Genetic polymorphisms in drug metabolizing enzymes and drug transporters may affect irinotecan toxicity. Although genetic polymorphisms have been shown to influence the irinotecan toxicity, data are ...limited in Thai population. Thus, the aim of this study was to assess the allele and genotype frequencies and the relationship between CYP3A4/5, DPYD, UGT1A1, ABCB1, and ABCC2 genetic variations and irinotecan-induced toxicity in Thai colorectal cancer patients. One hundred and thirty-two patients were genotyped, and the effect of genetic variations on irinotecan-induced toxicity was assessed in 66 patients who received irinotecan-based chemotherapy. Allele frequencies of ABCB1 c.1236C > T, ABCB1 c.3435C > T, ABCC2 c.3972C > T, ABCG2 c.421C > A, CYP3A4*1B, CYP3A4*18, CYP3A5*3, DPYD*5, UGT1A1*28, and UGT1A1*6 were 0.67, 0.43, 0.23, 0.27, 0.01, 0.02, 0.64, 0.19, 0.16, and 0.09, respectively. DPYD*2A and DPYD c.1774C > T variants were not detected in our study population. The ABCC2 c.3972C > T was significantly associated with grade 1-4 neutropenia (P < 0.012) at the first cycle. Patients carrying both UGT1A1*28 and *6 were significantly associated with severe neutropenia at the first (P < 0.001) and second (P = 0.017) cycles. In addition, patients carrying UG1A1*28 and *6 had significantly lower absolute neutrophil count (ANC) nadir at first (P < 0.001) and second (P = 0.001) cycles. This finding suggests that UGT1A1*28, *6, and ABCC2 c.3972C > T might be an important predictor for irinotecan-induced severe neutropenia.
Current guidelines recommend anti-epidermal growth factor receptor monoclonal antibodies (anti-EGFR Ab) as first-line treatment only in patients with left-sided
wild type
) metastatic colorectal ...cancer (mCRC). However, there are no guideline recommendations specific to tumor sidedness in subsequent-line treatment. This study aimed to investigate the effect of primary tumor location on second- or later-line treatment outcomes in patients with
mCRC.
Medical records of patients diagnosed with mCRC at 3 academic centers in Thailand (Siriraj, Chulalongkorn, and Ramathibodi hospital) between 2008 and 2019 were retrospectively reviewed. Patients with
mCRC who received anti-EGFR Ab in second- or later-line treatment were included. The impact of tumor sidedness on progression-free survival (PFS) was determined using Kaplan-Meier method, and those results were compared using log-rank test.
Among the 2,102 patients who had
analysis data, 1,130 (54%) patients had
. Of those, 413 patients received anti-EGFR Ab in second- or later-line treatment. One hundred and sixty-two of 413 (39%) patients had extended
analysis. Seventy (17%) patients had right-sided tumors. Two hundred and thirty-eight (58%) patients received anti-EGFR Ab in the third line, and 132 (32%) patients and 43 (10%) patients were treated in the second and more than third line, respectively. Single-agent irinotecan was the most commonly used backbone chemotherapy (303/413, 73%). Patients with right-sided tumors had non-significantly inferior PFS compared to patients with left-sided tumors (median PFS: 5.7 months (mo), 95% confidence interval CI: 3.9-7.5 vs. 7.5 mo, 95% CI 6.5-8.5; p=0.17). Subgroup analysis showed no difference in PFS when stratified by treatment lines. Patient with right-sided tumors had significantly inferior OS compared to patients with left-sided tumors (median OS: 23.3 mo vs. 29.9 mo; p=0.005).
To date, this is the largest real world data of the effect of primary tumor location on anti-EGFR Ab which demonstrated that tumor sidedness has no significant impact on treatment outcomes in
mCRC patients receiving second- or later-line therapy. Our findings do not support the utility of tumor sidedness for treatment selection in these settings. We confirmed that patients with right-sided tumors had significantly worse survival.
