Behaviour of polysulfone ultrafiltration membrane for dyes removal.

Although ultrafiltration membranes have been used for the separation of macromolecules and colloids from solutions, this process has a limited application in the removal of dyes present in coloured discharges of textile industry, as these typically have much lower molecular weight than the molecular cut-off of the membranes (MWCO). In the present work, we have evaluated the behaviour of a polysulfone ultrafiltration membrane in the removal of different dyes from aqueous solutions (Congo red, methyl green and amaranth). Different variables (tangential flow rate, concentration of dye and pH of the feed) were studied to determine their influence on the separation processes (permeate flux and rejection coefficient). The results show that Congo red is easily removed with a GR60PP membrane (MWCO = 25 kDa), whereas methyl green and amaranth show rejection coefficient values of approximately 25.78% and 13.85%, respectively, at neutral pH. Also, an interesting effect is observed for the rejection coefficient for methyl green at different pH values. In addition, several treatments were performed to the membrane so as to modify its surface, trying to improve the values obtained for permeate flux and rejection rate.

Dynamic soluble changes in sVEGFR1, HGF, and VEGF promote chemotherapy and bevacizumab resistance: A prospective translational study in the BECOX (GEMCAD 09-01) trial.

Despite initial responsiveness, acquired resistance to both bevacizumab and chemotherapy in metastatic colorectal cancer is universal. We have recently published that in vitro, chronically oxaliplatin resistance upregulates soluble vascular endothelial growth factor receptor 1, downregulates vascular endothelial growth factor, and also promotes c-MET, b-catenin/transcription factor 4, and AKT activation. We tested whether variation in three serum biomarkers such as the natural c-MET ligand (hepatocyte growth factor), soluble vascular endothelial growth factor receptor 1, and vascular endothelial growth factor-A was associated with efficacy in metastatic colorectal cancer patients treated in the prospective BECOX study. Serum levels of vascular endothelial growth factor-A165, soluble vascular endothelial growth factor receptor 1, and hepatocyte growth factor were assessed by enzyme-linked immunosorbent assay method basally and every 3 cycles (at the time of computed tomography evaluation) in a preplanned translational study in the first-line BECOX trial in metastatic colorectal cancer patients treated with CAPOX plus bevacizumab. Response was evaluated by routine contrast-enhanced computed tomography by RECIST 1.1 by investigator assessment and by three blinded independent radiologists. Ratios between soluble vascular endothelial growth factor receptor 1/vascular endothelial growth factor-A and hepatocyte growth factor/vascular endothelial growth factor-A were established and variations through time were related to RECIST 1.1 by investigator assessment and independent radiologist. The BECOX trial included 68 patients, and 27 patients were analyzed in the translational trial. A total of 80 RECIST 1.1 evaluations were done by investigator assessment and 56 by independent radiologist. We found that a 3.22-fold increase in soluble vascular endothelial growth factor receptor 1/vascular endothelial growth factor-A by investigator assessment and a 3.06-fold increase in soluble vascular endothelial growth factor receptor 1/vascular endothelial growth factor-A by independent radiologist from previous determination were associated with responses compared with 1.38-fold increase by investigator assessment and 1.59 by independent radiologist in non-responders (p = 0.0009 and p = 0.03, respectively). Responders had a 3.36-fold increase in hepatocyte growth factor/vascular endothelial growth factor-A from previous determination by investigator assessment and 3.66-fold increase in hepatocyte growth factor/vascular endothelial growth factor-A by independent radiologist compared with 1.43-fold increase by investigator assessment and 1.53 by independent radiologist for non-responders (p = 0.002 and 0.003, respectively). In conclusion, a decrease in vascular endothelial growth factor-A and an increase in soluble vascular endothelial growth factor receptor 1 during chemotherapy and bevacizumab exposure can contribute to both chemotherapy (due to c-MET/b-catenin activation) and bevacizumab (due to low vascular endothelial growth factor requirements) resistance. Because hepatocyte growth factor levels decrease also during acquired resistance, alternative strategies to hepatocyte growth factor-ligand inhibition should be investigated.

