Predictive factors and survival for hospitalized patients with advanced hepatocellular carcinoma encountering serious adverse drug reactions
Date Issued
2012
Date
2012
Author(s)
Ho, Shiang-Yih
Abstract
Background: Hepatocellular carcinoma (HCC) is the seventh most common malignancy and the third most common cause of canceru-related deaths worldwide. In Taiwan, HCC is the first leading cause of cancer-related death, accounting for more than 7000 deaths annually. HCC patients usually have high hospitalization rates and use a variety of therapeutic agents; and adverse drug reaction was one of the major causes of hospitalization, morbidity and mortality.
Objective: To understand the current status of serious adverse drug reactions (SADRs), SADRs’ predictors, and survival of advanced HCC inpatients. Methods: This was a retrospective and cross-sectional descriptive correlational study in which data were retrieved from medical charts. Patients with advanced HCC in treated with anticancer drugs and admitted to the medical center in northern Taiwan between January 1, 2010 and December 31, 2010 were included in this study. To explore the current status of serious adverse drug reactions, “demographic characteristics”, “disease and treatment status”, “medical care patterns” of study population effects on SADRs, and SADRs effects on survival. Risk and predictive factors of SADRs was analysis by using “Generalized estimating equation” (GEE) model. Survival time of post SADRs and overall survival was analyzed by using Kaplan-Meier method. Cox regression and proportional hazard model was used for analyzed the risk factors of mortality. Results: A total 155 hospitalizations of 81 patients were included, in which 43 hospitalized and 2 prolonged hospitalizations were due to SADRs. The incidence rate of SADRs of advanced HCC inpatients at admission was 27.74%, and during hospitalization was 1.29%. Compared with the “non-serious adverse drug reactions” (non-SADRs) the group had a significantly older average age, high percentage of protal vein thrombosis (PVT), hepatitis B, Child-Pugh Class B, ascites, “gastrointestinal ulcer”(GI ulcer) history, and a low percentage of hepatitis B infection or lung metastasis. In Kaplan-Meier survival analysis, we found that the median survival time after SADRs was significant shorter in the SADRs group compared with non-SADRs group (17±8.66 days, 95%CI 0.028- 33.97 vs. 61±9.34 days, 42.69-79.31, p=0.007), and the median overall survival time was also decreased in SADRs group, but no significant difference (130±77.48 days, 95% CI 0.00- 281.86 vs. 196±34.43days, 95% CI 128.52-263.47, p=0.137). In multivariate analysis of the SADR predictors by multiple logistic regression model with GEE method, we found three serious adverse drugs reactions predictive models: development of bleedings, infections and any kind of SADRs. For the development of bleeding SADRs, initial with higher serum albumin level (OR=5.27, 95% CI 1.42-19.59), PVT (OR=17, 3.41-84.79), more serious ascites (OR=4.56, 2.12-9.81), with cardiovascular disease (OR=45.2, 8.76-233.11), GI ulcer (OR=6.71, 1.74-25.78), non- Hodgkin’s lymphoma or gastric cancer history (OR=168.51, 22.51-1261.33), current treatment with Sorafenib base therapy or other target drug with/without metronomic therapy (OR=10.17, 3.37-30.65) pose a high risk for bleeding SADRs, except diabetes mellitus. For the development of infection SADRs, initial hepatic function was Child-Pugh Class B (OR=1.14, 95% CI 0.30-4.31), with hepatitis C infection (OR=5.06, 1.4-18.32), older (OR=1.11, 1.06-1.16) and current treatment with chemotherapy with/without target drug (OR=2.99, 0.63-14.08) were at a high risk for infection related serious adverse drug reactions, except hypertension and history of local therapy for HCC. For the development of any kind of SADRs, we found it was almost fully affected by bleeding and infection SADRs model, initial hepatic function was Child-Pugh Class B (OR=5.13, 95% CI 2.28-11.56), PVT (OR=2.28, 1.0-5.22), α-fetoprotein>400ng/ml (OR=2.26, 0.79-6.50), history of cardiovascular disease (OR=5.09, 0.86-30.32), older (OR=1.08, 1.04-1.11), and current treatment with other target drug ± metronomic therapy (OR=2.44, 0.94-6.34) were at a high risks for developing of any serious adverse drug reactions, except hypertension (OR=0.22, 0.07-0.68). Survival analysis: In univariate analysis, we found that survival rate was significant lower in patient with Eastern Cooperative Oncology Group (ECOG) performance status >1, history of surgery for HCC and with gastrointestinal ulcer, but high in current treatment with chemotherapy with/without target drug (p<0.05). In Cox regression model, initial α-FP >400ng/ml (HR=3.942 95% CI 2.04-7.614), tumor >5cm (HR=4.084, 1.909-8.735.), history of surgery (HR=3.331, 1.648-6.743) or systemic therapy for HCC (HR=2.280, 1.184-4.392 ), and development of a SADR (HR=2.912, 1.595-5.316) were high risks for mortality; in contrast initial with higher serum albumin level or current treatment with chemotherapy ± target drug were at a low risk for mortality.. Conclusion: SADRs of in-patients with advanced HCC has became a critical clinical issue. Approximately 30% of the advanced HCC hospitalizations are due to SADRs, as is high mortality. Bleeding and infection were the two most common cause of SADRs related deaths in our study group. Different SADRs were affected by various factors, and SADRs also affect the survival of patients. Our study results can be a reference for clinical staff who care for patients with advanced HCC, in order to identify the patients who are at risk for admission due to SADRs, to prevent or minimize the incidence of SADRs, as well as for future development of relevant research and policy.