Background
Multikinase inhibitors (MKIs) represent the main treatment options for advanced hepatocellular carcinoma (aHCC). However, accessibility in developing countries is limited. A chemotherapy, ...Fluorouracil and Oxaliplatin (FOLFOX), offers a less expensive treatment. Therefore, this study sought to compare the clinical effectiveness of FOLFOX with Sorafenib as a first‐line treatment for aHCC in real‐life practice.
Methods
A retrospective aHCC cohort from four Thai hospitals was investigated for patients who received FOLFOX or Sorafenib between 2013–2019. Multiple imputation by chained equations addressed missing covariate data in a treatment effect model using Weight‐adjusted‐censoring inverse‐probability‐weighted regression adjustment; overall survival (OS) and progression‐free survival (PFS) were estimated.
Results
A total of 504 patients were included, (Sorafenib n = 382 and FOLFOX n = 122). The treatment effect model estimated a median OS for Sorafenib and FOLFOX of 11.38 and 8.22 months, representing a significantly shorter OS (95% confidence interval) of −3.16 (−6.21, −0.11) months for FOLFOX, p = 0.042. A significant shorter median PFS of FOLFOX to Sorafenib of −2.13 (−3.03, −1.24) months, p < 0.001, was reported.
Conclusion
Despite significantly shorter median OS and PFS than Sorafenib, FOLFOX still extended OS by 8.22 months. This evidence may offer clinical utility to physicians considering treatment options for aHCC in low resource settings.
Hepatocellular carcinoma treatment in limited resource countries was limit due to cost. Real‐world evidence reflects clinical effectiveness in general practice. Even though FOLFOX had significant shorter survival than Sorafenib, but FOLFOX still extended median overall survival by 8.2 months.
Despite significant benefits of epidermal growth factor receptor-tyrosine kinase inhibitor (EGFR-TKI) treatment in patients with
-mutated NSCLC, access remains limited in Thailand and elsewhere.
...Retrospective analysis of patients with locally advanced/recurrent NSCLC and known
mutation (
m) status treated at Ramathibodi Hospital (2012-2017). Prognostic factors for overall survival (OS), including treatment type and healthcare coverage, were analyzed using Cox regression.
Of 750 patients, 56.3% were
m-positive. After first-line therapy (n=646), 29.4% received no subsequent (second-line) treatment. EGFR-TKI-treated
m-positive patients survived significantly longer than
m-negative patients without EGFR-TKIs (median OS mOS 36.4 vs. 11.9 months; hazard ratio HR=0.38 95%CI 0.32-0.46,
<0.001). Cox regression indicated significantly longer OS in patients with comprehensive healthcare coverage that included reimbursement of EGFR-TKIs, versus basic coverage (mOS 27.2 vs. 18.3 months; adjusted HR=0.73 95%CI 0.59-0.90). Compared with best supportive care (BSC; reference), EGFR-TKI-treated patients survived significantly longer (mOS 36.5 months; adjusted HR (aHR)=0.26 95%CI 0.19-0.34), and versus chemotherapy alone (14.5 months; aHR=0.60 95%CI 0.47-0.78). In
m-positive patients (n=422), relative survival benefit of EGFR-TKI treatment remained highly significant (aHREGFR-TKI=0.19 95%CI 0.12-0.29; aHR(chemotherapy only)=0.50 95%CI 0.30-0.85; reference:BSC), indicating that healthcare coverage (reimbursement) affected treatment choice and survival.
Our analysis describes
m prevalence and survival benefit of EGFR-TKI therapy for
m-positive NSCLC patients treated from 2012-2017, one of the largest such Thai datasets. Together with research by others, these findings contributed evidence supporting the decision to broaden erlotinib access on healthcare schemes in Thailand from 2021, demonstrating the value of local real-world outcome data for healthcare policy decision-making.
Background
The two common methylenetetrahydrofolate reductase (
MTHFR
) polymorphisms 677G>A and 1298A>C may have been affecting 5-FU toxicity in cancer patients for decades. Drug efficacy has also ...been shown by previous studies to be affected. In this study, we investigated the effects of these polymorphisms on 5-FU hematological toxicity and treatment efficacy, to provide enhanced pharmacological treatment for cancer patients.
