Antonio Rueda

Epidermal growth factor in plasma and saliva of patients with active breast cancer and breast cancer patients in follow-up compared with healthy women.

We measure EGF in saliva and plasma from 52 patients with active breast cancer, 22 breast cancer patients in follow-up (non-active) and 33 healthy women. EGF concentrations in saliva were significantly higher in patients with active and non-active breast cancer than healthy women, whereas the opposite results were found in plasma. The highest values of EGF in saliva were found in the local recurrence subgroup.

Six cycles of ABVD in the treatment of stage I and II Hodgkin's lymphoma: a pilot study.

PURPOSEnChemotherapy is the standard treatment in advanced Hodgkins lymphoma and a therapeutic alternative for early stages. Although polychemotherapy with doxorubicin, bleomycin, vinblastine, and dacarbazine (ABVD) is equivalent or superior to mechloretamine, vincristine, procarbazine, and prednisone (MOPP) in advanced disease, no series have been published using ABVD without associated radiotherapy in early stages. We report the results obtained with the administration of six cycles of ABVD alone in clinical stage I and II disease.nnnPATIENTS AND METHODSnFrom January 1990 to October 1994, 23 patients with stage I or II Hodgkins lymphoma were treated with six cycles of ABVD; six patients who met the criteria for mediastinal bulky disease also received radiotherapy to the mediastinum.nnnRESULTSnAfter six cycles, 20 complete responses (CRs) and three partial responses (PRs), which became CRs after radiotherapy, were obtained. Toxicity was moderate and manageable. With a median follow-up duration of 37 months (range, 12 to 75), three patients have relapsed and one has died. Overall and progression-free survival rates at 42 months are 95% and 84%, respectively.nnnCONCLUSIONnSix cycles of ABVD are effective and safe in the treatment of stage I and II Hodgkins lymphoma, at least in the short term, but long-term observation data are not yet available.

Aggressiveness features and outcomes of true interval cancers: comparison between screen-detected and symptom-detected cancers.

The question of whether screen detection confers an additional survival benefit in breast cancer is unclear and subject to several biases. Our aim was to examine the role of the diagnostic method (screen-detected, symptom-detected, and true interval cancers) and the clinical–pathological features in relapse-free survival and overall survival in breast cancer patients. We included 228 invasive breast cancers diagnosed in Barcelona from 1996 to 2008 among women aged 50–69 years. Ninety-seven patients were screen detected within the screening, 34 truly arose between 2-year screening mammograms (true interval cancers), and 97 were symptom detected outside the screening. The clinical–pathological features at diagnosis were compared. The overall and disease-free survival probabilities were computed using the Kaplan–Meier method. Cox proportional hazard models were applied, with adjustment by clinical–pathological variables. At diagnosis, symptom-detected and true interval cancers were in more advanced stages and were less differentiated. The highest proportion of triple-negative cancers was detected among true interval cancers (P=0.002). At 5 years of follow-up, the disease-free survival rates for screen-detected, true interval, and symptom-detected cancers were 87.5% (95% confidence interval, 80.5–95.2%), 64.1% (46.4–88.5%), and 79.4% (71.0–88.8%), respectively, and the overall survival rates were 94.5% (89.3–99.9%), 65.5% (47.1–91.2%), and 85.6% (78.3–93.6%), respectively. True interval cancers had the highest hazard ratio for relapse prediction (1.89; 0.67–5.31) and a hazard ratio of death of 5.55 (1.61–19.15) after adjustment for tumor–node–metastasis stage and phenotype. Clinically detected tumors, especially true interval cancers, more frequently showed biological features related to worse prognosis and were associated with poorer survival even after adjustment for clinical–pathological characteristics.

Adjuvant anthracycline therapy as a prognostic factor in metastatic breast cancer

AbstractBackground. Prognostic factors in metastatic breast cancer continue to be identified. Previous adjuvant chemotherapy appeared to have poor prognosis in some studies but, despite this, the prior use of anthracyclines in the adjuvant setting has not been clearly established as an adverse prognostic factor once metastatic disease develops.nPatients and methods. Patients (nu2009=u20091,436) with stages I–IIIa breast cancer were surgically treated with/without radiotherapy and/or systemic adjuvant treatment. Of these, 297 patients who relapsed with metastatic disease constitute the sample population of this retrospective study. Survival, as a function of time since diagnosis of metastatic disease, was assessed in relation to the following factors: age, size of the primary tumor, grade, number of positive axillary nodes, type of surgery, type of adjuvant treatment administered, time to relapse, number of metastatic sites, presence of visceral metastases and type of treatment employed at the time of relapse.nResults. In multivariable analysis three factors remained significant predictors of short survival time: more than 1 site of metastases (pu2009=u20090.00003), shorter time to relapse (pu2009=u20090.003) and the previous administration of anthracyclines as adjuvant therapy (pu2009=u20090.005).nConclusions. The prior use of adjuvant anthracyclines, with other known clinical prognostic factors, confers a poorer outcome in metastatic disease, perhaps as a result of resistant clones selection or by induction of de novo resistance.

