Displaying publications 1 - 20 of 122 in total

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  1. Zarina RS, Nik-Hussein NN
    J Clin Pediatr Dent, 2005;29(2):167-74.
    PMID: 15719924
    The treatment of haematological malignancy is multimodal and involves chemotherapy, radiotherapy and/or bone marrow transplants. With the advancement in cancer therapy, there is an increase in the survival of many children with childhood haematological malignancy. In addition, the late effect of the oncology treatment to the orofacial and dental development becomes significant in terms of the potential clinical impact that may affect the quality of life of the survivor. The severity of the long-term effects is dependent on the age of the child at initiation of treatment and whether chemotherapy is combined with radiation or not. The dental treatment may become more complex if the patient requires advanced restorative dental care and the roots malformation may complicate orthodontic treatment. Therefore these patients may require a scheduled careful preventive programme, long-term follow up, with prophylactic treatment and intervention at appropriate time to minimize the consequences of the disease and the given therapy.
    Matched MeSH terms: Antineoplastic Combined Chemotherapy Protocols/therapeutic use
  2. Zamaniah WI, Mastura MY, Phua CE, Adlinda A, Marniza S, Rozita AM
    Asian Pac J Cancer Prev, 2014;15(20):8987-92.
    PMID: 25374241
    BACKGROUND: The efficacy of concurrent chemoradiotherapy in the treatment of locally advanced cervical cancer is well established. We aimed to investigate the long-term efficacy of definitive concurrent chemoradiotherapy for cervical cancer in the University of Malaya Medical Centre.

    MATERIALS AND METHODS: A cohort of 60 patients with FIGO stage IB2-IVA cervical cancer who were treated with definitive concurrent chemoradiotherapy with cisplatin followed by intracavitary brachytherapy or external beam radiotherapy (EBRT) boost between November 2001 and May 2008 were analysed. Patients were initially treated with weekly intravenous cisplatin (40 mg/m2) concurrent with daily EBRT to pelvis of 45-50 Gy followed by low dose rate brachytherapy or EBRT boost to tumour. Local control rate, progression free survival, overall survival and treatment related toxicities graded by the RTOG criteria were evaluated.

    RESULTS: The mean age was 56. At the median follow-up of 72 months, the estimated 5-year progression-free survival (PFS) (median PFS 39 months) and the 5-year overall survival (OS) (median OS 51 months) were 48% and 50% respectively. The 5-year local control rate was 67.3%. Grade 3-4 late gastrointestinal and genitourinary toxicity occurred in 9.3% of patients.

    CONCLUSIONS: The 5-year PFS and the 5-year OS in this cohort were lower than in other institutions. More advanced stage at presentation, longer overall treatment time (OTT) of more than fifty-six days and lower total dose to point A were the potential factors contributing to a lower survival.

    Matched MeSH terms: Antineoplastic Combined Chemotherapy Protocols/therapeutic use*
  3. Yusof MM, Abdullah NM, Sharial MM, Zaatar A
    Asian Pac J Cancer Prev, 2016;17(3):973-8.
    PMID: 27039822
    BACKGROUND: Between October 2012 and February 2015, 25 patients with metastatic colorectal cancer (mCRC) (mean age, 57.0 ± 12.1 years) were granted access to aflibercept via the Aflibercept Named Patient Program at four centers.

    MATERIALS AND METHODS: Here we reported the initial experience of aflibercept / FOLFIRI in combination. We evaluated treatment-related adverse events (AEs), progression-free survival (PFS) and overall survival (OS).

    RESULTS: The majority of the patients experienced gastrointestinal toxicity (grade 1-2), with diarrhea (52%), mucositis (52%), and nausea/vomiting (20%) being largely observed. Neutropenia (16%) and febrile neutropenia (8%) were common grade 3-4 hematological events. Aflibercept-related toxicity was managed as per practice guidelines. No grade 5 event was reported. Median PFS was 6.12 months (95% CI, 4.80-7.20) and OS was 12 months (95% CI, 9.80-14.18). The partial response (PR), stable disease (SD), and progressive disease (PD) rates were 25% (95% CI: 23.4-27.0), 37.5% (95% CI: 31.6-43.3), and 37.5% (95% CI: 22.5-52.5), respectively.

    CONCLUSIONS: Aflibercept/FOLFIRI can be administered safely in a second line setting to Malaysian patients with mCRC, as the AEs experienced were generally reversible and manageable. The safety and efficacy outcomes were consistent with those observed in Western populations.

