CYP2D6 polymorphisms influence the efficacy of adjuvant tamoxifen in Thai breast cancer patients.

AIM: We evaluated single nucleotide polymorphisms (SNPs) of CYP2D6 to identify those that influence the efficiency of tamoxifen in adjuvant treatment of breast cancer through a matched case-control study. METHODS: Peripheral blood DNA was collected from 20 patients with disease recurrence during adjuvant tamoxifen treatment and from 19 patients who had completed 5 years of tamoxifen therapy without recurrence of breast cancer. CYP2D6*4 (1846G > A; rs3892097), CYP2D6*10 (100C > T, rs1065852), and CYP2D6*5 (deletion) were genotyped. The correlation between disease-free survival (DFS) and genotype and clinical outcome were assessed using Kaplan-Meier analysis and a log-rank test. RESULTS: We found the allelic frequency of CYP2D6*10 during this study. Patients with the CYP2D6*10 homozygous variant T/T genotype had a significantly shorter median of DFS than those with C/T (P = 0.036), but DFS was not significantly different from that of patients with the C/C genotype (P = 0.316). One patient who was a carrier both of CYP2D6 G/A (1846G > A) and T/T (100C > T) had DFS of 22.7 months. CONCLUSIONS: This study demonstrated that CYP2D6*10/*10 was significantly associated with shorter DFS in Thai breast cancer patients receiving tamoxifen. This was a pilot study investigating the correlation of CYP2D6 polymorphisms and their influence on clinical outcomes in Thai estrogen receptor-positive breast cancer patients.

Impact of CYP2D6 polymorphisms on tamoxifen responses of women with breast cancer: a microarray-based study in Thailand.

This study was designed to investigate the frequency of CYP2D6 polymorphisms and evaluate the association between genetic polymorphisms of CYP2D6 and tamoxifen therapeutic outcome in Thai breast cancer patients. We recruited 48 breast cancer patients who received adjuvant tamoxifen for evaluating CYP2D6 genetic polymorphisms using microarray-based technology. Associations between genotypes-phenotypes and disease free survival were analyzed. Median follow up time was 5.6 years. The mean age of the subjects was 50 years. The 3 common allelic frequencies were 43.8% (*10), 36.5 (*1) and 10.4% (*2) which are related to extensive metabolizer (EM) and intermediate metabolizer (IM) with 70.8% and 29.2 %, respectively. No association between CYP2D6 genotypes and DFS was demonstrated. Nevertheless, exploratory analysis showed statistically significant shorter DFS in the IM group of post-menopause patients (HR, 6.85; 95% CI, 1.48 -31.69; P = 0.005). Furthermore, we observed statistically significant shorter DFS of homozygous CYP2D6*10 when compared with heterozygous CYP2D6*10 and other genotypes (P=0.005). CYP2D6*10 was the most common genotype in our subjects. Post-menopause patients with homozygous CYP2D6*10 and IM have shorter DFS. To confirm this relationship, larger samples and comprehensively designed trials in Thailand are required.

Efficacy of bevacizumab with cisplatin and gemcitabine in Asian patients with advanced or recurrent non-squamous non-small cell lung cancer who have not received prior chemotherapy: a substudy of the Avastin in Lung trial.

