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  1. Hassan BA, Yusoff ZB
    Asian Pac J Cancer Prev, 2011;12(6):1573-6.
    PMID: 22126501
    INTRODUCTION: Anemia is one of the most frequent hematological demonstration of malignant diseases, leading to impairment of function in all tissues and organs of cancer patients and associated with serious stress. This major problem may be exacerbated by radiotherapy or chemotherapy. It is characterized by lower hemoglobin (Hb) level or inadequate circulating red blood cells (RBCs). The present study evaluated the effectiveness of treatment guidelines for anemia among solid cancer patients in Penang hospital and to find associations between treatments and anemia onset and severity.

    METHODS: This is a retrospective observational study was conducted on 534 cancer patients with anemia who were admitted to a government hospital on Penang island i.e., Penang General Hospital in the period between 2003 to 2009.

    RESULTS: Effectiveness of standard anemia treatment guidelines was not sufficient because correction of anemia was just temporary.

    CONCLUSION: According to the results, erythropoietin must be used as a cornerstone even for patients who suffer from moderate anemia and blood transfusion should be used just for emergency cases when anemia leads to a critical situation.
  2. Hassan BA, Yusoff ZB
    Asian Pac J Cancer Prev, 2011;12(1):185-91.
    PMID: 21517255
    INTRODUCTION: Nausea and vomiting are recognized as two separate and distinct conditions with a wide spectrum of etiologies either directly associated with cancer itself or its treatment. According to the new ranking of chemotherapy side effects, nausea is the number one or the most disturbing side effects while vomiting is the third and sometimes the fifth. The introduction of 5-HT3-recptor antagonists in the early of 1990s has revolutionized the treatment of nausea and vomiting, these agents remaining the mainstay of antiemetic therapy today. Ethnic variation (due to genetic polymorphisms) may lead to diversity in antiemetic treatment pharmacokinetic and pharmacodynamic properties, in terms of distribution, elimination, disposition and clinical effects. The aim of the present study was to clarify genetic polymorphism effects in the three main races in Malaysia i.e., Malay, Chinese and Indian, on the clinical antiemetic effects of granisetron.

    METHODS: In this longitudinal prospective observational study, 158 breast cancer patients treated with chemotherapy were monitored for nausea and vomiting in the first 24 hours after chemotherapy administration. The patients were then followed up again after 3 to 5 days of chemotherapy.

    RESULTS: Genetic polymorphisms in the three races in Malaysia have significant effect on granisetron clinical antiemetic action because each is characterized by variant CYP3A4 enzymatic action.

    CONCLUSION: According to the result, different type of 5-HT3 receptor antagonists, such as tropisetron and dolasetron which are predominantly metabolized by CYP2D6, should be used especially for Chinese breast cancer patients.

    Study site: Hospital Pulau Pinang
  3. Hassan BA, Yusoff ZB
    Asian Pac J Cancer Prev, 2010;11(6):1523-7.
    PMID: 21338191
    INTRODUCTION: Chemotherapy-induced nausea and vomiting (CINV) is one of the most important worries of cancer patients. Although not life-threatening, it has a great negative impact on quality of life (QOL).

    OBJECTIVE: The aim of this study was to determine the impact of CINV (i.e., acute and delayed) on breast cancer patients QOL and to discern opinions related with antiemetic guidelines used dependent on the three main races in Malaysia (Malay, Chinese, Indian).

    METHODS: In this longitudinal prospective observational study, 158 breast cancer patients treated with chemotherapy were interviewed and valid questionnaires (MANE and ONEM) were used to report the impact of CINV on their QOL within the first 24 hours and after 3 to 5 days of chemotherapy treatment.

    RESULTS: The main result was that delayed CINV has an impact on QOL greater than acute CINV. The impact of nausea was reportedly higher than that of vomiting. Also differences in race i.e., genetic polymorphisms (pharmacogenomics) influenced the utility of antiemetic treatments and patients opinions.

    CONCLUSION: Based on the results of our study a new guideline for antiemetic treatment should be used to reduce the impact of CINV on QOL, taking into account variation in genetic polymorphisms among the three races in Malaysia.

  4. Hassan BA, Yusoff ZB, Hassali MA, Othman SB
    Asian Pac J Cancer Prev, 2011;12(10):2753-8.
    PMID: 22320987
    INTRODUCTION: Anemia is considered as one of the most frequent hematological demonstration of malignant diseases, which lead to momentous impairment in every tissues and organs of cancer patients and put them under serious stress. This major problem may arise because of the underlining diseases (i.e., cancer diseases) or radiotherapy or chemotherapy treatment received. This present study tries to find the association between anemia onset and severity with different chemotherapeutics regimens used in the treatment of several solid cancers and to find the association of anemia onset and severity with different doses of these chemotherapeutics drugs.

    METHODS: This retrospective observational study was conducted in Penang General Hospital on 534 anemic solid cancer patients who were admitted between 2003 and 2009. The main statistical tests used were Chi-square test and Logistic regression test for categorical data. While for continues data the main statistical tests were Linear regression and correlation test. The significance of the result will be when the P<0.05, while the confidence interval for this study was 95%.

