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Sastre J.,HC San Carlos | Sastre J.,Charles III University of Madrid | Luisa Maestro M.,Genomic Unit | Gomez-Espana A.,Hospital Reina Sofia | And 14 more authors.
Oncologist | Year: 2012

Background. The Maintenance in Colorectal Cancer trial was a phase III study to assess maintenance therapy with single-agent bevacizumab versus bevacizumab plus chemotherapy in patients with metastatic colorectal cancer. An ancillary study was conducted to evaluate the circulating tumor cell (CTC) count as a prognostic and/or predictive marker for efficacy endpoints. Patients and Methods. One hundred eighty patients were included. Blood samples were obtained at baseline and after three cycles. CTC enumeration was carried out using the CellSearch® System (Veridex LLC, Raritan, NJ). Computed tomography scans were performed at cycle 3 and 6 and every 12 weeks thereafter for tumor response assessment. Results. The median progression-free survival (PFS) interval for patients with a CTC count ≥3 at baseline was 7.8 months, versus the 12.0 months achieved by patients with a CTC count <3 (p =.0002). The median overall survival (OS) time was 17.7 months for patients with a CTC count ≥3, compared with 25.1 months for patients with a lower count (p =.0059). After three cycles, the median PFS interval for patients with a low CTC count was 10.8 months, significantly longer than the 7.5 months for patients with a high CTC count (p =.005). The median OS time for patients with a CTC count <3 was significantly longer than for patients with a CTC count ≥3, 25.1 months versus 16.2 months, respectively (p =.0095). Conclusions. The CTC count is a strong prognostic factor for PFS and OS outcomes in metastatic colorectal cancer patients. ©AlphaMed Press.

Diaz-Rubio E.,HC San Carlos | Diaz-Rubio E.,RDc17 06 0020 0021 Instituto Carlos III | Gomez-Espana A.,Hospital Reina Sofia | Massuti B.,Hospital General | And 22 more authors.
Onkologie | Year: 2012

Purpose: The aim of this phase III trial was to compare the efficacy and safety of bevacizumab alone with those of bevacizumab and capecitabine plus oxaliplatin (XELOX) as maintenance treatment following induction chemotherapy with XELOX plus bevacizumab in the first-line treatment of patients with metastatic colorectal cancer (mCRC). Patients and Methods: Patients were randomly assigned to receive six cycles of bevacizumab, capecitabine, and oxaliplatin every 3 weeks followed by XELOX plus bevacizumab or bevacizumab alone until progression. The primary endpoint was the progression-free survival (PFS) interval; secondary endpoints were the overall survival (OS) time, objective response rate (RR), time to response, duration of response, and safety. Results: The intent-to-treat population comprised 480 patients (XELOX plus bevacizumab, n = 239; bevacizumab, n = 241); there were no significant differences in baseline characteristics. The median follow-up was 29.0 months (range, 0-53.2 months). There were no statistically significant differences in the median PFS or OS times or in the RR between the two arms. The most common grade 3 or 4 toxicities in the XELOX plus bevacizumab versus bevacizumab arms were diarrhea, hand-foot syndrome, and neuropathy. Conclusion: Although the noninferiority of bevacizumab versus XELOX plus bevacizumab cannot be confirmed, we can reliably exclude a median PFS detriment >3 weeks. This study suggests that maintenance therapy with singleagent bevacizumab may be an appropriate option following induction XELOX plus bevacizumab in mCRC patients.

Sastre J.,HC San Carlos | Gomez A.,Hospital Reina Sofia | Rivera F.,Hospital Marques de Valdecilla | Massuti B.,Hospital Universitario Of Alicante | And 6 more authors.
Clinical Colorectal Cancer | Year: 2013

