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1.
Rhinology ; 62(2): 183-191, 2024 Apr 01.
Article in English | MEDLINE | ID: mdl-38009582

ABSTRACT

BACKGROUND: Olfactory dysfunction (OD) is increasingly recognized as a hallmark of unhealthy aging and is intimately associated with mortality, but therapies remain elusive. Recognizing the increased prevalence of OD in individuals with diabetes, and the potential anti-aging effects of metformin, we studied the association of metformin use with OD. METHODS: Cross-temporal study of participants from Waves 2 (2010-11) and 3 (2015-16) of the National Social Life, Health, and Aging Project (NSHAP), a nationally representative cohort study of community-dwelling older adults. We included participants with diabetes who had complete data on olfaction and relevant covariates at Wave 2 and were not lost to follow-up at Wave 3. Olfactory identification (OI), the ability to identify the odorant, and olfactory sensitivity (OS), the ability to detect the presence of an odorant, were tested. Weighted multivariable logistic regression was used to study the association between metformin use at Wave 2 (baseline) and odds of having impaired OI/OS at Wave 3, adjusted for age, sex, race/ethnicity, education, smoking, BMI, HbA1c, years since diabetes diagnosis, and insulin use. RESULTS: Among 228 participants with diabetes (mean age=70 years, 53% female, 21% Black), 112 (49%) used metformin at baseline. Relative to nonusers, users had 58% lower odds of impaired OI and 67% lower odds of impaired OS at Wave 3. Among participants with normal baseline OS (N=62), users had 97% lower odds of impaired OS at Wave 3. CONCLUSIONS: Metformin use is associated with lower odds of OD among individuals with diabetes, suggesting a potential protective effect on olfaction. Future work including a larger sample and additional information on metformin use is needed to establish whether these findings are independent of diabetic control.


Subject(s)
Diabetes Mellitus , Metformin , Olfaction Disorders , Humans , Female , Aged , Infant , Male , Smell , Metformin/therapeutic use , Cohort Studies , Olfaction Disorders/prevention & control , Olfaction Disorders/epidemiology
2.
BMC Med Res Methodol ; 22(1): 81, 2022 03 27.
Article in English | MEDLINE | ID: mdl-35346056

ABSTRACT

BACKGROUND: Item response theory (IRT) methods for addressing differential item functioning (DIF) can detect group differences in responses to individual items (e.g., bias). IRT and DIF-detection methods have been used increasingly often to identify bias in cognitive test performance by characteristics (DIF grouping variables) such as hearing impairment, race, and educational attainment. Previous analyses have not considered the effect of missing data on inferences, although levels of missing cognitive data can be substantial in epidemiologic studies. METHODS: We used data from Visit 6 (2016-2017) of the Atherosclerosis Risk in Communities Neurocognitive Study (N = 3,580) to explicate the effect of artificially imposed missing data patterns and imputation on DIF detection. RESULTS: When missing data was imposed among individuals in a specific DIF group but was unrelated to cognitive test performance, there was no systematic error. However, when missing data was related to cognitive test performance and DIF group membership, there was systematic error in DIF detection. Given this missing data pattern, the median DIF detection error associated with 10%, 30%, and 50% missingness was -0.03, -0.08, and -0.14 standard deviation (SD) units without imputation, but this decreased to -0.02, -0.04, and -0.08 SD units with multiple imputation. CONCLUSIONS: Incorrect inferences in DIF testing have downstream consequences for the use of cognitive tests in research. It is therefore crucial to consider the effect and reasons behind missing data when evaluating bias in cognitive testing.


Subject(s)
Bias , Humans , Neuropsychological Tests
3.
J Int Neuropsychol Soc ; 28(2): 154-165, 2022 02.
Article in English | MEDLINE | ID: mdl-33896441