Chemoradiation, surgery and adjuvant chemotherapy versus induction chemotherapy followed by chemoradiation and surgery: long-term results of the Spanish GCR-3 phase II randomized trial†.

BACKGROUND: The primary results of our phase II randomized trial suggested that compared with conventional preoperative chemoradiation (CRT), the addition of chemotherapy (CT) before CRT and surgery allows most patients receive their planned treatment with a better toxicity profile without compromising the pathological complete response and complete resection rates. We now report the 5-year outcomes. PATIENTS AND METHODS: Patients with distal or middle third, T3-T4 and/or N+ rectal adenocarcinoma selected by magnetic resonance imaging, were randomly assigned to arm A-preoperative CRT followed by surgery and four cycles of postoperative adjuvant capecitabine and oxaliplatin (CAPOX)-or arm B-four cycles of CAPOX followed by CRT and surgery. The following 5-year actuarial outcomes were assessed: the cumulative incidence of local relapse (LR) and distant metastases (DM), disease-free (DFS) and overall survival (OS). RESULTS: A total of 108 eligible patients were randomly assigned to arm A (n = 52) or arm B (n = 56). With a median follow-up of 69.5 months, 5-year DFS was 64% in arm A and 62% in arm B (P = 0.85) and 5-year OS was 78% in arm A and 75% in arm B (P = 0.64). The 5-year cumulative incidence of LR was 2% and 5% (P = 0.61) and 5-year cumulative incidence of DM was 21% and 23%; (P = 0.79) in arms A and B, respectively. CONCLUSION: Both treatment approaches yield similar outcomes. Given the lower acute toxicity and improved compliance with induction CT compared with adjuvant CT, integrating effective systemic therapy before CRT and surgery is a promising strategy and should be examined in phase III trials.

Pazopanib in pretreated advanced neuroendocrine tumors: a phase II, open-label trial of the Spanish Task Force Group for Neuroendocrine Tumors (GETNE).

BACKGROUND: The management of advanced neuroendocrine tumors (NETs) has recently changed. We assessed the activity of pazopanib after failure of other systemic treatments in advanced NETs. METHODS: This was a multicenter, open-label, phase II study evaluating pazopanib as a single agent in advanced NETs (PAZONET study). The clinical benefit rate (CBR) at 6 months was the primary end point. Translational correlation of radiological response and progression-free survival (PFS) with circulating and tissue biomarkers was also evaluated. RESULTS: A total of 44 patients were enrolled. Twenty-five patients (59.5%) were progression-free at 6 months (4 partial responses, 21 stable diseases) with a median PFS of 9.5 months [95% confidence interval (CI) 4.8-14.1]. The CBR varied according to prior therapy received, with 73%, 60% and 25% in patients treated with prior multitarget inhibitors, prior mTOR inhibitors and both agents, respectively. A nonsignificant increase in PFS was observed in patients presenting lower baseline circulating tumor cell (CTC) counts (9.1 versus 5.8 months; P = 0.22) and in those with decreased levels of soluble-vascular endothelial growth factor receptor-2 (sVEGFR-2) (12.6 versus 9.1 months; P = 0.067). A trend toward reduced survival was documented in patients with VEGFR3 rs307821 and rs307826 missense polymorphisms [hazard ratio (HR): 12.3; 95% CI 1.09-139.2; P = 0.042 and HR: 6.9; 95% CI 0.96-49.9; P = 0.055, respectively]. CONCLUSIONS: Pazopanib showed clinical activity in patients with advanced NETs regardless of previous treatments. Additionally, CTCs, soluble-s VEFGR-2 and VEGFR3 gene polymorphisms constitute potential biomarkers for selecting patients for pazopanib (NCT01280201). CLINICAL TRIAL NUMBER: NCT01280201.

Role of circulating tumor cells as prognostic marker in resected stage III colorectal cancer.

