative weight was the body mass index (BMI), which was calculated from the pretreatment height and weight data. The BMI was evaluated both on a continuum and with patients grouped into BMI levels (normal, obese, and severely obese). Toxicity parameters were collected during induction chemotherapy and were compared with the BMI. In addition, the overall survival of the entire cohort was evaluated, with patients divided into different groups based on their BMI level. RESULTS: We performed 170 comparisons between the BMI as a continuum or the BMI level and the 15 toxicity parameters. There were no consistent associations of significance found between increasing BMI or BMI levels and increasing toxicity from therapy. When survival was evaluated, no statistically significant differences were found between the survival of patients within the different BMI levels. CONCLUSIONS: In this group of 262 patients with SCLC, obesity at the start of treatment was not associated with increased toxicity from treatment or a shortened survival. No support for empiric chemotherapy dose reductions based on ideal body weight was evident from this study.

Antineoplastic Combined Chemotherapy Protocols↗

PubMed2006

Impact on adherence and sustained virological response of psychiatric side effects during peginterferon and ribavirin therapy for chronic hepatitis C.

BACKGROUND: The psychiatric side effects of interferon, often responsible for dose reduction or treatment discontinuation, represent a major limitation in the treatment of chronic hepatitis C (CHC). AIM: To prospectively assess the impact on adherence and sustained virological response (SVR) of the occurrence of psychiatric side effects during peginterferon and ribavirin therapy for CHC. METHODS: Ninety-eight consecutive treatment-naïve CHC patients receiving a standard course of peginterferon plus ribavirin were systematically screened for psychiatric side effects, using DSM-IV, at baseline and both during and after treatment. RESULTS: Psychiatric side effects occurred in 38 patients (39%), mostly within the first 12 weeks (87%), and always consisted of mood disorders. Overall, 68% of patients achieved an SVR (71% of patients with mood disorders and 68% of those without; P = N.S.). Peginterferon and ribavirin dose reductions did not differ between patients with mood disorders and those without (46% vs. 37%, respectively; P = N.S. and 13% vs. 22%, respectively; P = N.S.). Anti-viral therapy had to be discontinued in four patients (nonresponse: two, hyperthyroidism: one, psychiatric event: one). CONCLUSION: Early detection and appropriate management of psychiatric side effects during peginterferon and ribavirin therapy for CHC allow optimizing adherence and virological efficacy.

Antiviral Agents↗

PubMed2006

[Dose-reduced 16-slice multidetector-row spiral computed tomography in children with bronchoscopically suspected vascular tracheal stenosis -- initial results].

PURPOSE: To evaluate the diagnostic accuracy of contrast-enhanced dose-reduced 16-slice multidetector-row CT (MDCT) in newborns and infants with fiberoptic bronchoscopically suspected vascular-induced tracheal stenosis. MATERIALS AND METHODS: 12 children (4 days to 3 years, 1.2 - 13.5 kg body weight) were examined using i. v. contrast-enhanced 16-slice MDCT (SOMATOM Sensation 16, Forchheim, Germany) without breath-hold and under sedation (11/12). All MDCTs were performed with a dose reduction. The beam collimation was 16 x 0.75 mm, except in the case of one child. MPRs along the tracheal axis in the x-, y- and z-directions and volume-rendering-reconstructions (VRTs) were calculated based on a secondary raw data set in addition to conventional axial slices. 2 radiologists used a three-point grade scale to evaluate the image quality, motion, and contrast media artifacts as well as the usefulness of the 2D- and 3D-reconstructions for determining the diagnosis. Statistical analysis was performed on the basis of a Kappa test. RESULTS: In all cases the cause of the fiberoptic bronchoscopically suspected tracheal stenosis was revealed: compression due to the brachiocephalic trunk (n = 7), double aortic arch (n = 2), lusorian artery (n = 1), vascular compression of the left main bronchus (n = 2). In 3 patients further thoracic anomalies, such as tracheobronchial (n = 2), and vascular (n = 2) and vertebral (n = 1) anomalies were found. The attenuation in the anomalous vessels was 307 +/- 140 HU. The image noise was 9.8 +/- 1.9 HU. The mean dose reduction was 82.7 +/- 3.2 % compared to a standard adult thoracic CT. All examinations were rated as diagnostically good (median 1, range 1, k = 1). 3D images did not show any stair artifacts (median 2, range 1 - 2, k = 1). The image noise was minor to moderate and hardly any motion artifacts were seen (median 1, range 1 - 2, k = 0.8). Contrast media artifacts were rated zero to minor (median 1.5, range 1 - 2, k = 0.676). MPRs (median 1, range 1, k = 1) and VRTs (median 1, range 1, k = 1) were found to be useful for diagnosis. Subsequent vascular surgery was performed on 8 patients. CONCLUSION: Contrast-enhanced dose-reduced 16-slice MDCT is effective for demonstrating the cause of fiberoptic bronchoscopically suspected vascular-induced tracheal stenosis even in very small and severely ill children despite the small contrast media amount and free breathing.

