Immuno-priming durvalumab with bevacizumab in HER2-negative advanced breast cancer: a pilot clinical trial.

BACKGROUND: Preclinical research suggests that the efficacy of immune checkpoint inhibitors in breast cancer can be enhanced by combining them with antiangiogenics, particularly in a sequential fashion. We sought to explore the efficacy and biomarkers of combining the anti-PD-L1 durvalumab plus the antiangiogenic bevacizumab after bevacizumab monotherapy for advanced HER2-negative breast cancer. METHODS: Patients had advanced HER2-negative disease that progressed while receiving single-agent bevacizumab maintenance as a part of a previous chemotherapy plus bevacizumab regimen. Treatment consisted of bi-weekly durvalumab plus bevacizumab (10 mg/kg each i.v.). Peripheral-blood mononuclear cells (PBMCs) were obtained before the first durvalumab dose and every 4 weeks and immunophenotyped by flow-cytometry. A fresh pre-durvalumab tumor biopsy was obtained; gene-expression studies and immunohistochemical staining to assess vascular normalization and characterize the immune infiltrate were conducted. Patients were classified as "non-progressors" if they had clinical benefit (SD/PR/CR) at 4 months. The co-primary endpoints were the changes in the percentage T cell subpopulations in PBMCs in progressors versus non-progressors, and PFS/OS time. RESULTS: Twenty-six patients were accrued. Median PFS and OS were 3.5 and 11 months; a trend for a longer OS was detected for the hormone-positive subset (19.8 versus 7.4 months in triple-negatives; P = 0.11). Clinical benefit rate at 2 and 4 months was 60% and 44%, respectively, without significant differences between hormone-positive and triple-negative (P = 0.73). Non-progressors' tumors displayed vascular normalization features as a result of previous bevacizumab, compared with generally abnormal patterns observed in progressors. Non-progressors also showed increased T-effector and T-memory signatures and decreased TREG signatures in gene expression studies in baseline-post-bevacizumab-tumors compared with progressors. Notably, analysis of PBMC populations before durvalumab treatment was concordant with the findings in tumor samples and showed a decreased percentage of circulating TREGs in non-progressors. CONCLUSIONS: This study reporting on sequential bevacizumab+durvalumab in breast cancer showed encouraging activity in a heavily pre-treated cohort. The correlative studies agree with the preclinical rationale supporting an immunopriming effect exerted by antiangiogenic treatment, probably by reducing TREGs cells both systemically and in tumor tissue. The magnitude of this benefit should be addressed in a randomized setting. TRIAL REGISTRATION: (www.clinicaltrials.gov): NCT02802098 . Registered on June 16, 2020.

Safe neoadjuvant trastuzumab-based treatment in HER2 + inflammatory early breast cancer in a glucose 6-phosphate dehydrogenase-deficient postmenopausal woman: A case report and review of the literature.

INTRODUCTION: Glucose 6-phosphate dehydrogenase (G6PD) is a basic antioxidant pathway for erythrocytes, being its deficiency the most common gene mutation worldwide. As breast cancer is one of the most frequent tumors, many of these patients may present with G6PD deficiency prior treatment without notice. CASE REPORT: We present the case of a woman deficient for G6PD with the diagnosis of Stage IIIB (cT4d cN1 cM0) HER2-enriched early breast cancer. MANAGEMENT AND OUTCOME: The patient underwent neoadjuvance with trastuzumab and anthracycline-free chemotherapy, based on docetaxel (75 mg/m2, 120 mg) and carboplatin (AUC 5, 560 mg). She did not present hemolytic crisis and no blood transfusions were needed. She achieved a good pathologic response and completed one-year adjuvant trastuzumab without incidences. DISCUSSION: Although the role of HER2 and trastuzumab in oxidative stress is not yet completely understood, we suggest that trastuzumab may be a suitable agent for treatment in patients with HER2-enriched breast cancer in a non-oxidative chemotherapy scheme, with acceptable responses and no triggering hemolytic crisis.