Efficacy and safety of weekly paclitaxel combined with cetuximab in the treatment of pretreated recurrent/metastatic head and neck cancer patients

INTRODUCTIONnThe addition of cetuximab to weekly paclitaxel has demonstrated high efficacy in the first-line treatment of patients with recurrent/metastatic squamous cell carcinoma of the head and neck (R/M-SCCHN). However, this combination has been widely extended to patients who present resistance to first line chemotherapy (CT) or those who are not candidates for platinum-based CT.nnnMATERIAL AND METHODSnWe have retrospectively analyzed the efficacy and safety of cetuximab in combination with weekly paclitaxel in patients with R/M-SCCHN who present disease progression after platinum schedules or those who were not candidates for platinum-based CT. Patients received weekly paclitaxel 80mg/m(2) and cetuximab 250mg/m(2) (initial dose of 400mg/m(2)) until progression or unacceptable toxicity.nnnRESULTSnTwenty-two patients were included. Median age was 58 (43-68), ECOG PS (0/1/2): 6/10/4, 19 patients had received prior platinum-based treatment (nine patients were platinum-sensitive and nine were platinum-refractory). With a median follow-up of 6.18months (range 1.3-29.7), overall response rate (ORR) was 55% (95% CI 31-76%):1 (5%) complete response and 9 (50%) partial responses. Median duration of response was 10.23months. Median progression free survival (PFS) and overall survival (OS) were 5.4 and 9.1months, respectively. There were no differences in response rate according to platinum sensitivity (66% sensitive vs 44% refractory; P=0.61). The main toxicity consisted of rash in 70% of patients (5% grade 3), with an association between rash severity and ORR (grade 0-1: 33% vs grade 2-3: 64%; P=0.03) and a trend for better PFS and OS.nnnCONCLUSIONnWeekly paclitaxel in combination with cetuximab is a well tolerated and highly active second-line treatment in patients with R/MSCCHN who experience disease progression after platinum-based CT, including those who present resistant disease. Our results suggest that the efficacy of this combination is apparently superior than the published data on single agent cetuximab in this setting.

Detection methods predict differences in biology and survival in breast cancer patients

BackgroundThe aim of this study was to measure the biological characteristics involved in tumorigenesis and the progression of breast cancer in symptomatic and screen-detected carcinomas to identify possible differences.MethodsFor this purpose, we evaluated clinical-pathological parameters and proliferative and apoptotic activities in a series of 130 symptomatic and 161 screen-detected tumors.ResultsAfter adjustment for the smaller size of the screen-detected carcinomas compared with symptomatic cancers, those detected in the screening program presented longer disease-free survival (RRu2009=u20090.43, CIu2009=u20090.19-0.96) and had high estrogen and progesterone receptor concentrations more often than did symptomatic cancers (ORu2009=u20093.38, CIu2009=u20091.72-6.63 and ORu2009=u20093.44, CIu2009=u20091.94-6.10, respectively). Furthermore, the expression of bcl-2, a marker of good prognosis in breast cancer, was higher and HER2/neu expression was lower in screen-detected cancers than in symptomatic cancers (ORu2009=u20091.77, CIu2009=u20091.01-3.23 and ORu2009=u20090.64, CIu2009=u20090.40-0.98, respectively). However, when comparing prevalent vs incident screen-detected carcinomas, prevalent tumors were larger (ORu2009=u20092.84, CIu2009=u20091.05-7.69), were less likely to be HER2/neu positive (ORu2009=u20090.22, CIu2009=u20090.08-0.61) and presented lower Ki67 expression (ORu2009=u20090.36, CIu2009=u20090.17-0.77). In addition, incident tumors presented a shorter survival time than did prevalent ones (RRu2009=u20094.88, CIu2009=u20091.12-21.19).ConclusionsIncident carcinomas include a variety of screen-detected carcinomas that exhibit differences in biology and prognosis relative to prevalent carcinomas. The detection method is important and should be taken into account when making therapy decisions.

