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PubMed1984

Rifampicin-induced adrenal crisis in addisonian patients receiving corticosteroid replacement therapy.

Rifampicin induced profound alterations in cortisol metabolism when administered to three patients with primary adrenal failure receiving adequate corticosteroid replacement therapy. In one patient, adrenal crisis was precipitated after the institution of rifampicin therapy for treatment of coexistent tuberculosis and in another, profound asthenia, decrease in blood pressure, hyperkalemia, and hyponatremia developed during the hydrocortisol kinetic study. The clinical symptoms subsided and the electrolyte abnormalities were corrected approximately 7 days after rifampicin withdrawal. The half-life of hydrocortisol and the area under the curve were decreased by 35% and 23%, respectively, whereas the systemic clearance was increased by 35% during rifampicin administration. It appears, that the effectiveness of glucocorticoids and mineralocorticoids were greatly impaired by rifampicin administration due to induction of liver steroid-metabolizing enzymes. It is strongly recommended that in patients with compromised adrenal function, treatment with rifampicin must be accompanied by doubling or tripling the dose of adrenal steroids to maintain adequate steroid replacement therapy.

Acute Disease↗
PubMed1991

A comparison of the efficacy and safety of pergolide and bromocriptine in the treatment of hyperprolactinemia.

UNLABELLED: Pergolide is a synthetic ergoline derivative with highly potent long-acting PRL-lowering activity, allowing therapy of hyperprolactinemia with a once daily administration of the drug. The results of two open-label, randomized controlled multicenter clinical trials are reported. Pergolide (taken once a day), was compared with bromocriptine (taken two to four times daily) regarding efficacy and safety in the reduction of PRL levels, the cessation of galactorrhea and amenorrhea, the improvement in sexual function, and tumor shrinkage in hyperprolactinemia without (trial I; 61 patients) and with radiologically evident pituitary tumors (trial II; 96 patients). Both drugs were equally effective in lowering PRL levels in both trials. A median optimal dose of 50 micrograms pergolide and 5 mg bromocriptine/day suppressed PRL levels in the 61 patients of trial I by more than 80%. During the 24-week investigational period galactorrhea disappeared in 96% and 87% of patients, whereas menstruation returned in 90% and 96% of patients, respectively. An equally high efficacy (optimal median dose: 75-100 micrograms pergolide, 7.5-10 mg bromocriptine daily) was observed in trial II, although the resumption of menses was less frequent than in the patients of trial I (50% and 58% of patients, respectively). Sexual dysfunction improved similarly on both drugs in about half the patients. In addition, tumor shrinkage occurred to a similar extent with both drugs. A high incidence of adverse events was noted especially at the initiation of therapy with both compounds: nausea, dizziness, vomiting, asthenia, headache, and decrease in blood pressure occurred at a similar incidence and extent during the use of pergolide and bromocriptine. Patients in trial I treated with pergolide reported a slightly higher incidence of fever, vasodilatation, and flu syndrome. CONCLUSIONS: in these 24-week studies comprising a total of 157 hyperprolactinemic patients, a once daily administration of pergolide was shown to be as safe and effective as the two to four times daily ingestion of bromocriptine. Longer-acting dopamine agonists like pergolide that can be taken once daily, are likely to increase the ease to adherence to the therapeutic regimen. This might result in a higher compliance to medical treatment of hyperprolactinemia.

Adult↗
PubMed2000

Novel human corticosteroid-binding globulin variant with low cortisol-binding affinity.