Nab-Paclitaxel plus Gemcitabine and FOLFOX in Metastatic Pancreatic Cancer.

BACKGROUND: Sequential nab-paclitaxel plus gemcitabine followed by modified FOLFOX-6 (oxaliplatin, leucovorin, and 5-fluorouracil) (nab-P/Gem-mFOLFOX) showed a good safety and clinical profile in metastatic pancreatic ductal adenocarcinoma (mPDAC) in the phase I SEQUENCE trial. METHODS: The safety and efficacy of sequential nab-P/Gem-mFOLFOX was compared with standard nab-paclitaxel plus gemcitabine (nab-P/Gem) as first-line treatment in a multi-institutional, randomized, open-label, phase II trial in patients with untreated mPDAC. We randomly assigned patients in a 1:1 ratio to receive nab-P/Gem on days 1, 8, and 15 followed by mFOLFOX on day 29 of a 6-week cycle (experimental group) or nab-P/Gem on days 1, 8, and 15 of a 4-week cycle (control group). The primary end point was the 12-month overall survival rate. RESULTS: A total of 157 patients were randomly assigned: 78 to nab-P/Gem-mFOLFOX and 79 to nab-P/Gem. Patients receiving nab-P/Gem-mFOLFOX had a 12-month overall survival of 55.3% (95% confidence interval [CI], 44.2 to 66.5) versus 35.4% (95% CI, 24.9 to 46) in the control group (P=0.02). Similarly, the 24-month survival was 22.4% (95% CI, 13 to 31.8) with nab-P/Gem-mFOLFOX versus 7.6% (95% CI, 1.8 to 13.4) with control treatment. The median overall survival was 13.2 months (95% CI, 10.1 to 16.2) with nab-P/Gem-mFOLFOX and 9.7 months (95% CI, 7.5 to 12) with nab-P/Gem (hazard ratio for death, 0.68; 95% CI, 0.48 to 0.95). The safety profile showed a higher incidence of grade 3 or higher neutropenia (35 of 76 vs. 19 of 79 patients, P=0.004), grade 3 or higher thrombocytopenia (18 of 78 vs. 6 of 79 patients, P=0.007), and two treatment-related deaths (2.6%) with nab-P/Gem-mFOLFOX compared with none with control treatment. CONCLUSIONS: Sequential nab-P/Gem-mFOLFOX showed a significantly higher 12-month survival when compared with the standard nab-P/Gem treatment; this came with greater treatment toxicity. (Funded by Celgene; EuCT number, 2014-005350-19; ClinicalTrials.gov number, NCT02504333.)

Relation of Malnutrition and Nosocomical Infections in Cancer Patients in Hospital: An Observational Study.

Aim: To investigate the relation between malnutrition and nosocomial infections (NI) in hospitalized cancer patients. Methods: This observational, cross-sectional, noninterventional, descriptive study was conducted in a 500-bed university hospital in Valencia (Spain). Adult cancer patients admitted to the oncology ward were consecutively enrolled regardless of their nutritional status between November 2019 and March 2020. Patients were nutritionally assessed 24 to 48 hours after admission. Body weight, height and BMI, body composition through measurement of bioelectrical impedance analysis (BIA), and muscle strength and functionality using hand grip strength (HGS) were prospectively collected. The diagnosis of malnutrition and sarcopenia was assessed using the Global Leadership Initiative on Malnutrition (GLIM) criteria and the European Working Group on Sarcopenia in Older People (EWGSOP) criteria, respectively. Patients were followed up during their hospital stay or outpatient oncology visits to identify possible NI. Results: A total of 107 patients were included in this study (mean age 66 years; 66.4% were men). The most frequent reason for admission was cancer treatment (19.6%), followed by infections (18.7%) and digestive tract symptoms (18.7%). Overall, 77.5% (83/107) of the patients were malnourished at admission according to the GLIM criteria, while 52.3% (56/107) were sarcopenic. Nosocomial infections (NI) were significantly more frequent in malnourished (52.1%; 25/48) and severely malnourished (42.1%; 8/19) patients, compared with well-nourished patients without malnutrition (25%; 10/40; p=0.035). The mean length of hospital stay was 13.9 days, significantly longer in patients with an NI compared to those without infections (18.6 vs. 10.8 days, p < 0.024). Conclusion: This study evidenced the need to implement a routine protocol for the nutritional assessment and support of cancer patients at risk of malnutrition and sarcopenia to reduce the risk of NI during their hospital stay.