    Matched MeSH terms: Antineoplastic Combined Chemotherapy Protocols/therapeutic use*
  4. Yeoh AEJ, Lu Y, Chin WHN, Chiew EKH, Lim EH, Li Z, et al.
    J Clin Oncol, 2018 09 10;36(26):2726-2735.
    PMID: 30044693 DOI: 10.1200/JCO.2018.78.3050
    Purpose Although IKZF1 deletion ( IKZF1del) confers a higher risk of relapse in childhood B-cell acute lymphoblastic leukemia (B-ALL), it is uncertain whether treatment intensification will reverse this risk and improve outcomes. The Malaysia-Singapore ALL 2010 study (MS2010) prospectively upgraded the risk assignment of patients with IKZF1del to the next highest level and added imatinib to the treatment of all patients with BCR- ABL1 fusion. Patients and Methods In total, 823 patients with B-ALL treated in the Malyasia-Singapore ALL 2003 study (MS2003; n = 507) and MS2010 (n = 316) were screened for IKZF1del using the multiplex ligation-dependent probe amplification assay. The impact of IKZF1del on the 5-year cumulative incidence of relapse (CIR) was compared between the two studies. Results Patient characteristics were similar in both cohorts, including IKZF1del frequencies (59 of 410 [14.4%] v 50 of 275 [18.2%]; P = .2). In MS2003, where IKZF1del was not used in risk assignment, IKZF1del conferred a significantly higher 5-year CIR (30.4% v 8.1%; P = 8.7 × 10-7), particularly in the intermediate-risk group who lacked high-risk features (25.0% v 7.5%; P = .01). For patients with BCR-ABL1-negative disease, IKZF1del conferred a higher 5-year CIR (20.5% v 8.0%; P = .01). In MS2010, the 5-year CIR of patients with IKZF1del significantly decreased to 13.5% ( P = .05) and no longer showed a significant difference in patients with BCR-ABL1-negative disease (11.4% v 4.4%; P = .09). The 5-year overall survival for patients with IKZF1del improved from 69.6% in MS2003 to 91.6% in MS2010 ( P = .007). Conclusion Intensifying therapy for childhood B-ALL with IKZF1del significantly reduced the risk of relapse and improved overall survival. Incorporating IKZF1del screening significantly improved treatment outcomes in contemporary ALL therapy.
    Matched MeSH terms: Antineoplastic Combined Chemotherapy Protocols/therapeutic use*
  5. Yeoh AE, Ariffin H, Chai EL, Kwok CS, Chan YH, Ponnudurai K, et al.
    J Clin Oncol, 2012 Jul 1;30(19):2384-92.
    PMID: 22614971 DOI: 10.1200/JCO.2011.40.5936
    PURPOSE: To improve treatment outcome for childhood acute lymphoblastic leukemia (ALL), we designed the Malaysia-Singapore ALL 2003 study with treatment stratification based on presenting clinical and genetic features and minimal residual disease (MRD) levels measured by polymerase chain reaction targeting a single antigen-receptor gene rearrangement.
    PATIENTS AND METHODS: Five hundred fifty-six patients received risk-adapted therapy with a modified Berlin-Frankfurt-Münster-ALL treatment. High-risk ALL was defined by MRD ≥ 1 × 10(-3) at week 12 and/or poor prednisolone response, BCR-ABL1, MLL gene rearrangements, hypodiploid less than 45 chromosomes, or induction failure; standard-risk ALL was defined by MRD ≤ 1 × 10(-4) at weeks 5 and 12 and no extramedullary involvement or high-risk features. Intermediate-risk ALL included all remaining patients.
    RESULTS: Patients who lacked high-risk presenting features (85.7%) received remission induction therapy with dexamethasone, vincristine, and asparaginase, without anthracyclines. Six-year event-free survival (EFS) was 80.6% ± 3.5%; overall survival was 88.4% ± 3.1%. Standard-risk patients (n = 172; 31%) received significantly deintensified subsequent therapy without compromising EFS (93.2% ± 4.1%). High-risk patients (n = 101; 18%) had the worst EFS (51.8% ± 10%); EFS was 83.6% ± 4.9% in intermediate-risk patients (n = 283; 51%).
    CONCLUSION: Our results demonstrate significant progress over previous trials in the region. Three-drug remission-induction therapy combined with MRD-based risk stratification to identify poor responders is an effective strategy for childhood ALL.
    Matched MeSH terms: Antineoplastic Combined Chemotherapy Protocols/therapeutic use
  6. Yap E, Wan Jamaluddin WF, Tumian NR, Mashuri F, Mohammed F, Tan GC, et al.
    Malays J Pathol, 2014 Dec;36(3):201-5.
    PMID: 25500520 MyJurnal
    NK/T cell lymphoma, nasal type is an aggressive and uncommon malignancy. Disease that occurs outside of the aerodigestive tract exhibits an even more aggressive clinical behaviour and does not respond as well to conventional therapy compared to its nasal counterpart. We report such a case of NK/T cell lymphoma, nasal type, that presented as an anterior chest wall mass, arising from the left pectoralis muscle. An interesting feature we wish to highlight is the associated eosinophilia that corresponded to disease activity, exhibiting fluctuations with surgical resection and chemotherapy. To the best of our knowledge this is the third reported case of NK/T cell lymphoma that is associated with peripheral eosinophilia. Our case highlights the role of certain NK cell subsets that play a major role in eosinophilic activation in NK/T lymphomas and calls for more research into further classification of this disease by virtue of its NK cell subsets.
    Matched MeSH terms: Antineoplastic Combined Chemotherapy Protocols/therapeutic use
  7. Yahaya NA, Subramanian P, Bustam AZ, Taib NA
    Asian Pac J Cancer Prev, 2015;16(2):723-30.
    PMID: 25684515
    BACKGROUND: This study was performed to assess patient symptoms prevalence, frequency and severity, as well as distress and coping strategies used, and to identify the relationships between coping strategies and psychological and physical symptoms distress and demographic data of cancer patients. This cross-sectional descriptive study involved a total of 268 cancer patients with various types of cancer and chemotherapy identified in the oncology unit of an urban tertiary hospital.

