This study examined the effects of folate environment of oligochitosan nanoparticles on their cellular internalization profiles in human melanoma cells. The conjugates and nanoparticles of oligochitosan-folate, oligochitosan-carboxymethyl-5-fluorouracil, and oligochitosan-folate-carboxymethyl-5-fluorouracil were synthesized by carbodiimide chemistry and prepared by nanospray drying technique respectively. The cellular internalization profiles of oligochitosan-folate nanoparticles against the human malignant melanoma cell line (SKMEL-28) were evaluated using confocal scanning electron microscopy technique through fluorescence labelling and endocytic inhibition, as a function of nanoparticulate folate content, size, polydispersity index, zeta potential, shape, surface roughness and folate population density. The cytotoxicity and cell cycle arrest characteristics of oligochitosan-folate-carboxymethyl-5-fluorouracil nanoparticles, prepared with an optimal folate content that promoted cellular internalization, were evaluated against the oligochitosan-folate and oligochitosan-carboxymethyl-5-fluorouracil conjugate nanoparticles. The oligochitosan-folate conjugate nanoparticles were endocytosed by melanoma cells via caveolae- and lipid raft-mediated endocytic pathways following them binding to the cell surface folate receptor. Nanoparticles that were larger and with higher folic acid contents and zeta potentials exhibited a higher degree of cellular internalization. Excessive conjugation of nanoparticles with folate resulted in a high nanoparticulate density of folate which hindered nanoparticles-cell interaction via folate receptor binding and reduced cellular internalization of nanoparticles. Conjugating oligochitosan with 20 %w/w folate was favorable for cellular uptake as supported by in silico models. Conjugating of oligochitosan nanoparticles with carboxymethyl-5-fluorouracil and 20 %w/w of folate promoted nanoparticles-folate receptor binding, cellular internalization and cancer cell death via cell cycle arrest at S phase at a lower drug dose than oligochitosan-carboxymethyl-5-fluorouracil conjugate nanoparticles and neat carboxymethyl-5-fluorouracil.
Ensuring adherence to chemotherapy is important to prevent disease progression, prolong survival and sustain good quality of life. Capecitabine is a complex chemotherapeutic agent with many side effects that might affect patient adherence to treatment. This cross sectional study aimed to determine adherence to capecitabine and its contributing factors among cancer outpatients in Malaysia. One hundred and thirteen patients on single regime capecitabine were recruited from Hospital Sultan Ismail and Hospital Kuala Lumpur from October 2013 to March 2014. Adherence was determined based on adherence score using validated Medication Compliance Questionnaire. Patient socio-demographics, disease, and treatment characteristics were obtained from medical records. Satisfaction score was measured using the validated Patient Satisfaction with Healthcare questionnaire. The mean adherence score was 96.1% (standard deviation: 3.29%). The significant contributing factors of adherence to capecitabine were Malay ethnicity [β=1.3; 95% confidence interval (CI): 0.21, 2.43; p value=0.020], being female [β=1.8; 95%CI: 0.61, 2.99; p value=0.003]), satisfaction score [β=0.08; 95%CI: 0.06, 1.46; p value=0.035], presence of nausea or vomiting [β=2.3; 95%CI: 1.12, 3.48; p value <0.001] and other side effects [β=1.45; 95%CI: 0.24, 2.65; p value=0.019]. Adherence to capecitabine was generally high in our local population. Attention should be given to non-Malay males and patients having nausea, vomiting or other side effects. Sufficient information, proactive assessment and appropriate management of side effects would improve patient satisfaction and thus create motivation to adhere to treatment plans.
A hospital based cross-sectional retrospective study was conducted to determine the frequency of hand foot syndrome (HFS) with Capecitabine as a single agent and in combination with Oxaliplatin. The study included 43 consecutive cases of colorectal carcinoma and conducted from June till December 2008. Patients on palliative care were excluded. SPSS was used for the application of chi-square test, by keeping the level of significance as p < 0.05. Fifteen (34.9%) patients developed HFS, 10 in the single-agent and 5 in the combination group. No significant association of HFS with either regimens was noted (p=0.876).
Recent observational studies showed that post-operative aspirin use reduces cancer relapse and death in the earliest stages of colorectal cancer. We sought to evaluate the cost-effectiveness of aspirin as an adjuvant therapy in Stage I and II colorectal cancer patients aged 65 years and older.
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.
Follow-up of colorectal carcinoma after therapy is based on symptoms, tumor markers, and imaging studies. Clinicians sometimes face diagnostic dilemmas because of unusual presentations on the imaging modalities coupled with rising serum markers. We report a case of colorectal carcinoma that presented with gastrointestinal symptoms 14 months after completion of treatment. Investigations showed rise in carcinoembryonic antigen (CEA). Suspecting disease recurrence, complete radioimaging workup was performed; the only abnormality detected was a smooth, hypodense area in the posterior third of the spleen on contrast-enhanced computed tomography abdomen. In view of the previous diagnosis of carcinoma colon, the symptoms reported by the patient, the elevated CEA, and the atypical CECT appearance, a diagnosis of splenic metastasis was made. The patient was subjected to splenectomy as a curative treatment. However, the histopathological report revealed it to be a splenic infarct. The present case reemphasizes the limitations of radiological studies in the follow-up of carcinoma colon.
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.