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Biomedical subjects

A Awada

Publications and source records attributed to A Awada.

At least 19 recordsLinked to original sources
PubMed2006

A phase I dose-finding clinical pharmacokinetic study of an oral formulation of irinotecan (CPT-11) administered for 5 days every 3 weeks in patients with advanced solid tumours.

BACKGROUND: Oral administration of irinotecan (CPT-11) should allow sustained exposure to the drug without the inconvenience of intravenous delivery and with fewer side-effects. PATIENTS AND METHODS: The present phase I trial of CPT-11, administered orally as a powder-filled capsule for 5 consecutive days every 3 weeks at doses ranging from 30 to 90 mg/m(2)/day, was conducted in 47 patients for whom a satisfactory standard treatment option was no longer available (24 males/23 females; median age 51 years, range 26-85). Tumour types included melanoma (11), colorectal (4), urinary tract (3), lung/pleura (4), thyroid (3), liver (3), gallbladder (2), cervix/uterus (3), breast (2), pancreas (2), carcinoma and other cancer types (10). RESULTS: A total of 171 cycles were administered (median 3, range 1-11). Dose limiting toxicities (DLTs) occurred during the first cycle in five of 31 patients in the dose-escalation part of the study: one patient at the 50 mg/m(2)/day dose level (diarrhoea grade 4); one patient at the 80 mg/m(2)/day dose level (prolonged neutropenia grade 4 and diarrhoea grade 3); and three patients at the 90 mg/m(2)/day dose level (diarrhoea, vomiting and neutropenia). The 80 mg/m(2)/day dose level was expanded, as a feasibility study, to include 16 additional patients, five of whom had received extensive prior pelvic irradiation. A further three patients in this cohort experienced DLTs, two of whom had received extensive prior pelvic irradiation. One patient died on study day 15 during the first cycle of oral CPT-11 following grade 3 diarrhoea, febrile neutropenia and a necrotic enterocolitis. Overall the grade 3/4 toxicities in 47 patients were asthenia (19%), anorexia (17%), neutropenia (14.9 %), diarrhoea (13%), nausea (12.7%), vomiting (8.5%) and thrombocytopenia (8.5%). Partial responses were observed in two melanoma patients and disease stabilisation was noted in 17 (36.1%) patients. Pharmacokinetic parameters were recorded for 46 patients. CONCLUSIONS: At the maximum tolerated dose, defined as 80 mg/m(2)/day for 5 days every 3 weeks, oral CPT-11 was shown to be well tolerated and safe with few of the haematological toxicities associated with the intravenous formulation.

Administration, Oral↗
PubMed2006

Pooled safety analysis of BAY 43-9006 (sorafenib) monotherapy in patients with advanced solid tumours: Is rash associated with treatment outcome?

In this analysis of the safety and efficacy of BAY 43-9006 (sorafenib) -- a novel, oral multi-kinase inhibitor with effects on tumour and its vasculature -- pooled data were obtained from four phase I dose-escalation trials. Time to progression (TTP) was compared in patients with/without grade 2 skin toxicity/diarrhoea. Grade 3 hand-foot skin reactions (HFS; 8%) and diarrhoea (6%) were common. At the recommended 400mg bid dose for phase II/III trials (RDP), 15% of patients experienced grade 2/3 HFS, and 24% experienced grade 2/3 diarrhoea. Sorafenib induced stable disease for 6 months in 12% of patients (6% stabilized for 1 year). Patients receiving sorafenib doses at or close to the RDP, who experienced skin toxicity/diarrhoea, had a significantly increased TTP compared with patients without such toxicity (P < 0.05). Sorafenib was well tolerated at the RDP, and induced sustained disease stabilization, particularly in patients with skin toxicity/diarrhoea.

Administration, Oral↗
PubMed2006

[Rapid sensory motor neuropathy after gastric restriction surgery].

INTRODUCTION: Central and peripheral neurological complications have been described in association with bariatric surgery over the last 20 years. CASE REPORT: A 40 year-old women developed a sensory motor neuropathy 3 months after a gastric restriction operation followed by a 30 kilograms weight loss. No specific vitamin or mineral deficiency was detected but she improved after multivitamin and minerals supplementation. CONCLUSION: Acute or subacute neuropathy may develop in 1 to 2p.cent of patients who undergo bariatric surgery. Its pathogenesis is not very clear but the most commonly associated factors are rapid weight loss and non-supplementation with vitamins and minerals post-operatively.

Adult↗
PubMed2006

High serum galectin-3 in advanced melanoma: preliminary results.