BACKGROUND: The prognostic role of circulating tumor cells (CTC) in early colorectal cancer (CRC) has not been determined yet. We evaluated the potential prognostic value of CTC in stage III CRC patients. PATIENTS AND METHODS: Prospective multicenter study of 519 patients with stage III CRC recruited between January 2009 and June 2010. CTC were enumerated with the CellSearch System after primary tumor resection and before the start of adjuvant therapy. A total of 472 patients were included in the analysis. RESULTS: CTC ≥1, ≥2, ≥3 and ≥5 were detected in 166 (35%), 93 (20%), 57 (12%) and 34 (7%) patients, respectively. Median follow-up was 40 months. In the overall population, CTC ≥1 (disease-free survival (DFS): HR 0.97, P = 0.85; overall survival (OS): HR 1.03, P = 0.89), ≥2 (DFS: HR 1.07, P = 0.76; OS: HR 1.02, P = 0.95), ≥3 (DFS: HR 0.96, P = 0.87; OS: HR 0.74, P = 0.41) and ≥5 (DFS: HR 0.72, P = 0.39; OS: HR 0.48, P = 0.21) were not associated with worse DFS and OS. No clinicopathological characteristics were significantly associated with the presence of CTC. In patients with disease relapse, the proportion with CTC ≥1 was not significantly different between those with single versus multiple metastatic locations (37.9% versus 31.4%, P = 0.761). In the multivariate analysis, CTC ≥1 was not an independent prognostic factor for DFS (HR 0.97, P = 0.87) and OS (HR 0.96, P = 0.89). CONCLUSION: CTC detection was not associated with worse DFS and OS in patients with stage III CRC. Given the scarcity of CTC in these patients, it is likely that CTC determined by CellSearch system does not have a prognostic role in this setting. However, a longer follow-up is needed.

First-line bevacizumab and capecitabine-oxaliplatin in elderly patients with mCRC: GEMCAD phase II BECOX study.

BACKGROUND: Subgroup analyses of clinical studies suggest that bevacizumab plus XELOX is effective and tolerable in elderly patients with metastatic colorectal cancer (mCRC). The prospective BECOX study examined the efficacy and safety of bevacizumab plus XELOX, followed by bevacizumab plus capecitabine in elderly patients with mCRC. METHODS: Patients aged ⩾70 years with Eastern Cooperative Oncology Group performance status 0 out of 1 and confirmed mCRC were included. Patients received bevacizumab 7.5 mg kg(-1) and oxaliplatin 130 mg m(-2) on day 1, plus capecitabine 1000 mg m(-2) bid orally on days 1-14 every 21 days; oxaliplatin was discontinued after 6 cycles. The primary end point was time to progression (TTP). RESULTS: The intent-to-treat population comprised 68 patients (65% male, median age 76 years). Median TTP was 11.1 months; median overall survival was 20.4 months; overall response rate was 46%. Grade 3 or 4 adverse events included diarrhoea (18%) and asthenia (16%). Grade 3 or 4 adverse events of special interest for bevacizumab included deep-vein thrombosis (6%) and pulmonary embolism (4%). CONCLUSIONS: Bevacizumab plus XELOX was effective and well tolerated in elderly patients in the BECOX study. The adverse-event profile was similar to previous reports; no new safety concerns were identified. Fit elderly patients with mCRC should be considered for treatment with bevacizumab plus XELOX.

Determining factors of pulse oximetry accuracy: a literature review.