Methods
This is a retrospective study involving 52 Thai colorectal cancer patients who were treated with 5-FU based therapy, using TaqMAN real-time PCR to genotype the
MTHFR
polymorphisms (677G>A and 1298A>C). The toxicity and response rate were assessed using standardized measures.
Results
Neutropenia was significantly more likely to be experienced (
P
=0.049, OR=7.286, 95% CI=0.697-76.181) by patients with the
MTHFR
677G>A polymorphism, in the same way as leukopenia (
P
=0.036, OR=3.333, 95%CI=2.183-5.090) and thrombocytopenia (
P
<0.001, OR=3.917, 95%CI=2.404-6.382). The
MTHFR
1298A>C polymorphism had no statistical association with hematological toxicity in 5-FU treatment. The response rate to 5-FU was not significantly affected by these two polymorphisms.
Conclusion
The
MTHFR
polymorphism 677G>A is a significant risk factor for developing leukopenia, neutropenia and thrombocytopenia as toxic effects of 5-FU therapy in cancer patients. Therefore, patients receiving 5-FU-based therapy should be aware of their polymorphisms as one risk factor for experiencing severe toxicity.
Atezolizumab plus bevacizumab treatment is a first-line therapy for unresectable hepatocellular carcinoma (HCC) worldwide. The efficacy, safety, and patient-reported outcomes (PROs) of HCC in ...Thailand have not yet been reported. This study aimed to evaluate the efficacy, safety, and PROs of atezolizumab plus bevacizumab.
From September 2020 to August 2021, 30 patients with unresectable HCC who met the inclusion criteria of atezolizumab plus bevacizumab as first-line treatment were enrolled. Analysis was assessed for progression-free survival, overall survival, adverse events (AEs), and quality of life (QoL).
The median progression-free survival and overall survival periods were 6.7 and 10.2 months, respectively. The disease control rate was 63.3%. The frequent AEs were proteinuria, hypertension, and hepatitis. Serious AEs included gastrointestinal bleeding, but none of the patients died from serious AEs. The discontinuation rate was 23.3%, and the median number of treatment cycles was 10.5 cycles. In total, 23.3% of the patients continued treatment after 1 year of therapy. The global health status/QoL and physical function scores showed less deterioration at baseline than at 3 and 6 months (median scores = 76.7, 71.6, and 64.1 in QoL and 84.7, 79.6, and 79.0 in physical function, respectively). The HCC18 symptom score index data showed a slow progression of symptom scores from baseline to 3 and 6 months (12.7, 19.6, and 22.3, respectively).
This study demonstrates that atezolizumab plus bevacizumab is effective and has a safety profile comparable with that of previous studies as first-line therapy for unresectable HCC in a real-world setting and in Thai populations. Data on PROs also demonstrate benefits in terms of patients' QoL and symptoms.
Aims:
Clinical decision making is challenging in men with metastatic prostate cancer (mPC), as heterogeneity in treatment options and patient characteristics have resulted in multiple scenarios with ...little or no evidence. The South East Asia Expert Panel 2019 addressed some of these challenges.
Methods:
Based on evidence in the literature and expert interviews, 19 statements were formulated for key challenges in the treatment of men with castration-sensitive and -resistant prostate cancer in clinical practice. A modified Delphi process was used to reach consensus among experts in the panel and develop clinical practice recommendations.
Results:
The majority of the panel preferred a risk-based stratification and recommended abiraterone or enzalutamide as first-line therapy for symptomatic chemotherapy naïve patients. Abiraterone is preferred over enzalutamide as a first-line treatment in these patients. However, the panel did not support the use of abiraterone in high risk lymph-node positive only (N+M0) or in non-metastatic (N0M0) patients. In select patients, low dose abiraterone with food may be used to optimize clinical outcomes. Androgen receptor gene splice variant status may be a useful guide to therapy. In addition, generic versions of approved therapies may improve access to treatment to a broader patient population. The choice of treatment, as well as sequencing are guided by both patient and disease characteristics, preferences, drug access, cost, and compliance.