Airway Obstruction↗

PubMed1988

Evaluation of a low-dose neonatal chest radiographic system.

A new low-dose chest radiographic system for use in the neonatal nursery was evaluated. This test system, composed of a Du Pont Kevlar fiber-front cassette, Quanta fast-detail screen, Cronex 4L film (wide latitude), and additional yttrium filtration (0.1 mm), reduced the radiation dose in neonatal chest radiography by 69% (0.9 vs 2.9 mrad [0.009 vs 0.029 mGy]) as compared with a conventional system without added yttrium filtration; the thyroid dose was reduced by 76% (0.9 vs 3.7 mrad [0.009 vs 0.037 mGy]). The cumulative dose reduction was achieved through a combination of factors, including (1) beam hardening by the added yttrium filter, (2) increased X-ray transmission through the Kevlar cassette, and (3) a fast film-screen combination. Scatter radiation at distances of 1 and 6 ft. (0.3 and 1.8 m) was negligible for both systems. Image sharpness was compared for the conventional system with and without added yttrium filtration and for the Kevlar system with yttrium. Although sharpness of bony detail was unchanged by adding yttrium filtration to the conventional system, a decrease in sharpness was noted with the Kevlar system. Because image sharpness was affected in the test system, we are not using the Kevlar-Cronex 4L system for mobile chest radiography in the neonatal intensive care unit, despite dose reductions. However, further study is recommended to determine if there is a slower film-screen combination with yttrium filtration that will not degrade image sharpness.

Evaluation Studies as Topic↗

PubMed2000

Patient radiation exposure during coronary angiography and intervention.

PURPOSE: To prospectively register fluoroscopic and cine times in a random fashion, and to measure patient radiation exposure from routine coronary angiography and coronary balloon angioplasty. We also evaluated an optional dose reduction system used during interventions. MATERIAL AND METHODS: The incident radiation to the patient was measured as kerma area product (KAP) in Gycm(2), obtained from an ionisation chamber mounted on the undercouch tube during 65 coronary angiography procedures and another 53 percutaneous transluminal coronary angioplasties (including 29 stent procedures), mostly directly following complete coronary angiography. RESULTS AND CONCLUSION: The values from coronary angiography were comparable to other reports with a mean fluoroscopic time of 4.4 min and a mean KAP value of 62.6 Gycm(2). The corresponding figures from coronary balloon angioplasty without stenting were lower than otherwise reported, with 8.2 min and 47.9 Gycm(2), respectively. The use of coronary stents did prolong the mean fluoroscopic time (10.5 min) but did not significantly enhance the patient mean radiation dose (51.4 Gycm(2)). The dose reduction technique resulted in a significant KAP value reduction of 57%. In conclusion, with regard to radiation exposure, coronary angiography and balloon angioplasty are considered safe procedures.

Angioplasty, Balloon, Coronary↗

PubMed1998

Forscarnet vs ganciclovir for cytomegalovirus (CMV) antigenemia after allogeneic hemopoietic stem cell transplantation (HSCT): a randomised study.

