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Biomedical subjects

A Awada

Publications and source records attributed to A Awada.

At least 19 recordsLinked to original sources
PubMed2000

Carzelesin phase II study in advanced breast, ovarian, colorectal, gastric, head and neck cancer, non-Hodgkin's lymphoma and malignant melanoma: a study of the EORTC early clinical studies group (ECSG).

PURPOSE: In a phase II trial, the activity of carzelesin, a cyclopropylpyrroloindole prodrug analog, was assessed. PATIENTS AND METHODS: Carzelesin was used as second- or third-line chemotherapy in patients with breast, ovarian, head and neck cancer and non-Hodgkin's lymphoma, and as first-line chemotherapy in patients with colorectal and gastric cancer and melanoma. The drug was given as a bolus infusion at a 4-weekly dose of 150 microg/m2. A total of 140 patients were entered and a total of 285 courses were administered. RESULTS: In general, the compound was well tolerated. Myelotoxicity was the most common toxicity. Grade 3 and 4 leukopenia was observed in 18.6% of the courses, neutropenia in 20.3%, thrombocytopenia in 16.2% and anemia in 8.7%. Double nadirs were seen in a total of 41 courses for neutrophils, in 40 for leukocytes and in 3 for platelets. Non-hematological toxicity was very mild. Only one partial response in a patient with melanoma was seen. CONCLUSIONS: At this dose and schedule carzelesin did not yield activity in the types of tumors studied.

Adult↗
PubMed2000

Paclitaxel versus doxorubicin as first-line single-agent chemotherapy for metastatic breast cancer: a European Organization for Research and Treatment of Cancer Randomized Study with cross-over.

PURPOSE: To compare the efficacy of paclitaxel versus doxorubicin given as single agents in first-line therapy of advanced breast cancer (primary end point, progression-free survival ¿PFS) and to explore the degree of cross-resistance between the two agents. PATIENTS AND METHODS: Three hundred thirty-one patients were randomized to receive either paclitaxel 200 mg/m(2), 3-hour infusion every 3 weeks, or doxorubicin 75 mg/m(2), intravenous bolus every 3 weeks. Seven courses were planned unless progression or unacceptable toxicity occurred before the seven courses were finished. Patients who progressed within the seven courses underwent early cross-over to the alternative drug, while a delayed cross-over was optional for the remainder of patients at the time of disease progression. RESULTS: Objective response in first-line therapy was significantly better (P =.003) for doxorubicin (response rate ¿RR, 41%) than for paclitaxel (RR, 25%), with doxorubicin achieving a longer median PFS (7.5 months for doxorubicin v 3.9 months for paclitaxel, P <.001). In second-line therapy, cross-over to doxorubicin (91 patients) and to paclitaxel (77 patients) gave response rates of 30% and 16%, respectively. The median survival durations of 18.3 months for doxorubicin and 15.6 months for paclitaxel were not significantly different (P =.38). The doxorubicin arm had greater toxicity, but this was counterbalanced by better symptom control. CONCLUSION: At the dosages and schedules used in the present study, doxorubicin achieves better disease and symptom control than paclitaxel in first-line treatment. Doxorubicin and paclitaxel are not totally cross-resistant, which supports further investigation of these drugs in combination or in sequence, both in advanced disease and in the adjuvant setting.

Adenocarcinoma↗
PubMed1999

Cerebrospinal fluid lavage in the treatment of inadvertent intrathecal vincristine injection.

Vincristine, a widely used antineoplastic agent, is extremely toxic to the central nervous system. If given intrathecally, it produces a rapidly ascending, usually fatal, neuromyeloencephalopathy. We report a case of this complication in a 7-year-old girl with acute lymphoblastic leukemia who was receiving maintenance chemotherapy. During one treatment 0.5 mg of vincristine was erroneously injected into the lumbar subarachnoid space. Cerebrospinal fluid lavage was established within 2 h and continued for 24 h. After 7 days she developed a progressive sensorimotor paraplegia, which eventually stabilized as a paraparesis. Neurophysiological studies were consistent with an axonal type sensorimotor neuropathy. Magnetic resonance imaging of the spine was normal. Vincristine binds to cells, blocking mitosis, thus causing cell death. The associated central nervous system lesions are those of an ascending chemical leptomeningitis and ventriculitis. Cerebrospinal fluid lavage dilutes and removes the drug, thus limiting neural damage. At present this is the only treatment for intrathecal vincristine injection, and its early use in such an event is considered mandatory.