OBJECTIVE: Identify and reach consensus on the variables that affect the measurement of oxygen saturation using pulse oximetry. METHODS: We applied inclusion and exclusion criteria to select relevant studies in databases such as Ebsco and PubMed. The search strategies, carried out until December 2023, focused on publications that addressed the technology of pulse oximeters and variables that influence their accuracy. We assessed the risk of bias of the included studies and used standardized methods for synthesis of results. RESULTS: 23 studies were included. The synthesis of the results highlighted that equipment with tetrapolar technology showed greater precision in oxygen saturation measurements. Increased skin pigmentation, hemoglobinopathies and high skin temperatures can lead to an overestimation of SpO2, while factors such as low perfusion, cold skin temperature, nail polish or tattoos, hypoxemia, anemia and high altitude training, they may underestimate it. On the other hand, motion artifacts, light pollution, frequency >150 beats per minute, electromagnetic interference and location of the sensor can cause distortion of the photoplethymography signal. CONCLUSIONS: The synthesis of the results highlighted that skin pigmentation and light interference can lead to an overestimation of SpO2, while other factors such as low perfusion and altitude tend to underestimate it. The studies presented variability and heterogeneity in their designs, evidencing limitations in the consistency and precision of the evidence. Despite these limitations, the results underscore the importance of considering multiple variables when interpreting pulse oximetry measurements to ensure their reliability. The findings have significant implications for clinical practice and future research.

[Agreement between verbal numerical scale and visual analog scale assessments in monitoring acute postoperative pain]. / Concordancia entre la escala verbal numérica y la escala visual analógica en el seguimiento del dolor agudo postoperatorlo.

OBJECTIVE: To determine the agreement between verbal numerical and visual analog scale assessments of acute postoperative pain on 3 consecutive days. METHODS: Pain data were recorded for 2 months for sequentially enrolled patients receiving parenteral opioids or neuraxial blocks for analgesia after major surgery in a tertiary level hospital. Each patient was asked to assess pain on the visual analog and verbal numerical scales every 24 hours for 3 consecutive days. Agreement was estimated by the intraclass correlation coefficient and the Spearman correlation coefficient. The results were analyzed in 2 age strata: age 65 years or younger and older than 65 years. RESULTS: Data for 159 patients (105 < or =65 years; 54 >65 years) were analyzed. The visual analog scale could not be used with 12 patients; all patients were able to assess pain on the verbal numerical scale. The intraclass correlation coefficient was > 0.70 for all 3 days; the highest coefficients were for patients over 65 years of age. CONCLUSIONS: Agreement between pain assessments on the visual analog and verbal numerical scales can be considered good or very good on all 3 days, with stronger agreement when the scales are used in patients over the age of 65 years. Cooperation was better for the numerical scale than for the visual analog scale. Scores on the verbal numerical scale were consistently higher than scores on the visual analog scale.

Capecitabine and bevacizumab as first-line treatment in elderly patients with metastatic colorectal cancer.

BACKGROUND: The efficacy and safety of capecitabine and bevacizumab in elderly patients with metastatic colorectal cancer (mCRC) considered unsuitable for receiving first-line chemotherapy with an irinotecan or oxaliplatin-based combination were assessed in a phase II, open, multicentre, uncontrolled study. METHODS: Treatment consisted of capecitabine 1250 mg m(-2) (or 950 mg m(-2) for patients with a creatinine clearance of 30-50 ml min(-1)) twice daily on days 1-14 and bevacizumab (7.5 mg kg(-1)) on day 1 every 3 weeks. RESULTS: A total of 59 patients aged >or=70 years with mCRC were enrolled. In an intention-to-treat analysis, the overall response rate was 34%, with 71% of patients achieving disease control. Median progression-free survival and overall survival were 10.8 months and 18 months, respectively. In all, 32 patients (54%) had grade 3/4 adverse events (AEs), the most common being hand-foot syndrome (19%), diarrhoea (9%) and deep venous thrombosis (7%). Four patients died because of treatment-related AEs. A relationship was detected between creatinine clearance

Painapple®. Validation and evaluation of an electronic application for the management of acute pain in pediatric patients. / PainAPPle. Validación y evaluación de una aplicación electrónica para el manejo del dolor agudo en pacientes pediátricos.