AIM: The phase III AVAiL study evaluated the efficacy and safety of the anti-vascular epidermal growth factor agent bevacizumab combined with platinum-based chemotherapy as first-line treatment in patients with advanced non-small-cell lung cancer (NSCLC). We report the results of a preplanned analysis of Asian patients enrolled in AVAiL. METHODS: Patients with recurrent or advanced non-squamous NSCLC were randomized to receive bevacizumab 7.5 mg/kg, bevacizumab 15 mg/kg or placebo, plus cisplatin 80 mg/m(2) and gemcitabine 1250 mg/m(2) for up to six cycles, followed by bevacizumab or placebo until disease progression. An exploratory analysis was undertaken to assess efficacy and safety in an Asian subgroup. RESULTS: Of the 1043 patients enrolled, 105 were Asian and were included in the subgroup analysis. Progression-free survival was 8.5 months (95% CI 7.3-10.8) in the bevacizumab 15-mg/kg group, 8.2 (95% CI 6.6-11.7) in the 7.5-mg/kg group and 6.1 (95% CI 5.1-8.0) in the placebo group. Median overall survival in the 7.5-mg/kg bevacizumab group was prolonged compared with placebo group (HR 0.46; 95% CI 0.22-0.97). Nausea was the most common adverse event, occurring at similar rates (ranging from 69-76%) in all study groups. Hypertension was the most common adverse event of special interest, seen in 29, 55 and 16% of patients in the 7.5-mg/kg and 15-mg/kg bevacizumab and placebo groups, respectively. CONCLUSION: Study results strongly suggest that bevacizumab at a dose of 7.5 mg/kg improves the duration of overall survival when combined with cisplatin-gemcitabine in Asian patients. Bevacizumab was well tolerated in this patient group.

Clinical features, management and outcomes of high-grade glioma patients in Ramathibodi Hospital.

OBJECTIVE: To identify prognostic factors for survival and evaluate the effect of treatment on survival of patients with high-grade glioma treated at Ramathibodi Hospital. MATERIAL AND METHOD: Medical records of patients with diagnosis of high-grade glioma registered in Ramathibodi cancer registry were reviewed. A total of 36 patients were reviewed, only 27 patients were included on survival analysis. RESULTS: Of the 36 patients, the male: female ratio was 1:1. Mean age of diagnosis was 41.86 years (range 18-71 years). Histological findings were anaplastic glioma (22.20%), glioblastoma multiforme (63.90%) and mixed glioma (13.90%). Of fifteen patients underwent total tumor removal, 17 patients had partial resection and in 4 cases biopsy alone was done. Two third of the patients had received radiotherapy with mean total dose 5,372 cGy. Nine patients also received chemotherapy (6 temozolomide and 3 BCNU). Median follow-up time was 413.2 days. An overall survival time was 604.04 days and median disease free survival time was 402.45 days. In univariated analysis, the following favorable prognostic factors were identified: histological findings of glioblastoma multiforme (GBM) and mixed glioma, received radiotherapy. In multivariate analysis, radiotherapy improves overall survival significantly. Re-resection at recurrence did not appear to improve overall survival. CONCLUSION: Adult high-grade glioma had poor prognosis despite aggressive treatment. Radiotherapy significantly improved survival while surgical tumor removal and chemotherapy did not. However due to the small number of patients the further studies should be performed.

The European Organization for Research and Treatment of Cancer Quality of Life Questionnaire (EORTC QLQ-C30): validation study of the Thai version.

The objective of this study was to assess the psychometric properties of the Thai version of the European Organization for Research and Treatment of Cancer Quality of Life Questionnaire (EORTC QLQ-C30) version 3.0. The questionnaire was completed by 310 cancer patients during their follow-up at 2 teaching hospital oncology clinics. About 70% of participants had advanced stage of cancer and 72% had been receiving chemotherapy. Cronbach's alpha coefficients of the six scales were above 0.7, except for cognitive and social function scales. All test-retest reliability coefficients were high. Multi trait scaling analysis showed that all item-scale correlation coefficients met the standards of convergent and discriminant validity. Most scales and items could discriminate between subgroups of patients with different clinical status assessed with the Eastern Cooperative Oncology Group (ECOG) scale. The results suggested that the EORTC QLQ-C30 and the Functional Assessment of Cancer Therapy - General (FACT-G) measured different aspects of quality of life and should be independently used. Testing psychometric properties of the EORTC QLQ-C30 in heterogeneous diagnostic group yield similar results as found in homogeneous group. These results support that the EORTC QLQ-C30 (version 3.0) has proven to be a reliable and valid measure of the quality of life in Thai patients with various types of cancer.