Child↗
PubMed1999

Phase I study of Carzelesin (U-80,244) given (4-weekly) by intravenous bolus schedule.

Carzelesin is a cyclopropylpyrroloindole analogue which acts as a DNA-sequence-specific alkylating agent. In this phase I study, Carzelesin was given as a 4-weekly 10 min i.v. infusion to 51 patients with advanced solid tumours. Patients received a median of two courses (range 1-5) at one of nine dose levels: 24, 48, 96, 130, 150, 170, 210, 250 and 300 microg m(-2). According to NCI-CTC criteria, non-haematological toxicities (grade 1/2) included fever, nausea and vomiting, mucositis and anorexia, none of which was clearly dose related. The dose-limiting toxicity was haematological and consisted mainly of neutropenia and to a lesser extent thrombocytopenia. From the dose level 150 microg m(-2), the haematological toxicity (particularly thrombocytopenia) was delayed in onset, prolonged and cumulative in some patients. In several courses, double WBC nadirs occurred. The maximum tolerated dose for a single course was 300 microg m(-2). From the dose level 170 microg m(-2), the intended dose intensity could not be delivered to most patients receiving > 2 courses owing to cumulative haematological toxicity. The dose level with the best dose intensity for multiple courses was 150 microg m(-2). The pharmacokinetics of Carzelesin and its metabolites (U-76,073; U-76,074) have been established in 31 patients during the first course of treatment using a HPLC method. Carzelesin exhibited linear pharmacokinetics. The concentration of U-76,074 (active metabolite) extended above the lower limit of quantitation (1 ng ml(-1)) for short periods of time and only at the higher dose levels. There was no relationship between neutropenia and the AUC of the prodrug Carzelesin, but the presence of detectable plasma levels of the active metabolite U-76,074 was usually associated with a substantial decrease in ANC values.

Adult↗
PubMed1999

Atypical brachial plexopathy with pseudotumor cerebri.

A 24-year-old woman with previously known pseudotumor cerebri syndrome (PTCS) presented with severe pain in the neck and shoulders followed by the classical symptoms and signs of bilateral brachial neuritis. At the same time, there was a recurrence of the PTCS which had been in remission for more than one-and-a-half years. Despite treatment with high doses of methylprednisolone, intravenous immunoglobulins and repeated cerebrospinal fluid drainage, both brachial plexopathy and the PTCS continued to worsen. Both lumbosacral plexuses became involved and the visual acuity deteriorated to a level such that a lumboperitoneal shunt had to be inserted. The neurological condition started to improve progressively after 8 weeks. This case is, to our knowledge, the first where brachial plexopathy has been described in association with a PTCS. Although the pathogenesis of this association is not clear, there are enough data to suggest the existence of a continuum between extended brachial plexopathy and Guillain Barre syndrome, with which PTCS has been associated in some instances.

Adult↗
PubMed1999

A unique effect of clonazepam on frontal lobe seizure control.

In a 16-year-old female, clonazepam (CZP) changed randomly occurring intractable tonic seizures of frontal lobe origin to a few sleep seizures when used as an adjunctive therapy. The significance of this change in the seizure pattern is discussed with an explanation of possible pathophysiologic mechanism.

Adolescent↗
PubMed1999

Late epileptic seizures after cerebral infarction.

OBJECTIVES: To determine the profile of late epileptic seizures following cerebral infarcts and the predictive clinical and radiological factors associated with their development. METHODS: We compared 86 patients who developed late seizures after cerebral infarction with 285 similar patients who did not develop seizures for at least 1 year after their stroke. Patients who had seizures only at the onset of the stroke were excluded. Odds' ratios were used for statistical analysis. RESULTS: Simple partial, and mainly motor seizures, with or without secondary generalization, accounted for 80% of the classifiable seizures but it was not possible to determine the seizure type in half of the cases. Factors that appeared to be predictive of seizure development were the presence of large cortical infarcts and the presence of apparently preserved cerebral tissue within the infarcted area. Seizures were rare in patients with lacunar infarction but the presence of associated leukoaraiosis increased the risk. The risk was also increased in patients with other medical problems known to lower seizure threshold, such as renal failure.

Adult↗
PubMed1999

[Residual cerebellar ataxia following acute phenytoin intoxication].

