RESUMEN
BACKGROUND: Tumor-infiltrating lymphocytes (TILs) are a robust and independent prognostic variable in localized colon cancer. Given reported differences in molecular features and prognosis of right- versus left-sided tumors, we examined the association of TIL densities with patient survival by primary tumor sidedness in stage III cancers, including clinical low- (T1-3, N1) and high-risk (T4 and/or N2) groups. PATIENTS AND METHODS: In a phase III trial of FOLFOX-based adjuvant chemotherapy, TIL densities were analyzed and dichotomized in colon carcinomas (N = 1532) based on a previously determined cut point optimized for disease-free survival (DFS). Right-sided tumors were defined as proximal to the splenic flexure. Associations of TILs and sidedness with 5-year DFS were examined using Kaplan-Meier methodology along with multivariable modeling and relative contribution analysis by Cox regression. RESULTS: Lower TIL densities were found in left- versus right-sided tumors (P < 0.0001). The association of TIL densities with DFS differed significantly by tumor sidedness (Pinteraction = 0.045). Overall, patient tumors with low (versus high) TILs had significantly poorer DFS in right-sided (hazard ratio 2.02, 95% confidence interval 1.45-2.82; Padj < 0.0001), but not left-sided tumors (Padj = 0.1731). Among clinical low-risk patients, low (versus high) TILs were adversely prognostic only in right-sided tumors (Padj = 0.0058). Among high-risk patients, low TILs were prognostic independent of sidedness (Padj < 0.025). The relative contribution of TILs to DFS was substantially greater in right- versus left-sided tumors (24% versus 1.5%). In high-risk tumors, TILs had the highest relative contribution to DFS (42%) of all variables. In low-risk tumors, the contribution of TILs (16%) to DFS was second to KRAS. CONCLUSIONS: The association of TIL densities with patient survival differed by primary tumor sidedness and clinical risk group, suggesting that TILs should be interpreted in this context among stage III colon cancers. GOV IDENTIFIER: NCT00079274; https://clinicaltrials.gov/ct2/show/NCT00079274.
Asunto(s)
Neoplasias del Colon , Linfocitos Infiltrantes de Tumor , Humanos , Quimioterapia Adyuvante , Neoplasias del Colon/tratamiento farmacológico , Neoplasias del Colon/genética , Supervivencia sin Enfermedad , Linfocitos Infiltrantes de Tumor/patología , Estadificación de Neoplasias , PronósticoRESUMEN
BACKGROUND: Tumor-infiltrating lymphocytes (TILs), tumor budding, and micropapillary architecture may influence tumor growth and metastatic potential, thereby enhancing prognostic stratification. We analyzed these features and their relative contribution to overall outcome and in low (T1-3 N1) and high (T4 and/or N2) risk groups that are used to inform the duration of adjuvant chemotherapy in patients with resected stage III colon cancers. PATIENTS AND METHODS: Among 1532 patients treated in a phase III adjuvant trial of FOLFOX-based therapy, intraepithelial TIL densities, tumor budding, and micropapillary features were analyzed and quantified in routine histopathological sections with light microscopy. Optimal cut-points were determined in association with disease-free survival (DFS) in training and validation sets. Associations or relative contributions of individual features or combined variables with DFS were determined using multivariable Cox regression models. RESULTS: TILs, tumor budding, and micropapillary features were shown to differ significantly by T, N risk groups and by mismatch repair (MMR) status. Low TILs, high budding, and their combined variable [hazard ratio = 2.07 (95% CI, 1.50% to 2.88%); Padj < 0.0001], but not micropapillary features, were each significantly associated with poorer DFS in a training data set and confirmed in a validation set. TILs were prognostic in proficient mismatch repair (pMMR) and deficient mismatch repair (dMMR) tumors; budding was prognostic only in pMMR tumors. The percentage relative contribution of budding/TILs to DFS was second only to nodal status overall, was second (24.4%) after KRAS in low-risk patients, and was the most important contributor (45.4%) in high-risk patients. CONCLUSIONS: TIL density and tumor budding were each validated as significant prognostic variables and their combined variable provided robust prognostic stratification by T, N risk groups, being the strongest predictor of DFS among high-risk stage III patients. CLINICALTRIALS. GOV IDENTIFIER: NCT00079274.