Corticosteroid-binding globulin (CBG) is the plasma transport protein that regulates the access of glucocorticoid hormones to target cells. Genetic deficiencies of CBG are rare, and only a single human CBG variant (Trancortin Leuven) has been related so far to decreased cortisol-binding affinity. We report here on a 43-yr-old woman, referred for chronic asthenia and hypotension, with repeatedly low morning serum cortisol levels (22-61 nmol/L; normal range, 204-546 nmol/L), normal plasma ACTH levels (38-49 pg/mL; normal, <50 pg/mL), and normal urinary cortisol (10-76 nmol/24 h; normal range, 10-105 nmol/24 h). An increased percent-free (dialysable fraction) serum cortisol (8.7-9.7%, normal range, 2.9-3.9%) suggested abnormal CBG binding activity. Indeed, she had a low serum CBG concentration (24 mg/L vs. 44+/-6 mg/L in normal women), and the affinity of her CBG for cortisol was decreased (association constant, Ka = 0.12 L/nmol vs. 0.82+/-0.29 L/nmol). In her immediate family members, the serum CBG concentration and cortisol-binding activity were normal in her husband, but the four living children had slightly lower serum CBG concentrations than the reference ranges for their pre- and postpubertal status. Measurements of cortisol distribution in undiluted serum indicated that an increase in the percentage of nonprotein-bound cortisol offsets the low cortisol levels to give approximately normal concentrations of free cortisol in serum. Direct sequencing of PCR-amplified exons encoding CBG revealed that the proband was homozygous for a polymorphism (GAC-AAC) in the codon for residue 367, which results in a Asp367-->Asn substitution. Her children were heterozygous for this polymorphism. When this nucleotide change was introduced into a normal human CBG complementary DNA, for expression in Chinese hamster ovary cells, Scatchard analysis demonstrated that the Asn367 substitution reduced the affinity of human CBG for cortisol by approximately 4-fold (Ka = 0.15 L/nmol), as compared to normal recombinant CBG (Ka = 0.66 L/nmol). These results suggest that Asp367 is an important determinant of CBG steroid-binding activity and that normal negative regulation of the hypothalamic-pituitary-adrenal axis is maintained by relatively normal serum-free cortisol concentrations, despite a marked reduction in the steroid-binding affinity of this novel human CBG variant, which we have designated as CBG-Lyon.

Adrenal Cortex Diseases↗
PubMed2004

Randomized, placebo-controlled trial of rofecoxib in the acute treatment of migraine.

OBJECTIVE: To investigate the clinical profile of rofecoxib, a long-acting (approximately 17-hour half-life) selective cyclo-oxygenase-2 inhibitor, for the acute treatment of migraine. METHODS: A randomized, double-blind, placebo-controlled, parallel-group study was conducted. Patients age > or =18 treated a moderate or severe migraine headache with placebo (n = 182), rofecoxib 25 mg (n = 183), or rofecoxib 50 mg (n = 192). The primary efficacy measure was headache relief (mild or no pain) 2 hours after dose. RESULTS: The proportions of patients with migraine headache relief at 2 hours after dose were 34.3% for placebo, 54.0% for rofecoxib 25 mg (p < 0.001 vs placebo), and 56.7% for rofecoxib 50 mg (p < 0.001 vs placebo). Rofecoxib 25 and 50 mg were superior to placebo in providing pain freedom at 2 hours, 24-hour sustained headache relief, and 24-hour sustained pain freedom; in reducing photophobia, phonophobia, nausea (50 mg only), and functional disability at 2 hours after dose; and in improving some quality-of-life scores over 24 hours. More patients on rofecoxib 50 mg reported adverse events (39.6%) than patients on rofecoxib 25 mg (26.8%) or placebo (23.6%) regardless of drug relatedness; however, the incidences of drug-related adverse events were similar between treatment groups. These adverse events were generally mild or moderate in severity. The most commonly reported adverse events were dry mouth, dizziness, somnolence, nausea, dyspepsia, paresthesia, and asthenia, with similar incidences between treatment groups. CONCLUSION: Rofecoxib 25 and 50 mg were effective and generally well tolerated for the acute treatment of migraine attacks.

Acute Disease↗
PubMed1991

Fulminating multiple sclerosis-like leukoencephalopathy revealing human immunodeficiency virus infection.