Secondary Prophylactic G-CSF (Filgrastim) Administration in Chemotherapy of Stage I and II Hodgkin's Lymphoma with ABVD

The purpose of this study was to determine the effect of granulocyte colony-stimulating factor (filgrastim, G-CSF) for maintenance of chemotherapy dose-intensity in patients with stage I or II Hodgkins lymphoma treated with six cycles of doxorubicin, bleomycin, vinblastine, and dacarbazine (ABVD). Fifty-six patients with stage I or II Hodgkins lymphoma treated with ABVD were eligible for secondary prophylactic G-CSF administration because of neutropenia (absolute neutrophil count < 1 × 109/L) causing treatment delay or febrile neutropenia. Patients received 300 μg (total dose) of G-CSF (filgrastim) subcutaneously on days 3 to 7 and 17 to 21 of each cycle in order to prevent dose reduction or delay in subsequent cycles of treatment continuing the G-CSF until completion of chemotherapy. Results showed that 30 (54%) of the patients required the use of G-CSF, 26 (47%) during the first or second cycle. After G-CSF administration delay in chemotherapy did not occur in 25 patients, whereas delays in the fifth or sixth cycle occurred in four patients. Despite treatment with G-CSF, one patient had febrile neutropenia. Dose intensity greater than 90% of that planned was delivered to more the 85% of patients. In conclusion: Secondary prophylactic G-CSF administration was necessary in more than half of patients with stage I or II Hodgkins lymphoma during chemotherapy with ABVD. The use of G-CSF allowed maintenance of chemotherapy schedule and dose intensity in the majority of patients.

Consolidation treatment with Yttrium-90 ibritumomab tiuxetan after new induction regimen in patients with intermediate- and high-risk follicular lymphoma according to the follicular lymphoma international prognostic index: a multicenter, prospective phase II trial of the Spanish Lymphoma Oncology Group

Abstract Relapse is the main cause of therapeutic failure in follicular lymphoma (FL). We set out to evaluate the role of consolidation with Yttrium-90 ibritumomab tiuxetan in patients with intermediate- and high-risk FL after four cycles of CHOP-R (cyclophosphamide, doxorubicin, vincristine, prednisone, rituximab) and two cycles of CHOP. Thirty patients were included. The overall response rate after consolidation therapy was 93%. Of the 18 patients who presented with a partial response after induction treatment, 11 had a complete response after consolidation treatment. The complete clinical response rate was 76.6%. The most important grade 3–4 toxicity was hematological, with 46% thrombopenia and 56% neutropenia. With a median follow-up of 26 months, the means for progression-free survival and overall survival were not reached. Our data support consolidation with Yttrium-90 ibritumomab tiuxetan as an effective treatment, which provides long progression-free and overall survival, in first line after a response to induction treatment in patients with intermediate- and high-risk FL.

Clinical practice guidelines for first-line/after-relapse treatment of patients with follicular lymphoma

Key points and recommendations Follicular lymphoma is a subgroup of non-Hodgkin lymphomas of B-cell origin, characterized by a pattern of remissions and continued relapses. It is the second most common type of lymphoid cancer in Western Europe, representing 22–40% of non-Hodgkin lymphomas. The annual incidence of the disease has increased in recent decades. At this time, and with the arrival of new treatment options, patients’ outcomes have significantly improved. It is therefore essential to standardize recommendations for the treatment and follow-up of patients with follicular lymphoma, in each clinical scenario. Searches were performed in Medline (PubMed, 1966–present) and The Cochrane Library, using MeSH (Medical Subject Headings) terms whenever possible. The best scientific evidence was obtained from selected randomized studies and meta-analyses. For recommendations where there was no scientific evidence, the consensus of clinical experts was obtained regarding clinical and therapeutic attitudes to improve the treatment of these patients. Recommendations are compiled according to: (i) induction treatment in first-line; (ii) post-induction treatment in first-line; (iii) rescue treatment after relapse; (iv) post-induction treatment in relapse and (v) subsequent treatments. There are different recommendations for each group. They take into account different variables, such as therapeutic options, patient follow-up, laboratory and imaging data, previous response and special groups. The recommendations contained in this guide have been assigned different grades (A, B, C and D), depending on the level of evidence on which they are based (where there is no scientific evidence, they follow the consensus of Good Clinical Practice: see the Appendix). These guidelines provide healthcare professionals with updated and consensual tools for the better management of patients with follicular lymphoma.

Vascular endothelial growth factor and vascular endothelial growth factor receptor‐2 tumor expression in patients with advanced laryngeal cancer after induction chemotherapy for organ preservation

Vascular endothelial growth factor (VEGF) expression seems to be associated with worse overall survival in patients with head and neck squamous cell carcinoma. The purposes of this study were to assess the prognostic values of the immunohistochemical expression of VEGF and vascular endothelial growth factor receptor‐2 (VEGFR‐2) in a cohort of patients with operable advanced laryngeal cancer who had been treated with induction chemotherapy.