Induction chemotherapy followed by concurrent chemoradiation for patients with non-operable stage III non-small-cell lung cancer.

Combined modality treatment with chemotherapy (CT) and radiotherapy (RT) in stage III non-small-cell lung cancer is considered as standard therapy. As concomitant CT appears to be beneficial, the choice of anticancer agents and the role of induction chemotherapy is still unresolved. We present our experience based on an induction CT scheme with carboplatin plus paclitaxel followed by RT and concomitant CT. 31 patients with non-operable stage IIIA or IIIB NSCLC without pleural effusion were included in this study: 30 males, 1 female; median age 66 years (range: 50-81); 32% with non-operable stage IIIA and 68% with stage IIIB without pleural effusion; 61% squamous cell carcinoma, 32% adenocarcinoma and 7% other histologies. Regarding performance status (PS), 9.7% PS 0 and 90% PS 1 were included. Patients received 3 courses of induction CT with carboplatin AUC=6 and paclitaxel 175 mg/m(2), administrated i.v. on day 1 of each 21-day cycle, followed by thoracic irradiation (total dose 60-65 Gy, daily fractions 1.8-2 Gy) with two concurrent courses of carboplatin/paclitaxel. 16.2% of the patients achieved complete response, 48.4% partial response, 25.8% stable disease and 9.6% progression of disease. Median progression-free and overall survival was 12 and 18 months, respectively. The most frequent haematological toxicities were grade (G) 3 anaemia in 19.3%, G3 neutropenia in 9.6% and G4 neutropenia in 12.9%. Esophageal G2 toxicity (RTOG) was observed in 28.1% of cases. The induction CT followed by concomitant chemoradiation used in this study appears feasible, safe and effective when administered to an unselected inoperable NSCLC stage III patient cohort in the everyday routine clinical practice. Further, our results are comparable to previously published phase III studies.

First line nab-paclitaxel plus gemcitabine in elderly metastatic pancreatic patients: a good choice beyond age.

BACKGROUND: Nab-paclitaxel plus gemcitabine represents one of the standard regimens for first line treatment of metastatic pancreatic cancer (mPC). Few data are available on nab-paclitaxel plus gemcitabine in geriatric population. Our study aims to show whether this schedule can be feasible in the elderly as first-line treatment for mPC. METHODS: We retrospectively analyzed the data of 64 mPC patients (≥65 years old) treated according to the MPACT schedule. RESULTS: Median age was 69.5 years (range, 65-80 years); after a median of 5 cycles administered (range, 1-12), the most common adverse events (AEs) were grade 2 alopecia (46.9%), anemia (17.2%) and hypertransaminasemia (10.9%); all grades neutropenia occurred in 20.3% of pts. Global incidence of grade 3 and 4 toxicities were 26.5% and 0%, respectively, and no patients stopped treatment due to unacceptable toxicity. Stable disease (SD) was observed in 31.2% of patients, with a disease control rate (DCR) and overall response rate of 57.8% and 26.6%, respectively. After a median follow-up of 18 months, median progression free survival (PFS) was 8 months (95% CI: 6.3-9.6) and median OS was 12.0 months (95% CI: 8.4-15.6). The univariate analysis for overall survival (OS) showed that only ECOG performance status was an independent prognostic factor for survival. CONCLUSIONS: Nab-paclitaxel plus gemcitabine schedule is feasible and effective in the "daily clinical practice" geriatric population.