A 66-year-old French homosexual man and a 42-year-old Brazilian man with no known risk factors for HIV infection developed headaches, asthenia, and neurologic episodes of abrupt onset. CT showed multiple hypodense, nonenhancing lesions. Serology for HIV was positive. They died respectively 2 months and 1 month after onset of the illnesses. Autopsy in both cases showed multiple, well-demarcated, demyelinating foci in the white matter of the cerebral hemispheres, brainstem, and cerebellum with histologic features characteristic of recent plaques of multiple sclerosis. There were no multinucleated giant cells or microglial nodules. Immunostaining for HIV was negative. Although a random coincidence of MS and HIV infection cannot be ruled out, the close temporal relationship between the 2 disorders suggests a possible etiologic association.

Adult↗
PubMed1995

Progesterone therapy in women with complex partial and secondary generalized seizures.

This open trial assessed the effects of adjunctive progesterone therapy on seizure frequency in 25 women with catamenial exacerbation of complex partial (CPS) and secondary generalized motor (SGMS) seizures. Progesterone was well tolerated by 23 of the 25 women and had readily reversible dose-related side effects of asthenia and emotional depression in two. Eighteen women (72%) experienced a decline in seizure frequency during a 3-month treatment period compared with the 3 months prior to therapy (p < 0.01). Average daily CPS frequency declined by 54% (p < 0.01), SGMS by 58% (p < 0.02).

Adolescent↗
PubMed1996

A confirmatory dose-ranging study of riluzole in ALS. ALS/Riluzole Study Group-II.

ALS is a progressive motor neuron disease with no effective treatment. The anti-excitotoxic drug riluzole (100 mg/day) has been shown to decrease mortality and muscular deterioration in ALS patients. To confirm and extend the therapeutic effect of riluzole, we performed a double-blind, placebo-controlled, multicenter, international, dose-ranging (50, 100, 200 mg/day), stratified study in 959 ALS outpatients treated for up to 18 months. Primary efficacy criterion was survival and the effect of treatment was analyzed before (Wilcoxon and log rank tests) and after adjustment on prognostic factors (Cox model). Secondary efficacy criterion was disease progression assessed through change in functional measures. Tracheostomy-free survival rates were: 50.4% (placebo), 55.3% (50 mg riluzole) (p = 0.23, Wilcoxon test; p = 0.25, log-rank test), 56.8% (100 mg riluzole) (p = 0.05, Wilcoxon test; p = 0.076, log-rank test), and 57.8% (200 mg riluzole) (p = 0.061, Wilcoxon test; p = 0.075, log-rank test). At the end of the 18-month study, there was a significant dose-related decrease in risk of death or tracheostomy (p = 0.04). Adjustment for baseline prognostic factors showed a 35% decreased risk of death with the 100-mg dose compared with placebo (p = 0.002). No significant treatment effects were detected for the functional assessments. The most frequent dose-related adverse events included nausea, asthenia, and elevated liver enzyme levels. This study confirms the therapeutic effect of riluzole in a large representative ALS sample, over an 18-month period. Riluzole is well tolerated and decreases the risk of death or tracheostomy in ALS patients.

Amyotrophic Lateral Sclerosis↗
PubMed1997

Safety and efficacy of divalproex sodium monotherapy in partial epilepsy: a double-blind, concentration-response design clinical trial. Depakote Monotherapy for Partial Seizures Study Group.

This is the first randomized, double-blind, parallel-group, multicenter trial that evaluated the efficacy of divalproex sodium monotherapy by comparing seizure frequency in 143 patients with poorly controlled partial epilepsy randomly assigned to high (80 to 150 micrograms/mL; 555 to 1,040 mumol/L) or low (25 to 50 micrograms/mL; 175 to 345 mumol/L) plasma valproate groups. There was a statistically significant reduction from baseline in the 8-week frequency of complex partial (p = 0.001) and secondarily generalized tonic-clonic seizures (p = 0.018) for patients in the high, compared with the low, plasma valproate group. Compared with baseline, there was a 30% median reduction in complex partial seizures for patients in the high group and a 19% increase for those in the low group. The median reduction for secondarily generalized tonic-clonic seizures was 70% for patients in the high group compared with a 22% increase in the low group. Adverse events that occurred significantly more frequently in the high group included tremors, thrombocytopenia, alopecia, asthenia, diarrhea, vomiting, and anorexia. This study demonstrates the efficacy of divalproex sodium as monotherapy for the treatment of partial-onset seizures and supports its role as one of the first-line antiepileptic drug treatments for patients with partial epilepsy.

