Interaction between warfarin and Chinese herbal medicines.

In traditional Chinese medicine (TCM), the human body is divided into Yin and Yang. Diseases occur when the Yin and Yang balance is disrupted. Different herbs are used to restore this balance, achieving the goal of treatment. However, inherent difficulties in designing experimental trials have left much of TCM yet to be substantiated by science. Despite that, TCM not only remains a popular form of medical treatment among the Chinese, but is also gaining popularity in the West. This phenomenon has brought along with it increasing reports on herb-drug interactions, beckoning the attention of Western physicians, who will find it increasingly difficult to ignore the impact of TCM on Western therapies. This paper aims to facilitate the education of Western physicians on common Chinese herbs and raise awareness about potential interactions between these herbs and warfarin, a drug that is especially susceptible to herb-drug interactions due to its narrow therapeutic range.

A phase II trial of weekly i.v. KW-2170 in advanced castrate-resistant prostate cancer.

AIM: KW-2170 is a novel pyrazoloacridone derivative that intercalates nucleic acids. It has promising in vitro properties against prostate and other cancers and is active in vivo against doxorubicin-resistant cell lines. We wished to investigate its activity and toxicity profile in this Phase II trial in androgen independent prostate cancer. METHODS: Overall 44 men were recruited to this multicenter, open label, non-randomized study, with 35 evaluable for prostatic specific antigen (PSA) response. RESULTS: Five patients had a PSA fall greater than 50% (overall RR 14.3%, 95% CI 4.8-30.3%). Overall median survival was 16 months. In the evaluable group (n = 35), median survival was 18.9 months. The drug was very well tolerated, with the most common toxicities being hematological (anemia, leucopenia, thrombocytopenia), alopecia, fatigue, and nausea. However, most of these were National Cancer Institute Grade 1 or 2; Grade 3 neutropenia occurred in only 11% of patients, and there was no Grade 4 neutropenia. Quality of life as measured by the FACT-P scale was not compromised. CONCLUSION: KW-2170 is a very well tolerated chemotherapy agent. It has a relatively low PSA response rate, and did not meet the pre-specified criteria for further studies.

Management of HER2-positive breast cancer in Asia: consensus statement from the Asian Oncology Summit 2009.

Patients with breast cancer positive for human epidermal growth-factor receptor type 2 (HER2) are an important subgroup for consideration in the Asian context. Rationally designed, anti-HER2 targeted agents that can substantially improve treatment outcomes have become commercially available, but are still too costly for some groups in developed countries and for underdeveloped and developing nations. This review discusses the available evidence for optimum management of HER2-positive early and advanced breast cancer, and how this evidence can be applied to Asian countries with different levels of health-care resources and economic development--using framework provided by the Breast Health Global Initiative. We provide a brief overview of HER2 testing and discuss management of early and advanced HER2-positive breast cancer, and formulate a consensus statement for the management of breast cancer in the context of basic, limited, enhanced, and maximum health-care resource availability.

Measurement properties of the Chinese language version of the functional assessment of cancer therapy-general in a Singaporean population.

INTRODUCTION: Health-related quality of life is an important aspect of health outcome. The assessment of it must be done by validated instruments. There is no published data on the validity, reliability and sensitiveness to change of the official Chinese translation of the Functional Assessment of Cancer Therapy-General (version 4; FACT-G). MATERIALS AND METHODS: A Chinese questionnaire package comprising the FACT-G and Functional Living Index-Cancer (FLIC, which was translated, modified and validated in Singapore) was filled in by 165 ethnic Chinese patients recruited from the National Cancer Centre, Singapore. Four weeks later, the patients were assessed again by a postal questionnaire survey. RESULTS: The FACT-G and FLIC total scores were strongly correlated (r = 0.85). The Physical, Social/Family, Emotional and Functional Well-being scales of the FACT-G converged to and diverged from FLIC components as conceptually expected. The FACT-G and its 4 scales also demonstrated known-groups validity in differentiating patients with different performance status (each P <0.001). Their internal consistency ranged from 0.81 to 0.93 and test-retest reliability ranged from 0.74 to 0.85. The FACT-G and its Physical, Emotional and Functional Well-being scales showed trends of change in relation to change in performance status. The Social/Family Well-being scale was sensitive to decline but not improvement in performance status. CONCLUSIONS: The Chinese version of the FACT-G can be used to assess overall level and some specific aspects of health-related quality of life. However, researchers should be cautious in using this instrument to specifically investigate the social aspect of quality of life.

Green tea, soy, and mammographic density in Singapore Chinese women.