Asunto(s)
Neoplasias del Colon , Linfocitos Infiltrantes de Tumor , Microambiente Tumoral , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Quimioterapia Adyuvante , Neoplasias del Colon/tratamiento farmacológico , Neoplasias del Colon/patología , Reparación de la Incompatibilidad de ADN , Supervivencia sin Enfermedad , Humanos , Linfocitos Infiltrantes de Tumor/patología , Estadificación de Neoplasias , PronósticoRESUMEN
BACKGROUND: Carboplatin (C) and paclitaxel (P) are standard treatments for carcinoma of unknown primary (CUP). Everolimus, an mTOR inhibitor, exhibits activity in diverse cancer types. We did a phase II trial combining everolimus with CP for CUP. We also evaluated whether a gene expression profiling (GEP) test that predicts tissue of origin (TOO) could identify responsive patients. PATIENTS AND METHODS: A tumor biopsy was required for central confirmation of CUP and GEP. Patients with metastatic, untreated CUP received everolimus (30 mg weekly) with P (200 mg/m(2)) and C (area under the curve 6) every 3 weeks. The primary end point was response rate (RR), with 22% needed for success. The GEP test categorized patients into two groups: those having a TOO where CP is versus is not considered standard therapy. RESULTS: Of 45 assessable patients, the RR was 36% (95% confidence interval 22% to 51%), which met criteria for success. Grade ≥3 toxicities were predominantly hematologic (80%). Adequate tissue for GEP was available in 38 patients and predicted 10 different TOOs. Patients with a TOO where platinum/taxane is a standard (n = 19) tended to have higher RR (53% versus 26%) and significantly longer PFS (6.4 versus 3.5 months) and OS (17.8 versus 8.3 months, P = 0.005), compared with patients (n = 19) with a TOO where platinum/taxane is not standard. CONCLUSIONS: Everolimus combined with CP demonstrated promising antitumor activity and an acceptable side-effect profile. A tumor biomarker identifying TOO may be useful to select CUP patients for specific antitumor regimens. CLINICALTRIALSGOV: NCT00936702.
Asunto(s)
Antineoplásicos/uso terapéutico , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Carboplatino/uso terapéutico , Everolimus/uso terapéutico , Neoplasias Primarias Desconocidas/tratamiento farmacológico , Neoplasias Primarias Desconocidas/genética , Paclitaxel/uso terapéutico , Adulto , Anciano , Supervivencia sin Enfermedad , Femenino , Perfilación de la Expresión Génica , Humanos , Masculino , Persona de Mediana Edad , Neoplasias Primarias Desconocidas/patología , Estudios Prospectivos , Resultado del TratamientoRESUMEN
BACKGROUND: This study investigated the activity of MK-2206, an AKT inhibitor, in metastatic or recurrent nasopharyngeal carcinoma (NPC). METHOD: Oral MK-2206 at a dose of 200 mg was administered on days 1, 8, 15 and 22 of a 28-day cycle until progression. Plasma EBV DNA clearance during the first month of treatment was measured, and archived tumors were analyzed for the expression of AKT and PIK3CA mutation and PIK3CA amplification. The dual primary endpoint was objective response rate and 6-month progression-free survival (PFS) rate. RESULTS: 21 patients were enrolled and one patient achieved a partial response (5 %) and 11 had stable disease (52 %), with a median PFS of 3.5 months (95 % confidence interval, CI: 0.9-7.3). The 6-month PFS rate was 43 % (95 % CI: 22-66 %) and the median OS was 10 months (95 % CI: 5.9 months-not reached). Seven patients (33 %) experienced grade 3 toxicities which could be related to MK-2206. Macular-papular rash was the most common (n = 6), followed by hyperglycemia (n = 2) and fatigue (n = 1). In the 12 tumor samples analyzed, PIK3CA amplification was detected in one patient's primary NPC, who had SD lasting over 12 months. Patients with decreasing EBV DNA values over time were more likely to be alive and progression-free for at least 6 months than those without a decrease (p = 0.001). CONCLUSION: The study was terminated due to the limited activity observed in this heavily pre-treated group of patients. Further studies are needed to elucidate the optimal way of selecting patients for AKT inhibitors.