Adolescent↗
PubMed2000

Levetiracetam for partial seizures: results of a double-blind, randomized clinical trial.

OBJECTIVE: To evaluate the efficacy and safety of 500 mg bid and 1500 mg bid levetiracetam as adjunctive therapy for refractory partial seizures in a double-blind, randomized, placebo-controlled, parallel-group, multicenter trial. METHODS: The authors studied patients with uncontrolled partial seizures (minimum 12 per 12 weeks), regardless of whether they became secondarily generalized, for 38 weeks. A 12-week baseline was followed by random assignment to adjunctive therapy with placebo (n = 95), levetiracetam 1000 mg/day (n = 98), or levetiracetam 3000 mg/day (n = 101). Upward titration over 4 weeks was followed by 14 weeks of fixed dose treatment, and concluded with an 8-week medication withdrawal period or entering a follow-up study. RESULTS: Of 294 patients randomized, 268 completed the study. Partial seizure frequency during the entire evaluation period (primary efficacy variable) was lower with levetiracetam compared to placebo (p </= 0.001 for both groups). More patients responded (defined as minimum 50% reduction in partial seizure frequency) to levetiracetam than placebo, with rates of 33. 0% in the 1000 mg/day and 39.8% in the 3000 mg/day group, compared to 10.8% in the placebo group (p < 0.001). Of 199 patients receiving levetiracetam, 11 became seizure free; no patient became seizure free in the placebo group. Treatment-emergent adverse events (>/=10%), mostly mild to moderate in severity, with incidences higher than placebo were asthenia, dizziness, flu syndrome, headache, infection, rhinitis, and somnolence. CONCLUSION: Adjunctive therapy with levetiracetam was effective and well tolerated in controlling partial seizures.

Adolescent↗
PubMed1997

Recombinant human interferon-beta in the treatment of condylomata acuminata.

The number of clinic consultations for condylomata acuminata (genital warts) has increased substantially during the last 30 years. Most infections produce benign lesions but a few types may be associated with cervical and penile cancers. Interferons (IFN) have shown antiviral properties to these infections and IFN-beta in particular has demonstrated a specific cytopathic effect in humans. A total of 124 patients with condylomata acuminata, the majority of whom had failed previous therapy, were treated intralesionally with either recombinant human interferon-beta la (r-hIFN-beta-1a) or placebo. Up to 6 lesions were treated in each patient, and injections were made 3 times per week for a total of 9 injections. The patients were then followed up for 3 months. Efficacy assessments at all time points (day 19, week 6 and month 3) showed a clear advantage for the r-hIFN-beta-1a interferon-beta treatment. Patients receiving r-hIFN-beta-1a showed a greater proportion of treatment success in terms of the complete or partial reduction (at least 50%) of the total area of the treated lesions. The treatment was also well tolerated. Headache, flu-like symptoms and asthenia were more common in patients receiving r-hIFN-beta-1a, but these adverse events were generally mild in severity and rarely led to patient withdrawal. It was concluded that r-hIFN-beta-1a has good efficacy in condylomata acuminata, and therefore presents a useful therapeutic alternative in this hard-to-treat condition.

Adult↗
PubMed2000

Tamsulosin for the treatment of benign prostatic hypertrophy.