    RESULTS: FEC, 5-FU+5-FU, Docetaxel and Cisplatin+ 5-FU regimen has strong association and correlation with anemia onset and severity. However the associations and correlations with anemia severity were stronger than those with the onset. Different doses of 5-FU, cyclophosphamide, docetaxel and cisplatin play a critical role in anemia onset and severity.

    CONCLUSION: Monitoring and determination of hemoglobin levels for cancer patients treated with FEC, 5-FU+5-FU, Docetaxel, Cisplatin+ 5-FU specifically with high doses must be emphasized and a focus of particular attention.

  5. Abdul Rasool Hassan B, Yusoff ZB, Bin Othman S
    Asian Pac J Cancer Prev, 2011;12(6):1425-8.
    PMID: 22126475
    INTRODUCTION: Neutropenia, defined as a decrease in the absolute neutrophil count lower than the normal that is < 1500 cell/ ?l, has a detrimental effect on cancer patients' quality of life, also possibly resulting in a reduction in the chemotherapy dose which could lead to an increment in the size of a cancer. There are so many causative factors for neutropenia like hematological disorders, autoimmune diseases and infection, drugs reactions and chemotherapy or radiotherapy. So the main aim of this study is to find the association between chemotherapy drug or regimens, schedule of administration used for treatment of solid cancer diseases with neutropenia onset and severity.

    METHODS: This is an observational retrospective study carried out in a general hospital on 117 solid tumor patients who admitted between January 2003 to December 2006. The main statistical tests used were Chi- square test and Fisher' s Exact test. The significance of the result will be when the P<0.05, while the confidence interval for this study was 95%.

    RESULTS: The highest chemotherapeutic regimen was (5-FU+epirubicin+cyclophosphamide) (47, 40.2%) followed by (gemcitabine+cisplatin) (6, 5.1%) and many others. Majority of the patients receive their chemotherapy schedule of administration was one day schedule (90, 76.9%) followed by more than one day schedule (27, 23.1%).

    CONCLUSION: The doses of these drugs were not high enough to produce a sufficient pharmacological effect to cause bone marrow suppression and lead to neutropenia. Besides the schedule of administration for each drug was long enough to overcome neutropenia also the high uses of granulocyte colony stimulation factor (G-CSF) which will play a major role in reducing the time and severity of neutropenia. All these factors play an important role in giving non- significant association between neutropenia onset and severity with chemotherapeutics drugs and their schedule of administration.

  6. Rasool Hassan BA, Yusoff ZB, Othman SB
    Asian Pac J Cancer Prev, 2010;11(5):1273-7.
    PMID: 21198276
    INTRODUCTION: Neutropenia remains one of the serious side effects of chemotherapeutics drugs making cancer patients face serious risk of infections. Fever and clinical signs are considered as important indicators. The objectives of this study were to assess fever and clinical signs with neutropenia onset and/ or severity in solid cancer cases, using culture tests to determine the type of bacteria predominating, whether gram positive or gram negative.

    METHODS: This observational retrospective study was conducted on files of all solid cancer patients who admitted to a general hospital between 1 January 2003 and 31 December 2006. All data were categorical and analyzed for association with neutropenia.

    RESULTS: 117 neutropenic patients were studied, 83 (70.9%) of them suffering from fever ranging between 38.5-39 °C, with hypotension (53; 27.3%) and headache 51 (26.3%) as the most common clinical signs. Only 34 (29.1%) neutropenic patients underwent culture testing and only 14 (41.2%) showed positive growth, gram negative types predominating (9; 64.2%), mainly Escherichia coli (5; 35.7%), with gram positive only in 5 (35.7%). Significant associations were found for fever and clinical signs with neutropenia severity (P<0.05), but not neutropenia onset (P>0.05). Logistic regression results showed strong significant association between presence of fever (P=0.02, OR=1.3) (95% confidence interval (CI)) hypotension and headache (P=0.001, OR=1.148) (95% CI) with neutropenia severity.

    CONCLUSION: Fever and clinical signs specifically headache and hypotension are symptoms associated with severe neutropenia in solid cancer patients. Both may primarily result from bacterial infection, particularly gram negative forms.

  7. Hassan BA, Yusoff ZB, Othman SB
    Asian Pac J Cancer Prev, 2009 Oct-Dec;10(4):641-4.
    PMID: 19827886
    INTRODUCTION: Neutropenia has a detrimental effect on cancer patients' quality of life, also possibly resulting in a reduction in the chemotherapy dose which could lead to an increment in the size of a cancer. The main danger associated with neutropenia is the risk of bacterial, fungal or viral infection, which may lead to patient death. Treatment including granulocyte-colony stimulating factors (G-CSF, filgrastim) so as to increase the body immunity is given to neutropenic patients with no infection i.e., absence of fever. However, when infection is present, antibiotics such as ceftazidime, imipenem and vancomycin need to be used.

    OBJECTIVE: The aim of this study was to find the association between neutropenia severity and treatment with filgrastim (Neupogen) alone or in combination with antibiotics in solid cancer patients.