Asunto(s)
Antineoplásicos/uso terapéutico , Compuestos Heterocíclicos con 3 Anillos/uso terapéutico , Neoplasias Nasofaríngeas/tratamiento farmacológico , Recurrencia Local de Neoplasia/tratamiento farmacológico , Inhibidores de Proteínas Quinasas/uso terapéutico , Adulto , Anciano , Antineoplásicos/efectos adversos , Carcinoma , ADN Viral/sangre , Supervivencia sin Enfermedad , Femenino , Herpesvirus Humano 4/genética , Compuestos Heterocíclicos con 3 Anillos/efectos adversos , Humanos , Masculino , Persona de Mediana Edad , Carcinoma Nasofaríngeo , Neoplasias Nasofaríngeas/sangre , Neoplasias Nasofaríngeas/virología , Recurrencia Local de Neoplasia/sangre , Recurrencia Local de Neoplasia/virología , Inhibidores de Proteínas Quinasas/efectos adversos , Proteínas Proto-Oncogénicas c-akt/antagonistas & inhibidores , Resultado del TratamientoRESUMEN
BACKGROUND: This pooled analysis evaluated the outcomes of prophylactic cranial irradiation (PCI) in 739 small-cell lung cancer (SCLC patients with stable disease (SD) or better following chemotherapy ± thoracic radiation therapy (TRT) to examine the potential advantage of PCI in a wider spectrum of patients than generally participate in PCI trials. PATIENTS AND METHODS: Three hundred eighteen patients with extensive SCLC (ESCLC) and 421 patients with limited SCLC (LSCLC) participated in four phase II or III trials. Four hundred fifty-nine patients received PCI (30 Gy/15 or 25 Gy/10) and 280 did not. Survival and adverse events (AEs) were compared. RESULTS: PCI patients survived significantly longer than non-PCI patients {hazard ratio [HR] = 0.61 [95% confidence interval (CI): 0.52-0.72]; P < 0.0001}. The 1- and 3-year survival rates were 56% and 18% for PCI patients versus 32% and 5% for non-PCI patients. PCI was still significant after adjusting for age, performance status, gender, stage, complete response, and number of metastatic sites (HR = 0.82, P = 0.04). PCI patients had significantly more grade 3+ AEs (64%) compared with non-PCI patients (50%) (P = 0.0004). AEs associated with PCI included alopecia and lethargy. Dose fractionation could be compared only for LSCLC patients and 25 Gy/10 was associated with significantly better survival compared with 30 Gy/15 (HR = 0.67, P = 0.018). CONCLUSIONS: PCI was associated with a significant survival benefit for both ESCLC and LSCLC patients who had SD or a better response to chemotherapy ± TRT. Dose fractionation appears important. PCI was associated with an increase in overall and specific grade 3+ AE rates.
Asunto(s)
Irradiación Craneana , Neoplasias Pulmonares/radioterapia , Carcinoma Pulmonar de Células Pequeñas/radioterapia , Adulto , Anciano , Anciano de 80 o más Años , Supervivencia sin Enfermedad , Fraccionamiento de la Dosis de Radiación , Humanos , Neoplasias Pulmonares/tratamiento farmacológico , Neoplasias Pulmonares/mortalidad , Persona de Mediana Edad , Carcinoma Pulmonar de Células Pequeñas/tratamiento farmacológico , Carcinoma Pulmonar de Células Pequeñas/mortalidad , Tasa de Supervivencia , Resultado del TratamientoRESUMEN
BACKGROUND: Evidence suggests that epidermal growth factor receptor (EGFR)-activation status may better predict the clinical behaviour of colon cancers than does EGFR expression. However, the prognostic effect of phospho-EGFR in primary colon cancer remains undefined. METHODS: Phospho-EGFR (Tyr-1173) and EGFR expression were analysed by immunohistochemistry (IHC) in tissue microarrays of TNM stage II and III colon cancers from completed adjuvant therapy trials (n=388). Staining intensity was scored and correlated with clinicopathological variables, DNA mismatch repair (MMR) status, rates of cell proliferation (Ki-67), apoptosis (caspase-3), and patient survival. RESULTS: Phospho-EGFR expression was detected in 157 of 388 (40%) tumours, whereas EGFR was found in 214 of 361 (59%). Although phospho-EGFR was unrelated to clinicopathological variables, strong EGFR intensity was associated with higher tumour stage (P=0.03). Tumours overexpressing EGFR (P=0.0002) or phospho-EGFR (P=0.015) showed increased Ki-67, but not caspase-3 expression. Phospho-EGFR was not prognostic. EGFR intensity was associated with worse disease-free survival (DFS) (hazard ratio (HR): 1.21 (1.03, 1.41); P=0.019) and overall survival (OS) (HR: 1.19 (1.02, 1.39); P=0.028). Tumours expressing both EGFR and phospho-EGFR had similar survival as EGFR alone. Stage and lymph node number were prognostic for DFS and OS, and histological grade for OS. EGFR was an independent predictor of DFS (P=0.042) after adjustment for stage, histological grade, age, and MMR status. CONCLUSION: Phospho-EGFR and EGFR expression were associated with tumour cell hyperproliferation. Phospho-EGFR was not prognostic, whereas increased EGFR intensity was independently associated with poor DFS.