ABSTRACT

OBJECTIVES: Vision and hearing impairments affect 55% of people aged 60+ years and are associated with lower cognitive test performance; however, tests rely on vision, hearing, or both. We hypothesized that scores on tests that depend on vision or hearing are different among those with vision or hearing impairments, respectively, controlling for underlying cognition. METHODS: Leveraging cross-sectional data from the Baltimore Longitudinal Study of Aging (BLSA) and the Atherosclerosis Risk in Communities Neurocognitive Study (ARIC-NCS), we used item response theory to test for differential item functioning (DIF) by vision impairment (better eye presenting visual acuity worse than 20/40) and hearing impairment (better ear .5-4 kHz pure-tone average > 25 decibels). RESULTS: We identified DIF by vision impairment for tests whose administrations do not rely on vision [e.g., Delayed Word Recall both in ARIC-NCS: .50 logit difference between impaired and unimpaired (p = .04) and in BLSA: .62 logits (p = .02)] and DIF by hearing impairment for tests whose administrations do not rely on hearing [Digit Symbol Substitution test in BLSA: 1.25 logits (p = .001) and Incidental Learning test in ARIC-NCS: .35 logits (p = .001)]. However, no individuals had differences between unadjusted and DIF-adjusted measures of greater than the standard error of measurement. CONCLUSIONS: DIF by sensory impairment in cognitive tests was independent of administration characteristics, which could indicate that elevated cognitive load among persons with sensory impairment plays a larger role in test performance than previously acknowledged. While these results were unexpected, neither of these samples are nationally representative and each has unique selection factors; thus, replication is critical.


Subject(s)
Atherosclerosis , Cognitive Dysfunction , Hearing Loss , Aged , Aging , Atherosclerosis/complications , Baltimore , Cognitive Dysfunction/complications , Cognitive Dysfunction/etiology , Cross-Sectional Studies , Hearing Loss/complications , Hearing Loss/diagnosis , Hearing Loss/psychology , Humans , Longitudinal Studies , Neuropsychological Tests
4.
J Laryngol Otol ; 134(5): 387-397, 2020 May.
Article in English | MEDLINE | ID: mdl-32468973

ABSTRACT

BACKGROUND: Hearing loss affects over 1.3 billion individuals worldwide, with the greatest burden among adults. Little is known regarding the association between adult-onset hearing loss and employment. METHODS: Seven databases (PubMed, Embase, Cochrane Library, ABI/Inform Collection, Business Source Ultimate, Web of Science and Scopus) were searched through to October 2018. The key word terms used related to hearing loss and employment, excluding paediatric or congenital hearing loss and deaf or culturally deaf populations. RESULTS: The initial search resulted in 13 144 articles. A total of 7494 articles underwent title and abstract screening, and 243 underwent full-text review. Twenty-five articles met the inclusion criteria. Studies were set in 10 predominantly high-income countries. Seven of the 25 studies analysed regionally or nationally representative datasets and controlled for key variables. Six of these seven studies reported associations between hearing loss and employment. CONCLUSION: The highest quality studies currently available indicate that adult-onset hearing loss is associated with unemployment. However, considerable heterogeneity exists, and more rigorous studies that include low- and middle-income countries are needed.


Subject(s)
Cost of Illness , Employment/statistics & numerical data , Hearing Loss/complications , Adult , Aged , Aged, 80 and over , Employment/economics , Hearing Loss/economics , Humans , Middle Aged , Pensions/statistics & numerical data , Persons With Hearing Impairments/statistics & numerical data , Unemployment/statistics & numerical data
5.
Clin Oncol (R Coll Radiol) ; 30(8): 461-462, 2018 08.
Article in English | MEDLINE | ID: mdl-29935926
6.
BJOG ; 125(11): 1451-1458, 2018 Oct.
Article in English | MEDLINE | ID: mdl-29460478

ABSTRACT

OBJECTIVE: To determine the rates of germline BRCA1 and BRCA2 mutations in Scottish patients with ovarian cancer, before and after a change in testing policy. DESIGN: Retrospective cohort study. SETTING: Four cancer/genetics centres in Scotland. POPULATION: Patients with ovarian cancer undergoing germline BRCA1 and BRCA2 (gBRCA1/2) sequencing before 2013 (under the 'old criteria', with selection based solely on family history), after 2013 (under the 'new criteria', with sequencing offered to newly presenting patients with non-mucinous ovarian cancer), and in the 'prevalent population' (who presented before 2013, but were not eligible for sequencing under the old criteria but were sequenced under the new criteria). METHODS: Clinicopathological and sequence data were collected before and for 18 months after this change in selection criteria. MAIN OUTCOME MEASURES: Frequency of germline BRCA1, BRCA2, RAD51C, and RAD51D mutations. RESULTS: Of 599 patients sequenced, 205, 236, and 158 were in the 'old criteria', 'new criteria', and 'prevalent' populations, respectively. The frequency of gBRCA1/2 mutations was 30.7, 13.1, and 12.7%, respectively. The annual rate of gBRCA1/2 mutation detection was 4.2 before and 20.7 after the policy change. A total of 48% (15/31) 'new criteria' patients with gBRCA1/2 mutations had a Manchester score of <15 and would not have been offered sequencing based on family history criteria. In addition, 20 patients with gBRCA1/2 were identified in the prevalent population. The prevalence of gBRCA1/2 mutations in patients aged >70 years was 8.2%. CONCLUSIONS: Sequencing all patients with non-mucinous ovarian cancer gives a much higher annual gBRCA1/2 mutation detection rate, with the frequency of positive tests still exceeding the 10% threshold upon which many family history-based models operate. TWEETABLE ABSTRACT: BRCA sequencing all non-mucinous cancer patients increases mutation detection five fold.