BACKGROUND: Galectin-3 (Gal-3) is a member of the family of beta-galactoside-binding mammalian lectins, and has been implicated in tumour invasion and metastatic process in vitro and in vivo. AIM: To determine whether an increase in serum Gal-3 production could be found in patients with advanced metastatic melanoma. METHODS: We collected 18 sera from patients with AJCC stage IV metastatic melanomas and 20 sera from healthy volunteers. Determination of Gal-3 was performed by ELISA, and in the group of patients with melanoma, these results were compared with the serum lactate dehydrogenase (LDH) and the C-reactive protein (CRP) concentrations. RESULTS: Gal-3 concentration was shown to be significantly higher in the group of patients with melanoma compared with healthy volunteers, and Gal-3 concentration was significantly correlated with both LDH and CRP in the melanoma group. We also selected four patients in the melanoma group for Gal-3 retrospective immunostaining analysis on cutaneous metastases. Two of these patients, who had a higher Gal-3 serum level, showed more intense staining and the other two patients, with a lower serum level of Gal-3, had moderate immunostaining, suggesting that at least part of serum Gal-3 might be produced by metastatic melanoma tissue. CONCLUSIONS: Gal-3 might play a role in melanoma progression and/or inflammation, and warrants further study.

Adult↗
PubMed2005

Long-term survival in pituitary metastasis from breast cancer.

We report the interesting case of a patient who is a long-term survivor of breast cancer with metastasis to the pituitary gland. This patient was treated with surgery and radiotherapy in 1995 and during her second relapse, which occurred in 2004, chemotherapy was given. This treatment resulted in a partial response.

Breast Neoplasms↗
PubMed2005

Phase I safety and pharmacokinetics of BAY 43-9006 administered for 21 days on/7 days off in patients with advanced, refractory solid tumours.

BAY 43-9006 is a novel dual-action Raf kinase and vascular endothelial growth factor receptor (VEGFR) inhibitor that targets tumour cell proliferation and tumour angiogenesis. This Phase I study was undertaken to determine the safety profile, maximum tolerated dose (MTD), dose-limiting toxicities (DLTs), pharmacokinetics, and tumour response profile of oral BAY 43-9006 in patients with advanced, refractory solid tumours. BAY 43-9006 was administered daily for repeated cycles of 21 days on/7 days off. A total of 44 patients were enrolled at doses from 50 to 800 mg b.i.d. Pharmacokinetic profiles of BAY 43-9006 in plasma were determined during the first treatment cycle. The most frequently reported adverse events over multiple cycles were gastrointestinal (75%), dermatologic (71%), constitutional (68%), pain (64%), or hepatic (61%) related. A MTD of 400 mg b.i.d. BAY 43-9006 was defined. BAY 43-9006 was absorbed rapidly; steady-state conditions were reached within 7 days. BAY 43-9006 exposure increased nonproportionally with increasing dose. In all, 32 patients were evaluated for tumour response: 15 patients showed tumour progression, 16 patients experienced stable disease (>6 months in eight patients), and one patient with renal cell carcinoma achieved a partial response. BAY 43-9006 given for 21 days with 7 days off treatment was safe, well tolerated, and showed antitumour activity.

Adult↗
PubMed2005

Phase II study of E7070 in patients with metastatic melanoma.

E7070 is a synthetic chloro-indolyl sulphonamide that is being developed as an anti cancer agent. In this phase II study, 28 patients with metastatic melanoma received 700 mg/m(2) of E7070 as a 60-min infusion repeated every 3 weeks. Although therapy was well tolerated, with one patient receiving 14 courses of treatment, there were only minor responses on independent radiological review. E7070 does not warrant further development as a single agent for the treatment of metastatic melanoma.

Adult↗
PubMed2004

Rates of topoisomerase II-alpha and HER-2 gene amplification and expression in epithelial ovarian carcinoma.

OBJECTIVES: Topoisomerase II-alpha (T2a) is being actively investigated as a potential predictive marker of response to anthracyclines in breast cancer (BC). Although the role of T2a inhibitors as upfront and salvage treatment for epithelial ovarian carcinoma (EOC) remains unclear, we speculated that a small subgroup of ovarian cancer patients could derive a selective benefit from these agents. In this study, we investigated the actual rates of T2a and HER-2 amplification and overexpression by fluorescence in situ hybridisation (FISH) and immunohistochemistry (IHC), respectively. METHODS: Seventy-three samples of chemotherapy-naive patients with EOC were selected from our archives. FIGO stage and histology were available for most patients. RESULTS: Based on arbitrary cut-offs of > or =1.5 and > or =2 (ratio copies/centromere17), amplification rates for HER-2 were 15/64 (23.4%) and 8/64 (12.5%) versus 16/64 (25%) and 5/64 (7.8%) for T2a. We found only 3/72 (4.2%) cases of HER-2 overexpression (3+) versus 15/70 (21.4%) for T2a (staining of >10% of the cells). There was a modest correlation between T2a amplification and overexpression (P=0.01) and a strong correlation between T2a and HER-2 amplification when these markers were analysed as continuous variables (P<0.001). T2a amplification significantly correlated with advanced FIGO stage (P=0.02). CONCLUSION: The assessment of HER-2 and T2a amplification and overexpression by FISH and IHC, respectively, is feasible in EOC. These tests can be used for large-scale evaluation of the potential predictive and prognostic value of these markers in the future. Further studies with a special focus on T2a are needed to determine the best cut-offs for potential clinical use in the future.