Asunto(s)
Adenocarcinoma/enzimología , Neoplasias del Colon/enzimología , Receptores ErbB/metabolismo , Proteínas de Neoplasias/metabolismo , Fosfotirosina/análisis , Procesamiento Proteico-Postraduccional , Adenocarcinoma/tratamiento farmacológico , Adenocarcinoma/mortalidad , Adenocarcinoma/patología , Adenocarcinoma/cirugía , Anciano , Apoptosis , División Celular , Quimioterapia Adyuvante , Neoplasias del Colon/tratamiento farmacológico , Neoplasias del Colon/mortalidad , Neoplasias del Colon/patología , Neoplasias del Colon/cirugía , Terapia Combinada , Reparación de la Incompatibilidad de ADN , Supervivencia sin Enfermedad , Activación Enzimática , Receptores ErbB/análisis , Femenino , Fluorouracilo/administración & dosificación , Estudios de Seguimiento , Genes erbB-1 , Humanos , Estimación de Kaplan-Meier , Masculino , Persona de Mediana Edad , Estudios Multicéntricos como Asunto , Proteínas de Neoplasias/análisis , Proteínas de Neoplasias/genética , Fosforilación , Pronóstico , Análisis por Matrices de Proteínas , Ensayos Clínicos Controlados Aleatorios como Asunto/estadística & datos numéricosRESUMEN
The dissolution rate of a drug into the biological environment can be enhanced by forming complexes with cyclodextrins and their derivatives. In this study, ibuprofen-methyl-beta-cyclodextrin complexes were prepared successfully by passing ibuprofen-laden CO(2) through a methyl-beta-cyclodextrin packed bed. The maximum drug loading obtained in this work was 10.8 wt.%, which was comparable to that of a 1:1 complex (13.6 wt.% of ibuprofen). The complex exhibited instantaneous dissolution profiles in water solution. The enhanced dissolution rate was attributed to the amorphous character and improved wettability of the product.
Asunto(s)
Antiinflamatorios no Esteroideos/química , Ibuprofeno/química , beta-Ciclodextrinas , Rastreo Diferencial de Calorimetría , Dióxido de Carbono/química , Cristalografía por Rayos X , Ciclodextrinas , Composición de Medicamentos , Excipientes , Cinética , Microscopía Electrónica de Rastreo , Presión , SolubilidadRESUMEN
PURPOSE: The synergic combination of oxaliplatin and capecitabine has demonstrated activity against various gastrointestinal cancers, including colon cancer. We therefore undertook this phase II study to test this first-line combination in patients with metastatic adenocarcinoma of the esophagus, gastroesophageal junction and gastric cardia. PATIENTS AND METHODS: Forty-three patients with histologic or cytologic confirmation of the above malignancy were recruited. The cohort had Eastern Cooperative Oncology Group performance statuses of 0, 1 and 2 in 47%, 51%, and 2%, respectively. Median age was 61 years (range 32-80). All had adequate organ function. Initially, patients were prescribed 130 mg/m2 intravenously on day 1 and capecitabine 1000 mg/m2 orally twice a day, on days 1-14 of a 21-day cycle. Four treatment-related deaths in the first 24 patients led to a reduction in capecitabine to 850 mg/m2 orally twice a day, days 1-14, for the remainder of the cohort. RESULTS: The tumor response rate was 35% [95% confidence intervals (CI) 23% to 50%]. All responses were partial; seven of 24 occurred before the capecitabine dose reduction, and eight of 19 after. Median time to tumor progression was 4 months (95% CI 3.1-4.6), and median survival 6.4 months (95% CI 4.6-10). To date, there have been 36 deaths. Four were treatment-related (one infection, two myocardial infarctions, one respiratory failure), and all occurred before the capecitabine dose reduction. Notable grade 4 events from the entire cohort included diarrhea (two patients), vomiting (three), dyspnea (one), thrombosis (two) and anorexia (two). Grade 3 events included nausea (12 patients), diarrhea (12), fatigue (10), abdominal pain (seven), vomiting (six), dyspnea (six), hypokalemia (six), dehydration (five), hypokalemia (five) and infection (four). CONCLUSIONS: Oxaliplatin and capecitabine in combination demonstrates activity in metastatic adenocarcinoma of the esophagus, gastroesophageal junction and gastric cardia. The lower dose (capecitabine 850 mg/m2 orally twice a day, days 1-14, and oxaliplatin 130 mg/m2 intravenously on day 1) yielded an acceptable toxicity profile and merits further study.