Conclusion:
Expert recommendations are key to guidance for the optimal management of mPC. Appropriate choice, timing, and sequence of treatment options can help to tailor therapy to maximize outcomes in men with mPC.
In Thailand, data on colorectal cancer (CRC) patient characteristics and overall survival (OS) rates are limited. We aimed to describe the overall 5-year, 10-year survival and to examine factors ...effecting the survival outcome among patients who were diagnoses of colorectal cancer.
We reviewed medical records of patients diagnosed with invasive CRC from 2007 through 2016. Demographic and clinical data were collected upon diagnosis. Kaplan-Meier method and Cox proportional hazards model to evaluate the association of overall (OS) with risk factors.
A total of 3,402 CRC patients (colon 59.4%, rectum 34. 5%, and rectosigmoid 6.1%) were identified. Mean (SD) and median age were 62.9 (12.7) and 63 years old (rang 14-98 years). Stages at diagnosis were I (10.1%), II (23.3), III (35.9%) and IV (30.7%). Five-year and 10-year OS of the entire cohort were 52.7% and 41.5%, respectively. Over the part 10 years, there was a trend toward improved 5-year OS in stages I, II and III. However, 3-year OS in stage IV patients remained unchanged. Confirmed poor prognostic factors included patient age ≥65 years, high grade, and advanced stage at diagnosis.
Advanced disease was a significant prognostic factor for shorter survival. A trend toward improvement in 5-year OS in early stages over the past decade might be related to better surgical quality, improved radiation technique, and adjuvant chemotherapy. Given that patients received better systemic treatment in stage IV disease, the reason their OS was not improved should be examined.
Cholangiocarcinoma is the most common cancer in males in Thailand. The outcome is poor although systemic chemotherapy has been used in attempts to improve disease control, quality of life and prolong ...survival in patient with unresectable and advanced disease.
In this retrospective study the medical records of all patients diagnosed as having unresectable and metastatic cholangiocarcinoma and receiving systemic chemotherapy at Udonthani Cancer Hospital during January 2007 to December 2010 were reviewed.
Among the total of 105 patients, 21 received gemcitabine-based chemotherapy and 84 5FU-based chemotherapy. Most received platinum doublet regimens. 5FU-based regimens yielded an overall response rate (tumor control) of 23.8% and a median survival of 7.2 months while gemcitabine-based regimens yielded an overall response rate (tumor control) 19.1% and a median survival of 10.0 months.
Tumor control and survival of patient with advanced cholangiocarcinoma treated with gemcitabine-based and 5FU-based chemotherapy do not markedly differ.
AIM： To evaluate and characterize the patterns of disease progression of metastatic or unresectable gastrointestinal stromal tumor （GIST） treated with imatinib mesylate, and to determine the ...prognostic significance associated with disease progression. METHODS： Clinical data and computed tomography （CT） images were retrospectively reviewed in 17 GIST patients who were treated with imatinib mesylate from October 2002 to October 2006. Apart from using size measurement for evaluation of tumor response Response Evaluation Criteria in Solid Tumors （RECIST） criteria, patterns of CT changes during treatment were evaluated and correlated with clinical data. RESULTS： There were eight non-responders and nine responders. Five patterns of CT change during treatment were found： focal progression （FP）, generalized progression （GP）, generalized cystic change （GC）, new cystic lesion （NC） and new solid lesion （NS）. At the end of study, all non-responders showed GP, whereas responders showed cystic change （GC and NC） and response according to RECIST criteria. Overall survival was significantly better in patients with cystic change or response within the RECIST criteria compared with GP patients （P = 0.0271）. CONCLUSION： Various patterns of CT change in patients with GIST who responded to imatinib mesylate were demonstrated, and might determine the prognosis of the disease. A combination of RECIST criteria and pattern of CT change are proposed for response evaluation in GIST.
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