A 30-year-old man was given high doses of phenytoin together with 4 antituberculous drugs for a seizure associated with a probable brain tuberculoma. He developed hepatic toxicity and his serum phenytoin reached the high level of 298 mumol/l (therapeutic range 40-79 mumol/l). All drugs were stopped and the biological parameters returned progressively to normal over the next 15 days. However, he remained with a cerebellar axial syndrome and was still severely ataxic 2 months later. Brain CT and MRI showed mild cerebellar atrophy. This case and the few other published ones, together with some recent experimental data, show that high doses of phenytoin can be toxic to the cerebellar cortical cells. The rarity of similar cases, while millions of epileptics are under phenytoin treatment, would however suggest that individual susceptibility may play a role in this toxicity.

Adult↗
PubMed1999

The Saudi Stroke Data Bank. Analysis of the first 1000 cases.

OBJECTIVES: To determine the types of stroke, their risk factors and their most likely causes in Saudi patients. METHODS: Data on stroke cases admitted to 2 major hospitals in Saudi Arabia since 1982 were collected retrospectively up to 1991 then prospectively since then. By January 1995, the number of cases with first-ever-stroke stored in our Saudi Stroke Data Bank reached 1280. This article describes the findings in the first 1000 Saudi patients investigated by brain computed tomography. RESULTS: Males (68%) outnumbered females. There was no significant difference between the retrospective cases and the prospective ones in relation to the types of stroke or the risk factors. Ischemic strokes accounted for 76% of the cases and one third of them were lacunar infarcts. Most of the hemorrhagic strokes were intracerebral hemorrhages (ICHs) and only 2% of all strokes were subarachnoid hemorrhages (SAHs). Hypertension (52%), diabetes mellitus (41%) and cardiac disorders were common risk factors. The commonest causes of cerebral infarcts were atherosclerosis 36%, hypertensive and/or diabetic arteriolopathy 24% and cardiac embolisms 19%. Hypertensive arteriolopathy accounted for two-thirds of the cerebral hemorrhages. Strokes related to small artery disease, i.e. lacunar infarcts and ICHs accounted for 47% of the cases. CONCLUSION: The overall distribution of stroke types in Saudis is not very different from that reported in western studies, except for the low frequency of SAH. However, the important role of small artery disease in stroke pathogenesis and the high number of diabetic patients are quite distinctive.

Adolescent↗
PubMed1998

Molecular analysis of the SMN and NAIP genes in Saudi spinal muscular atrophy patients.

In this study we examined the deletion of the SMN and NAIP genes in 14 Saudi families (16 patients and 38 relatives of the patients, including parents and siblings) and six healthy Saudi volunteers. The homozygous deletions of exons 7 and 8 of the telomeric SMN gene and exon 5 of the NAIP gene were found in seven out of eight spinal muscular atrophy (SMA) type-I patients. In seven SMA type-II patients, exons 7 and 8 of telomeric SMN were deleted in six cases and exon 5 of NAIP was deleted in three cases. Three patients with SMA diagnosis did not show either of the above deletions. All control Saudi volunteers and all but two family members of the patients had both normal SMN and NAIP genes. Our results show that the incidence of NAIP deletion is higher in the more severe SMA cases and the dual deletions of the SMN and NAIP genes are more common in Saudi SMA type-I patients compared to patients of other ethnic groups.

Arabs↗
PubMed1998

A clinical pharmacokinetics study of carzelesin given by short-term intravenous infusion in a phase I study.

We investigated the pharmacokinetic behavior of carzelesin in 31 patients receiving this drug by 10-min intravenous infusion in a Phase I clinical trial, which was conducted at institutions in Nijmegen (institution 1) and Brussels (institution 2). The dose steps were 24, 48, 96, 130, 150, 170, 210, 250, and 300 microg/m2. Carzelesin is a cyclopropylpyrroloindole prodrug that requires metabolic activation via U-76,073 to U-76,074. The lower limit of quantitation (LLQ) of the high-performance liquid chromatography (HPLC) method used in this study was 1 ng/ml for the parent drug and its metabolic products. Carzelesin was rapidly eliminated from plasma (elimination half-life 23 +/- 9 min; mean value +/- SD). At all dose levels, U-76,073 was found as early as in the first samples taken after the start of the infusion. However, the concentration of U-76,074 exceeded the LLQ for only short periods and only at the higher dose levels. Although the plasma levels of all three compounds were well above the respective IC50 values obtained by in vitro clonogenic assays, they were much lower than those observed in a preclinical study in mice. There was a substantial discrepancy in the mean plasma clearance observed between patients from institution 1 (7.9 +/- 2.1 l h[-1] m[-2]) and those from institution 2 (18.4 +/- 13.6 l h[-1] m[-2]; P = 0.038), probably reflecting problems with drug administration in the latter institution. The results recorded for patients in institution 1 indicated that the AUC increased proportionately with increasing doses. There was a good correlation between the maximal plasma concentration and the AUC, enabling future monitoring of drug exposure from one timed blood sample. Urinary excretion of carzelesin was below 1% of the delivered dose.