    MATERIALS AND METHODS: Data were collected using questionnaires (demographic questionnaire, Medical characteristics, Memorial Symptom Assessment Scale (MSAS) and Brief COPE scales and analyzed for demographic, and disease-related variable effects on symptom prevalence, severity, distress and coping strategies.

    RESULTS: Symptom prevalence was relatively high and ranged from 14.9% for swelling of arms and legs to 88.1% for lack of energy. This latter was the highest rated symptom in the study. The level of distress was found to be low in three domains. Problem-focused coping strategies were found to be more commonly employed compared to emotion-focused strategies, demonstrating significant associations with sex, age group, educational levels and race. However, there was a positive correlation between emotion-focused strategies and physical and psychological distress, indicating that patients would choose emotion-focused strategies when symptom distress increased.

    CONCLUSIONS: These findings demonstrate that high symptom prevalence rates and coping strategies used render an improvement in current nursing management. Therefore development of symptoms management groups, encouraging the use of self-care diaries and enhancing the quality of psycho- oncology services provided are to be recommended.

    Matched MeSH terms: Antineoplastic Combined Chemotherapy Protocols/therapeutic use*
  8. Wu YL, Zhou C, Liam CK, Wu G, Liu X, Zhong Z, et al.
    Ann Oncol, 2015 Sep;26(9):1883-1889.
    PMID: 26105600 DOI: 10.1093/annonc/mdv270
    BACKGROUND: The phase III, randomized, open-label ENSURE study (NCT01342965) evaluated first-line erlotinib versus gemcitabine/cisplatin (GP) in patients from China, Malaysia and the Philippines with epidermal growth factor receptor (EGFR) mutation-positive non-small-cell lung cancer (NSCLC).

    PATIENTS AND METHODS: Patients ≥18 years old with histologically/cytologically confirmed stage IIIB/IV EGFR mutation-positive NSCLC and Eastern Cooperative Oncology Group performance status 0-2 were randomized 1:1 to receive erlotinib (oral; 150 mg once daily until progression/unacceptable toxicity) or GP [G 1250 mg/m(2) i.v. days 1 and 8 (3-weekly cycle); P 75 mg/m(2) i.v. day 1, (3-weekly cycle) for up to four cycles]. Primary end point: investigator-assessed progression-free survival (PFS). Other end points include objective response rate (ORR), overall survival (OS), and safety.

    RESULTS: A total of 217 patients were randomized: 110 to erlotinib and 107 to GP. Investigator-assessed median PFS was 11.0 months versus 5.5 months, erlotinib versus GP, respectively [hazard ratio (HR), 0.34, 95% confidence interval (CI) 0.22-0.51; log-rank P < 0.0001]. Independent Review Committee-assessed median PFS was consistent (HR, 0.42). Median OS was 26.3 versus 25.5 months, erlotinib versus GP, respectively (HR, 0.91, 95% CI 0.63-1.31; log-rank P = .607). ORR was 62.7% for erlotinib and 33.6% for GP. Treatment-related serious adverse events (AEs) occurred in 2.7% versus 10.6% of erlotinib and GP patients, respectively. The most common grade ≥3 AEs were rash (6.4%) with erlotinib, and neutropenia (25.0%), leukopenia (14.4%), and anemia (12.5%) with GP.

    CONCLUSION: These analyses demonstrate that first-line erlotinib provides a statistically significant improvement in PFS versus GP in Asian patients with EGFR mutation-positive NSCLC (NCT01342965).

    Matched MeSH terms: Antineoplastic Combined Chemotherapy Protocols/therapeutic use
  9. Wu YL, Lee V, Liam CK, Lu S, Park K, Srimuninnimit V, et al.
    Lung Cancer, 2018 12;126:1-8.
    PMID: 30527172 DOI: 10.1016/j.lungcan.2018.10.004
    OBJECTIVE: Patients with advanced non-small-cell lung cancer (NSCLC) with an adenocarcinoma component are recommended to undergo epidermal growth factor receptor (EGFR) mutation testing when being considered for EGFR targeted therapy. We conducted an exploratory analysis to inform the clinical utility of EGFR mutation testing in blood cell-free DNA using the cobas®EGFR Mutation Test v2.