Retrospective analysis of the prognostic role of p16 protein inactivation in plasma in patients with locally advanced non-small cell lung cancer.

It has been analyzed the frequency of p16 inactivation in 67 blood samples of patients diagnosed with advanced non-small cell lung cancer (NSCLC), to establish the relationship between p16 inactivation and time to progression (TTP) and overall survival (OS), and its relationship with various clinical parameters. This is a retrospective study of 67 patients diagnosed with advanced NSCLC between August 2000 and July 2003 in the Hospital General de Valencia analysing p16 inactivation by assessing in plasma either loss of heterozygosity (LOH) or p16 promoter methylation. The study shows p16 inactivation in 28.3% (either by LOH or by p16 methylation). No significant differences were found between the group with p16 inactivation and the group without p16 inactivation, either in patients' TTP (31 weeks vs. 24 weeks; p=0.7) or in OS (53 weeks vs. 43 weeks; p=0.48). No relationship was found between the state of p16 and the clinical parameters analyzed (stage, ECOG, histology). Despite the fact that p16 is important in NSCLC carcinogenesis, the data obtained in our study do not allow the prognostic impact of this biological marker to be established.

Sweet syndrome as the leading symptom in the diagnosis of gastric cancer.

Sweet syndrome is a neutrophilic infiltration of the papillary dermis, which may be associated with the presence of unknown malignancies, either haematological or solid tumours, in 1 out of 5 cases, being considered then as a paraneoplastic syndrome. We present the case of a male with a locally advanced gastric cancer whose final diagnosis was led by the prior debut of Sweet syndrome not explained by other causes.

Endoscopic evaluation of immunotherapy-induced gastrointestinal toxicity.

Immunotherapy is any treatment aimed at boosting or enhancing the immune system. It includes a wide range of options, from vaccines to treatment for conditions such as allergy and cancer. In the case of cancer, unlike other available treatments, immunotherapy is not aimed at destroying the tumor cells but at stimulating the patient's immune system so that it attacks the tumor. In cancer, immunotherapy provides a series of advantages. Nevertheless, immunotherapy administered for treatment of cancer is associated with immune-mediated enterocolitis. Colitis mediated by monoclonal anti-cytotoxic T lymphocyte-associated antigen 4 and to programmed cell death protein 1 and its ligand PDL1 shares characteristics with chronic inflammatory bowel disease (IBD), and similar findings have been reported for both the endoscopy images and the segment involved. The most frequent lesions on endoscopy are ulcer and erythema, and the most frequently affected site is the sigmoid colon. A segmental pattern has been reported to be slightly more frequent than a continuous pattern. In addition, upper gastrointestinal lesions have been reported in up to half of patients, with the most frequent findings being gastritis and erosive duodenitis. As is the case in IBD, systemic corticosteroids and immunosuppressive treatment (anti-TNF agents) are the approaches used in patients with a more unfavorable progression. Immunotherapy must be suspended completely in some cases.

Gene expression and polymorphisms of DNA repair enzymes: cancer susceptibility and response to chemotherapy.

Platinum compounds play a central role in cancer chemotherapy. Although treatment is limited by side effects, they continue to have widespread application. One of the main aims of clinical or translational research in cancer is the search for genetic factors that could foresee treatment outcomes, in biologic activity and toxic effects. This genetic analysis might allow selection of patients who will have the greatest benefit from chemotherapy. Furthermore, a better knowledge of the underlying molecular profile of the host and the tumor will facilitate screening for lung cancer susceptibility and tailoring of chemotherapy in individual patients, choosing those most likely to respond, adjusting doses more precisely in order to reduce less adverse effects, and establishing safety profiles based on individual genetic analyses. Herein, we discuss current knowledge regarding gene expression and polymorphisms of DNA repair enzymes in regard to cancer susceptibility and response to chemotherapy.