INTRODUCTION: The digital version of the assessment scales recommended for the pediatric patient could contribute to its improvement and to implement the quality indicators described for the management of acute pain. MATERIAL AND METHODS: Psychometric validation (validity and reliability) of pain assessment and treatment side effects scales incorporated in the electronic application PainAPPle. For this, both formats (paper and electronic) of all the scales were applied in two measurements with 30minutes of difference in 44 patients from 4 to 18years of the Acute Pain Unit in the immediate postoperative period. In addition, the data collected by PainAPPle was evaluated by retrospectively applying the quality indicators described for the management of acute postoperative pain. RESULTS: Reliability was studied analyzing the high correlation (Spearman greater than 0.5, P<.001) that we obtained for the values of each scale in two moments with 30minutes of difference, in the same patients. For validity, the high correlation (Spearman greater than 0.5, P<.001) between the values of the paper scales (gold rule) and PainAPPle at both minute 0 and 30 was analyzed. Concordance obtained taking into account the cut-off point of the scales that would force a treatment were also statistically significant (P<.005). CONCLUSIONS: PainAPPle is a validated instrument for the management of acute pain in pediatric patients. The collected data allow to apply the quality indicators described for the management of acute postoperative pain.

Anesthetic management during anterior mediastinal mass resection in a pediatric patient. A case report. / Manejo anestésico para la resección de masa mediastínica anterior (MMA) en paciente pediátrico. Descripción de un caso clínico.

Complications induced by general anesthesia (GA) and neuromuscular relaxation (NMR) in anterior mediastinal mass (AMM) resection can be serious, especially when there are signs of compression of the airway or large vessels (dyspnea, orthopnea, etc.) (1). It is preferable to perform the procedure in spontaneous ventilation to avoid respiratory or cardiovascular collapse due to the supine position or to loss of negative intrathoracic pressure with GA and NMR. If the supine position and NMR are unavoidable, procedures should be performed in a step-wise manner, and rescue strategies should be prepared (rescue position, bronchoscope, sternotomy). Correct preoperative evaluation, adequate planning, and a multidisciplinary approach will ensure patient safety. We present the case of a child with a history of severe orthopnea and a diagnosis of AMM and lymphoblastic lymphoma (respiratory arrest and cardiovascular collapse during sedation for lumbar puncture and bone marrow biopsy) that did not respond to medical treatment and required resection surgery under GA with NMR.

[Assessment of training in the control of acute postoperative pain based on analysis of pretraining and posttraining measures]. / Evaluación de una intervención educativa en el control del dolor agudo postoperatorio: estudio antes-después.

OBJECTIVE: To assess the efficacy of an acute pain unit's training on postoperative pain control for staff of trauma-orthopedic and general surgery departments. METHODS: Prospective pretest-posttest study in a tertiary care hospital. Physicians and nurses in the 2 surgical departments were given training sessions that included discussion with visual support and presentation of the acute pain unit's treatment protocols. Outcome measures used were visual analog scale (VAS) scores, patient satisfaction scores, number of days of treatment in accordance with the acute pain unit's protocol, and reasons for stopping treatment. Data for the year before and after the training program were analyzed. RESULTS: Data for 854 patients before training and 971 after training were analyzed. There were no differences between surgical specialties in the mean number of days of treatment. Nor did patient satisfaction scores differ (trauma-orthopedic surgery, -0.379, P = .352; general surgery, -0.927, P = .177). VAS score differences of less than 0.5 points were found in active and resting pain from the second and third days, respectively. There was improvement in both specialties in terms of the number of patients who completed the treatment initially prescribed by the acute pain unit. CONCLUSIONS: The staff training in postoperative pain control did not affect patient satisfaction, though a small improvement in active and resting VAS scores was noted. The training did have an effect on significantly improving overall compliance with the acute pain unit's treatment protocols.

Color tunable pressure sensors based on polymer nanostructured membranes for optofluidic applications.

