Showing papers by "Albiruni Ryan Abdul Razak published in 2011"
TL;DR: Neuropsychological testing is feasible in squamous cell carcinoma of the head-and-neck survivors and the findings were suggestive of treatment-related cognitive dysfunction, which warrant additional investigation.
Abstract: Purpose To perform a comprehensive cognitive function (CF) assessment in patients who were relapse free after curative intent radiotherapy (RT) or chemoradiotherapy for squamous cell carcinoma of the head and neck. Methods and Materials Patients underwent neuropsychological tests to assess their objective CF; completed questionnaires to assess subjective CF, quality of life, and affect; and underwent blood tests to assess hematologic, biochemical, endocrine, and cytokine status. Retrospectively, the dosimetry of incidental radiation to the brain was determined for all patients, and the dose intensity of cisplatin was determined in those who had undergone chemoradiotherapy. Results A total of 10 patients were enrolled (5 treated with radiotherapy only and 5 with radiotherapy and cisplatin). The mean time from the end of treatment was 20 months (range, 9–41). All patients were able to complete the assessment protocol. Of the 10 patients, 9 had impaired objective CF, with memory the most severely affected. The severity of memory impairment correlated significantly with the radiation dose to the temporal lobes, and impaired dexterity correlated significantly with the radiation dose to the cerebellum, suggesting that these deficits might be treatment related. Patients receiving cisplatin appeared to have poorer objective CF than patients receiving only RT, although this difference did not achieve statistical significance, likely owing to the small sample size. Consistent with the published data, objective CF did not correlate with subjective CF or quality of life. No association was found between objective CF and patients' affect, hematologic, biochemical, endocrine, and cytokine status. Conclusion Neuropsychological testing is feasible in squamous cell carcinoma of the head-and-neck survivors. The findings were suggestive of treatment-related cognitive dysfunction. These results warrant additional investigation.
71 citations
TL;DR: The safety, dose-limiting toxicity, recommended phase II dose (RPTD), as well as pharmacokinetic (PK) and pharmacodynamic (PD) profiles of SB939 in a daily × 5 schedule in advanced solid tumours are determined.
Abstract: SB939 is an orally available, competitive histone deacetylase (HDAC) inhibitor selective for class I, II and IV histone deacetylases. Preclinical evaluation of SB939 revealed a profile suggesting improved efficacy compared to other HDAC inhibitors. This phase I study was carried out to determine the safety, dose-limiting toxicity, recommended phase II dose (RPTD), as well as pharmacokinetic (PK) and pharmacodynamic (PD) profiles of SB939 in a daily × 5 schedule in advanced solid tumours. Sequential dose-escalating cohorts of patients were enrolled into 8 dose levels. At dose level 1, SB939 was taken on days 1–3 and 15–17 every 4 weeks, then on days 1–5 and 15–19 for other dose levels. Detailed PK sampling was performed in cycle 1, days 1 and 5. Peripheral blood mononuclear cells (PBMCs) were collected on cycle 1 at various time points for determination of acetylated histone H3 (AcH3) levels. In total, 38 patients received a total of 96 cycles of treatment. The maximal administered dose was 90 mg and the RPTD was 60 mg given 5 consecutive days every 2 weeks. The most frequent non-hematologic adverse events (AEs) of at least possible attribution to SB939 were fatigue, nausea, vomiting, anorexia and diarrhoea. Pharmacokinetic analysis showed dose-proportional increases in AUC across the doses evaluated. Elimination half-life was 5.6–8.9 h. There was no clear relationship between AcH3 changes and dose level or anti-tumour response. SB939 is well tolerated in patients with advanced solid tumours. The RPTD of this drug is 60 mg on a schedule of 5 consecutive days every 2 weeks. The toxicities of SB939 are consistent with other HDAC inhibitors.
58 citations
TL;DR: The results do not support a standardisation of the definition of DLT, but the inclusion of following specifications in its definition when relevant would reduce the heterogeneity observed across trials.
56 citations
TL;DR: A better understanding of the biology of ACC will be crucial to the future success of developing targeted agents for this disease, and molecular targeted agents may have a role, although the agents tested to date in non-lacrimal ACC have been disappointing.
Abstract: Adenoid cystic carcinoma (ACC) is the most common malignant epithelial cancer of the lacrimal gland. Despite a slow rate of growth, ACCs are ultimately associated with poor clinical outcome. Given the rarity of this disease, most recommendations regarding therapy are guided by expert opinion and retrospective data rather than level 1 evidence. Surgery and postoperative radiation therapy are commonly used as initial local treatment. In patients at high risk of recurrence, concomitant platinum-based chemotherapy may be added to postoperative radiotherapy in an attempt to enhance radio-sensitivity. While encouraging responses have been reported with intra-arterial neoadjuvant chemotherapy, this strategy is associated with substantial toxicity and should be considered investigational. For patients with metastatic disease not amenable to surgery or radiotherapy, chemotherapy may have a role based on its modest efficacy in non-lacrimal ACC. Similarly, molecular targeted agents may have a role, although the agents tested to date in non-lacrimal ACC have been disappointing. A better understanding of the biology of ACC will be crucial to the future success of developing targeted agents for this disease.
28 citations
TL;DR: BKM120 monotherapy was well tolerated and showed biological and antitumor activity and a trend towards better activity was observed at the higher dose cohorts, also expressed as metabolic FDG-PET response.