    MATERIALS AND METHODS: Two EGFR mutation tests, a tissue-based assay (cobas® v1) and a tissue- and blood-based assay (cobas® v2) were used to analyze matched biopsy and blood samples (897 paired samples) from three Asian studies of first-line erlotinib with similar intent-to-treat populations. ENSURE was a phase III comparison of erlotinib and gemcitabine/platinum, FASTACT-2 was a phase III study of gemcitabine/platinum plus erlotinib or placebo, and ASPIRATION was a single-arm phase II study of erlotinib. Agreement statistics were evaluated, based on sensitivity and specificity between the two assays in subgroups of patients with increasing tumor burden.

    RESULTS: Patients with discordant EGFR (tissue+/plasma-) mutation status achieved longer progression-free and overall survival than those with concordant (tissue+/plasma+) mutation status. Tumor burden was significantly greater in patients with concordant versus discordant mutations. Pooled analyses of data from the three studies showed a sensitivity of 72.1% (95% confidence interval [CI] 67.8-76.1) and a specificity of 97.9% (95% CI 96.0-99.0) for blood-based testing; sensitivity was greatest in patients with larger baseline tumors.

    CONCLUSIONS: Blood-based EGFR mutation testing demonstrated high specificity and good sensitivity, and offers a convenient and easily accessible diagnostic method to complement tissue-based tests. Patients with a discordant mutation status in plasma and tissue, had improved survival outcomes compared with those with a concordant mutation status, which may be due to their lower tumor burden. These data help to inform the clinical utility of this blood-based assay for the detection of EGFR mutations.

    Matched MeSH terms: Antineoplastic Combined Chemotherapy Protocols/therapeutic use*
  10. Wu YL, Lu S, Lu Y, Zhou J, Shi YK, Sriuranpong V, et al.
    J Thorac Oncol, 2018 10;13(10):1539-1548.
    PMID: 29966800 DOI: 10.1016/j.jtho.2018.06.012
    INTRODUCTION: The phase III randomized PROFILE 1014 study demonstrated superiority of crizotinib to first-line chemotherapy in prolonging progression-free survival (PFS) in previously untreated patients with ALK receptor tyrosine kinase gene (ALK)-positive advanced nonsquamous NSCLC. This result was consistent with that in the smaller subset of East Asian patients in PROFILE 1014. The subsequent study reported here prospectively evaluated crizotinib in a larger East Asian patient population.

    METHODS: In this open-label phase III study (PROFILE 1029), patients were randomized 1:1 to receive orally administered crizotinib 250 mg twice daily continuously (3-week cycles) or intravenously administered chemotherapy (pemetrexed 500 mg/m2, plus cisplatin 75 mg/m2, or carboplatin [at a dose to produce area under the concentration-time curve of 5-6 mg·min/mL]) every 3 weeks for a maximum of six cycles. PFS confirmed by independent radiology review was the primary end point.

    RESULTS: Crizotinib significantly prolonged PFS (hazard ratio, 0.402; 95% confidence interval [CI]: 0.286-0.565; p < 0.001). The median PFS was 11.1 months with crizotinib and 6.8 months with chemotherapy. The objective response rate was 87.5% (95% CI: 79.6-93.2%) with crizotinib versus 45.6% (95% CI: 35.8-55.7%) with chemotherapy (p < 0.001). The most common adverse events were increased transaminase levels, diarrhea, and vision disorders with crizotinib and leukopenia, neutropenia, and anemia with chemotherapy. Significantly greater improvements from baseline in patient-reported outcomes were seen in crizotinib-treated versus chemotherapy-treated patients.

    CONCLUSIONS: First-line crizotinib significantly improved PFS, objective response rate, and patient-reported outcomes compared with standard platinum-based chemotherapy in East Asian patients with ALK-positive advanced NSCLC, which is similar to the results from PROFILE 1014. The safety profiles of crizotinib and chemotherapy were consistent with those previously published.