This trial was designed to compare foscarnet with ganciclovir as pre-emptive therapy for CMV infection in patients undergoing allogeneic hemopoietic stem cell transplant (HSCT). Thirty-nine patients were randomized to receive foscarnet 90 mg/kg every 12 h (n = 20) or ganciclovir 5 mg/kg every 12 h (n = 19) for 15 days at the time of development of CMVAg-emia. Primary-end points of the study were (1) outcome of CMVAg-emia; (2) progression to CMV disease; and (3) side-effects of treatment. The secondary end-point was transplant-related mortality (TRM). The two groups were comparable for diagnosis, status of disease, donor type, acute graft-versus-host (aGVHD) prophylaxis, interval between HSCT and CMVAg-emia and number of CMVAg positive cells; the donor and recipient age were borderline older in the foscarnet group. Increments of serum creatinine in the foscarnet group, and cytopenia in the ganciclovir group were controlled by reducing the administered dose: in the first 15 days of therapy 9/20 foscarnet and 10/19 ganciclovir patients had a dose reduction greater than 20% (P = 0.43). Clearance of CMVAg-emia was faster in the foscarnet group although with borderline statistical significance. Failures of treatment occurred in 3/20 patients in foscarnet group vs 8/19 patients in ganciclovir group (P= 0.06): causes of failure were the need for combination therapy to control antigenemia (1/20 vs 5/19), and reactivation during treatment for 2 vs 3 patients, respectively. CMV disease was diagnosed in 1 vs 2 patients (P = 0.5) who subsequently died. The actuarial 1-year TRM was 25 vs 12%, respectively (P = 0.3). This study suggests that foscarnet and ganciclovir are both effective for pre-emptive therapy of CMVAg-emia, although the number of failures would seem to be slightly higher in the ganciclovir patients. Side-effects are seen in both groups and can be managed with appropriate dose reduction.

Adolescent↗

PubMedDate not supplied

S-adenosylmethionine (AdoMet) supplementation for treatment of chemotherapy-induced liver injury.

BACKGROUND: Liver toxicity can be observed during treatment with most chemotherapic agents, and represents one of the principal causes of dose reduction or chemotherapy delays. S-Adenosylmethionine (AdoMet) plays a critical role in the synthesis of polyamines and provides cysteine for the production of glutathione (GSH), the major endogenous hepatoprotective agent. Our study was aimed at assessing the protective effect of AdoMet supplementation in cancer chemotherapy-induced liver toxicity. PATIENTS AND METHODS: Fifty cancer patients who developed, for the first time, anticancer chemotherapy-induced liver toxicity were studied. Enrolled patients received oral AdoMet supplementation. RESULTS: AST, ALT and LDH levels recorded at the moment of the recognition of liver toxicity were significantly reduced after one week of AdoMet therapy (respectively p: 0.009, 0.0005 and 0.012). AST, ALT and LDH decrease was confirmed after two weeks of treatment. Furthermore, the effect on these enzyme levels persisted in the following chemotherapy courses, permitting our patients to perform the scheduled chemotherapy courses with a minimal number of dose reductions or administration delays. The efficacy of AdoMet supplementation was not influenced by the presence of liver metastases, and no appreciable side-effects were recognized. CONCLUSION: The results of our study clearly demonstrate a protective effect of AdoMet in cancer chemotherapy-induced liver toxicity. Further large phase III studies are required to assess the real clinical benefit associated with AdoMet supplementation.

Adult↗

PubMed2000

A real-time flat-panel X-ray pixel imaging system for low-dose medical diagnostics and craniofacial applications.

The aim of this study was to evaluate on-line performance of a real-time digital imaging system based on amorphous silicon technology and to compare it with conventional film-screen equipment. The digital detecting imager consists of (1) a converter, which transforms the energy of the incident X rays into light; (2) a real-time digital detecting system, capable of producing as many as 10 pictures per second using a large-area pixel matrix (20 x 20 cm2) based on solid-state amorphous silicon sensor technology with a pitch of 400 microns; and (3) appropriate computer tools for control, real-time image treatment, data representation, and off-line analysis. Different phantoms were used for qualitative comparison with the conventional film-screen technique, with images obtained with both systems at the normal dose (used as a reference), as well as with dose reduction by a factor of 10 to 100. Basic image quality parameters evaluated showed that the response of the detector is linear in a wide range of entrance air kerma; the dynamic range is higher compared with the conventional film-screen combination; the spatial resolution is 1.25 lp per millimeter, as expected from the pixel size; and good image quality is ensured at doses substantially lower than for the film-screen technique. The flat-panel X-ray imager based on amorphous silicon technology implemented in standard radiographic equipment permits acquisition of real-time images in radiology (as many as 10 images per second) of diagnostic quality with a marked reduction of dose (as much as 100 times) and better contrast compared with the standard film technique. Preliminary results obtained with a 100-micron pitch imager based on the same technology show better quality but a less substantial dose reduction. Applications in craniofacial surgery look promising.