Asunto(s)
Adenocarcinoma/tratamiento farmacológico , Adenocarcinoma/secundario , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Cardias/efectos de los fármacos , Neoplasias Esofágicas/tratamiento farmacológico , Unión Esofagogástrica/efectos de los fármacos , Adulto , Anciano , Anciano de 80 o más Años , Capecitabina , Cardias/patología , Desoxicitidina/administración & dosificación , Desoxicitidina/análogos & derivados , Relación Dosis-Respuesta a Droga , Neoplasias Esofágicas/patología , Unión Esofagogástrica/patología , Femenino , Fluorouracilo/análogos & derivados , Humanos , Masculino , Persona de Mediana Edad , Compuestos Organoplatinos/administración & dosificación , Oxaliplatino , Resultado del TratamientoRESUMEN
BACKGROUND: PS-341 is a proteasome inhibitor with preclinical activity in pancreatic cancer tumor models and synergistic activity with gemcitabine. This randomized phase II study determined the tumor response rate (RR) for PS-341 alone and the 6-month survival and RR for the combination of gemcitabine and PS-341 in patients with metastatic pancreatic adenocarcinoma. PATIENTS AND METHODS: Patients were randomized to receive 3-week cycles of either arm A: PS-341 1.5 mg/m(2) i.v. bolus (over 3--5 s) on days 1, 4, 8 and 11 or arm B: PS-341 1.0 mg/m(2) (same as arm A otherwise) plus gemcitabine 1,000 mg/m(2) i.v. on days 1 and 8. Patients progressing on arm A were allowed to receive arm B treatment. RESULTS: Arm A: 42 evaluable patients were enrolled with a confirmed RR of 0% (95% CI 0% to 8%), median survival of 2.5 months (95% CI 2.0-3.3), and median time to progression (TTP) of 1.2 months (95% CI 1.1--1.3). Twelve of 43 evaluable patients (28%) experienced at least one grade 4+ AE. Arm B: 39 evaluable patients yielded a 6-month survival rate of 41% (16/39, 95% CI 29.8% to 67.0%), median survival of 4.8 months (95% CI 2.4--7.4), median TTP of 2.4 months (95% CI 1.5--3.1), and confirmed RR of 10% (4 partial responses/0 complete responses, 95% CI 3% to 24%). Eleven of 43 evaluable patients (26%) experienced at least one grade 4+ AE. One patient had grade 5 hypotension. CONCLUSION: The use of PS-341 alone or in combination with gemcitabine did not result in an overall survival and RR better than that expected for gemcitabine alone. Based on the lack of efficacy and the toxicity seen in our trial, there does not appear to be a role for PS-341 in pancreatic adenocarcinoma with either of the schedules used in this trial.