    Matched MeSH terms: Antineoplastic Combined Chemotherapy Protocols/therapeutic use*
  11. Wong KK, Gascoyne DM, Brown PJ, Soilleux EJ, Snell C, Chen H, et al.
    Leukemia, 2014 Feb;28(2):362-72.
    PMID: 23884370 DOI: 10.1038/leu.2013.224
    We previously identified autoantibodies to the endocytic-associated protein Huntingtin-interacting protein 1-related (HIP1R) in diffuse large B-cell lymphoma (DLBCL) patients. HIP1R regulates internalization of cell surface receptors via endocytosis, a process relevant to many therapeutic strategies including CD20 targeting with rituximab. In this study, we characterized HIP1R expression patterns, investigated a mechanism of transcriptional regulation and its clinical relevance in DLBCL patients treated with immunochemotherapy (rituximab, cyclophosphamide, doxorubicin, vincristine and prednisone, R-CHOP). HIP1R was preferentially expressed in germinal center B-cell-like DLBCL (P<0.0001) and inversely correlated with the activated B-cell-like DLBCL (ABC-DLBCL) associated transcription factor, Forkhead box P1 (FOXP1). HIP1R was confirmed as a direct FOXP1 target gene in ABC-DLBCL by FOXP1-targeted silencing and chromatin immunoprecipitation. Lower HIP1R protein expression (≤ 10% tumoral positivity) significantly correlated with inferior overall survival (OS, P=0.0003) and progression-free survival (PFS, P=0.0148) in R-CHOP-treated DLBCL patients (n=157). Reciprocal expression with ≥ 70% FOXP1 positivity defined FOXP1(hi)/HIP1R(lo) patients with particularly poor outcome (OS, P=0.0001; PFS, P=0.0016). In an independent R-CHOP-treated DLBCL (n=233) microarray data set, patients with transcript expression in lower quartile HIP1R and FOXP1(hi)/HIP1R(lo) subgroups exhibited worse OS, P=0.0044 and P=0.0004, respectively. HIP1R repression by FOXP1 is strongly associated with poor outcome, thus further understanding of FOXP1-HIP1R and/or endocytic signaling pathways might give rise to novel therapeutic options for DLBCL.
    Matched MeSH terms: Antineoplastic Combined Chemotherapy Protocols/therapeutic use
  12. Wong KK, Gascoyne DM, Soilleux EJ, Lyne L, Spearman H, Roncador G, et al.
    Oncotarget, 2016 Aug 16;7(33):52940-52956.
    PMID: 27224915 DOI: 10.18632/oncotarget.9507
    FOXP2 shares partially overlapping normal tissue expression and functionality with FOXP1; an established diffuse large B-cell lymphoma (DLBCL) oncogene and marker of poor prognosis. FOXP2 is expressed in the plasma cell malignancy multiple myeloma but has not been studied in DLBCL, where a poor prognosis activated B-cell (ABC)-like subtype display partially blocked plasma cell differentiation. FOXP2 protein expression was detected in ABC-DLBCL cell lines, and in primary DLBCL samples tumoral FOXP2 protein expression was detected in both germinal center B-cell-like (GCB) and non-GCB DLBCL. In biopsies from DLBCL patients treated with immunochemotherapy (R-CHOP), ≥ 20% nuclear tumoral FOXP2-positivity (n = 24/158) correlated with significantly inferior overall survival (OS: P = 0.0017) and progression-free survival (PFS: P = 0.0096). This remained significant in multivariate analysis against either the international prognostic index score or the non-GCB DLBCL phenotype (P < 0.05 for both OS and PFS). Expression of BLIMP1, a marker of plasmacytic differentiation that is commonly inactivated in ABC-DLBCL, did not correlate with patient outcome or FOXP2 expression in this series. Increased frequency of FOXP2 expression significantly correlated with FOXP1-positivity (P = 0.0187), and FOXP1 co-immunoprecipitated FOXP2 from ABC-DLBCL cells indicating that these proteins can co-localize in a multi-protein complex. FOXP2-positive DLBCL had reduced expression of HIP1R (P = 0.0348), which is directly repressed by FOXP1, and exhibited distinct patterns of gene expression. Specifically in ABC-DLBCL these were associated with lower expression of immune response and T-cell receptor signaling pathways. Further studies are warranted to investigate the potential functional cooperativity between FOXP1 and FOXP2 in repressing immune responses during the pathogenesis of high-risk DLBCL.
    Matched MeSH terms: Antineoplastic Combined Chemotherapy Protocols/therapeutic use*
  13. Wijayahadi N, Haron MR, Stanslas J, Yusuf Z
    J Chemother, 2007 Dec;19(6):716-23.
    PMID: 18230556
    Anthracyclines are the most widely used anticancer agents for breast cancer, of which doxorubicin and epirubicin have been reported to have equal efficacy. Unfortunately, the integrity of the immune system of breast cancer patients is severely affected by chemotherapy. This study compared the effect of combination chemotherapy with epirubicin (5-fluorouracil, epirubicin, cyclophosphamide (FEC)) and doxorubicin (5-fluorouracil, doxorubicin, cyclophosphamide (FDC)) regimens on subsets of the immune cells of patients with primary malignant breast tumors. Our aim was to determine the best regimen that produces the least degree of myelosuppression. Blood from 80 breast cancer patients undergoing chemotherapy (40 FEC and 40 FDC) was taken before chemotherapy and after every cycle (3 weeks) for 6 cycles. Blood was also taken from 40 normal healthy