There is increasing evidence from observational studies that breast cancer risk is inversely associated with soy and green tea consumption. We investigated the effects of these two dietary agents on mammographic density, a well-established biomarker for breast cancer risk, in a cross-sectional analysis of mammograms and validated food frequency questionnaires from 3,315 Chinese women in Singapore. Percent mammographic density (PMD) was assessed using a reproducible computer-assisted method. We used generalized linear models to estimate PMD by intake of soy, green tea, and black tea while adjusting for potential confounders. Daily green tea drinkers showed statistically significantly lower PMD (19.5%) than non-tea drinkers (21.7%; P = 0.002) after adjusting for relevant covariates. This difference in PMD between daily green tea drinkers and non-tea drinkers remained statistically significant after adjustment for soy (P = 0.002); the effect was more apparent among lower soy consumers (Q1-Q3; 21.9% versus 19.4%; P = 0.002) than in higher (Q4) consumers (20.9% versus 19.5%; P = 0.32). Black tea intake was unrelated to PMD. Only among postmenopausal women who reported very high soy intake (Q4) compared with those with less soy intake was there any association noted between PMD and soy intake (18.9% versus 20.5%; P = 0.035). Following adjustment for green tea intake, the association between soy and PMD was no longer statistically significant (P = 0.52). Our findings suggest that both regular green tea and high soy intake may have beneficial effects on the breast; the effect of green tea on PMD may be stronger than the effect of soy.

Phase I/II study of gemcitabine with pegylated liposomal doxorubicin as first-line therapy in Asian women with metastatic breast cancer.

This was a single institution phase I/II study to determine the maximum tolerated dose (MTD) and efficacy of pegylated liposomal doxorubicin (PLD) and gemcitabine in Asian women with metastatic breast cancer. PLD was administered on day 1 and gemcitabine on days 1 and 8 every 3 weeks at escalating doses from 25 mg/m(2) and 1000 mg/m(2) onwards respectively. The median age was 56 years with a median disease-free interval of 43 months. Majority of the patients had visceral involvement. At PLD 35 mg/m(2) and gemcitabine 1200 mg/m(2), the overall response rate for 23 evaluable patients was 83% (1 CR, 18 PR, 3 SD, 1 PD). Six had prior adjuvant anthracyclines (3 PR, 1 SD). The median follow-up was 81 weeks and progression free interval was 29 weeks. Overall survival was 23.9 months. The dose limiting toxicities were mucositis and myelosuppression. This regimen is active and reasonably tolerated as first-line therapy.

Gemcitabine and split-dose paclitaxel or docetaxel in metastatic breast cancer: a randomised phase II study.

PURPOSE: The purpose was to evaluate the activity and toxicity of split-dose paclitaxel or docetaxel in combination with gemcitabine in patients with metastatic breast cancer (MBC) who had previously received anthracyclines. PATIENTS AND METHODS: A total of 210 patients were randomly assigned to one of three treatment arms: gemcitabine 1,250 mg/m(2) Days 1 and 8 and paclitaxel 175 mg/m(2) as a 3-h infusion on Day 1 (GP1); gemcitabine 1,000 mg/m(2) Days 1 and 8 and paclitaxel 100 mg/m(2) as a 1-h infusion on Days 1 and 8 (GP2); gemcitabine 1,000 mg/m(2) Days 1 and 8 and docetaxel 40 mg/m(2) as a 1-h infusion on Days 1 and 8 (GD). Cycles were repeated every 3 weeks. RESULTS: For the 204 patients evaluable for response assessment, the response rates were 48.6% for GP1, 52.2% for GP2, and 52.3% for GD. Median response duration, time to treatment failure, and time to progression (TTP) were similar in each arm. Median TTP for GP1, GP2 and GD was 7.5, 7.0 and 7.4 months, respectively. For the 208 patients evaluable for safety, the most common grade 3/4 toxicity for each regimen was neutropaenia, with 64%, 57%, and 68% for GP1, GP2, and GD, respectively. Grade 4 neutropaenia, grade 3/4 anaemia, febrile neutropaenia, and diarrhoea were more common in the docetaxel arm, as was the use of intravenous antibiotics and blood transfusions. CONCLUSION: The study confirmed the high activity of gemcitabine-taxane combinations in MBC. Split-dose paclitaxel had similar activity and toxicity to the 3-weekly administration. The split-dose docetaxel regimen had similar activity to the paclitaxel combinations though associated with higher toxicity.

Quality of life scores differed according to mode of administration in a review of three major oncology questionnaires.