Subject(s)
BRCA1 Protein/genetics , BRCA2 Protein/genetics , Carcinoma/genetics , Genetic Testing/statistics & numerical data , Ovarian Neoplasms/genetics , Adult , Aged , Carcinoma/epidemiology , Female , Genetic Predisposition to Disease/epidemiology , Genetic Predisposition to Disease/genetics , Genetic Testing/standards , Germ-Line Mutation , Humans , Middle Aged , Ovarian Neoplasms/epidemiology , Prevalence , Retrospective Studies , Scotland/epidemiology
8.
QJM ; 108(5): 361-8, 2015 May.
Article in English | MEDLINE | ID: mdl-25267727

ABSTRACT

BACKGROUND: Phaeochromocytoma (phaeo) and paraganglioma (PGL) are rare conditions, which are malignant in up to 30%. Optimal treatment is controversial, but in patients with metastatic iodine-131-meta-iodobenzylguanidine ((123)I-MIBG) avid tumours, we offer (131)I-MIBG therapy. We summarize response rates, survival and safety in a cohort of such patients treated with (131)I-MIBG in our centre from 1986 to 2012. DESIGN/METHODS: Retrospective analysis of the case notes of patients with metastatic phaeo/PGL who received (131)I-MIBG was undertaken; patients underwent clinical, biochemical and radiological evaluation within 6 months of each course of (131)I-MIBG therapy. RESULTS: Twenty-two patients (9 males) were identified, 12 with metastatic PGL and 10 with phaeo. Overall median follow-up time after first dose of (131)I-MIBG was 53 months. In total, 68 doses of (131)I-MIBG were administered; average dose was 9967 MBq (269.4 mCi). After the first dose, >50% of patients demonstrated disease stability or partial response; progressive disease was seen in 9%. A subset of patients underwent repeated treatment with the majority demonstrating partial response or stable disease. No life-threatening adverse events were reported, but three patients developed hypothyroidism and two developed ovarian failure after repeated dosing. Five-year survival after original diagnosis was 68% and median (+inter quartile range) survival from date of diagnosis was 17 years (7.6-26.4) with no difference in survival according to diagnosis (P < 0.1). CONCLUSIONS: (131)I-MIBG is well tolerated and associates with disease stabilization or improvement in the majority of patients with metastatic phaeo/PGL. However, stronger conclusions on treatment effectiveness are limited by lack of a directly comparable 'control group' as well as an alternative 'gold standard' treatment.


Subject(s)
3-Iodobenzylguanidine/administration & dosage , Adrenal Gland Neoplasms/radiotherapy , Paraganglioma/radiotherapy , Pheochromocytoma/radiotherapy , Radiopharmaceuticals/administration & dosage , 3-Iodobenzylguanidine/adverse effects , Adolescent , Adrenal Gland Neoplasms/secondary , Adult , Aged , Disease Management , Female , Genetic Testing , Humans , Male , Middle Aged , Paraganglioma/metabolism , Pheochromocytoma/metabolism , Radiopharmaceuticals/adverse effects , Retrospective Studies , Tertiary Care Centers , Treatment Outcome , Young Adult
9.
Clin Oncol (R Coll Radiol) ; 24(2): e31-8, 2012 Mar.
Article in English | MEDLINE | ID: mdl-21703829