donors who served as normal control. Subsets of lymphocytes T-helper cells (CD3(+)CD4(+)), T-cytotoxic cells (CD3(+) CD8(+)), B-cells (CD19(+) CD20(+)) and NK cells (CD16(+)/CD56(+)CD3(-)) were analyzed by flow cytometry (FacsCalibur, BD) using monoclonal antibodies (Multitest, BD). All patients in the FEC and FDC groups suffered from myelosuppressive side effects. Both regimens led to an increase in the counts of monocytes but decreased polymorphonuclear cells (PMNs) and lymphocytes. Percentages of T-cytotoxic cells and NK cells were increased, but the percentage of B-cells was dramatically decreased. The phagocytic and intracellular killing ability of PMNs were also suppressed (p<0.01). No significant difference was found between the epirubicin-based regimen and doxorubicin-based regimen with regard to numbers of immune cells, percentages of lymphocytes subsets, Th/CTL ratio, engulfment and killing abilities of PMNs. In conclusion, we found that the epirubicin-based regimen is not superior to the doxorubicin-based regimen with respect to their toxicity of the immune cells, Th/CTL ratio and PMN count and functions. Moreover, both FEC and FDC regimens appear to conserve the cell-mediated immunity response needed for fighting against cancer cells.
    Matched MeSH terms: Antineoplastic Combined Chemotherapy Protocols/therapeutic use*
  14. Wahab NA, Zainudin S, AbAziz A, Mustafa N, Sukor N, Kamaruddin NA
    Arch Iran Med, 2016 Sep;19(9):671-3.
    PMID: 27631184 DOI: 0161909/AIM.0012
    Adrenal cell carcinoma is a rare tumor and more than 70% of patients present with advanced stages. Adrenal cell carcinoma is an aggressive tumor with a poor prognosis. Surgical intervention is the gold standard treatment and mitotane is the only drug approved for the treatment of adrenal cell carcinoma. Until recently in 2012, the etoposide, doxorubicin, cisplatin plus mitotane are approved as first-line therapy based on response rate and progression-free survival. This case illustrates a case of advanced adrenal cell carcinoma in a young girl who presented with huge adrenal mass with inferior vena cava thrombosis and pulmonary embolism. Multi-approach of therapy was used to control the tumor size and metastasis. Therefore, it may prolong her survival rate for up to 5 years and 4 months.
    Matched MeSH terms: Antineoplastic Combined Chemotherapy Protocols/therapeutic use
  15. Tippett VL, Tattersall L, Ab Latif NB, Shah KM, Lawson MA, Gartland A
    Oncogene, 2023 Jan;42(4):259-277.
    PMID: 36434179 DOI: 10.1038/s41388-022-02529-x
    Over the last 40 years osteosarcoma (OS) survival has stagnated with patients commonly resistant to neoadjuvant MAP chemotherapy involving high dose methotrexate, adriamycin (doxorubicin) and platinum (cisplatin). Due to the rarity of OS, the generation of relevant cell models as tools for drug discovery is paramount to tackling this issue. Four literature databases were systematically searched using pre-determined search terms to identify MAP resistant OS cell lines and patients. Drug exposure strategies used to develop cell models of resistance and the impact of these on the differential expression of resistance associated genes, proteins and non-coding RNAs are reported. A comparison to clinical studies in relation to chemotherapy response, relapse and metastasis was then made. The search retrieved 1891 papers of which 52 were relevant. Commonly, cell lines were derived from Caucasian patients with epithelial or fibroblastic subtypes. The strategy for model development varied with most opting for continuous over pulsed chemotherapy exposure. A diverse resistance level was observed between models (2.2-338 fold) with 63% of models exceeding clinically reported resistance levels which may affect the expression of chemoresistance factors. In vitro p-glycoprotein overexpression is a key resistance mechanism; however, from the available literature to date this does not translate to innate resistance in patients. The selection of models with a lower fold resistance may better reflect the clinical situation. A comparison of standardised strategies in models and variants should be performed to determine their impact on resistance markers. Clinical studies are required to determine the impact of resistance markers identified in vitro in poor responders to MAP treatment, specifically with respect to innate and acquired resistance. A shift from seeking disputed and undruggable mechanisms to clinically relevant resistance mechanisms may identify key resistance markers that can be targeted for patient benefit after a 40-year wait.
    Matched MeSH terms: Antineoplastic Combined Chemotherapy Protocols/therapeutic use
  16. Ting CY, Gan GG, Bee-Lan Ong D, Tan SY, Bee PC
    Int J Clin Pract, 2020 Oct;74(10):e13594.
    PMID: 32583545 DOI: 10.1111/ijcp.13594
    BACKGROUND: About 20%-30% of diffuse large B-cell lymphoma (DLBCL) patients experience early disease progression despite R-CHOP chemotherapy treatment. Revised international prognostic index (R-IPI) score could risk stratify DLBCL patients but does not identify exactly which patient will be resistant to R-CHOP therapy or experience early relapse.

