A randomized, double-blind, placebo-controlled study evaluating the efficacy of combination olanzapine, ondansetron and dexamethasone for prevention of chemotherapy-induced nausea and vomiting in patients receiving doxorubicin plus cyclophosphamide.

BACKGROUND: Since most of Thai cancer patients receiving high emetogenic chemotherapy do not have access to neurokinin-1 (NK-1) receptor antagonists or palonosetron as recommended by international guidelines for chemotherapy-induced nausea and vomiting (CINV) prevention. We decided to evaluate the efficacy of olanzapine with the real-life practice antiemetic drugs ondansetron and dexamethasone, in prevention of CINV resulting from doxorubicin plus cyclophosphamide regimen in early-stage breast cancer patients. METHODS: In this randomized, double-blind, placebo-controlled trial, we compared olanzapine with a placebo in combination with ondansetron and dexamethasone in early-stage breast cancer patients receiving doxorubicin 60 mg/m2 plus cyclophosphamide 600 mg/m2. The intervention group received olanzapine 10 mg orally while the control group received a matching placebo daily on day 1 through day 4. All patients received ondansetron 8 mg and dexamethasone 20 mg intravenously 30 minutes before chemotherapy administration and then dexamethasone 10 mg daily orally from day 1 through day 4. The primary endpoint was no nausea rate in the early period. The secondary endpoints were no nausea rate in the delayed and overall periods and a complete response (no vomiting and no use of rescue drug). Outcomes were determined by patients' self-reported daily records of episodes of vomiting or retching, use of rescue therapy and daily levels of nausea based on a visual-analogue scale from the first cycle of chemotherapy. RESULTS: A total of 39 female patients were randomized in a 1:1 ratio to receive olanzapine (20 patients) or a matching placebo (19 patients). A significantly greater proportion of patients reported no nausea in the olanzapine group than in the placebo group in both the early period (0-24 hours after chemotherapy) and the overall period (0-120 hours after chemotherapy). Patients who reported no nausea in the early period accounted for 50% and 10.5% in the olanzapine group and in the placebo group respectively (P=0.008). In the overall period, 30.0% and 0% of patients reported no nausea in the olanzapine and placebo groups respectively (P=0.009). In the early period, there was a significantly different complete response rate between two treatment groups; 75.0% in the olanzapine group and 36.8% in the placebo group (P=0.016). Overall treatment-related adverse events were not significantly different between the two study groups except that somnolence was significantly more common in the olanzapine group than in the placebo group. CONCLUSIONS: Olanzapine 10 mg combined with ondansetron and dexamethasone was more effective than a placebo in preventing CINV resulting from doxorubicin plus cyclophosphamide in early-stage breast cancer patients, especially in the first 24 hours after chemotherapy administration. The short duration of olanzapine was safe and well tolerated.

Survival and Prognostic Factors of Metastatic Breast Cancer.

Background: Prognostic factors for survival of metastatic breast cancer (MBC) patients are important for identifying risks and deciding on patient treatment; however, few studies of prognostic factors in MBC have been performed in Thailand. Objective: To determine the survival duration and prognostic factors for overall survival in metastatic breast cancer. Material and Method: This retrospective cohort study was conducted by reviewing 232 files of MBC patients treated in the Oncology Unit, Department of Medicine, Rajavithi Hospital from January 1st 2005 to December 31th 2013. Results: There were 232 patients whose median age was 51.5 years. The 1-year, 3-year and 5-year overall survival rates for MBC patients were 53.2%, 18.7% and 7.3% respectively, and the median overall survival time of all MBC patients was 13.43 months. Multivariate analysis showed that large tumor size T4 (HR = 1.89, 95% CI 1.04-3.44; p = 0.038), ECOG performance status 3-4 (HR = 2.44, 95% CI 1.48-4.00; p<0.001) and treatment with best supportive care only (HR = 5.95, 95% CI 3.56-9.96; p<0.001) were significant prognostic factors for poor overall survival in MBC. Breast cancer subtype analysis showed that luminal-A subtype was associated with a high rate of late recurrence (beyond 2 years) (p = 0.016) and HER-2 enriched subtype was related to a high rate of early relapse (before 2 years (p = 0.001)). Conclusion: The important prognostic factors for overall survival in MBC were tumor size, ECOG PS and type of first-line treatment. In order to improve survival outcomes, patients with large tumor size should be treated with intensive chemotherapy and targeted therapy if HER-2 status positive. It is essential that early breast cancer patients have an awareness of recurrent diseases in order to identify good performance status in MBC patients suitable for active treatment.