OBJECTIVE: To assess whether scores on the three major quality-of-life questionnaires in oncology (FACT-G, FLIC, and EORTC QLQ-C30) are associated with modes of administration in a realistic clinical research setting. STUDY DESIGN AND SETTING: A heterogeneous sample of 1,265 cancer patients was recruited in Singapore. About one-fourth of the patients chose to have the interview administered by research staff; the rest self-completed the questionnaires. Multiple regression was used to adjust for differences in demographic and clinical characteristics between patients. An equivalence margin was defined as 0.25 standard deviations. RESULTS: Apart from one exception (the EORTC QLQ-C30 global functioning scale), all scales showed higher mean values in patients who were interviewed than patients who self-administered the questionnaires. For the physical and functional well-being scales of FACT-G and the physical and social functioning scales of EORTC QLQ-C30, the differences were small and the confidence intervals fell totally within the equivalence zone. The emotional well-being score of the FACT-G was different across modes of administration and the confidence interval fell outside the equivalence zones. There was no interaction between modes of administration and respondents' education level. CONCLUSION: The physical aspect of quality-of-life is not sensitive to interviewer administration but the psychological aspect is. Statistical adjustment for some scales is recommended.

Associations between soy, diet, reproductive factors, and mammographic density in Singapore Chinese women.

Although the evidence is not completely consistent, soy intake has been inversely associated with breast cancer risk, and the strongest results have been observed in certain Asian populations. To address this issue and to examine the association between mammographic density and reproductive factors in this population, we conducted a cross-sectional analysis of mammograms and validated food-frequency questionnaires from 380 Chinese women living in Singapore. Percent mammographic density, a biomarker for breast cancer risk, was assessed using a validated computer-assisted method. We used generalized linear models to estimate mean mammographic density by quartiles of soy intake and intake of other dietary factors while adjusting for potential confounders. Percent mammographic density was inversely associated with age, body mass index, parity, breastfeeding, and soy intake. The difference in mammographic density between the highest and lowest quartiles of soy intake was 4-5%; this difference was statistically significant for soy protein and soy isoflavone intake and is similar in magnitude to what has been reported in Western populations when women undergo menopause or commence hormone therapy. We found no evidence that high fiber, fruit, or vegetable intake has protective effects on mammographic density. Our results suggest that the effect of soy intake on percent mammographic density is moderate but possibly of clinical relevance.

Over-expression of c-erbB-2 correlates with nuclear morphometry and prognosis in breast carcinoma in Asian women.

AIM: We aimed to investigate the immunohistochemical expression of c-erbB-2 in invasive breast carcinoma in Asian women and its correlations with clinicopathological parameters and nuclear morphometry. Patients were followed up for disease relapse and overall survival, and the data were reviewed in conjunction with c-erbB-2 over-expression. METHODS: Paraffin sections from 321 invasive breast cancers were immunohistochemically stained with anti-human c-erbB-2 antibody using the streptavidin-biotin technique. RESULTS: c-erbB-2 was over-expressed in 110 (34.3%) cases, with an inverse correlation with oestrogen receptor (ER) and progesterone receptor (PR) status (p=0.0001) and a positive correlation with histological grade (p=0.017). Nuclear morphometry in 96 cases revealed rounder nuclei in c-erbB-2 negative tumours (p=0.0322) when compared with c-erbB-2 positive tumours. Among c-erbB-2 positive cases, malignant cells of histological grade 3 tumours revealed larger nuclear area and perimeter than grade 1 and 2 cases (p=0.0095, p=0.03, respectively) while increasing tumour size correlated with greater nuclear perimeter (p=0.046). c-erbB-2 positivity was significantly associated with poor survival when all patients were included in the analysis (p=0.0166) and for subsets of node positive, histological grade 1 and 2, and ER positive tumours, and in women aged over 50 years (p=0.0047, p=0.0367, p=0.0092, p=0.0096, respectively). CONCLUSIONS: c-erbB-2 was independently prognostic when histological grade, nodal and ER status were considered. Our results show that c-erbB-2 over-expression correlates with poor histological grade and negative ER/PR status, and predicts poor overall survival in Asian women with breast cancer.

Variability and sample size requirements of quality-of-life measures: a randomized study of three major questionnaires.

PURPOSE: To compare the variability and sample size requirements of the global quality-of-life (QOL) scores of the following three major QOL instruments: the Functional Assessment of Cancer Therapy-General (FACT-G), Functional Living Index-Cancer (FLIC), and European Organisation for Research and Treatment of Cancer Core Quality of Life Questionnaire C30 (EORTC QLQ-C30). PATIENTS AND METHODS: Cancer patients were randomly assigned to answer two of the three instruments using an incomplete block design (n = 1,268). The instruments were compared in terms of coefficient of variation, effect size in detecting a difference between patients with different performance status, and correlation coefficient between scores at baseline and follow-up. RESULTS: The FACT-G and FLIC had significantly smaller coefficients of variation than the EORTC QLQ-C30 (both P < .05). The FLIC also had significantly larger correlation coefficients between scores at baseline and follow-up than the EORTC QLQ-C30 (P < .05). The FACT-G and the FLIC had a larger effect size in a cross-sectional and longitudinal setting, respectively, than the EORTC QLQ-C30 in differentiating patients with different performance status (both P < .05). CONCLUSION: In some aspects, the FACT-G and FLIC global QOL scores had smaller variability and larger discriminative ability than the EORTC QLQ-C30. Further research using other criteria to compare the three instruments is recommended.

