Displaying publications 21 - 33 of 33 in total

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  1. Taghizadeh Davoudi E, Ibrahim Noordin M, Kadivar A, Kamalidehghan B, Farjam AS, Akbari Javar H
    Biomed Res Int, 2013;2013:495319.
    PMID: 24288681 DOI: 10.1155/2013/495319
    Gastrointestinal disturbances, such as nausea and vomiting, are considered amongst the main adverse effects associated with oral anticancer drugs due to their fast release in the gastrointestinal tract (GIT). Sustained release formulations with proper release profiles can overcome some side effects of conventional formulations. The current study was designed to prepare sustained release tablets of Capecitabine, which is approved by the Food and Drug Administration (FDA) for the treatment of advanced breast cancer, using hydroxypropyl methylcellulose (HPMC), carbomer934P, sodium alginate, and sodium bicarbonate. Tablets were prepared using the wet granulation method and characterized such that floating lag time, total floating time, hardness, friability, drug content, weight uniformity, and in vitro drug release were investigated. The sustained release tablets showed good hardness and passed the friability test. The tablets' floating lag time was determined to be 30-200 seconds, and it floated more than 24 hours and released the drug for 24 hours. Then, the stability test was done and compared with the initial samples. In conclusion, by adjusting the right ratios of the excipients including release-retarding gel-forming polymers like HPMC K4M, Na alginate, carbomer934P, and sodium bicarbonate, sustained release Capecitabine floating tablet was formulated.
    Matched MeSH terms: Fluorouracil/administration & dosage
  2. Mishra RK, Ramasamy K, Ahmad NA, Eshak Z, Majeed AB
    J Mater Sci Mater Med, 2014 Apr;25(4):999-1012.
    PMID: 24398912 DOI: 10.1007/s10856-013-5132-x
    Stimuli responsive hydrogels have shown enormous potential as a carrier for targeted drug delivery. In this study we have developed novel pH responsive hydrogels for the delivery of 5-fluorouracil (5-FU) in order to alleviate its antitumor activity while reducing its toxicity. We used 2-(methacryloyloxyethyl) trimetylammonium chloride a positively charged monomer and methacrylic acid for fabricating the pH responsive hydrogels. The released 5-FU from all except hydrogel (GEL-5) remained biologically active against human colon cancer cell lines [HT29 (IC50 = 110-190 μg ml(-1)) and HCT116 (IC50 = 210-390 μg ml(-1))] but not human skin fibroblast cells [BJ (CRL2522); IC50 ≥ 1000 μg ml(-1)]. This implies that the copolymer hydrogels (1-4) were able to release 5-FU effectively to colon cancer cells but not normal human skin fibroblast cells. This is probably due to the shorter doubling time that results in reduced pH in colon cancer cells when compared to fibroblast cells. These pH sensitive hydrogels showed well defined cell apoptosis in HCT116 cells through series of events such as chromatin condensation, membrane blebbing, and formation of apoptotic bodies. No cell killing was observed in the case of blank hydrogels. The results showed the potential of these stimuli responsive polymer hydrogels as a carrier for colon cancer delivery.
    Matched MeSH terms: Fluorouracil/administration & dosage*
  3. Lee WC, Yusof MM, Lau FN, Phua VC
    Asian Pac J Cancer Prev, 2013;14(6):3941-4.
    PMID: 23886211
    BACKGROUND: The use of preoperative chemoirradiation is the commonest treatment strategy employed in Malaysia for locally advanced rectal cancer. We need to determine the local control and survival rates for comparison with established rates in the literature.

    MATERIALS AND METHODS: This retrospective study analyzed all newly diagnosed patients with rectal adenocarcinoma who underwent long course preoperative radiotherapy (RT) at the Department of Radiotherapy and Oncology, Kuala Lumpur Hospital (HKL) between 1st January 2004 and 31st December 2010. The aim of the study was to determine the radiological response post radiotherapy, pathological response including circumferential resection margin (CRM) status, 3 years local control, 3 years overall survival (OS) and 3 years disease free survival (DFS). Statistical analysis was performed using the SPSS software. Kaplan-Meier and log rank analysis were used to determine survival outcomes.