    METHODS: This is an observational retrospective study on 117 cases suffering from neutropenia after chemotherapy administration. The patients were admitted to a government hospital for cancer treatment between the years 2003-2006. The types of data collected were categorical and not normally distributed, covering demography, chemotherapy, severity of neutropenia (classified on absolute neutrophil count into mild, moderate and severe) and treatment of neutropenia, either filgrastim (Neupogen) alone or in combination with antibiotics. Statistical tests used were the Chi-square test, Fisher's exact test and logistic regression.

    RESULTS: The majority (69.2%) of the patients were treated with filgrastim (81) alone, only 30.8% receiving the combination. Significant associations between both treatments and neutropenia severity. Both Chi-square and Fisher's exact tests showed P= 0.001. Logistic regression showed that filgrastim is the major treatment for severe neutropenic patients since the result showed an infinity (E) and P= 0.001 for filgrastim alone more than its combination with antibiotic.

    CONCLUSION: The use of filgrastim is highly associated with treatment of severe neutropenia in solid cancer patients who received chemotherapy. So filgrastim is considered as the drug of choice in the presence of severe neutropenic cases.
  8. Hassan BA, Yusoff ZB, Hassali MA, Bin Othman S
    Asian Pac J Cancer Prev, 2011;12(11):2841-5.
    PMID: 22393951
    INTRODUCTION: Thrombocytopenia denotes abnormal decreases in platelet numbers and is a major detrimental side effect of the chemotherapy or cancer disease itself which cal lead to hemorrhage from vital organ. This is particularly a problem for the brain specifically within solid cancer patients and has a great negative effect on cancer patients quality of life (QOL). It ranges from mild bleeding from small blood vessels to severe bleeding from large blood vessels. The present study was conducted to evaluate the effectiveness of treatment guidelines for thrombocytopenia among solid cancer patients in Penang hospital and to find associations between these treatments and thrombocytopenia onset and severity and to suggest changes in the guidelines.

    METHODS: This retrospective observational study, conducted in a government hospital on Penang island included 341 cancer patients with thrombocytopenia who were admitted in the period between 2003 to 2009. The main statistical tests used were Chi-square test and Logistic regression test. The level of significance was set at P < 0.05.

    RESULTS: Of the total of 341, 21 (6.2%) showed thrombocytopenia before receiving chemotherapy and the remaining 320 (93.8%) after chemotherapy. The majority suffered from moderate thrombocytopenia (n=172; 53.8%), followed by mild a (n=97; 30.3%) and finally severe (n=51; 15.9%). For treatment, chemotherapy was delayed/ reduced (n=223; 65.4%) or platelets were transfused (n=51; 34.6%). However, thrombocytopenia problems were only temporarily solved.

    CONCLUSION: Effectiveness of thrombocytopenia treatment guidelines was found to be insufficient. It is advisable that thrombopoietin be used as a cornerstone even for patients who suffer from moderate thrombocytopenia and platelets transfusion should be used just for emergency cases when thrombocytopenia leads to a critical situation.

  9. Hassan BA, Yusoff ZB, Hassali MA, Othman SB, Weiderpass E
    Asian Pac J Cancer Prev, 2012;13(9):4373-8.
    PMID: 23167346
    INTRODUCTION: Hypercalcemia is mainly caused by bone resorption due to either secretion of cytokines including parathyroid hormone-related protein (PTHrP) or bone metastases. However, hypercalcemia may occur in patients with or without bone metastases. The present study aimed to describe the effect of chemotherapy treatment, regimens and doses on calcium levels among breast and lung cancer patients with hypercalcemia.

    METHODS: We carried a review of medical records of breast and lung cancer patients hospitalized in years 2003 and 2009 at Penang General Hospital, a public tertiary care center in Penang Island, north of Malaysia. Patients with hypercalcemia (defined as a calcium level above 10.5 mg/dl) at the time of cancer diagnosis or during cancer treatment had their medical history abstracted, including presence of metastasis, chemotherapy types and doses, calcium levels throughout cancer treatment, and other co-morbidity. The mean calcium levels at first hospitalization before chemotherapy were compared with calcium levels at the end of or at the latest chemotherapy treatment. Statistical analysis was conducted using the Chi-square test for categorical data, logistic regression test for categorical variables, and Spearman correlation test, linear regression and the paired sample t tests for continuous data.

    RESULTS: Of a total 1,023 of breast cancer and 814 lung cancer patients identified, 292 had hypercalcemia at first hospitalization or during cancer treatment (174 breast and 118 lung cancer patients). About a quarter of these patients had advanced stage cancers: 26.4% had mild hypercalcemia (10.5-11.9 mg/dl), 55.5% had moderate (12-12.9 mg/dl), and 18.2% severe hypercalcemia (13-13.9; 14-16 mg/dl). Chemotherapy lowered calcium levels significantly both in breast and lung cancer patients with hypercalcemia; in particular with chemotherapy type 5-flurouracil+epirubicin+cyclophosphamide (FEC) for breast cancer, and gemcitabine+cisplatin in lung cancer.

    CONCLUSION: Chemotherapy decreases calcium levels in breast and lung cancer cases with hypercalcemia at cancer diagnosis, probably by reducing PTHrP levels.

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