Gemcitabine-erlotinib versus gemcitabine-erlotinib-capecitabine in the first-line treatment of patients with metastatic pancreatic cancer: Efficacy and safety results of a phase IIb randomised study from the Spanish TTD Collaborative Group.

BACKGROUND: Gemcitabine and erlotinib have shown a survival benefit in the first-line setting in metastatic pancreatic cancer (mPC). The aim of this study was to assess whether combining capecitabine (C) with gemcitabine + erlotinib (GE) was safe and effective versus GE in patients with mPC. PATIENTS AND METHODS: Previously untreated mPC patients were randomised to receive G (1000 mg/m2, days 1, 8, 15) + E (100 mg/day, days 1-28) + C (1660 mg/m2, days 1-21) or GE, q4 weeks, until progression or unacceptable toxicity. Primary end-point: progression-free survival (PFS); secondary end-points: overall survival (OS), response rate, relationship of rash with PFS/OS and safety. RESULTS: 120 patients were randomised, median age 63 years, ECOG status 0/1/2 33%/58%/8%; median follow-up 16.5 months. Median PFS in the gemcitabine-erlotinib-capecitabine (GEC) and GE arms was 4.3 and 3.8 months, respectively (hazard ratio [HR]: 0.88, 95% confidence interval [CI]: 0.58-1.31; p = 0.52). Median OS in the GEC and GE arms was 6.8 and 7.7 months, respectively (HR: 1.09, 95% CI: 0.72-1.63; p = 0.69). Grade 3/4 neutropenia (GEC 43% versus GE 15%; p = 0.0008) and mucositis (GEC 9% versus GE 0%; p = 0.03) were the only statistically significant differences in grade 3/4 adverse events. PFS and OS were significantly longer in patients with rash (grade ≥1) versus no rash (grade = 0): PFS 5.5 versus 2.0 months (HR = 0.39, 95% CI: 0.26-0.6; p < 0.0001) and OS: 9.5 versus 4.0 months (HR = 0.51, 95% CI: 0.33-0.77; p = 0.0014). CONCLUSION: PFS with GEC was not significantly different to that with GE in patients with mPC. Skin rash strongly predicted erlotinib efficacy. The study was registered with ClinicalTrials.gov: NCT01303029.

[Effectiveness of endovascular prostheses as initial treatment for superior vena cava syndrome of malignant cause]. / Tratamiento inicial del síndrome de vena cava superior de causa neoplásica mediante endoprótesis.

BACKGROUND AND OBJECTIVE: Superior vena cava syndrome (SVCS) is caused by venous return obstruction often originated by an invading mediastinal tumour. Our objective was to evaluate the usefulness of stents as initial treatment for SVCS of malignant origin. PATIENTS AND METHODS: From December 1996 to August 2010, 120 patients with SVCS were referred for percutaneous treatment. Seventy-six were under oncological follow-up cases and in 44 cases the tumour was unknown. A non-concurrent prospective study was made of 113 patients without prior chemotherapy or radiotherapy, who opted for endovascular treatment as first option. RESULTS: One hundred and two men and 11 women were treated, mean age 61.18 years old (range 45-85). SVCS causes included lung cancer (100), lung metastases (6), compression by enlarged lymph nodes (6), and an embryonic tumour. One hundred and fifty-five prostheses were implanted. One stent was enough in 75 patients, 2 stents in 34, and 3 in 4. Technical success rate was 98.2%. Symptoms disappeared completely in 97 patients and partially in 13. Complications were stent migration (5), epistaxis (1), and post-procedure groin hematoma (1). Seventy-three asymptomatic patients had a mean survival of 210 days (75% primary permeability and 52.9% secondary permeability). CONCLUSIONS: The use of stents in malignant SVCS is a safe and effective procedure for venous obstruction, leading to the immediate disappearance of symptoms, allowing the underlying tumour staging, facilitating the establishment of the best treatment and improving life quality.