Preoperative chemoradiotherapy in locally advanced rectal cancer: Ramathibodi experience.

A retrospective study of the preoperative chemoradiotherapy in locally advanced rectal cancer performed at Ramathibodi Hospital. The median age of twelve patients was 52 years. The tumor locations (upper-, mid-, lower rectum) were 25%, 50% and 25%, respectively. Eleven patients had clinical stage 111 disease. All received concurrent 5-FU-based chemoradiotherapy followed by surgery (if resectable) and chemotherapy. The most common toxicity of preoperative treatment was gr. 1-2 diarrhea (58.3%). The response rate was 41.7%. Five patients (41.7%) underwent sphincter-sparing surgery. Four patients underwent AP resection. Twenty-five percent achieved pathological complete response. Pathological downstaging occurred in 33.3%. The remaining three patients had unresectable disease. With the median follow up of 13 months, five patients had progressive disease and one has expired. The local failure rate was 16.7%. The one-year recurrence-free survival was 75%. The authors conclude that preoperative chemoradiotherapy is an effective treatment with favorable outcome in locally advanced rectal cancer.

Doxetaxel in previously treated non-small cell lung cancer patients: clinical efficacy and quality of life.

Docetaxel (Taxotere) is one of the most active new generation chemotherapy agents against advanced non-small cell lung cancer (NSCLC). This study aimed to determine the activity, toxicity and impact on the quality of life (QOL) in patients treated with docetaxel after failure with first-line platinum-based combination chemotherapy. Twenty-one patients with advanced NSCLC who had previously received the platinum-containing regimen were treated with docetaxel 75 mg/m2 every 3 weeks. QOL was assessed at intervals during the treatment period using the Functional Assessment of Cancer Treatment - Lung (FACT-L). Of the 21 patients enrolled, 16 were able to be evaluated for response and 20 were included in the toxicity analysis. The median age was 57 (range, 39-75 years). A median of 3 cycles was given (range, 1-9). Of the 16 evaluatable patients, there was one partial response (6.3%) and 4 with stable disease (25%). The median survival time was 8.1 months and the 1-year survival rate was 25%. Myelosuppression and peripheral neuropathy were the major toxicities. Grade 3/4 neutropenia and paresthesia occurred in 6 patients (30%) and 3 patients (15%), respectively. There was no significant improvement or deterioration in the overall FACT-L, TOI (Trial Outcome Index) and lung cancer symptom scores during the treatment. Symptom improvement was noted, in particular for shortness of breath and weight loss in the majority of patients. It is concluded that docetaxel is a well tolerated second-line treatment for recurrent NSCLC. Of particular importance was that the treatment did not negatively impact the overall quality of life, on the contrary, did palliate some of the lung cancer related dash symptoms in many patients.

The European Organization for Research and Treatment of Cancer quality of life questionnaire: translation and reliability study of the Thai version.

In the past decade, increasing attention is being given to more systematic and quantitative ways to evaluate explicitly the impact of disease and medical interventions on quality of life (QOL). Pertaining to the field of oncology, two relatively new instruments--the European Organization for Research and Treatment of Cancer (EORTC) QLQ-C30 and the FACT-G, have received growing attention and appear to be excellent QOL instruments in clinical settings. FACT-G has already been validated and has been used in Thailand. Thus in the present study, the English version of the EORTC quality of life questionnaire (QLQ-C30) was translated into Thai and the initial descriptive statistic and scale reliability were reported. Mean score in this study of 75 cancer patients was comparable with the original report. Cronbach's alpha coefficient for multi-item scales range from 0.64 to 0.89. The validity of this translated version will be reported at a later date. The initial findings of the present study indicate that the Thai version of the EORTC QLQ-C30 is reliable. A validating process of this version is in progress with active patients accrual ongoing at present.