Antineoplastic Agents↗
PubMed1998

Evolution of brain tuberculomas under standard antituberculous treatment.

The treatment of brain tuberculomas is primarily medical. Surgery, excision or biopsy, is generally performed when the diagnosis is in doubt or there is no response to medical therapy. The aim of this study was to determine the radiological evolution of intracranial tuberculomas under standard anti-tuberculous drug therapy and to establish guidelines for better management of these patients. Eighteen patients were studied retrospectively. None of them had surgical intervention and all were treated by standard antituberculous drugs and had serial computed tomography (CT) scans until disappearance or stabilization of brain lesions. The regression of lesions' size and number was slow in the first month (mean -7.3%) then became rapid after this (-15% to -20% per month). A paradoxical increase in size was noted in three patients in the first month. All three had associated meningitis. All tuberculomas disappeared on CT scan after 12 months of therapy. Most of the edema images disappeared by 6 months. This study would suggest that a long treatment regimen of 15-18 months may not be necessary in most intracranial tuberculomas occurring in non-immunocompromised patients. It also demonstrates that medical trial in well tolerated suspected cases should last for at least 2 months before considering other etiologies or surgical exploration.

Adolescent↗
PubMed1998

Pharmacokinetic and phase I studies of brequinar (DUP 785; NSC 368390) in combination with cisplatin in patients with advanced malignancies.

Brequinar (DUP 785; NSC 368390) is a quinoline carboxylic acid derivative that inhibits pyrimidine synthesis at the level of dihydro-orotate dehydrogenase and revealed synergy with cisplatin in preclinical models. In this study investigating the pharmacokinetic and toxicity of brequinar in combination with cisplatin, patients were initially treated with weekly brequinar, in combination with an every-three-week administration of cisplatin. Due to toxicity, the schedule was modified to a 28-day cycle with brequinar given on days 1, 8, 15, and cisplatin on day 1. A total of 24 patients (16 male, 8 female; median age 57; median performance status 1) received 69 courses of therapy. Six dose levels were explored, with cisplatin/ brequinar doses, respectively, of 50/500, 50/650, 50/860, 60/860, 75/650, and 75/860 mg/m2. The serum concentration versus time curves for brequinar were biphasic. A comparison of the pharmacokinetic results after the first and third doses of brequinar indicate that the presence of 50, 60, and 75 mg/m2cisplatin did not change the protein binding and the pharmacokinetics of brequinar in any of the three brequinar-dose groups. Total cisplatin plasma pharmacokinetic followed a triphasic-shape curve and unbound cisplatin decayed at a very rapid rate. Since pharmacokinetic parameters for total cisplatin in this study were similar to those reported in the literature, the presence of brequinar is unlikely to alter the pharmacokinetics of cisplatin. Main dose-limiting toxicities included myelosuppression (including neutropenia and thrombocytopenia) and mucositis. Cisplatin/brequinar doses of 50/500, 50/650, 50/860, 60/860, 75/650, and 75/860 mg/m2, were associated with dose limiting toxicity in 0/3, 1/3, 1/3, 1/3, 2/4, 2/5, and 4/6 patients, respectively. This study shows that co-administration of brequinar and cisplatin does not affect the pharmacokinetic properties of either drug and that the MTDs of cisplatin/brequinar combinations are 60/860 mg/m2 or 75/650 mg/m2. From this study, we conclude that full dose of 75 mg/m2 cisplatin (day 1) can be administered with 650 mg/m2 brequinar (days 1, 8 and 15) without significant modifications of individual drug pharmacokinetic parameters.

Adolescent↗
PubMed1998

Spontaneous cervical epidural hematoma: case report.

Spontaneous spinal epidural hematoma (SSEH) is an uncommon cause of acute nontraumatic myelopathy. We report a 14 year-old boy who had tetraplegia on awakening. Diagnosis of spinal epidural hematoma was made by magnetic resonance imaging. Despite spinal cord decompression within 9 h from onset, he remained tetraplegic. No cause for the bleeding was found. The pathogenic hypotheses of SSEH are discussed and the importance of rapid diagnosis and treatment is emphasized.

Adolescent↗