ABSTRACT

AIMS: Radical pelvic radiotherapy is one of the main treatment modalities for cancers of the bladder and cervix. The side-effects of pelvic radiotherapy include urinary symptoms, such as urinary frequency and cystitis. The therapeutic effects of cranberry juice in the prevention and treatment of urinary tract infections in general are well documented. The purpose of this study was to evaluate the effectiveness of cranberry juice on the incidence of urinary tract infections and urinary symptoms in patients undergoing pelvic radiotherapy for cancer of the bladder or cervix. MATERIALS AND METHODS: The study was a placebo-controlled, double-blind design. Participants were randomised to receive cranberry juice, twice a day (morning and night) for the duration of their radiotherapy treatment and for 2 weeks after treatment (6 weeks in total) or a placebo beverage, for the same duration. RESULTS: The incidence of increased urinary symptoms or urinary tract infections was 82.5% on cranberry and 89.3% on placebo (P=0.240, adjusted odds ratio [cranberry/placebo] 0.48, 95% confidence interval 0.14-1.63). CONCLUSIONS: The power of the study to detect differences was limited by the below target sample size and poor compliance. Further research is recommended, taking cognisance of the factors contributing to the limitations of this study.


Subject(s)
Beverages , Radiation Injuries/prevention & control , Urinary Bladder Neoplasms/radiotherapy , Urinary Tract Infections/prevention & control , Urologic Diseases/prevention & control , Uterine Cervical Neoplasms/radiotherapy , Vaccinium macrocarpon , Adult , Aged , Aged, 80 and over , Double-Blind Method , Female , Humans , Incidence , Male , Middle Aged , Placebos , Urinary Tract Infections/etiology , Urologic Diseases/etiology
10.
Gynecol Oncol ; 123(1): 105-9, 2011 Oct.
Article in English | MEDLINE | ID: mdl-21723596

ABSTRACT

OBJECTIVE: The aim of the study was to determine the response rate and response duration of cervical cancer previously treated by cisplatin (with or without radiation) to a combination of docetaxel and gemcitabine. Secondary endpoints were assessment of toxicity and quality of life (QoL) of patients receiving the treatment. METHODS: This was a multicentre phase II trial of 3 weekly docetaxel 75 mg/m(2) day 1 (reduced to 60 mg/m(2) after 32 cycles had been administered) and gemcitabine 1000 mg/m(2) (days 1 and 8). A two stage Gehan design was used initially. Twenty-nine patients recruited had disease outside the irradiated pelvis (Group 1), and 21 had disease confined to the irradiated pelvis (Group 2). The target response for the Gehan 2 design was 25% (Group 1) and 10% (Group 2). RESULTS: The overall response rate for Group 1 was 21.4% (95% CI 8.3-41.0%). Amongst those who had at least 3 cycles of chemotherapy the response rate was 27.3% (95% CI 10.7-50.2%). The median survival was 7.3 months (95% CI 5.4 to 9.2 months) with 39.3% (95% CI 21.7-56.5%) alive at 1 year. In Group 2 the overall response rate was 9.5% (95% CI 1.2%-30.4%). The response rate for those who had at least 3 cycles of chemotherapy was 12.5% (95% CI 1.6-38.4%). The median survival was 7.9 months (95% CI 2.2-13.6 months). Toxicity was mainly haematological with 51% developing grade 3 or 4 neutropenia after at least 1 cycle of chemotherapy. QoL showed a significant deterioration from baseline for physical and role function but there was an improvement in emotional function during treatment. CONCLUSION: Response rates and survival duration were similar to those reported following treatment with platinum based doublets. In view of the relatively poor response rates (no more than 36%) to conventional chemotherapy future developments should be a combination of chemotherapy and biological agents such as VEGFR inhibitors.


Subject(s)
Antineoplastic Combined Chemotherapy Protocols/therapeutic use , Uterine Cervical Neoplasms/drug therapy , Adult , Antineoplastic Combined Chemotherapy Protocols/adverse effects , Cisplatin/administration & dosage , Deoxycytidine/administration & dosage , Deoxycytidine/adverse effects , Deoxycytidine/analogs & derivatives , Docetaxel , Drug Resistance, Neoplasm , Female , Humans , Middle Aged , Neoadjuvant Therapy , Neoplasm Recurrence, Local/drug therapy , Neoplasm Recurrence, Local/pathology , Quality of Life , Taxoids/administration & dosage , Taxoids/adverse effects , Uterine Cervical Neoplasms/pathology , Uterine Cervical Neoplasms/radiotherapy , Gemcitabine
11.
Ann Oncol ; 22(9): 2036-2041, 2011 Sep.
Article in English | MEDLINE | ID: mdl-21273348