Analysis of the prognostic value of soluble epidermal growth factor receptor plasma concentration in advanced non-small-cell lung cancer patients.

BACKGROUND: Epidermal growth factor receptor (EGFR) is overexpressed in a variety of epithelial malignancies including lung cancer. A soluble fragment of the EGFR extracellular domain (sEGFR) can be detected in the blood of patients who have non-small-cell lung cancer (NSCLC), but its clinical/ prognostic role must be further elucidated. METHODS: sEGFR concentration was retrospectively determined by enzyme-linked immunosorbent assay in plasma samples from 308 advanced NSCLC patients (before treatment) and 109 healthy controls and correlated with clinico-pathological variables. RESULTS: The concentration of sEGFR was lower in NSCLC patients than in controls (P < .0001). sEGFR behaves as a sensitive but not specific screening biomarker. No significant associations were observed between sEGFR concentration and demographic/clinical characteristics such as gender, Eastern Cooperative Oncology Group performance status, stage, and number or location of the metastatic sites. sEGFR was lower in patients with progressive disease or in squamous cell carcinoma compared with adenocarcinoma, but these differences were not significant. Patients with sEGFR ≤ 34.56 ng/mL showed a shorter overall survival (median 9.1 versus 12.2 months, P = .019) than others. Moreover, in multivariate analysis, sEGFR remained a significant independent prognostic marker. CONCLUSION: Low baseline sEGFR is associated with reduced survival in advanced NSCLC. Therefore, our findings in this large cohort of patients suggest that the determination of sEGFR concentration provides valuable prognostic information.

Chemotherapy-induced neutropenia does not correlate with DNA repair gene polymorphisms and treatment efficacy in advanced non-small-cell lung cancer patients.

BACKGROUND: Platinum doublets are standard chemotherapy for advanced non-small-cell lung cancer (NSCLC). The aim of this study was to assess whether neutropenia is: (1) an indicator for treatment efficacy, or (2) associated with specific polymorphisms. PATIENTS AND METHODS: Four hundred ninety-four patients, treated with cisplatin-docetaxel were retrospectively analyzed. Relative dose intensity (RDI) was assessed for both drugs. Neutrophil counts were assessed only on Day 21 of each cycle. Genotyping was performed for 4 different polymorphisms in ERCC1, XRCC3, XPD-23, and XPD-10. RESULTS: The median overall survival was 9 months. The mean RDI was 0.94 for cisplatin and 0.93 for docetaxel. Four hundred three patients received ≥ 3 cycles of chemotherapy, and 239 received ≥ 6 cycles. Thirty-one percent developed neutropenia, and 19% had Grade (G)3-4 neutropenia. RDI was lower in patients with neutropenia (G1-4; 0.87-0.93) when compared with those without (G0; 0.94-0.95; P < .02). Male patients (P = .02) had inferior survival when compared with female patients, and ECOG (Eastern Cooperative Oncology Group) 1-2 patients (P < .001) had worse survival when compared with ECOG 0. There was no significant survival difference with respect to Grade of neutropenia (G0, 8.7 vs. G1-2, 11.6 vs. G3-4, 9.6 months; P = .41). In ECOG 0 patients, survival was significantly better for neutropenic G1-4 (hazard ratio [HR], 0.55; 95% confidence interval [CI], 0.31-0.96; P = .034) when compared with non-neutropenic (G0) patients. No association was observed between examined polymorphisms and neutropenia. CONCLUSION: RDI was significantly higher in patients who did not develop neutropenia during treatment, but as the nadir period was not explored in our study, the low occurrence of neutropenia in our cohort is considered underestimated. There was no significant survival difference with respect to grade of neutropenia. Finally, none of the examined single nucleotide polymorphisms (SNPs) were associated with the presence of neutropenia, disease characteristics, response rates, or survival.