Need for Internal Medicine Subspecialists in Thailand.

Background: Matching supply side of the Internal Medicine (IM) subspecialists to the demand for complex medical care at referral medical centers would lead to more efficient health system management and ultimately optimal clinical outcome. The second decade of the universal health coverage policy in Thailand has raised the awareness on how to reach equitable utilization goals of good quality medical services, while barriers of accession have been removed. More accurate evidence-based human resource planning is timely needed. Objective: To estimate the number of the ten subspecialists in internal medicine (neurologist, cardiologist, endocrinologist, gastroenterologist and hepatologist, nephrologist, hematologist, oncologist, rheumatologist, pulmonologist, and infectious disease specialist) needed for complex medical care based on the workload in the year 2013. Material and Method: The present study applied a needs assessment model with evidence-based approach. Claimed data of inpatients in the year 2013 from the three government insurance schemes (the Civil Servant Medical Benefit, the Social Security and the Universal Health Coverage schemes), and out-patient data from Universal Coverage System were used to estimate demand for subspecialists. The Human Resource Working Group of the Royal College of Physicians of Thailand agreed on the conceptual framework to estimate the need for ten subspecialists based on clinical activities of outpatient consultations, inpatient ward rounds and non-operating room procedures on medical cases of respective diagnosis related group with severe and catastrophic comorbidities and complications by the Thai-DRG version 5. Representatives from the Associations of IM subspecialties approved the lists of ICD-10 diagnosis and ICD-9-CM procedure codes specific to each subspecialist care and proposed assumptions on rates of consultations from other specialists. Surveys were done to subspecialists in 6 major provincial clusters and representatives from IM subspecialty Associations asking time spent on main activities of patient care. The number of full-time-equivalent (FTE) subspecialists needed was calculated by multiplying the clinical workloads measured in minutes spent for each activity (ward round, ward work, inpatient and outpatient consultations) to get the total time needed, then divided by the available time for clinical activity of one subspecialist. Results: From 5.9 million inpatient discharges in the year 2013, primary responsibility of patients in respective severe and catastrophic DRGs related to specific subspecialist workloads were summed up for teaching hospitals and regional hospitals ranging from as lowest the 2,849 cases for rheumatology to the highest 24,610 cases for gastroenterology and hepatology. The number of inpatient non-operating room procedures by ICD-9-CM as listed by IM subspecialty Associations ranged from 8 times for endocrinologists to 22,927 times for cardiologists for the whole year. Of ten subspecialists, the estimated numbers of cardiologist, nephrologist, neurologist, gastroenterologist and hepatologist, endocrinologist, oncologist, rheumatologist, hematologist, pulmonologist and infectious disease subspecialist needed at teaching and regional hospitals were 516, 241; 345, 144; 312, 143; 195, 124; 189, 45; 137, 170; 90, 47; 96, 111; 203, 87 and; 129, 44 respectively according to the workload recorded in the year 2013. The forecast FTE found the overall gap of discrepancy at 7 percent. If the distributions of these subspecialists in public and private hospitals were taken into account, the gap of discrepancy in public hospitals increased to 47 percent. Conclusion: The demand-based forecast for the number of subspecialist needed was made possible with assumptions on conceptual framework for case selection, the rates of consultation and time-spent related to activities of patient care. The estimated numbers of subspecialists were anticipated far from optimum since the workload in the year 2013 was derived as a consequence of pre-existing suboptimal infrastructure of healthcare system. In addition, the deficit of subspecialists may increase in the near future when highly efficient, non- or mildly invasive, time-consuming procedures of acute illness increase. Sustainable matching demand and supply of human resource for health needed further validations of these assumptions.