ABSTRACT

BACKGROUND: A previous dose-escalation trial of the vascular disrupting agent combretastatin A4 phosphate (CA4P) given before carboplatin, paclitaxel, or both showed responses in 7 of 18 patients with relapsed ovarian cancer. PATIENTS AND METHODS: Patients with ovarian cancer that had relapsed and who could start trial therapy within 6 months of their last platinum chemotherapy were given CA4P 63 mg/m(2) minimum 18 h before paclitaxel 175 mg/m(2) and carboplatin AUC (area under the concentration curve) 5, repeated every 3 weeks. RESULTS: Five of the first 18 patients' disease responded, so the study was extended and closed after 44 patients were recruited. Grade ≥2 toxic effects were neutropenia in 75% and thrombocytopenia in 9% of patients (weekly blood counts), tumour pain, fatigue, and neuropathy, with one patient with rapidly reversible ataxia. Hypertension (23% of patients) was controlled by glyceryl trinitrate or prophylactic amlodipine. The response rate by RECIST was 13.5% and by Gynecologic Cancer InterGroup CA 125 criteria 34%. CONCLUSIONS: The addition of CA4P to paclitaxel and carboplatin is well tolerated and appears to produce a higher response rate in this patient population than if the chemotherapy was given without CA4P. A planned randomised trial will test this hypothesis.


Subject(s)
Antineoplastic Combined Chemotherapy Protocols/administration & dosage , Ovarian Neoplasms/drug therapy , Adult , Aged , Antineoplastic Combined Chemotherapy Protocols/adverse effects , Carboplatin/administration & dosage , Carboplatin/adverse effects , Drug Administration Schedule , Drug Resistance, Neoplasm , Female , Humans , Middle Aged , Organoplatinum Compounds/pharmacology , Paclitaxel/administration & dosage , Paclitaxel/adverse effects , Stilbenes/administration & dosage , Stilbenes/adverse effects
12.
Eur J Cancer ; 45(4): 517-26, 2009 Mar.
Article in English | MEDLINE | ID: mdl-19013789

ABSTRACT

INTRODUCTION: Surgery is the mainstay of staging and treatment of ovarian cancer. Optimal quality of ovarian cancer surgery implies complete staging and removal of all macroscopic tumour with minimal harm to the patient in order to ensure best patient outcome. However, variation in the quality of ovarian cancer surgery is apparent. In order to assess and improve the quality of care, quality indicators can be used. METHODS: To identify candidate quality indicators, a literature search was performed using relevant MESH terms. These were assessed for validity, feasibility and measurability. RESULTS: Five quality indicators for staging of presumed early-stage ovarian cancer and six for primary debulking surgery for advanced disease are proposed. CONCLUSION: The defined quality indicators can be used to monitor and improve the quality of surgery for ovarian cancer.


Subject(s)
Ovarian Neoplasms/surgery , Quality Indicators, Health Care , Abdomen/surgery , Female , Humans , Hysterectomy/standards , Lymph Node Excision/standards , Lymphatic Metastasis , Neoplasm Invasiveness , Neoplasm Staging , Ovarian Neoplasms/pathology , Ovariectomy/standards , Practice Guidelines as Topic , Prognosis , Time Factors
13.
Clin Oncol (R Coll Radiol) ; 20(6): 470-8, 2008 Aug.
Article in English | MEDLINE | ID: mdl-18572394

ABSTRACT

Uterine sarcomas remain challenging tumours to manage and need multi-disciplinary care. This article reviews the surgical and adjuvant treatments for these tumours. The importance of surgical staging is discussed and the need for careful review of the pathology. Newer classifications will help to distinguish the different types as we now recognise that carcinosarcomas are most likely to be epithelial cancers rather then sarcomas. A critical discussion of the roles of both adjuvant chemotherapy and radiation are discussed. Some recent important trials have helped to give better evidence base on which to plan future treatment strategies. The routine place of adjuvant pelvic radiation seems limited as it only leads to improved local control. To date chemotherapy studies have equally failed to show a benefit. More trials are needed to address these issues. We cannot be complacent as we still see too high a relapse rate and new treatment approaches are required, investigation of the new targeted agents may offer a more promising return. Given their relative uncommonness, centralisation of care and discussion at multi-disciplinary tumour boards is essential. International collaboration is essential.