Asunto(s)
Adenocarcinoma/tratamiento farmacológico , Antineoplásicos/uso terapéutico , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Ácidos Borónicos/uso terapéutico , Neoplasias Pancreáticas/tratamiento farmacológico , Pirazinas/uso terapéutico , Adenocarcinoma/patología , Adulto , Anciano , Ácidos Borónicos/administración & dosificación , Bortezomib , Desoxicitidina/administración & dosificación , Desoxicitidina/análogos & derivados , Progresión de la Enfermedad , Femenino , Humanos , Infusiones Intravenosas , Inyecciones Intravenosas , Masculino , Persona de Mediana Edad , Metástasis de la Neoplasia , Neoplasias Pancreáticas/patología , Pirazinas/administración & dosificación , Análisis de Supervivencia , Resultado del Tratamiento , GemcitabinaRESUMEN
PURPOSE: To investigate the feasibility of using the Aerosol Solvent Extraction System (ASES) to generate microparticles of proteins suitable for aerosol delivery from aqueous-based solutions. METHODS: The ASES technique using high-pressure carbon dioxide modified with ethanol was utilised for the generation of microparticles of proteins (lysozyme, albumin, insulin and recombinant human deoxyribonuclease (rhDNase)) from aqueous solutions. Particle size, morphology, size distributions and powder aerosol performance were examined. The biochemical integrity of the processed proteins was assessed by testing the level of molecular aggregation using size exclusion chromatography and by bioassay technique for lysozyme. RESULTS: Proteins were precipitated as spherical particles ranging in size from 100 to 500 nm. The primary nano-sized particles agglomerated to form micron-sized particles during the precipitation process. The median size of the particles was a function of the operating conditions. In-vitro aerosol performance tests showed that the percent fine particle mass (< 5 microm) was approximately 65%, 40% and 20% for lysozyme, albumin and insulin, respectively. Negligible loss in the monomer content or biological activity was observed for lysozyme. Insulin exhibited slight aggregation and 93% of the monomer was retained after processing. Albumin was affected by processing and only 50-75% of the monomer was retained compared with 86% in the original material. However, rhDNase was substantially denatured during processing as shown by the significantly reduced monomer content. CONCLUSIONS: Micron-sized particles of lysozyme, albumin and insulin with satisfactory inhalation performance were successfully generated from aqueous solutions using the modified ASES technique. The biochemical integrity of the processed proteins was a function of the operating conditions and the nature of the individual protein.
Asunto(s)
Dióxido de Carbono/química , Proteínas/administración & dosificación , Administración por Inhalación , Aerosoles , Albúminas/administración & dosificación , Albúminas/química , Precipitación Química , Química Farmacéutica , Estabilidad de Medicamentos , Etanol/química , Insulina/administración & dosificación , Insulina/química , Muramidasa/administración & dosificación , Muramidasa/química , Nebulizadores y Vaporizadores , Tamaño de la Partícula , Presión , Proteínas/química , Solventes/químicaRESUMEN
The three most common methods of sterilization in use today are ethylene oxide exposure, gamma-irradiation, and steam sterilization. Each of these methods has serious limitations for the sterilization of some materials used in medicine, especially thermally and hydrolytically sensitive polymers by themselves and in combination with proteins. In this work, we demonstrate a potential new method of sterilization by using supercritical fluid carbon dioxide. Using this method we achieve complete inactivation of a wide variety of bacterial organisms at moderate temperatures and in the absence of organic solvents or irradiation. Sterilization is a function of both the proximity to the fluid's critical point and the chemical nature of the fluid itself. When biodegradable polymers poly(lactic-co-glycolic) acid and polylactic acid were included in the sterilization process, there was no effect on the inactivation efficiency, yet no physical or chemical damage to these thermally and hydrolytically labile materials was observed.
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Bacterias/crecimiento & desarrollo , Fenómenos Fisiológicos Bacterianos/efectos de los fármacos , Dióxido de Carbono/farmacología , Esterilización/métodos , Bacterias/efectos de los fármacos , Biodegradación Ambiental , Cinética , Ácido Láctico , Microesferas , Ácido Poliglicólico , Copolímero de Ácido Poliláctico-Ácido Poliglicólico , Polímeros , Espectroscopía Infrarroja por Transformada de Fourier , Esporas Bacterianas , Esterilización/instrumentaciónRESUMEN
Supercritical fluids are increasingly being used as a replacement for more conventional organic solvents in the extraction of biomolecules from a range of matrices. Supercritical fluid extraction of essential fatty acids from fish oils is discussed. Supercritical CO2 was used to fractionate two fatty acids, EPA and DHA from fish oil ethyl esters. EPA and DHA were obtained with a purity of 58% and 67% respectively from Sardine oil with an original composition of 17% and 12%.