Survival and prognostic factors of stage I-III breast cancer.

OBJECTIVE: To determine the survival duration of stage I-III breast cancer patients, and to determine prognostic factors for overall survival and disease-free survival in stage I to III breast cancer patients treated with surgery and adjuvant therapy. MATERIAL AND METHOD: This retrospective cohort study was conducted by reviewing 166files of stage I-III breast cancer patients treated with surgery and adjuvant therapy in the Oncology Unit, Department of Medicine, Rajavithi Hospital from January 1st 1998 to December 31st 2007. RESULTS: There were 166 patients whose median age was 48 years. The 5-year overall survival rates for stage I, stage II and stage III were 100.0%, 89.0% and 80.8% respectively (p = 0.11). Multivariate analysis showed that pathological lymph node pN2 status was a significant poor prognostic factor for overall survival (HR = 4.32, 95% CI 1.24-15.04; p = 0.022). The one-, three- and five-year disease-free survival (DFS) rates were 96.7%, 81.4% and 76.7% respectively. Multivariate analysis revealed that pathological pN2 (HR = 4.43, 95% CI 1.44-13.57; p = 0.009), pN3 (HR = 5.16, 95% CI 1.54-17.30; p = 0.008) and progesterone receptor status negative (HR = 5.53, 95% CI 1.85-16.59; p = 0.002) were poor prognostic factors for disease-free survival. CONCLUSION: The most important prognostic factor affecting disease-free survival and overall survival of stage I-III breast cancer patients was axillary lymph node metastasis. Progesterone receptor status negative influenced disease relapse. Patients with multiple unfavorable risk factors such as lymph node metastasis and progesterone receptor status negative showed poor DFS, and therefore more aggressive adjuvant chemotherapy is required for these patients.

Management of colon cancer: resource-stratified guidelines from the Asian Oncology Summit 2012.

Colon cancer is seen with increasing frequency in the Asia-Pacific region, and it is one of the most important causes of cancer mortality worldwide. This article reviews the available evidence for optimum management of colon cancer-in particular, with respect to screening and early detection of colon cancer, laparoscopic surgical treatment, adjuvant treatment of individuals with high-risk stage II and stage III cancer, palliative treatment of patients with metastatic disease, and management of resectable and potentially resectable metastases-and how these strategies can be applied in Asian countries with different levels of health-care resources and economic development, stratified by basic, limited, enhanced, and maximum resource levels.

Prognostic factors for survival in colorectal cancer patients.

OBJECTIVE: To determine the prognostic value for survival of pretreatment characteristics and treatments in stage 1-IV colorectal cancer (CRC) patients. MATERIAL AND METHOD: The present retrospective cohort study was conducted by reviewing 287files of stage I-IV CRC patients. Fifteen clinical variables were investigated through analysis as prognostic factors for survival. RESULTS: The median survival time for CRC patients, colon and rectal cancer patients were 37.2, 43.2, and 29.5 months respectively The 5-year survival rates of CRC patients were 38.6%. 5-year stage-specific survivals for stage I, II, III and IV CRC were 100%, 68%, 44%, and 2% respectively (p < 0.001). Sixty eight percent of CRC patients were in stages III and IV Multivariate analysis revealed age > or =60 years old, WHO performance status 3, stage III and IV disease and poorly differentiated histology as poor prognostic factors for survival, whereas treatment with complete surgical resection and adjuvant chemotherapy was a good prognostic factor for survival in CRC. CONCLUSION: As the majority of patients were in advanced stages with poor prognosis, early stage disease identification and treatment with newer agents would likely improve survival of high-risk CRC patients.