Subject(s)
Sarcoma, Endometrial Stromal/surgery , Uterine Cervical Neoplasms/surgery , Carcinosarcoma/surgery , Disease Progression , Female , Humans , Leiomyosarcoma/surgery , Neoplasm Recurrence, Local/surgery , Postoperative Period , Time Factors , Uterine Cervical Neoplasms/drug therapy , Uterine Cervical Neoplasms/radiotherapy
14.
Eur J Cancer ; 44(6): 808-18, 2008 Apr.
Article in English | MEDLINE | ID: mdl-18378136

ABSTRACT

The management of uterine sarcomas continues to present many difficulties. Primary surgery is the optimal treatment but the role of post-operative radiation remains uncertain. In the mid-1980s, the European Organisation for Research and Treatment of Cancer Gynaecological Cancer Group Study proposed a trial to evaluate adjuvant radiotherapy, as previous non-randomised studies had suggested a survival advantage and improved local control when post-operative radiation was administered. The study opened in 1987 taking 13 years to accrue 224 patients. All uterine sarcoma subtypes were permitted. Patients were required to have undergone as a minimum, TAH and BSO and wahsings (166 patients) but nodal sampling was optional. There were 103 leiomyosarcomas (LMS), 91 carcinosarcomas (CS) and 28 endometrial stromal sarcomas (ESS). Patients were randomised to either observation or pelvic radiation, 51 Gy in 28 fractions over 5 weeks. Hundred and twelve were recruited to each arm. The initial analysis has shown a reduction in local relapse (14 versus 24, p=0.004) but no effect on either OS or PFS. No unexpected toxicity was seen in the radiation arm. No difference in either overall or disease-free survival was demonstrated but there is an increased local control for the CS patients receiving radiation but without any benefit for LMS. Prognostic factor analysis shows that stage, age and histological subtype were important predictors of behaviour which may explain differences between CS and LMS. CS appears to show more kinship to poorly differentiated endometrial carcinomas in behaviour. LMS did not show the same benefit from radiation. These results will help shape future management and clinical trials in uterine sarcomas.


Subject(s)
Carcinosarcoma/radiotherapy , Leiomyosarcoma/radiotherapy , Sarcoma, Endometrial Stromal/radiotherapy , Uterine Neoplasms/radiotherapy , Adult , Aged , Aged, 80 and over , Carcinosarcoma/pathology , Disease Progression , Disease-Free Survival , Female , Humans , Leiomyosarcoma/pathology , Middle Aged , Neoplasm Recurrence, Local/prevention & control , Radiotherapy/adverse effects , Radiotherapy, Adjuvant/methods , Sarcoma, Endometrial Stromal/pathology , Treatment Outcome , Uterine Neoplasms/pathology
15.
Br J Cancer ; 94(1): 62-8, 2006 Jan 16.
Article in English | MEDLINE | ID: mdl-16404361

ABSTRACT

The feasibility of sequential carboplatin followed by docetaxel-based therapy for untreated ovarian cancer was determined. Patients received four q3w cycles of carboplatin AUC 7, then four q3w cycles of either docetaxel 100 mg m(-2) (day 1) (arm A); docetaxel 75 mg m(-2) (day 8) and gemcitabine 1250 mg m(-2) (days 1,8) (arm B) or docetaxel 25 mg m(-2) and gemcitabine 800 mg m(-2) (both given weekly (days 1,8,15)) (arm C). A total of 44 patients were randomised to each treatment arm. None of the arms demonstrated an eight cycle completion rate (70.5/72.7/45.5% in arms A/B/C, respectively), which was statistically greater than 60% (P=0.102, P=0.056, P=0.982) which was our formal feasibility criteria, although only the completion rate in arm C was clearly worse than this level. The overall response rate (ORR) after carboplatin was 65.7% in 70 evaluable patients. In evaluable patients, ORRs after docetaxel-based cycles were: arm A 84.0% (21 out of 25); arm B 77.3% (17 out of 22); arm C 69.6% (16 out of 23). At follow-up (median 30 months), median progression-free survival times were: arm A 15.5 months (95% CI: 10.5-20.6); arm B 18.1 months (95% CI: 15.9-20.3); arm C, 13.7 months (95% CI: 12.8-14.6). Neutropenia was the predominant grade 3-4 haematological toxicity: 77.8/85.7/54.4% in arms A/B/C, respectively. Dyspnoea was markedly increased in both gemcitabine-containing arms (P=0.001) but was worse in arm C. Although just failing to rule out eight cycle completion rates less than 60%, within the statistical limitations of these small cohorts, the overall results for arms A and B are encouraging. Larger phase III studies are required to test these combinations.