Abstract: 3043 Background: PI3K pathway is frequently altered in cancer and can have an impact on tumor survival and proliferation. BKM120 is a potent and highly specific oral pan-class I PI3K inhibitor with...
24 citations
TL;DR: Only low quality evidence is found on the use of chemotherapy in malignant germ cell tumours of the ovaries so a trans-global approach would be essential in order to perform such trials and good quality randomised studies are warranted.
Abstract: BACKGROUND Malignant germ cell tumour of the ovary occurs in up to 0.07% of woman globally. Due to its rarity, evidence for treatment is lacking and often extrapolates clinical trial results of testicular germ cell cancers. The investigation on this rare tumour is further compounded by the fact that its occurrence in the adult population is even less compared to their paediatric counterpart. At present, the effectiveness of chemotherapy, regardless of stage in malignant germ cell tumour of the ovary is not entirely clear. OBJECTIVES To evaluate the effectiveness and safety of chemotherapy in adult women with early stage, advanced and recurrent malignant germ cell ovarian cancers. SEARCH STRATEGY We searched the Cochrane Central Register of Controlled Trials (CENTRAL), Issue 1, 2010, Cochrane Gynaecological Cancer Group Trials Register, MEDLINE and EMBASE up to April 2010. We also searched registers of clinical trials, abstracts of scientific meetings and reference lists of included studies. SELECTION CRITERIA We searched for randomised controlled trials (RCTs), quasi-RCTs and non-randomised studies that compared systemic therapy in adult women diagnosed with germ cell ovarian cancer who have confirmed pathological diagnoses. DATA COLLECTION AND ANALYSIS Two review authors independently assessed whether potentially relevant studies met the inclusion criteria, abstracted data and assessed risk of bias. MAIN RESULTS We found one RCT and one retrospective study that met our inclusion criteria. The data from these studies were too sparse to adequately assess the effectiveness and safety of adjuvant chemotherapy in the treatment of malignant germ cell ovarian cancer. All comparisons were restricted to single study analyses and this review was only based on 32 women, so it was not adequately powered to detect differences in survival. Adverse effects of treatment and recurrence-free survival were incompletely documented and QoL was not reported in any of the studies. We did not find any studies that reported specifically on adults so there were problems in separating data on adults and children in many of the potentially relevant studies. AUTHORS' CONCLUSIONS We found only low quality evidence on the use of chemotherapy in malignant germ cell tumours of the ovaries. Therefore we are unable to reach definite conclusions about the relative benefits and harms of chemotherapy use in this disease regardless of disease stage. Due to the benefit of chemotherapy in germ cell cancer of the testis, a trial of chemotherapy versus best supportive care is unlikely to be feasible. Despite this, good quality randomised studies are warranted in this disease to define the role of chemotherapy (type of chemotherapy, duration of treatment, benefit, short and long term toxicities). Given the rarity of this disease, we feel a trans-global approach would be essential in order to perform such trials.
15 citations
TL;DR: Combination therapy of taxotere and anti-androgen manipulation is safe and well tolerated and the gene profiling results may provide important information in selecting patients who will benefit from more aggressive initial therapy.
Abstract: 147 Background: Anti-androgen manipulation (AA) is considered the standard initial therapy for high-risk/metastatic prostate cancer. The role of chemotherapy and anti-androgen manipulation (TAA) is still undefined in this group. GenTax is a phase II trial investigating clinical outcome and gene profiling in prostate cancer before and after AA or TAA. Here we present the clinical outcome data. Methods: Patients with T3/4 disease, PSA ≥ 50 ng/ml or Gleason score ≥ 8, or metastatic disease were enrolled. Patients were randomised at histological diagnosis to AA or TAA (goserelin 3.6 mgs q28 ± taxotere 75 mg/m2 q21 for 6 cycles). TRUS biopsies were taken at randomisation and 22 weeks after treatment initiation. Clinical assessment including KPS, QOL using QLQ-C30, bloods/PSA were measured 3 weekly until 22 weeks then 3 monthly. Data was analysed for PFS, OS, toxicities and QOL. Results: 30 patients were recruited with 15 patients in each arm from 10/13/2005 to 12/02/2009. The median age was 62.2 yrs (range 48....
6 citations
TL;DR: C/B-RT in HNC pts may be associated with NCF decline at 1-yr and can affect multiple domains and subjective declines in NCF and QOL were more frequent than objective NCF declines.
Abstract: 5522 Background: There is evidence that cancer and/or its treatment can impair thinking abilities. To date, there have been no longitudinal studies exploring NCF in HNC pts. We present a prospective NCF assessment in HNC pts treated with C/B-RT. Methods: Baseline information including pt demographics, primary tumor site, stage, smoking/alcohol history, systemic therapy details and RT dosimetry were collected. All pts underwent a 2-hour battery of NCF testing at baseline and at 1-year (yr). Domains evaluated included memory, motor skills, intelligence, language, attention, processing speed and executive function (EF). Performances on the various tests were transformed to Z-scores using normative data. NCF decline was defined as a Z-score decrease of ≥-1 and improvement as a Z-score increase of ≥+1. Pts also had subjective assessments of anxiety, depression, NCF and quality of life (QOL) using the Hospital Anxiety and Depression Scale and FACT questionnaires. QOL was considered significantly altered if FACT...
2 citations