Analog-Digital Conversion↗

PubMed2005

Age does not impair the efficacy of immunochemotherapy in patients with metastatic renal carcinoma.

PURPOSE: Based on the increasing proportion of elderly cancer patients, we compared the efficacy of subcutaneous cytokine based home therapy in older (age > or = 60 years) and younger (age < 60 years) patients with metastatic renal cell carcinoma. PATIENTS AND METHODS: As a rule, patients at an age of 60 years or older received a 20% dose reduction of s.c. IL-2. Treatment consisted of (A) s.c. interferon-alpha2a (s.c. INF-alpha2a), s.c. interleukin-2 (s.c. IL-2), (B) s.c. IFN-alpha2a, s.c. IL-2 and i.v. 5-fluorouracil (5-FU) or (C) s.c. IFN-alpha2a, s.c. IL-2 and i.v. 5-FU combined with p.o. 13-cis-retinoic acid (p.o. 13cRA). RESULTS: Patient age groups > or = 60 years (n=174) and < 60 years (n=251) showed no significant difference in objective response (27% versus 31%), in median overall survival (22 months versus 19 months), and in progression-free survival (6 months versus 5 months). Within the elderly patients group, median overall survival was 20 months (pts. 60-64 years) versus 23 months (pts. > or = 65 years) and median progression-free survival was 4 months (pts. 60-64 years) versus 8 months (pts. > or = 65 years). CONCLUSION: Our results demonstrated that patient age and related IL-2 dose reduction do not impair the efficacy of s.c.-IL-2 plus s.c.-INF-2a based outpatient immunochemotherapy in metastatic renal carcinoma.

Age Factors↗

PubMed2004

The significance of myelosuppression during therapy with imatinib mesylate in patients with chronic myelogenous leukemia in chronic phase.

BACKGROUND: Imatinib mesylate induces high rates of hematologic and cytogenetic response in patients with chronic myelogenous leukemia (CML). During therapy with imatinib, up to 45% of patients with CML reportedly experience myelosuppression > or = Grade 3, requiring interruption of therapy and/or dose reductions. The significance of myelosuppression for response to imatinib is unknown. METHODS: The authors analyzed 143 patients with late chronic-phase CML who were treated with imatinib after failing interferon. Univariate and multivariate analyses were performed to determine patient characteristics that were correlated with myelosuppression response and the association between myelosuppression and cytogenetic response. RESULTS: Neutropenia > or = Grade 3 (according to National Cancer Institute Common Toxicity Criteria) occurred in 64 patients (45%), and thrombocytopenia > or = Grade 3 occurred in 31 patients (22%). Any myelosuppression > or = Grade 3 was associated with a lower rate of major (P = 0.04) or complete (P = 0.01) cytogenetic responses. This was more pronounced with myelosuppression that lasted > 2 weeks. The major cytogenetic response rate was 58% with Grade > or = 3 myelosuppression compared with a rate of 75% without Grade > or =3 myelosuppression (P = 0.03); the complete cytogenetic response rates were 36% and 63%, respectively (P = 0.001). In a multivariate analysis, pretreatment platelet count, imatinib dose reductions, and duration of myelosuppression were associated significantly with response. CONCLUSIONS: Myelosuppression is an independent adverse factor for achieving cytogenetic response with imatinib in patients with CML. Intervention with hematopoietic growth factors in patients with CML who are treated with imatinib should be investigated.

Aged↗

PubMed1993

The dose-dependent reduction in blood pressure through administration of magnesium. A double blind placebo controlled cross-over study.

Seventeen patients with a diastolic blood pressure over 90 mm Hg were recruited from a running health screening program to participate in a double blind cross-over study of magnesium supplementation (15 mmol Mg2+/day (Emgesan, Kabi Pharmacia) for 3 weeks, followed by 30 mmol Mg2+/day for another 3 weeks, finishing with 40 mmol Mg2+/day for a final 3 weeks). A significant decrease in the mean systolic blood pressure was recorded from 154.0 +/- 10.7 mm Hg to 146.1 +/- 16.9 mm Hg (P = .031) while the mean diastolic blood pressure decreased from 100.2 +/- 4.2 mm Hg to 92.0 +/- 6.6 mm Hg (P = .0001).

Adult↗

PubMed2002

Phase II study of irinotecan (CPT-11) in children with high-risk malignant brain tumors: the Duke experience.