A longitudinal study of pediatric body mass index values predicted health in middle age.

BACKGROUND AND OBJECTIVE: To characterize the use of pediatric body mass index (BMI) to predict obesity, overweight, and diseases in middle age. METHODS: A longitudinal study of people born in a week in 1958 (n=12,327). The main outcome measures are obesity (BMI > or = 30) and overweight (BMI > or = 25) at age 33 and disease history self-reported at age 42. Receiver operating characteristic (ROC) analysis was performed using BMI measured at ages 7, 11, and 16 years as predictors. RESULTS: BMI values measured at age 11 could predict obesity at age 33 with areas under ROC curve (AUC) of 0.78 for males and 0.80 for females (each P < .001). BMI values at age 11 predicted overweight with slightly smaller AUC (each P < .001). They could also predict history of diabetes and hypertension (AUC=0.60 and 0.56, respectively, each P < .01), both sexes pooled. Prediction based on BMI at age 7 was less satisfactory; that at 16 gave limited improvement. Cutoff points based on ROC curves, the international reference, and the 85th and 95th percentiles gave very different profiles of diagnostic features. CONCLUSION: Pediatric BMI may predict adult obesity and overweight with a reasonable profile of sensitivity and specificity.

The equivalence and difference between the English and Chinese versions of two major, cancer-specific, health-related quality-of-life questionnaires.

BACKGROUND: English and Chinese are two of the most widely used primary languages in the world. Patients in many cancer centers have a variety of ethnic backgrounds and primary languages. The comparability of version 4 of the English and Chinese versions of the Functional Assessment of Cancer Therapy-General (FACT-G) and version 3 of the European Organization for the Research and Treatment of Cancer Core Quality of Life Questionnaire (EORTC QLQ-C30) have not been established. METHODS: In total, 1136 ethnic Chinese patients with cancer were recruited from the National Cancer Centre of Singapore. Patients chose to answer an English or Chinese questionnaire, according to their own preference. Multiple regression analysis was used to adjust for differences in demographic and health characteristics. Equivalence was confirmed if the 90% confidence intervals of the adjusted mean difference fell completely within an equivalence zone of +/- 0.25 standard deviations (SD). RESULTS: The English and Chinese versions of the Total, Emotional, and Functional Well Being Scales of the FACT-G and the Physical and Emotional Functioning Scales of the EORTC QLQ-C30 were equivalent. Scores for the other scales on the two questionnaires, at most, had a small differences that did not exceed 0.5 SD. Nevertheless, the Chinese translation of the question "I have a lack of energy" in the Physical Well Being Scale of the FACT-G produced results that differed from the results produced by the original English version. CONCLUSIONS: Data collected from English-speaking and Chinese-speaking respondents were capable of being pooled, and either version could be used for bilingual respondents. Nevertheless, the authors recommend modification of the Physical Well Being question that produced different results ("I have a lack of energy").

Quick-FLIC--a short questionnaire for assessing quality of life of cancer patients.

Health-related quality of life instruments tend to include a great many items. This imposes a burden on the respondents as well as undermining response rate and data quality. In this study we developed a shortened version of the Functional Living Index-Cancer (FLIC), now called Quick-FLIC, and examined its measurement properties. A questionnaire package, self-administered by 140 patients, included the FLIC and the Functional Assessment of Cancer Therapy-General. A factor analysis and clinical judgement were used to shorten the FLIC, which included 22 items. Each subscale of FLIC was shortened to include two or three items only. The Quick-FLIC included a total of only 11 items. Nevertheless, the measurement properties of the Quick-FLIC and its subscales were comparable to those of the original FLIC. It is concluded that the shortening of established health-related quality of life instruments is viable in oncology research.

Age at diagnosis and the choice of survival analysis methods in cancer epidemiology.

A young age at diagnosis of cancer is often seen as an indicator of the aggressiveness of the tumor. However, empirical studies have shown conflicting results on the association between age at diagnosis and survival. There are two choices of time scale for a Cox regression model: time since diagnosis, and age. The regression analysis of relative survival rates is an alternative to the Cox model. Using breast cancer data from a population-based cancer registry, we illustrate the features of Cox models using the two time scales and compare them with the relative survival approach. Using a Cox model with time since diagnosis as the time scale, a younger age at diagnosis is associated with a lower mortality; using age as the time scale gives the opposite result. The relative survival approach agrees with the Cox model with age as the time scale. We maintain that a careful clarification of research purpose and a careful choice of methods are necessary.