    RESULTS: A total of 507 patients with rectal cancer underwent RT at HKL. Sixty seven who underwent long course preoperative RT were eligible for this study. The median age at diagnosis was 60 years old with a range of 26-78 years. The median tumour location was 6 cm from the anal verge. Most patients had suspicion of mesorectum involvement (95.5%) while 28.4% of patients had enlarged pelvic nodes on staging CT scan. All patients underwent preoperative chemo-irradiation except for five who had preoperative RT alone. Only 38 patients underwent definitive surgery (56.7%). Five patients were deemed to be inoperable radiologically and 3 patients were found to have unresectable disease intraoperatively. The remaining 21 patients defaulted surgery (31.3%). The median time from completion of RT to surgery was 8 weeks (range 5.6 to 29.4 weeks). Fifteen patients (39.5%) had surgery more than 8 weeks after completion of RT. Complete pathological response was noted in 4 patients (10.5%). The pathological CRM positive rate after RT was 18.4%. With a median follow-up of 38.8 months, the 3 year local control rate was 67%. The 3 years rate for CRM positive (<2 mm), CRM clear (>2 mm) and pCR groups were 0%, 88.1% and 100% respectively (p-value of 0.007). The 3 year OS and DFS were 57.3% and 44.8% respectively.

    CONCLUSIONS: In conclusion, the approach of long course preoperative chemoirradiation for rectal cancer needs to be re-examined in our local setting. The high rate of local recurrence is worrying and is mainly due to patient defaulting post-preoperative chemoirradiation or delayed definitive surgery.
    Matched MeSH terms: Fluorouracil/administration & dosage
  4. Chong HY, Taib NA, Rampal S, Saad M, Bustam AZ, Yip CH
    Asian Pac J Cancer Prev, 2010;11(4):913-7.
    PMID: 21133600
    BACKGROUND: Locally advanced breast cancer (LABC) is characterized by the presence of a large primary tumour (>5 cm) associated with or without skin or chest-wall involvement (T4) or with fixed (matted) axillary lymph nodes in the absence of any evidence of distant metastases. These cancers are classified as stage IIIA and IIIB according to the AJCC Staging System. Treatment of choice involves combinations of surgery, chemotherapy, radiotherapy and/or hormonal therapy. Current guidelines recommend primary surgery or neoadjuvant therapy followed by surgery. The primary objective of this study was to compare the outcome of LABC patients subjected to neoadjuvant chemotherapy before surgery and those who underwent surgery as the primary treatment and to determine prognostic predictors. Secondary objectives were to evaluate the response after neoadjuvant therapy and to determine the treatment compliance rate.

    METHODS: This retrospective study of Stage III breast cancer patients was conducted over a 5 year period from 1998 to 2002. The survival data were obtained from the National Registry of Births and Deaths with the end-point of the study in April 2006. The Kaplan Meier method was applied for survival analysis. Cox regression analysis by stepwise selection was performed to identify important prognostic factors.

    RESULTS: Out of a 155 evaluable patients, 74 (47.7%) had primary surgery, 62 (40%) had neoadjuvant chemotherapy, 10 patients (6.5%) were given Tamoxifen as the primary treatment, while 9 patients (5.8%) defaulted any form of treatment. After neoadjuvant chemotherapy, 9 patients defaulted further treatment, leaving 53 evaluable patients. Out of these 53 evaluable patients, 5 patients (9.4%) had complete pathological response, 5 (9.4%) a complete clinical response, and 26 (49.1%) had partial response after neoadjuvant chemotherapy. The 5-year survival in the primary surgery group was 56.7 % compared to 44.7% in the neoadjuvant chemotherapy group (p<0.01). The important prognostic factors were race, size of tumour, nodal status, estrogen receptor status and response to neoadjuvant chemotherapy.

    CONCLUSION: Patients who had primary surgery had better survival than those who underwent neoadjuvant chemotherapy, which may be due to bias in the selection of patients for neoadjuvant chemotherapy. Out of a total of 155 patients, 25.1% defaulted part of the treatment, or did not receive optimal treatment, emphasizing the importance of psychosocial support and counselling for this group of patients.