OBJECTIVE: To review the information necessary to assess the efficacy and safety of tamsulosin compared with other adrenergic antagonists for treatment of symptomatic benign prostatic hyperplasia. DATA SOURCES: A search was conducted of Cumulated Index Medicus, January 1993-August 1999, which was restricted to human trials and English-language journals. STUDY SELECTION AND DATA EXTRACTION: Efficacy studies were included if the design was randomized and included a control group. Drug safety was assessed using data from any patient series or controlled study. DATA SYNTHESIS: Tamsulosin, a uroselective alpha1A-adrenergic receptor antagonist, relaxes smooth muscle in the prostate and bladder neck, thereby enhancing bladder emptying. In randomized, controlled clinical trials using standardized instruments, tamsulosin improves obstructive voiding symptoms by at least 25% in 65-80% of patients with symptomatic benign prostatic hyperplasia. Tamsulosin also improves peak urinary flow rate by 1.4-3.6 mL/sec in various studies and reduces post-void residual urine volume. The usual dosage of tamsulosin was 0.4 or 0.8 mg orally once a day in the studies performed in the US and Europe; daily doses of 0.1-0.4 mg were used in studies performed in Japan. The beneficial effects of tamsulosin on voiding symptoms, peak urinary flow rate, and bladder emptying appear to be dose-related, up to a ceiling dose of 0.4 mg. The most common adverse effects are headache, asthenia, dizziness, and rhinitis-like complaints. Retrograde or delayed ejaculation occurs in 4.5-14.0% of patients and has required discontinuation of treatment in a minority of these patients. At the usual dose of 0.4-0.8 mg/d, tamsulosin does not appear to significantly reduce blood pressure, increase heart rate, or cause first-dose syncope; therefore, dosage titration is not necessary when initiating treatment. Use of nifedipine, enalapril, atenolol, furosemide, or digoxin does not require dosage modification when tamsulosin is initiated concomitantly; hypotension has not been reported with combined use of tamsulosin and these commonly used agents. CONCLUSIONS: Tamsulosin is an improvement over other alpha-adrenergic antagonists for the management of symptoms of benign prostatic hyperplasia. It is a more convenient alternative that does not require initial dosage titration, has a fast onset of action, and has a low potential to cause hypotension when used alone or in combination with commonly used antihypertensive agents. It is more costly than some of the other second-generation alpha-adrenergic antagonists.

Adrenergic alpha-Antagonists↗
PubMed2004

Aprepitant: a novel antiemetic for chemotherapy-induced nausea and vomiting.

OBJECTIVE: To evaluate the safety and efficacy of aprepitant in the prevention of acute and delayed chemotherapy-induced nausea and vomiting (CINV). DATA SOURCES: MEDLINE and PubMed database searches were conducted from 1966 to May 2004 using the following search terms: aprepitant, Emend, substance P, neurokinin-1, chemotherapy, nausea, vomiting, L-754,030, and MK-869. STUDY SELECTION AND DATA EXTRACTION: Large, randomized Phase II and III clinical trials examining the use of aprepitant for CINV, as well as all published drug interaction studies with aprepitant, were included and reviewed. Data lacking in published trials were supplemented with the manufacturer product information. DATA SYNTHESIS: The pharmacokinetics of aprepitant are favorable for once-daily oral dosing. Based on the results of published clinical trials, aprepitant appears to augment the effects of corticosteroids and 5-HT3 antagonists when given prior to highly emetogenic chemotherapy, including cisplatin. Aprepitant appears to have the most benefit in the prevention of delayed CINV and in preventing emesis rather than nausea. Data in pediatric patients, patients undergoing stem-cell transplantation, and those receiving multiple-day or moderately emetogenic chemotherapy are lacking. Common adverse effects are limited to hiccups, asthenia, and diarrhea. More serious but rare adverse effects include neutropenia. Because aprepitant is a CYP3A4 substrate, a 3A4 inhibitor and inducer, and a 2C9 inducer, close monitoring for drug interactions is warranted. CONCLUSIONS: Triple antiemetic therapy with aprepitant, a corticosteroid, and a 5-HT3 antagonist appears to provide improved efficacy in the prevention of emesis in patients receiving highly emetogenic chemotherapy. Due to its novel mechanism of action and demonstrated efficacy in this combination, aprepitant should be considered for formulary addition.