A phase II study of irinotecan (CPT-11) was conducted at Duke University Medical Center, Durham, NC, to evaluate the activity of this agent in children with high-risk malignant brain tumors. A total of 22 children were enrolled in this study, including 13 with histologically verified recurrent malignant brain tumors (glioblastoma multiforme [GBM] 4, anaplastic astrocytoma 1, ependymoma 5, and medulloblastoma/primitive neuroectodermal tumor 3), 5 with recurrent diffuse pontine glioma, and 4 with newly diagnosed GBM. All patients with recurrent tumor had prior chemotherapy and/or irradiation. Each course of CPT-11 consisted of 125 mg/m ( 2 ) per week given i.v. for 4 weeks followed by a 2-week rest period. Patients with recurrent tumors received therapy until disease progression or unacceptable toxicity. Patients with newly diagnosed tumors initially received 3 cycles of treatment to assess tumor response and then were allowed radiotherapy at physician's choice; patients who demonstrated a response to CPT-11 prior to radiotherapy were allowed to continue the drug after radiation until disease progression or unacceptable toxicity. A 25% to 50% dose reduction was made for grade III-IV toxicity. Responses were assessed after every course by gadolinium-enhanced MRI of the brain and spine. Twenty-two patients received a median of 2 courses of CPT-11 (range, 1-16). Responses were seen in 4 of 9 patients with GBM or anaplastic astrocytoma (44%; 95% confidence interval, 11%-82%) (complete response in 2 patients with recurrent GBM lasting 9 months and 48+ months; partial response in one patient with a newly diagnosed midbrain GBM lasting 18 months prior to radiotherapy; and partial response lasting 11 months in 1 patient with recurrent anaplastic astrocytoma), 1 of 5 patients with recurrent ependymoma (partial response initially followed by stable disease lasting 11 months), and none of 5 patients with recurrent diffuse pontine glioma. Two of 3 patients with medulloblastoma/primitive neuroectodermal tumor had stable disease for 9 and 13 months. Toxicity was mainly myelosuppression, with 12 of 22 patients (50%) suffering grade II-IV neutropenia. Seven patients required dose reduction secondary to neutropenia. CPT-11, given in this schedule, appears to be active in children with malignant glioma, medulloblastoma, and ependymoma with acceptable toxicity. Ongoing studies will demonstrate if activity of CPT-11 can be enhanced when combined with alkylating agents, including carmustine and temozolomide.

Adolescent↗

PubMed2004

Enteric-coated mycophenolate sodium: therapeutic equivalence to mycophenolate mofetil in de novo renal transplant patients.

The introduction of mycophenolate mofetil (MMF)--the morpholino ester prodrug of mycophenolic acid (MPA)--has improved graft and patient survival, but its use has been linked with the occurrence of adverse events, particularly gastrointestinal (GI) side effects. These can be sufficiently severe to require dose reductions or discontinuation, which may lead to acute rejection episodes or graft failure. An enteric-coated formulation delivering mycophenolic acid-enteric-coated mycophenolate sodium (EC-MPS)-has been developed with the aim of improving upper GI tolerability. Therapeutic equivalence of EC-MPS 720 mg b.i.d. vs MMF 1000 mg b.i.d. has been established in a pivotal phase III, 12-month, international, randomized, double-blind, parallel group study, involving patients undergoing de novo renal transplantation. The incidence of efficacy failure (composite variable of biopsy-proven acute rejection [BPAR], graft loss, death or loss to follow-up) was similar between the two groups at 6 months (EC-MPS 25.8% vs MMF 26.2%; 95% CI [-8.7, +8.0]), demonstrating therapeutic equivalence. Efficacy failure remained similar between the two treatment groups at 12 months. The overall incidence of adverse events and GI side effects were also comparable between treatment groups throughout the 12-month study period, although fewer patients in the EC-MPS group experienced study drug discontinuations, interruptions, or dose reductions (12 months: EC-MPS 15.0% vs MMF 19.5%). Subgroup analysis revealed similar safety profiles for EC-MPS and MMF in elderly patients and patients with diabetes at baseline. The EC-MPS 720 mg b.i.d. and MMF 1000 mg b.i.d. show therapeutic equivalence in de novo renal transplant patients. Therefore, EC-MPS offers transplant physicians and their patients an alternative MPA therapy that is as effective and safe as MMF.

Chemistry, Pharmaceutical↗