Oncology outside hospital: a new experience for the benefit of longer survivors.

In May 2007, the Consorcio Hospital General Universitario de Valencia created the position of "Liaison Oncologist". The holder of this position is responsible for coordinating specialised and primary hospital care in the geographic area of Valencia known as Health Care Department 9 to reduce the waiting time between cancer diagnosis and treatment. In this article we describe the implementation of the innovative proposal of the Liaison Oncologist's Consultation Clinic, which, apart from speeding up and directing diagnostic processes, facilitates access to treatment, prevents duplication of consultations and exploratory procedures by establishing therapeutic plans (preferential channels), gives continuity to diagnostic and therapeutic mechanisms, and permits active follow-up of patients who have finished treatment. An analysis of the results obtained shows that the clinic has allowed us to integrate the various aspects of medical oncology into one system and make it available to patients and primary and specialised care professionals. This system provides the patient with the highest quality of integrated health care, ensures the availability of continued health care to long-term survivors and establishes preferential channels between primary care and specialised cancer care to achieve a quick diagnosis.

Phase II clinical trial with gemcitabine and paclitaxel sequential monotherapy as first-line treatment for advanced non-small-cell lung cancer (SLCG 01-04).

BACKGROUND: In advanced-stage (IIIB or IV) non-small-cell lung cancer (NSCLC), combination chemotherapy has demonstrated response rates of 20% and a 1-year survival rate of 30%. We conducted a multicentre, open-label, nonrandomised phase II trial to determine the efficacy and tolerability of sequential monotherapy with gemcitabine followed by paclitaxel in chemotherapy-naïve patients with advanced NSCLC. MATERIALS AND METHODS: Between December 2002 and July 2004, the Spanish Lung Cancer Group (SLCG) conducted a study in which 34 patients with advanced (stage IIIB or IV) NSCLC received 1200 mg/m(2) of i.v. gemcitabine on days 1, 8 and 15 of each 28-day cycle for a total of 3 cycles followed by 100 mg/m(2) of weekly i.v. paclitaxel for a maximum of 8 weeks. If objective response or stable disease was achieved, 70 mg/m(2) of weekly i.v. paclitaxel was maintained until disease progression was evident or toxic effects were intolerable. Lung Cancer Symptom Scale (LCSS) analysis was performed. Baseline levels of serum VEGF, EGFR, telomerase reverse transcriptase (hTERT) and K-ras mutations were analysed. The primary endpoint was the objective response rate. RESULTS: The median age of the 34 patients who were enrolled was 67 years (range 46-77), but later 8 patients were excluded; 78.8% were men, 81.8% had performance status 1 and also 81.8% had metastatic disease at diagnosis. The objective response rate was 28% (95% CI, 14.2-47.8); the median overall survival was 7.2 months (95% CI, 2.1-12.3) and the median time to progression (TTP) was 3.1 months (95% CI, 2.5-5.3). Grade 3 or 4 drug-related haematological toxicities were observed in 6 patients. Patients with lower baseline serum VEGF levels had significantly longer survival. CONCLUSIONS: Sequential therapy with gemcitabine followed by paclitaxel was well tolerated with a low proportion of grade 3 or 4 adverse events, the absence of unexpected toxicity and with an improvement in quality of life. Unfortunately, the response rate did not meet the minimally required rate of 20% and the study was prematurely closed. VEGF was identified as a poor prognostic factor for TTP and survival.

Anorexia-Cachexia syndrome in cancer: implications of the ubiquitin-proteasome pathway.