Antiemetics↗
PubMed1998

Tiagabine.

Tiagabine inhibits gamma-aminobutyric acid uptake into neurons and glia. This mechanism of action is specific and unique among the antiepileptic drugs (AEDs). Tiagabine is efficacious in animal seizure models at subtoxic doses. There is no evidence of clinically important teratogenicity, carcinogenicity or mutagenicity in animals treated acutely or chronically with tiagabine. Tiagabine has no clinically relevant effect on hepatic metabolism or serum levels of other AEDs, has no clinically significant effects on laboratory values and has not been shown to have any clinically important interactions with common non-AEDs. Tiagabine has linear, predictable pharmacokinetics that do not vary significantly with age. Adverse effects are usually mild to moderate in severity and almost always resolve without medical intervention. The most common adverse events in controlled studies are dizziness, asthenia, somnolence, accidental injury, infection, headache, nausea and nervousness. Tiagabine is effective as add-on therapy for partial seizures in patients with medically refractory epilepsy in doses ranging from 32-56 mg daily. Despite its short half-life of 2-3 hours in patients on enzyme-inducing AEDs, tiagabine is effective when dosed 2-3 times a day. Conversion to tiagabine monotherapy can be achieved in patients with medically refractory epilepsy, though additional studies are needed to establish the effective dosage range. The introduction of drugs like tiagabine that have known mechanisms of action which differ from existing treatments further increases the range of options for patients with epilepsy.

Journal Article↗
PubMed2001

Levetiracetam: A new antiepileptic drug for the adjunctive therapy of chronic epilepsy.

Levetiracetam has recently been licensed in Europe and the U.S.A. for use as an adjunctive agent in partial epilepsy with or without secondary generalization. The mode of action has yet to be elucidated, but may involve a new brain-specific binding site, the ligand for which is unknown. Levetiracetam has a favorable pharmacokinetic profile, with rapid and almost complete oral absorption, almost 100% bioavailability, linear, dose-dependent maximum plasma concentrations and minimal plasma protein binding. Excretion is mainly renal, with most of the drug being eliminated unchanged. Levetiracetam does not have an effect on the major drug-metabolizing hepatic enzymes, and thus is associated with a low incidence of interactions with other antiepileptic drugs (AEDs). These properties make it a well-tolerated drug, with the most common reported side effects being asthenia, somnolence, headache and dizziness. Antiepileptic properties of levetiracetam demonstrated in animal studies have been borne out by large double-blind, placebo-controlled clinical trials, with significantly improved responder rates (>/= 50% reduction in seizure frequency from baseline) and number of seizure- free patients versus placebo. In addition, efficacy appears to be maintained over the long term and no evidence for the development of tolerance to the effects of levetiracetam has been seen. (c) 2001 Prous Science. All rights reserved.

Journal Article↗
PubMed1992

Orthostatic and exercise-induced advanced nodal atrioventricular block.

A 69-year-old woman was referred for asthenia and dizziness when walking in the last two months. No clinical abnormalities were found, and sinus rhythm was present when lying down. On orthostatism and walking, advanced AV block developed. Atropine and isoproterenol ameliorated the AV conduction abnormality, suggesting a nodal block. The patient remained asymptomatic after pacemaker implantation.

Aged↗
PubMed2004

Sarcoidosis diagnosed in elderly subjects: retrospective study of 30 cases.