We demonstrate an integrated optical pressure sensing platform for multiplexed optofluidics applications. The sensing platform consists in an array of elastomeric on-side nanostructured membranes -effectively 2D photonic crystal- which present colour shifts in response to mechanical stress that alter their nanostructure characteristical dimensions, pitch or orientation. The photonic membranes are prepared by a simple and cost-effective method based on the infiltration of a 2D colloidal photonic crystal (CPC) with PDMS and their integration with a microfluidic system. We explore the changes in the white light diffraction produced by the nanostructured membranes when varying the pneumatic pressure in the microfluidics channels as a way to achieve a power-free array of pressure sensors that change their reflective colour depending on the bending produced on each sensor. The structural characterization of these membranes was performed by SEM, while the optical properties and the pressure-colour relation were evaluated via UV-Vis reflection spectrometry. Maximum sensitivities of 0.17 kPa-1 is obtained when measuring at Littrow configuration (θin = -θout), and close to the border of the membranes. The reflected colour change with pressure is as well monitorized by using a smartphone camera.

Phase I/II study of gefitinib and capecitabine in patients with colorectal cancer.

OBJECTIVE: The objectives of this phase I/II study were to determine the maximum tolerated dose (MTD), characterise the principal toxicities in the phase I part and assess the efficacy in the phase II part of gefitinib, an oral selective inhibitor of the epidermal growth factor receptor, in combination with capecitabine in patients with advanced colorectal cancer (CRC). METHODS AND PATIENTS: Patients with advanced CRC were treated with gefitinib administered daily for 21 days and capecitabine administered twice daily for 14 days of a 21-day cycle. The dose levels of gefitinib (mg) and capecitabine (mg/m(2) bid) assessed were 250/1000 and 250/ 1250. An expanded cohort was enrolled at the MTD to better characterise toxicity and efficacy. A total of 32 previously treated patients were accrued. In the phase I part 10 subjects were treated, with one dose-limiting toxicity. Overall 26 patients were treated at the MTD of the combination, which was gefitinib 250 mg/day and capecitabine 1250 mg/m(2) twice daily. RESULTS: The most frequent treatment-related adverse events included asthenia, diarrhoea, nausea, rash and anorexia. The incidence profile was very similar in phases I and II. No objective responses were documented but 53% of the patients achieved stable disease as best response to therapy. CONCLUSIONS: Capecitabine 1250 mg/m(2) twice daily 14 of 21 days and gefitinib at 250 mg/day can be safely administered in combination. The combination is relatively well tolerated. There were no objective responses, although an interesting stabilisation rate was documented, in previously treated advanced CRC patients.

[Comparison of intrathecal fentanyl and bupivacaine in combined spinal-epidural obstetric analgesia]. / Comparación del efecto de fentanilo frente a bupivacaína intratecal en una técnica anestésica combinada durante la analgesia obstétrica.

OBJECTIVES: To compare intrathecal injection of the opioid fentanyl to injection of bupivacaine, in terms of their effect of labour in the context within the combined spinal-epidural analgesia. METHODS: Prospective single-blind trial in primiparas randomized to 2 groups for sedation with 25 microg of fentanyl or 2.5 mg of bupivacaine, followed in both cases by epidural infusion of ropivacaine. We measured time from puncture to delivery of the neonate, rescue analgesia, pain assessed on a visual analog scale (VAS), motor block, side effects, sensory level, Apgar score, and maternal satisfaction. RESULTS: Sixty-four women were studied. The mean time elapsed between puncture and birth was 168.59 minutes (95% confidence interval [CI], 134.16 to 203.03 minutes) in the bupivacaine group and 189.13 minutes (95% CI, 151.93 to 226.32 minutes) in the fentanyl group. The mean difference was -20.53 minutes (95% CI, -70.21 to 29.15 minutes). Survival analysis applied to duration of labor, using type of delivery as the final outcome, also failed to show a significant between-group difference (chi2=0.59, P=.447). No significant differences in use of rescue analgesia, VAS scores, or motor block were observed. The incidence of pruritus in the fentanyl group was 34.37%, but there were no differences in maternal satisfaction. CONCLUSIONS: Our findings do not support the use of intradural fentanyl with the aim of shortening labor. Fentanyl leads to more pruritus, although this side effect does not affect maternal satisfaction.