Objective: To understand the current status of serious adverse drug reactions (SADRs), SADRs’ predictors, and survival of advanced HCC inpatients. Methods: This was a retrospective and cross-sectional descriptive correlational study in which data were retrieved from medical charts. Patients with advanced HCC in treated with anticancer drugs and admitted to the medical center in northern Taiwan between January 1, 2010 and December 31, 2010 were included in this study. To explore the current status of serious adverse drug reactions, “demographic characteristics”, “disease and treatment status”, “medical care patterns” of study population effects on SADRs, and SADRs effects on survival. Risk and predictive factors of SADRs was analysis by using “Generalized estimating equation” (GEE) model. Survival time of post SADRs and overall survival was analyzed by using Kaplan-Meier method. Cox regression and proportional hazard model was used for analyzed the risk factors of mortality. Results: A total 155 hospitalizations of 81 patients were included, in which 43 hospitalized and 2 prolonged hospitalizations were due to SADRs. The incidence rate of SADRs of advanced HCC inpatients at admission was 27.74%, and during hospitalization was 1.29%. Compared with the “non-serious adverse drug reactions” (non-SADRs) the group had a significantly older average age, high percentage of protal vein thrombosis (PVT), hepatitis B, Child-Pugh Class B, ascites, “gastrointestinal ulcer”(GI ulcer) history, and a low percentage of hepatitis B infection or lung metastasis. In Kaplan-Meier survival analysis, we found that the median survival time after SADRs was significant shorter in the SADRs group compared with non-SADRs group (17±8.66 days, 95%CI 0.028- 33.97 vs. 61±9.34 days, 42.69-79.31, p=0.007), and the median overall survival time was also decreased in SADRs group, but no significant difference (130±77.48 days, 95% CI 0.00- 281.86 vs. 196±34.43days, 95% CI 128.52-263.47, p=0.137). In multivariate analysis of the SADR predictors by multiple logistic regression model with GEE method, we found three serious adverse drugs reactions predictive models: development of bleedings, infections and any kind of SADRs. For the development of bleeding SADRs, initial with higher serum albumin level (OR=5.27, 95% CI 1.42-19.59), PVT (OR=17, 3.41-84.79), more serious ascites (OR=4.56, 2.12-9.81), with cardiovascular disease (OR=45.2, 8.76-233.11), GI ulcer (OR=6.71, 1.74-25.78), non- Hodgkin’s lymphoma or gastric cancer history (OR=168.51, 22.51-1261.33), current treatment with Sorafenib base therapy or other target drug with/without metronomic therapy (OR=10.17, 3.37-30.65) pose a high risk for bleeding SADRs, except diabetes mellitus. For the development of infection SADRs, initial hepatic function was Child-Pugh Class B (OR=1.14, 95% CI 0.30-4.31), with hepatitis C infection (OR=5.06, 1.4-18.32), older (OR=1.11, 1.06-1.16) and current treatment with chemotherapy with/without target drug (OR=2.99, 0.63-14.08) were at a high risk for infection related serious adverse drug reactions, except hypertension and history of local therapy for HCC. For the development of any kind of SADRs, we found it was almost fully affected by bleeding and infection SADRs model, initial hepatic function was Child-Pugh Class B (OR=5.13, 95% CI 2.28-11.56), PVT (OR=2.28, 1.0-5.22), α-fetoprotein>400ng/ml (OR=2.26, 0.79-6.50), history of cardiovascular disease (OR=5.09, 0.86-30.32), older (OR=1.08, 1.04-1.11), and current treatment with other target drug ± metronomic therapy (OR=2.44, 0.94-6.34) were at a high risks for developing of any serious adverse drug reactions, except hypertension (OR=0.22, 0.07-0.68). Survival analysis: In univariate analysis, we found that survival rate was significant lower in patient with Eastern Cooperative Oncology Group (ECOG) performance status >1, history of surgery for HCC and with gastrointestinal ulcer, but high in current treatment with chemotherapy with/without target drug (p<0.05). In Cox regression model, initial α-FP >400ng/ml (HR=3.942 95% CI 2.04-7.614), tumor >5cm (HR=4.084, 1.909-8.735.), history of surgery (HR=3.331, 1.648-6.743) or systemic therapy for HCC (HR=2.280, 1.184-4.392 ), and development of a SADR (HR=2.912, 1.595-5.316) were high risks for mortality; in contrast initial with higher serum albumin level or current treatment with chemotherapy ± target drug were at a low risk for mortality.. Conclusion: SADRs of in-patients with advanced HCC has became a critical clinical issue. Approximately 30% of the advanced HCC hospitalizations are due to SADRs, as is high mortality. Bleeding and infection were the two most common cause of SADRs related deaths in our study group. Different SADRs were affected by various factors, and SADRs also affect the survival of patients. Our study results can be a reference for clinical staff who care for patients with advanced HCC, in order to identify the patients who are at risk for admission due to SADRs, to prevent or minimize the incidence of SADRs, as well as for future development of relevant research and policy.
Subjects
Hepatocellular carcinoma
serious adverse drug reactions
risk factor
predictive factor
survival
SDGs
Type
thesis
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