    Matched MeSH terms: Fluorouracil/administration & dosage
  5. Mirakhorli M, Rahman SA, Abdullah S, Vakili M, Rozafzon R, Khoshzaban A
    Mol Med Rep, 2013 Feb;7(2):613-7.
    PMID: 23232902 DOI: 10.3892/mmr.2012.1226
    Multidrug resistance protein 2 (MRP2), encoded by the ATP-binding cassette C2 (ABCC2) gene, is an efflux pump located on the apical membrane of many polarized cells, which transports conjugate compounds by an ATP-dependent mechanism. The correlation of G1249A ABCC2 polymorphism with the development of colorectal cancer (CRC) and poor prognosis was evaluated in patients who were treated with fluorouracil/-leucovorin (FL) plus oxaliplatin (FOLFOX-4). A total of 50 paraffin‑embedded tissue samples collected from CRC patients were analyzed to identify the polymorphism. Patients were in stage II/III and received postoperative FOLFOX-4 chemotherapy. As a control group, an equal number of unrelated healthy subjects were enrolled in the study. The polymorphism was genotyped by the polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) method, and results were compared with clinicopathological markers, early relapse and survival rates. During the 12 months of follow-up, local and distant recurrences were observed in 15 (30%) patients. No significant difference in the distribution of wild-type and polymorphic genotypes was observed between the patient and control groups and between the patients who experienced recurrence within 1 year and those who did not (all P>0.05). In conclusion, the G1249A polymorphism is not associated with CRC risk and early recurrence. However, significant correlation was observed between G1249A polymorphism and the overall survival and disease-free survival of the patients.
    Matched MeSH terms: Fluorouracil/administration & dosage
  6. 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: Fluorouracil/administration & dosage
  7. Hassan AS, Naicker M, Yusof KH, Wan Ishak WZ
    Asian Pac J Cancer Prev, 2015;16(6):2237-43.
    PMID: 25824744
    BACKGROUND: Adjuvant chemotherapy improves survival in Dukes C colon cancers post-curative resection. However, the evidence for a role with Dukes B lesions remains unproven despite frequent use for disease characterized by poor prognostic features. In view of limited Asia-specific data, this study aimed to determine survival outcomes and identify prognostic factors in a tertiary teaching hospital in Malaysia.

    MATERIALS AND METHODS: A total of 116 subjects who underwent curative surgery with and without adjuvant chemotherapy for Duke B and C primary colon adenocarcinomas diagnosed from 2004-2009 were recruited and data were collected retrospectively. Five-year overall survival (OS) and disease free survival (DFS) were analysed using Kaplan-Meier survival analysis and log-rank (Mantel-Cox) test. Prognostic factors were determined using Cox proportional hazards regression with both univariate and multivariate analyses.

    RESULTS: The survival analysis demonstrated a 5-year OS of 74.0% for all patients, with 74.9% for Dukes C subjects receiving chemotherapy compared to 28.6% in those not receiving chemotherapy (p=0.001). For Dukes B disease, the 5-year survival rate was 82.6% compared to 75.0% for subjects receiving and not receiving chemotherapy, respectively (p=0.17). Independent prognostic factors identified included a CEA level more than 3.5 ng/ml (hazard ratio (HR)=4.78; p=0.008), serosal involvement (HR=3.75; p=0.028) and completion of chemotherapy (HR= 0.20; p=0.007).

    CONCLUSIONS: In a regional context, this study supports current evidence from the West that adjuvant chemotherapy improves survival in Dukes C colon cancers post curative surgery. However, although a clear benefit has yet to be proven for Dukes B disease, our results suggest survival improvement in selected cases.
    Matched MeSH terms: Fluorouracil/administration & dosage
  8. Tiong V, Rozita AM, Taib NA, Yip CH, Ng CH
    World J Surg, 2014 Sep;38(9):2288-96.
    PMID: 24700093 DOI: 10.1007/s00268-014-2542-y
    Breast cancer is increasingly reported in young premenopausal women in Asia. Adjuvant chemotherapy improves survival; however, it has a unique consequence of ovarian failure in premenopausal patients.
    Matched MeSH terms: Fluorouracil/administration & dosage
  9. Cheng AL, Cornelio G, Shen L, Price T, Yang TS, Chung IJ, et al.
    Clin Colorectal Cancer, 2017 06;16(2):e73-e88.
    PMID: 27780749 DOI: 10.1016/j.clcc.2016.08.005
    BACKGROUND: In patients with KRAS wild-type (wt) metastatic colorectal cancer (mCRC), outcomes with first-line chemotherapies are improved by adding weekly cetuximab. The APEC study investigated first-line once-every-2-weeks cetuximab plus chemotherapy for patients with KRAS wt mCRC; additional biomarker subgroups were also analyzed.

    PATIENTS AND METHODS: APEC was a nonrandomized phase 2 trial conducted in the Asia-Pacific region. Patients (n = 289) received once-every-2-weeks cetuximab with investigator's choice of chemotherapy (FOLFOX or FOLFIRI). The primary end point was best confirmed overall response rate (BORR); progression-free survival (PFS) and overall survival (OS) were secondary end points. Early tumor shrinkage (ETS) and depth of response (DpR) were also evaluated.