    AIMS OF THE STUDY: To analyse pre-treatment clinical features of DLBCL patients that are predictive of R-CHOP therapy resistance and early disease relapse after R-CHOP therapy treatment.

    METHODS USED TO CONDUCT THE STUDY: A total of 698 lymphoma patients were screened and 134 R-CHOP-treated DLBCL patients were included. The Lugano 2014 criteria was applied for assessment of treatment response. DLBCL patients were divided into R-CHOP resistance/early relapse group and R-CHOP sensitive/late relapse group.

    RESULTS OF THE STUDY: 81 of 134 (60%) were R-CHOP sensitive/late relapse, while 53 (40%) were R-CHOP resistance/early relapse. The median follow-up period was 59 months ± standard error 3.6. Five-year overall survival rate of R-CHOP resistance/early relapse group was 2.1%, while it was 89% for RCHOP sensitive/late relapse group. Having more than one extranodal site of DLBCL disease is an independent risk factor for R-CHOP resistance/early relapse [odds ratio = 5.268 (1.888-14.702), P = .002]. The commonest extranodal sites were head and neck, gastrointestinal tract, respiratory system, vertebra and bones. Advanced age (>60 years), advanced disease stage (lll-lV), raised pre-treatment lactate dehydrogenase level, bone marrow involvement of DLBCL disease high Eastern Cooperative Oncology Group status (2-4) and high R-IPI score (3-5) showed no significant association with R-CHOP therapy resistance/early disease relapse (multivariate analysis: P > .05).

    CONCLUSION AND CLINICAL IMPLICATIONS: DLBCL patients with more than one extranodal site are 5.268 times more likely to be R-CHOP therapy resistance or experience early disease relapse after R-CHOP therapy. Therefore, correlative studies are warranted in DLBCL patients with more than one extranodal site of disease to explore possible underlying mechanisms of chemoresistance.

    Matched MeSH terms: Antineoplastic Combined Chemotherapy Protocols/therapeutic use*
  17. Teoh CS, Lee SY, Chiang SK, Chew TK, Goh AS
    Asian Pac J Cancer Prev, 2018 May 26;19(5):1229-1236.
    PMID: 29801406
    Background: Diffuse large B-cell lymphoma (DLBCL) with double expression of c-MYC and BCL2 protein is
    associated with dismal outcome after treatment with R-CHOP. Local data on disease burden and survival outcome in
    DLBCL is limited. We investigated the prognostic values of c-MYC/BCL2 protein co-expression and cell of origin
    subtypes using immunohistochemistry (IHC) and to determine their associations with multiethnic groups under
    resource limited setting. Methods: This was a retrospective study which recruited 104 patients in between June 2012
    and December 2015 for IHC review and analysis. Result: We demonstrated that patients with high International
    Prognostic Index (IPI) (score 3-5) and co-expression of c-MYC/BCL2 protein had significant inferior overall survival
    (OS) and event free survival (EFS) respectively (P<0.05). c-MYC/BCL2 protein co-expression was more common in
    non-germinal center B-cell (non-GCB) (P=0.048) and contributed to adverse prognosis in this group of patients (OS,
    P=0.004; EFS, P=0.005). In multivariate analysis, double-protein co-expression was a significant independent predictor
    of inferior outcome after adjusted for IPI and cell of origin subtypes (OS hazard ratio [HR], 2.11; 95% CI, 1.01 to 4.04;
    P=0.048; EFS HR, 2.31; 95% CI, 1.05 to 5.04; P=0.036). In addition, non-GCB subtype was more common than GCB
    in Malays (60% vs 40%, P=0.106) and Chinese (81.2% vs 18.8%, P=0.042). Indians had more DLBCL without c-MYC/
    BCL2 protein co-expression compared to double-protein positive cases (66.7% vs 33.3%, P=0.414). Otherwise, the
    prognostic impact of ethnicity on survival outcome was insignificant (P=0.961). Conclusion: c-MYC/BCL2 protein
    co-expression in non-GCB subtype constituted a unique group with extremely inferior outcome regardless of ethnicity.
    Gene expression profile (GEP) may possibly provide insights into the cause of discrepancies in DLBCL subtypes and
    protein expression among the multiethnic groups.
    Matched MeSH terms: Antineoplastic Combined Chemotherapy Protocols/therapeutic use*
  18. Tayib S, van Wijk L, Denny L
    Int. J. Gynecol. Cancer, 2011 Dec;21(9):1684-91.
    PMID: 21997172 DOI: 10.1097/IGC.0b013e31822d8ffd
    OBJECTIVES: The objective of the study was to describe the management of gestational trophoblastic neoplasia (GTN), with particular reference to concurrent human immunodeficiency virus (HIV) infection.

    METHODS: This retrospective descriptive study comprised all cases of GTN managed at Groote Schuur Hospital over a 10-year period (1999-2008).