Antigens, Neoplasm↗
PubMed2004

A clinical and genetic study of 56 Saudi Wilson disease patients: identification of Saudi-specific mutations.

Wilson disease (WD) is a hereditary disorder, with recessive transmission and genetic heterogeneity. Several mutations of ATP7B, the gene underlying WD, were reported in many ethnic groups. In this study, mutation screening in ATP7B of 56 Saudi Arabian WD patients was undertaken. The clinical data of all patients were recorded. The entire ATP7B coding sequence, including intron-exon boundaries were screened for mutation by the polymerase chain reaction (PCR)-based mutation detection technique and DNA sequencing. Thirty-nine patients were symptomatic at presentation and 17 subjects were pre-symptomatic siblings of affected patients. Fourteen patients had neurological, 11 patients had mixed (hepatic and neurological), and 14 patients had hepatic presentations. Family history suggestive of WD was present in 72% of cases and 68% had consanguineous parents. Genetic analysis showed disease-causing mutations in three exons (exons 8, 19 and 21) of the ATP7B gene in 28 patients (50%). Mutations in exons 21 (18 cases) and 19 (one case) were unique for Saudis. This large series of Saudi patients with WD has shown wide variability in the genomic substrate of WD. There is no correlation between genotype and clinical presentation.

Adenosine Triphosphatases↗
PubMed2004

Docetaxel, cisplatin and 5-fluorouracil in patients with locally advanced unresectable head and neck cancer: a phase I-II feasibility study.

PURPOSE: To determine the safety profile and activity of the combination of docetaxel, cisplatin and 5-fluorouracil (5-FU) in chemotherapy-naive patients with squamous cell carcinoma of the head and neck (SCCHN). PATIENTS AND METHODS: Patients with locally advanced unresectable SCCHN were treated with docetaxel and cisplatin both as a 1-h infusion on day 1 followed by a continuous infusion of 5-FU for 5 days. Cycles were planned every 3 weeks up to four cycles, whereafter the patients were treated with locoregional radiotherapy. Two dose levels were studied. Doses in level I were 75 mg/m(2) of docetaxel, 75 mg/m(2) of cisplatin and 750 mg/m(2)/day of 5-FU; in level II the cisplatin dose was escalated to 100 mg/m(2). Following chemotherapy, all patients were to receive curative radiotherapy according to the standards in the different institutions. RESULTS: Twenty-five patients were treated at dose level I with 86 cycles (median four; range one to four), and 23 at dose level II with 84 cycles (median four; range two to four). The median relative dose intensity was 0.99 (range 0.86-1.04) at level I and 0.94 (range 0.79-1.02) at level II. The response rate in the intention-to-treat population was 64% [95% confidence interval (CI) 42.5% to 82%] in level I and 78.3% (95% CI 56.3% to 92.5%) in level II; all were partial responses. The maximum tolerated dose was reached at level II with renal toxicity, nausea, stomatitis and thrombocytopenia as principal dose-limiting toxicities. The median survival of the 48 patients was 18.5 months. The survival at 12, 18, 24 and 30 months was 69, 54, 41 and 31%, respectively. CONCLUSIONS: The combination of docetaxel, cisplatin and 5-FU associated with prophylactic ciprofloxacin is feasible and active in patients with SCCHN. Dose level I is recommended for phase III testing.

Adult↗
PubMed2004

Primary chemotherapy for breast cancer: the evidence and the future.

The first generation of randomised trials assessing the role of primary chemotherapy in breast cancer has failed to demonstrate the expected survival benefit. However, it has established the role of this treatment in 'downstaging' tumours of patients with locally advanced disease and, consequently, in improving breast conservation rates. Also, a number of surrogates of outcome have been identified, which will hopefully lead to earlier results in breast cancer clinical trials. Encouraging results have also been reported in trials investigating a number of novel approaches.

Antineoplastic Combined Chemotherapy Protocols↗
PubMed2004

Molecular profiling of head and neck tumors.