    RESULTS: In the KRAS wt population, BORR was 58.8%, median PFS 11.1 months, and median OS 26.8 months. Expanded RAS mutational analysis revealed that patients with RAS wt mCRC had better outcomes (BORR = 64.7%; median PFS = 13.0 months; median OS = 28.4 months). The data suggest that ETS and DpR may be associated with survival outcomes in the RAS wt population. Although this study was not designed to formally assess differences in outcome between treatment subgroups, efficacy results appeared similar for patients treated with FOLFOX and FOLFIRI. There were no new safety findings; in particular, grade 3/4 skin reactions were within clinical expectations.

    CONCLUSION: The observed activity and safety profile is similar to that reported in prior first-line pivotal studies involving weekly cetuximab, suggesting once-every-2-weeks cetuximab is effective and tolerable as first-line therapy and may represent an alternative to weekly administration.

    Matched MeSH terms: Fluorouracil/administration & dosage
  10. Liew AC, Peh KK, Tan BS, Zhao W, Tangiisuran B
    Support Care Cancer, 2019 Dec;27(12):4515-4524.
    PMID: 30911917 DOI: 10.1007/s00520-019-04724-1
    PURPOSE: This observational study aimed to compare the outcome and health-related quality of life (HRQOL) amongst breast cancer patients using Chinese herbal medicine (CHM) and those not using CHM during chemotherapy.

    METHODS: A prospective, non-randomised longitudinal study was conducted in two government integrated hospitals over an 8-month period. Early-stage breast cancer patients who were (1) either already using complementary and alternative medicine (CAM) or not and (2) who were on a regime of 5-fluorouracil, epirubicin, and cyclophosphamide were included in the study. Patients who agreed to receive CHM were assigned to receive individualised CHM prescriptions deemed suitable for the individual at a particular time. Those who were not willing to take Chinese herbal medicines (CHM) were assigned to the non-CHM control group. Blood profile and chemotherapy-induced AE were recorded whilst HRQOL assessment was done using the EORTC QLQ-C30 questionnaire on first, third, and sixth cycles.

    RESULTS: Forty-seven patients [32 female vs. 1 male, p = 0.31; mean year of age: 52.2(SD = 7.6), p = 0.28)}] were recruited during the study period. Demographics of both groups were comparable. Fifty percent of respondents reported using some kind of CAM before chemotherapy. Diet supplements (40.6%) were the most common CAM used by the respondents. The study showed that patients using CHM had significantly less fatigue (p = 0.012), nausea (p = 0.04), and anorexia (p = 0.005) during chemotherapy. There were no significant differences in patients' HRQOL (p = 0.79). There were no AEs reported during the study.

    CONCLUSION: The use of CHM as an adjunct treatment with conventional chemotherapy have been shown to reduce fatigue, nausea, and anorexia in breast cancer patients but did not reduce chemotherapy-associated hematologic toxicity. The sample size of this study was not powered to assess the significance of HRQOL between two groups of patients.

    Matched MeSH terms: Fluorouracil/administration & dosage
  11. Goodman KA, Ou FS, Hall NC, Bekaii-Saab T, Fruth B, Twohy E, et al.
    J Clin Oncol, 2021 09 01;39(25):2803-2815.
    PMID: 34077237 DOI: 10.1200/JCO.20.03611
    PURPOSE: To evaluate the use of early assessment of chemotherapy responsiveness by positron emission tomography (PET) imaging to tailor therapy in patients with esophageal and esophagogastric junction adenocarcinoma.

    METHODS: After baseline PET, patients were randomly assigned to an induction chemotherapy regimen: modified oxaliplatin, leucovorin, and fluorouracil (FOLFOX) or carboplatin-paclitaxel (CP). Repeat PET was performed after induction; change in maximum standardized uptake value (SUV) from baseline was assessed. PET nonresponders (< 35% decrease in SUV) crossed over to the alternative chemotherapy during chemoradiation (50.4 Gy/28 fractions). PET responders (≥ 35% decrease in SUV) continued on the same chemotherapy during chemoradiation. Patients underwent surgery at 6 weeks postchemoradiation. Primary end point was pathologic complete response (pCR) rate in nonresponders after switching chemotherapy.