Subject(s)
Antineoplastic Combined Chemotherapy Protocols/therapeutic use , Fallopian Tube Neoplasms/drug therapy , Ovarian Neoplasms/drug therapy , Peritoneal Neoplasms/drug therapy , Adult , Aged , Antineoplastic Combined Chemotherapy Protocols/adverse effects , Area Under Curve , Carboplatin/administration & dosage , Deoxycytidine/administration & dosage , Deoxycytidine/analogs & derivatives , Disease Progression , Docetaxel , Drug Administration Schedule , Dyspnea/chemically induced , Fallopian Tube Neoplasms/pathology , Female , Humans , Infusions, Intravenous , Middle Aged , Ovarian Neoplasms/pathology , Peritoneal Neoplasms/pathology , Survival Analysis , Taxoids/administration & dosage , Treatment Outcome , Gemcitabine
16.
Eur J Cancer ; 42(2): 179-85, 2006 Jan.
Article in English | MEDLINE | ID: mdl-16337372

ABSTRACT

The management of older and unfit women with advanced ovarian cancer requires post-operative chemotherapy but many of these patients are not suitable for high-dose cisplatin-based regimes. Carboplatin has been an easier alternative and can be given in the ambulatory setting. Historical data suggests that oral alkylating agents to be just effective with similar efficacy. In this study we have compared platinum-based carboplatin to the alkylating agent treosulfan in a population unfit to receive high-dose cisplatin. The trial randomised patients to either intravenous carboplatin or treosulfan as single agent. The trial was stopped prematurely after the interim analysis showed improved survival and response rates in the carboplatin arm. We conclude that carboplatin is a safe and effective drug in a population that is unfit for high-dose cisplatin. Treosulfan showed limited activity but may be considered along with other oral drugs in limited circumstances. With the exception of myelosuppression, toxicity was mild in both arms. Carboplatin remains the gold standard in this older and less fit group of patients.


Subject(s)
Antineoplastic Agents/therapeutic use , Busulfan/analogs & derivatives , Carboplatin/therapeutic use , Ovarian Neoplasms/drug therapy , Aged , Antineoplastic Agents, Alkylating/therapeutic use , Busulfan/therapeutic use , CA-125 Antigen/metabolism , Female , Humans , Infusions, Intravenous , Middle Aged , Quality of Life , Survival Analysis , Treatment Outcome
17.
Gynecol Oncol ; 100(3): 615-7, 2006 Mar.
Article in English | MEDLINE | ID: mdl-16242761

ABSTRACT

BACKGROUND: The association between Guillain-Barre syndrome (GBS) and malignancy is uncommon and has not been previously reported in gynecological cancers. CASE: Our case documents this syndrome occurring in a patient shortly after completion of adjuvant chemo-radiotherapy for endometrial carcinoma. We review the current literature and discuss potential pathogenic mechanisms of this likely paraneoplastic association. CONCLUSION: GBS in cancer patients is a potentially life-threatening condition and should be differentiated from simple chemotherapy toxicity, particularly as effective treatment is available.


Subject(s)
Endometrial Neoplasms/complications , Guillain-Barre Syndrome/complications , Paraneoplastic Syndromes/complications , Chemotherapy, Adjuvant , Endometrial Neoplasms/therapy , Female , Humans , Middle Aged , Radiotherapy, Adjuvant
18.
Br J Cancer ; 86(9): 1385-90, 2002 May 06.
Article in English | MEDLINE | ID: mdl-11986768