The association of anti-r-HuEpo-associated pure red cell aplasia with HLA-DRB1*09-DQB1*0309.

BACKGROUND: Anti-r-HuEpo associated PRCA developed in patients received subcutaneous injection of r-HuEpo for treatment of renal anemia in chronic kidney disease. This adverse immunological effect of r-HuEpo causes sudden loss of r-HuEpo efficacy, low circulating reticulocyte count and bone marrow biopsy shows an absence of erythroid precursor cells with normal cell population of non-erythroid lineage. There are postulation cause of anti-r-HuEpo associated PRCA including genetic factor, immunogenicity factor, storage and handlings factor and formulation of r-HuEpo product. Previous observation of our report showed an aggregation of HLA-DRB1*09 in four anti-r-HuEpo associated PRCA cases. This allele is rare in Caucasian (<1%) but more common in Thai population (8.4-12.5%). This study was aimed to investigate the possible association between HLA-DRB1*09 or other specific HLA and anti-r-HuEpo associated PRCA. METHODS: Twenty two cases of proven anti-r-HuEpo associated PRCA were recruited and studied retrospectively based on the incidence report of serious adverse drug reaction. The EDTA bloods were drawn for HLA typing using sequence specific primer polymerase chain reaction (SSP-PCR). The HLA data of 1,800 potential cadaveric kidney transplantation recipients in the waiting list as chronic kidney disease control and 1,500 potential bone marrow stem cell donors in national stem cell registry as healthy population control were retrieved from the database of Thai Red Cross for comparison. RESULTS: The distribution of gene frequency of HLA-A, -B, -DR and -DQ alleles in anti-r-HuEpo associated PRCA cases showed high gene frequency of HLA-A*02, HLA-A*11 and HLA-A*24 for HLA-A loci, HLA-B*18, HLA-B*46, HLA-B*60 and HLA-B*62 for HLA-B loci, and HLA-DRB1*09, HLA-DRB1*12 and HLA-DRB1*15 for HLA-DR loci. There was a significant difference of HLA-DRB1*09 gene frequency (P < 0.001) which associated with HLA-DQB1*0309 between anti-r-HuEpo associated PRCA cases, and potential cadaveric kidney transplantation in the waiting list or potential national stem cell registry donor. The odd ratio of HLA-DRB1*09 allele for anti-r-HuEpo associated PRCA was 2.89 (95% CI: 1.88-4.46; p-value: <0.001). CONCLUSIONS: Our data demonstrated the association of HLA-DRB1*09-DQB1*0309 and anti-r-HuEpo associated PRCA cases. This association may be used in identifying the risk of the patients.

Prognostic factors for survival in advanced non-small cell lung cancer.

OBJECTIVE: To determine the prognostic value for survival of various pretreatment characteristics and treatments in advanced non-small cell lung cancer (NSCLC) patients. PATIENTS AND METHOD: The retrospective study was conducted by reviewing the 81 files of advanced NSCLC patients treated with chemotherapy at the Oncology Unit, Rajavithi Hospital. Eighteen clinical variables were investigated and analysed as prognostic factors for survival. RESULTS: The first chemotherapy regimens for the 81 patients included: etoposide plus platinum derivatives (41), new drugs (taxanes or gemcitabine) plus platinum derivatives (39) and one other platinum based regimen (1). The overall survival time for all patients was 39.4 weeks with a 95% confidence interval of 30 to 49 weeks. In the multivariate analysis, male gender; bone metastasis and liver metastasis are poor prognostic factors. Receiving palliative surgery and achieving objective response to first regimen chemotherapy are good prognostic factors. Patients who received either old or new drug combinations showed no difference in their survival as determined by univariate or multivariate analyses which could be due to limitations in the present retrospective study. However; this may show that regimens consisting of older, less expensive drug combinations still provide survival advantages in advanced NSCLC and should be considered in limited financial circumstances.