    RESULTS: Two hundred forty-one eligible patients received Protocol treatment, of whom 225 had an evaluable repeat PET. The pCR rates for PET nonresponders after induction FOLFOX who crossed over to CP (n = 39) or after induction CP who changed to FOLFOX (n = 50) was 18.0% (95% CI, 7.5 to 33.5) and 20% (95% CI, 10 to 33.7), respectively. The pCR rate in responders who received induction FOLFOX was 40.3% (95% CI, 28.9 to 52.5) and 14.1% (95% CI, 6.6 to 25.0) in responders to CP. With a median follow-up of 5.2 years, median overall survival was 48.8 months (95% CI, 33.2 months to not estimable) for PET responders and 27.4 months (95% CI, 19.4 months to not estimable) for nonresponders. For induction FOLFOX patients who were PET responders, median survival was not reached.

    CONCLUSION: Early response assessment using PET imaging as a biomarker to individualize therapy for patients with esophageal and esophagogastric junction adenocarcinoma was effective, improving pCR rates in PET nonresponders. PET responders to induction FOLFOX who continued on FOLFOX during chemoradiation achieved a promising 5-year overall survival of 53%.

    Matched MeSH terms: Fluorouracil/administration & dosage
  12. Cheng AL, Li J, Vaid AK, Ma BB, Teh C, Ahn JB, et al.
    Clin Colorectal Cancer, 2014 Sep;13(3):145-55.
    PMID: 25209093 DOI: 10.1016/j.clcc.2014.06.004
    Colorectal cancer (CRC) is among the most common cancers worldwide, but marked epidemiological differences exist between Asian and non-Asian populations. Hence, a consensus meeting was held in Hong Kong in December 2012 to develop Asia-specific guidelines for the management of metastatic CRC (mCRC). A multidisciplinary expert panel, consisting of 23 participants from 10 Asian and 2 European countries, discussed current guidelines for colon or rectal cancer and developed recommendations for adapting these guidelines to Asian clinical practice. Participants agreed that mCRC management in Asia largely follows international guidelines, but they proposed a number of recommendations based on regional 'real-world' experience. In general, participants agreed that 5-fluorouracil (5-FU) infusion regimens in doublets can be substituted with UFT (capecitabine, tegafur-uracil) and S1 (tegafur, 5-chloro-2,4-dihydroxypyridine and oxonic acid), and that the monoclonal antibodies cetuximab and panitumumab are recommended for KRAS wild type tumors. For KRAS mutant tumors, bevacizumab is the preferred biological therapy. FOLFOX (folinic acid, 5-FU, and oxaliplatin) is preferred for initial therapy in Asian patients. The management of mCRC is evolving, and it must be emphasized that the recommendations presented here reflect current treatment practices and thus might change as more data become available.
    Matched MeSH terms: Fluorouracil/administration & dosage
  13. Bose A, Elyagoby A, Wong TW
    Int J Pharm, 2014 Jul 1;468(1-2):178-86.
    PMID: 24709212 DOI: 10.1016/j.ijpharm.2014.04.006
    In situ coating of 5-fluorouracil pellets by ethylcellulose and pectin powder mixture (8:3 weight ratio) in capsule at simulated gastrointestinal media provides colon-specific drug release in vitro. This study probes into pharmacodynamic and pharmacokinetic profiles of intra-capsular pellets coated in vivo in rats with reference to their site-specific drug release outcomes. The pellets were prepared by extrusion-spheronization technique. In vitro drug content, drug release, in vivo pharmacokinetics, local colonic drug content, tumor, aberrant crypt foci, systemic hematology and clinical chemistry profiles of coated and uncoated pellets were examined against unprocessed drug. In vivo pellet coating led to reduced drug bioavailability and enhanced drug accumulation at colon (179.13 μg 5-FU/g rat colon content vs 4.66 μg/g of conventional in vitro film-coated pellets at 15 mg/kg dose). The in vivo coated pellets reduced tumor number and size, through reforming tubular epithelium with basement membrane and restricting expression of cancer from adenoma to adenocarcinoma. Unlike uncoated pellets and unprocessed drug, the coated pellets eliminated aberrant crypt foci which represented a putative preneoplastic lesion in colon cancer. They did not inflict additional systemic toxicity. In vivo pellet coating to orally target 5-fluorouracil delivery at cancerous colon is a feasible therapeutic treatment approach.
    Matched MeSH terms: Fluorouracil/administration & dosage*
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