PURPOSE OF REVIEW: Head and neck squamous cell carcinoma is the fifth most common cancer worldwide. Unfortunately, patients with the same diagnostic and prognostic profile can have markedly different clinical outcomes. This most likely results from the fact that the current taxonomy of head and neck squamous cell carcinoma groups molecularly different diseases with distinct clinical phenotypes into classifications based mainly on morphology. A combination of circumstances, including the advent of array-based technology and progress in the human genome initiative, now provides an ideal opportunity to begin performing comprehensive molecular and genetic profiling of head and neck squamous cell carcinoma. This article reviews recently reported studies that have used such approaches. RECENT FINDINGS: Comparison of gene expression profiles between head and neck squamous cell carcinoma and normal tissues showed altered expression levels of genes involved in the control of cell growth and differentiation, angiogenesis, apoptosis, cell cycle, and signaling, most of which have not been previously described in head and neck squamous cell carcinoma. Additionally, they revealed the implication of different signaling and metabolic pathways such wnt and noch, highlighting the potential role of these pathways in oral cancer development. Their results provide new insights into the carcinogenesis of head and neck squamous cell carcinoma as well as a source of potential prognostic and predictive markers and targets for its prevention and therapeutics. SUMMARY: Although the sample sizes of these studies were small and their findings therefore require further validation in larger trials, such preliminary results provide important clues to the understanding of the various gene networks implicated in oral carcinogenesis and may contribute to the selection of target genes for possible molecular diagnosis and therapy in the future.

Carcinoma, Squamous Cell↗
PubMed2004

Prolonged schedule of temozolomide (Temodal) plus liposomal doxorubicin (Caelyx) in advanced solid cancers.

Temozolomide (Temodal) is an oral imidazotetrazine. Increased temozolomide exposure and subsequent depletion of O-alkylguanine alkyltransferase may improve the activity of temozolomide. The rationale for investigating temozolomide plus Caelyx is based on their antitumor activity, their formulation and no significant overlapping toxicities. We conducted a study of a prolonged schedule of temozolomide (orally on days 1-7 and 15-21) plus Caelyx (day 1) every 28 days. Twenty-one patients (melanoma n=10, sarcoma n=7 and other n=4) were assigned to four dose levels (DL; temozolomide+Caelyx, mg/m): DL1: 100+30 (n=3 patients), DL2: 100+40 (n=6 patients), DL3: 125+40 (n=6 patients) and DL4: 150+40 (n=6 patients). Dose-limiting toxicities were noted after 2 or more cycles in one patient at DL3 (stomatitis) and one patient at DL4 (grade 4 ANC >/=7 days). Treatment delays and/or dose reductions (due to hematological toxicity) were necessary in five of six patients receiving DL4 compared with one of six patients at DL3, and one patient at DL1 and 2. Thus, the recommended dose was temozolomide 125 mg/m (daily for 7 days every other week) plus Caelyx 40 mg/m (day 1 every 4 weeks). Other toxicities were mild. Antitumor activity was observed in eight patients, including one complete response (melanoma), three partial responses (one melanoma, two sarcomas) and four patients with stable disease (three melanomas, one Ewing), with a duration lasting from 14 to 135+weeks. Two melanoma patients showed tumor stabilization in non-irradiated cerebral lesions. This schedule of temozolomide allowed higher dose intensity (1750 mg/m in 4 weeks) compared to the standard 5-day regimen (1000 mg/m in the same amount of time).

Adult↗
PubMed2004

Ovarian cancer: state of the art and future directions.

The median survival of patients with ovarian cancer has increased steadily, mainly due to a multidisciplinary approach including surgery and chemotherapy. This editorial article summarizes the important messages taken from clinical research performed in this field over the last 15 years. It deals with the following issues: screening, prevention, management of early and advanced disease, maintenance/consolidation therapies and the treatment of relapsing patients. It also gives some future directions with the hope to improve the management and the outcome of this highly lethal disease.

Combined Modality Therapy↗
PubMed2004

[Topical photodynamic therapy in cutaneous oncology].

Photodynamic therapy (PDT) or photodynamic chemotherapy is a new therapeutic two-step procedure consisting of an administration of a photosensitizer followed by light irradiation. PDT has been used for the treatment of cutaneous malignancies and offers the advantage over surgery of being a selective and non-invasive approach. The authors present a review of Medline-indexed experiences and trials of topical PDT in cutaneous oncology, and, by the way, remind anatomoclinical features of non-melanoma skin cancers. Complete response rates and cosmetic outcome after topical PDT with 5-aminolevulinic acid are encouraging and enable from now to consider this promising procedure as a new effective approach to manage skin cancers, particularily superficial and extensive lesions including actinic keratoses, superficial basocellular carcinomas and Bowen's disease.

Humans↗