STUDY OBJECTIVE: This study investigated the clinical features and disease course of sarcoidosis diagnosed in patients > 70 years of age. METHODS: A retrospective analysis was made of cases treated at the University Hospital in Nantes, France, between 1986 and 2000. The diagnosis of sarcoidosis was confirmed histopathologically. Cases involving progressive cancer and active tuberculosis were excluded. RESULTS: Thirty white patients with sarcoidosis diagnosed after age 70 years (mean, 74 years) were included. An alteration of general health (asthenia and/or anorexia and/or weight loss) was frequent (53%) and characteristic of the systemic form of the disease. Dyspnea was a fairly common sign (23%). The intrathoracic form of sarcoidosis was most frequent (43.3%). Diagnosis was difficult and lengthy, and symptomatology was atypical. Accessory salivary gland biopsy was an important contributing factor to diagnosis (70.6% were positive). Oral corticosteroid therapy was often required (60.7%). The disease course was satisfactory overall (81.8% of cases), but only for 50% of patients in intrathoracic stage IV. CONCLUSIONS: The clinical presentation of sarcoidosis in elderly subjects is mainly characterized by an alteration of general health. Diagnosis is difficult and should include accessory salivary gland biopsy. Therapy frequently involves corticosteroids. Overall prognosis is similar to that for young subjects.

Aged↗
PubMed1983

Effects of long-term clonidine administration on the hemodynamic and neuroendocrine postural responses of patients with dysautonomia.

Patients with mitral valve prolapse syndrome (MVPS), vasoregulatory asthenia, and poor postural adjustment often have orthostatic intolerance characterized by tachycardia and a narrow pulse pressure on standing. Autonomic dysfunction is thought to play an important role. Increased alpha-adrenergic activity has been shown in MVPS patients with orthostatic intolerance. We measured hemodynamic and neuroendocrine responses to long-term oral clonidine therapy in eight women, aged 36 +/- 1.8 years (27 to 44 years). None had responded favorably to beta-blockers. Heart rate, blood pressure, oxygen consumption, cardiac output, and plasma norepinephrine levels were measured in both supine and standing positions, before and after one to four weeks of clonidine (0.3 to 0.4 mg daily). Clonidine reduced standing plasma norepinephrine levels, total peripheral resistance, and diastolic blood pressure; a smaller decrease in cardiac output on standing was noted. Plasma volumes increased 12 percent. Mild reductions in plasma catecholamines and total peripheral resistance are associated with fewer, not more, orthostatic symptoms in this group of patients. "Placebo" or mild sedative effects may explain part of the response to clonidine, but the hemodynamic and neuroendocrine data suggest that decreased alpha-adrenergic hyperactivity may also be important.

Adult↗
PubMed2004

Raltitrexed plus weekly oxaliplatin as first-line chemotherapy in metastatic colorectal cancer: a multicenter non-randomized phase ii study.

AIM: The primary aims of this study were activity and toxicity evaluation of a new raltitrexed and oxaliplatin-based regimen, as a first-line chemotherapy, in patients with metastatic colorectal cancer (MCC). Survival evaluation was considered a secondary endpoint. PATIENTS AND METHODS: Forty-four patients were enrolled into this phase II trial. Treatment consisted of raltitrexed 3 mg/m2 iv on d 1 and oxaliplatin 70 mg/m2 iv on d 1 and d 8 every 3 wk. RESULTS: Twenty patients (45.5%) achieved a response [95% confidence interval (CI): 30.1% to 54.1%], 18 (40.9%) had stable disease, and only 6 (13.6%) developed progressive disease. After a median follow-up time of 14.7 mo (range 6.3-18.6 mo), the median time to disease progression was 6 mo (range 2.0-16.7) (95% CI: 4.4-7.6) and the overall survival was 14.8 mo (range 3-23) (95% CI: 11.2-18.4). Neutropenia was the most common hematological side effect, while transient AST/ALT increase, neurotoxicity, asthenia, and diarrhea were the most common nonhematological side effects. CONCLUSIONS: Our data confirmed that oxaliplatin administered weekly plus raltitrexed is an active combination in newly diagnosed patients with advanced colorectal carcinoma that merits further investigation versus the classic schedule in a randomized, phase III trial.

Adult↗