ABSTRACT

The docetaxel-carboplatin combination is active and well tolerated in patients with epithelial ovarian cancer. We added epirubicin to this combination to investigate additional benefits of anthracyclines in epithelial ovarian cancer. Twenty-one patients, FIGO Ic-IV, performance status 0-1, were treated in four dose cohorts. Docetaxel was fixed at 75 mg m(-2), carboplatin doses were AUC 4-5 and epirubicin doses were 50-60 mg m(-2). Drugs were given on day 1, every 3 weeks, except in cohort 3, where epirubicin was given on day 8. Dexamethasone was given prophylactically. One dose-limiting toxicity occurred in cohorts 1, 2 and 4, two occurred in cohort 3. Complicated neutropenia occurred in two patients in cohorts 1 and 2 and one patient in cohorts 3 and 4. Two patients experienced grade III diarrhoea or stomatitis in cohort 1 and two in cohort 3. There were no treatment-related deaths. Grade II sensory neuropathy occurred in one patient. No cardiac toxicity or significant oedema was observed. The overall response rate was 36%, and 62% were CA125 responders. The predefined maximum tolerated dose was exceeded in cohort 3. The cohort 4 dose level (epirubicin 50 mg m(-2), carboplatin AUC 4, docetaxel 75 mg m(-2)), warrants further study.


Subject(s)
Antineoplastic Combined Chemotherapy Protocols/therapeutic use , Ovarian Neoplasms/drug therapy , Paclitaxel/analogs & derivatives , Taxoids , Adult , Aged , Area Under Curve , Carboplatin/administration & dosage , Carboplatin/adverse effects , Carboplatin/pharmacokinetics , Diarrhea/chemically induced , Docetaxel , Dose-Response Relationship, Drug , Epirubicin/administration & dosage , Epirubicin/adverse effects , Epirubicin/pharmacokinetics , Female , Humans , Middle Aged , Ovarian Neoplasms/pathology , Paclitaxel/administration & dosage , Paclitaxel/adverse effects , Paclitaxel/pharmacokinetics , Stomatitis/chemically induced
20.
Br J Cancer ; 84(2): 170-8, 2001 Jan.
Article in English | MEDLINE | ID: mdl-11161372

ABSTRACT

A prospective, non-randomized, multicentre, open, dose-finding study of a carboplatin-docetaxel (C-D) combination as first-line chemotherapy in FIGO stage Ic-IV epithelial ovarian cancer. C-D was given 3-weekly for 6 planned cycles, with a 3-day prophylactic dexamethasone regimen (8 mg b.i.d.). 139 eligible patients (Pts) (median age 56 years, range 28-85) were given a total of 750 cycles of chemotherapy in 5 cohorts: Co1, 32 pts, 169 cycles (C at AUC 5 + D 60 mg/m(2)); Co2, 22 pts, 122 cycles (5 + 75), Co3, 29 pts, 156 cycles (6 + 75), Co4, 27 pts, 146 cycles (7 + 75), Co5, 30 pts, 157 cycles (6 + 85). 110 patients (79%) completed 6 cycles; 17 (12%) stopped due to toxicity. 104 patients (75%) had CTC grade IV neutropenia, and 5 patients (4%) had this associated with fever. There were 2 probable treatment-related deaths. Only 8 patients (6%) experienced grade II-III neurotoxicity (all sensory; no motor > grade I). The maximum tolerated dose was reached in cohorts 4 and 5, and the dose limiting toxicities were myelosuppression and diarrhoea. The overall response rate for the study was 66% (49/74); CA125 response was 75% (70/93). Median progression-free survival was 16.6 months (95% CI 13.3-19.1). Recommended doses are carboplatin AUC 5 (via(51)Cr EDTA) or AUC 6 (if calculated) plus docetaxel 75 mg/m(2). A randomized trial comparing this regimen with carboplatin-paclitaxel has just completed recruitment.


Subject(s)
Adenocarcinoma/drug therapy , Antineoplastic Combined Chemotherapy Protocols/therapeutic use , Ovarian Neoplasms/drug therapy , Paclitaxel/analogs & derivatives , Taxoids , Adenocarcinoma/pathology , Adult , Aged , Aged, 80 and over , Antineoplastic Combined Chemotherapy Protocols/adverse effects , Carboplatin/administration & dosage , Carboplatin/adverse effects , Constipation/chemically induced , Diarrhea/chemically induced , Docetaxel , Dose-Response Relationship, Drug , Fatigue/chemically induced , Female , Hematologic Diseases/chemically induced , Humans , Middle Aged , Nausea/chemically induced , Neoplasm Staging , Ovarian Neoplasms/pathology , Paclitaxel/administration & dosage , Paclitaxel/adverse effects , Prospective Studies , Survival Analysis , Treatment Outcome , Vomiting/chemically induced
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