    RESULTS: Seventy-six patients, with a median age of 30 years at presentation, were included in the study. Only 36 patients (47.4%) had known HIV status. Fourteen (18.4%) were HIV positive, and of these, 4 (28.6%) were on antiretroviral treatment (ARV). The mean CD4 count was 142 cells/μL for those on ARV and 543 cells/μL for those not on ARV (P = 0.001). Histologically, 44 patients (58%) had hydatidiform mole, and 21 (28%) had choriocarcinoma. In the remaining 10 cases, a clinical diagnosis was made. Based on the revised International Federation of Gynecology and Obstetrics (FIGO)/modified World Health Organization scoring, 43 patients (56.6%) were low risk, and 33 (43.4%) were high risk. Thirty-eight patients (50%) were staged as FIGO stage I. Of 73 patients who received chemotherapy, 56 (76.7%) achieved complete remission, 9 (12.3%) did not achieve any remission, 7 (9.6%) had a relapse, and 1 (1.4%) was lost to follow-up. Patients who never went into remission had frequent treatment delays due to poor compliance or inadequate blood counts. The overall survival at 60 months was 81.9%. Of the 13 patients (17.1%) who have died, 5 (38.5%) were HIV positive. The overall 5-year survival rates for FIGO stages I, II, III, and IV were 97.4%, 66.7%, 77.8%, and 46.2%, respectively. The overall 5-year survival for HIV-positive patients was 64.3% versus more than 85% for both the HIV-negative and HIV-unknown groups.

    CONCLUSIONS: Apart from more advanced stage, HIV seropositivity and poor compliance with treatment also portend poorer outcome in GTN patients. In HIV-positive patients with poor CD4, little clarity is available whether ARV should be commenced speedily, and the administration of chemotherapy delayed until immune reconstitution occurs.

    Matched MeSH terms: Antineoplastic Combined Chemotherapy Protocols/therapeutic use*
  19. Tang YL, Raja Sabudin RZ, Leong CF, Ko CC, Chia WK, Salwati S, et al.
    Malays J Pathol, 2015 Dec;37(3):275-9.
    PMID: 26712675 MyJurnal
    A rare case of double Philadelphia chromosome-positive B Acute lymphoblastic Leukaemia (B-ALL) is reported here. A 60-year-old lady presented with one month history of fever, submandibular lymphadenopathy, loss of appetite and weight loss. Physical examination revealed multiple palpable cervical lymph nodes. Blood film showed leucocytosis with 72% blasts. Bone marrow assessment confirmed a diagnosis of B-ALL with presence of double Philadelphia (Ph) chromosomes. As she was very ill, she was initially treated with an attenuated regimen of induction chemotherapy consisting of rituximab, cyclophosphamide, vincristine and prednisolone (R-CVP) along with intrathecal chemotherapy comprising methotrexate, cytarabine and hydrocortisone. Bone marrow examination post-induction chemotherapy showed >5% blasts. She was subsequently re-induced with rituximab, cyclophosphamide, doxorubicin, vincristine and prednisolone (R-CHOP) along with intrathecal chemotherapy, following which she went into complete remission. Consolidation chemotherapy consisting of methotrexate, methylprednisolone, cytarabine, intrathecal chemotherapy and imatinib was subsequently administered followed by maintenance chemotherapy consisting of vincristine, prednisolone and imatinib (IDEAMOP). She developed spontaneous bruises and relapsed four months into her maintenance chemotherapy with 90% blasts in the bone marrow which was treated with fludarabine, cytarabine and granulocyte colony stimulating factor (FLAG). Unfortunately she developed neutropenic sepsis which was complicated by invasive lung aspergillosis. Bone marrow examination post-FLAG showed 80% blasts. Despite aggressive antifungal therapy, her lung infection worsened and she finally succumbed to her illness 13 months after the initial diagnosis. We highlight a rare case of elderly B-ALL with double Ph chromosomes which carries a poor prognosis despite aggressive treatment for the disease and its complications.
    Matched MeSH terms: Antineoplastic Combined Chemotherapy Protocols/therapeutic use
  20. Tan HCL, Tan JH, Vellusamy VM, Vasavan Y, Lim CS
    Malays J Pathol, 2020 Aug;42(2):267-271.
    PMID: 32860380
    INTRODUCTION: Majority of Wilms tumour (WT) responds well to pre-operative chemotherapy. In Malaysia, incidence of WT is rare with only two cases reported per one million populations yearly. This case report is to highlight on the awareness of WT in an Asian population and highlight two cases and challenges faced after pre-operative chemotherapy.

    CASE REPORT: In this case series, we report on two cases of WT which had poor response to pre-operative chemotherapy. Both cases underwent surgery after pre-operative chemotherapy and recovery was uneventful during a two-year follow-up.

    DISCUSSION: Both patients had chemotherapy prior planned surgery, but had unfortunate poor tumour response. The tumour progressed in size which required a radical nephrectomy. The histology report for the first case had more than 60% blastemal cells remaining despite giving pre-operative chemotherapy with no focal anaplasia. This showed poor response to chemotherapy evidenced by the high number of blastemal cells. The second case was a stromal type WT which is known for poor response and may lead to enhancement of growth and maturation induced by chemotherapy. These were the possible reason of poor response of WT in these two cases.

    Matched MeSH terms: Antineoplastic Combined Chemotherapy Protocols/therapeutic use
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