INTRODUCTION: Malnutrition is a common problem in cancer patients. Its incidence varies according to disease stage (between 15 and 90%) and is considered a possible prognostic factor for therapeutic response and survival. It is also one of the causes contributing to the increase in morbidity and mortality in patients. Tumor cachexia is defined as a nutritional defect caused by tumor growth in the patient and presents as a significant weight loss. This weight loss is mainly caused by a degradation of skeletal muscle proteins. CONCLUSION: The ubiquitin-proteasome system is the most important pathway of protein degradation. As a regulatory system governing protein half-life, it is involved in the regulation of the cell cycle, signal transmission, immune system response, apoptosis, and oncogenesis. Knowledge of the molecular pathways involved in the induction of cancer-associated cachexia will favor a more rational approach to its treatment as well as possible quality of life and survival benefit for the patient.

Tratamiento inicial del síndrome de vena cava superior de causa neoplásica mediante endoprótesis / Effectiveness of endovascular prostheses as initial treatment for superior vena cava syndrome of malignant cause

Fundamento y objetivo: El síndrome de vena cava superior (SVCS) se origina por la dificultad del retorno venoso, producida frecuentemente por un tumor invasor del mediastino. El objetivo de este estudio fue valorar la utilidad de las endoprótesis como tratamiento inicial del SVCS de causa maligna. Pacientes y método: Desde diciembre de 1996 hasta agosto de 2010 se remitieron 120 pacientes con SVCS para tratamiento percutáneo. Setenta y seis se hallaban en seguimiento oncológico y en 44 casos se desconocía un proceso tumoral. Realizamos un estudio prospectivo no concurrente de 113 pacientes sin tratamiento radioterápico o quimioterápico previo y en los que se optó por el tratamiento intravascular como primera opción. Resultados: Se trataron 102 varones y 11 mujeres, con una media de edad de 61,18 años (extremos 45-85). Las causas del SVCS fueron: neoplasia pulmonar (100 casos), metástasis pulmonares (6), compresión por adenopatías (6) y un tumor embrionario. Se implantaron 155 prótesis. Fue suficiente un stent en 75 pacientes, 2 stents en 34 y 3 en 4. El éxito técnico fue del 98,2%. La sintomatología desapareció por completo en 97 pacientes y parcialmente en 13. Como complicaciones destacaron: migración del stent (5), epistaxis (1) y hematoma inguinal pospunción (1). Setenta y tres pacientes tuvieron una supervivencia asintomática media de 210 días (permeabilidad primaria 75%, permeabilidad secundaria 52,9%). Conclusiones: El empleo de endoprótesis en el SVCS de causa maligna es un procedimiento seguro y eficaz que palía la obstrucción venosa, consigue la inmediata desaparición de los síntomas, permite la estadificación del tumor subyacente, facilita la instauración del mejor tratamiento y mejora la calidad de vida (AU)

Background and objective: Superior vena cava syndrome (SVCS) is caused by venous return obstruction often originated by an invading mediastinal tumour. Our objective was to evaluate the usefulness of stents as initial treatment for SVCS of malignant origin. Patients and methods: From December 1996 to August 2010, 120 patients with SVCS were referred for percutaneous treatment. Seventy-six were under oncological follow-up cases and in 44 cases the tumour was unknown. A non-concurrent prospective study was made of 113 patients without prior chemotherapy or radiotherapy, who opted for endovascular treatment as first option. Results: One hundred and two men and 11 women were treated, mean age 61.18 years old (range 45-85). SVCS causes included lung cancer (100), lung metastases (6), compression by enlarged lymph nodes (6), and an embryonic tumour. One hundred and fifty-five prostheses were implanted. One stent was enough in 75 patients, 2 stents in 34, and 3 in 4. Technical success rate was 98.2%. Symptoms disappeared completely in 97 patients and partially in 13. Complications were stent migration (5), epistaxis (1), and post-procedure groin hematoma (1). Seventy-three asymptomatic patients had a mean survival of 210 days (75% primary permeability and 52.9% secondary permeability). Conclusions: The use of stents in malignant SVCS is a safe and effective procedure for venous obstruction, leading to the immediate disappearance of symptoms, allowing the underlying tumour staging, facilitating the establishment of the best treatment and improving life quality (AU)