Whole-body computed tomography as a factor associated with lower mortality in severe geriatric trauma with thoracic-abdominal-pelvic injury. / La tomografía computarizada corporal como factor asociado a menor mortalidad en el traumatismo geriátrico grave con afectación toracoabdominopélvica.

OBJECTIVE: To determine the relationship between the use of whole-body computed tomography (WB-CT) and hospital mortality in elderly patients with thoracic-abdominal-pelvic injury requiring admission to an intensive care unit. PATIENTS AND METHOD: An observational, descriptive and retrospective study was conducted on 140 patients aged 65 years and older admitted to the intensive care unit after a thoracic-abdominal-pelvic injury. Two groups were established, depending on whether a WB-CT was performed as a routine part of the study or the diagnosis was established by conventional radiography or ultrasound. A comparative analysis was performed on both groups, as well as an analysis of mortality through logistic regression. RESULTS: The mean age of the patients was 75.16±8.89 years. The mean score on the APACHE II scale was 16.25±8.4 points, and on the Injury Severity Score scale, 22.38±15.45 points. WB-CT was performed on 102 patients (72.9%). In these patients, there was a lower mortality rate (15.7 vs. 52.6%, P˂.001), a lower need for mechanical ventilation (47.1 vs. 65.8%, P=.049), and a lower score on the APACHE II scale (14.75±7.19 vs. 20.26±10.06 points, P=.003). The multivariate analysis showed a lower mortality in the patients in whom WB-CT was performed, with an OR of 0.21 (95% CI 0.07-0.68; (P=.010), after adjusting for the APACHE II and ISS scores. CONCLUSIONS: Performing a WB-CT scan as part of the trauma study could improve the management of elderly patients with thoracic-abdominal-pelvic involvement admitted to the intensive care unit.

Phase II study with the combination of gemcitabine and DTIC in patients with advanced soft tissue sarcomas.

PURPOSE: Based on the promising results of a Phase I study with a combination of gemcitabine and DTIC performed in advanced soft tissue sarcoma (ASTS) patients, and due to the limited efficacy of second or third line therapies in those patients, we designed a Phase II study to determine the activity of this new regimen. METHODS: Patients with ASTS, measurable disease, pretreated with chemotherapy, received gemcitabine 1,800 mg/m2 infused over 180 min followed by DTIC 500 mg/m2 (one cycle), every 2 weeks. The pharmacokinetics (PK) of gemcitabine and 2',2'-difluorodeoxyuridine (dFdU), and the accumulation of gemcitabine triphosphate (dFdCTP) by peripheral blood mononuclear cells were studied. The influence of the sequence of administration on those parameters was examined to exclude potential drug interactions. RESULTS: Twenty-six patients received a total of 158 cycles (mean four cycles, range 1-18). Grade 3-4 anemia (23% of patients), granulocytopenia (46%) or thrombocytopenia (12%), and grade 3 increase in AST (18%), ALT (21%), or gamma-glutamyl-transferase (9%) were noted. Response rate in 23 patients was 4% (95% CI: 0-24%), and in 8 of 11 patients stable disease lasted > 6 months. Progression-free rate (PFR) at 3 and 6 months was, respectively, 48 and 28%, and median overall survival 37 weeks. Pooled data from the Phase I and Phase II studies showed clinical benefit in patients with leiomyosarcomas (LMS) (57%) and malignant fibrous histiocytomas (MFH) (33%). The sequence of administration did not influence PK of gemcitabine or dFdU. There was a trend (P = 0.11) toward a lower accumulation of dFdCTP when DTIC preceded gemcitabine. CONCLUSIONS: Although the remission rate was low, PFR figures indicate that this regimen has activity in patients with ASTS. It should be compared with DTIC, or other gemcitabine-containing combinations, in patients with LMS or MFH, to determine whether this combination offers advantages in PFR or in overall activity.