Objective Circulating tumor cells (CTCs) and v-Ki-ras2 Kirsten rat sarcoma viral oncogene homolog (KRAS) status were identified as prognostic factors for progression-free survival (PFS) and overall survival (OS) in patients with metastatic colorectal cancer treated with chemotherapy and bevacizumab in analyses of the MACRO (Maintenance Treatment in Advanced Colorectal Cancer) trial. In this post hoc analysis of the MACRO trial, the potential additive effect of these 2 factors on patient outcomes was explored. Methods A total of 158 of the 480 patients involved in the MACRO trial were included in the biological marker substudy. CTC isolation and enumeration were centralized and performed using the CellSearch System (Veridex LLC, Raritan, NJ) in 7.5 mL of whole blood. Evaluation of KRAS status was performed retrospectively by the standard method used at each center. PFS and OS were analyzed by the Kaplan-Meier method according to CTC count and KRAS status. Results Patients with < 3 CTC per 7.5 mL blood at baseline and KRAS wild-type tumors had a median PFS of 14.2 months compared with 6.2 months in patients with ≥ 3 CTCs and KRAS mutated tumors (P <.0001; hazard ratio, 3.0; 95% confidence interval, 1.8-5.2). Similar findings were observed for OS (28.9 and 13.7 months, respectively, P =.0004; hazard ratio 2.8; 95% confidence interval, 1.6-4.9). Multivariate analyses showed that CTC count ≥ 3 and KRAS status were the only independent prognostic factors for both PFS and OS. Conclusions This post hoc analysis showed that CTC count and KRAS status were independent prognostic factors for outcomes in patients with metastatic colorectal cancer treated with bevacizumab ± chemotherapy. These factors should be taken into account in the design of future phase III trials. © 2013 Elsevier Inc. All rights reserved.

Benavides M.,Hospital Regional Universitario Carlos Haya | Abad A.,Hospital Sanitas Milenium Iradier | Ales I.,Hospital Regional Universitario Carlos Haya | Carrato A.,Hospital Universitario Ramon y Cajal | And 10 more authors.
Clinical and Translational Oncology | Year: 2014

Exocrine pancreatic cancer (PC) is a very aggressive and heterogeneous tumor with several cellular signaling pathways implicated in its pathogenesis and maintenance. Several risk factors increase the risk of developing PC. Therapeutic strategies used are dictated by the extent of disease. Supportive treatment is critical because of the high frequency of symptoms. For localized disease, surgery followed by adjuvant gemcitabine is the standard. Neoadjuvant and new adjuvant chemotherapy regimens are being evaluated. Locally advanced disease should respond best guided by a multidisciplinary team. Various treatment options are appropriate such as chemotherapy alone or chemoradiotherapy with integration of rescue surgery if the tumor becomes resectable. In metastatic disease, chemotherapy should be reserved for patients with ECOG 0–1 using Folfirinox or gemcitabine plus nab-paclitaxel as the most recommended options. Several therapeutic strategies targeting unregulated pathways are under evaluation with an unmet need for biomarkers to guide management. © 2014, Federación de Sociedades Españolas de Oncología (FESEO).

Rivera F.,Hospital Universitario Marques Of Valdecilla | Massuti B.,Hospital General | Salcedo M.,Hospital Universitario Marques Of Valdecilla | Sastre J.,HC San Carlos | And 20 more authors.
Cancer Chemotherapy and Pharmacology | Year: 2015

Purpose: Chemotherapy has improved the overall survival (OS) in patients (pts) with advanced gastric cancer (AGC). Docetaxel (D), oxaliplatin (O) and capecitabine (C) have shown interesting activity in this setting. We defined "suboptimal" pts as those with PS ECOG = 2, weight loss 10-25 % and/or age ≥70 years. This population is usually underrepresented in AGC clinical trials. Methods: We explored in 43 previously untreated "suboptimal" AGC pts the effect of "miniDOX" regimen (D: 40 mg/m2 iv, day 1; O: 80 mg/m2 iv, day 1; C: 625 mg/m2 po bid, day 1 to day 21, every 21 days; after six courses, only C was maintained). Primary end point was response rate (RR), and secondary end points were adverse events (AE), progression-free survival (PFS) and overall survival (OS). Results Patients characteristics: PS ECOG = 2: 12 pts; weight loss 10-25 %: 23 pts; median age 73.3 years (range 40-87; 28 pts were ≥70 years); 32 males; locally advanced: 8 pts/metastatic: 35 pts; primary site: gastric 32 pts/EGJ 11. Worst AE per pt (grade 3-4): neutropenia: 5 pts (febrile neutropenia: 3); pulmonary embolism (PE): 4 pts (3 of them suffered sudden death); diarrhea: 9 pts; paronychia: 2 pts; ictus: 1 pt; renal failure: 1 pt (this pt suffered infection/bacteriemia without neutropenia and died); hand-foot syndrome: 4 pts and asthenia: 5 pts. Response: CR: 1 pt, PR: 23 pts (RR: 56 %), SD: 12 pts, progression: 3 pts, no determined: 4 pts. Median and 1 year actuarial PFS and OS were 5.5 months/18 % and 13.3 months/52 %, respectively. Conclusions: Although miniDOX's toxicity (mainly PE) has been important, its activity has been promising in "suboptimal" pts with AGC, and this combination should be further investigated in this setting. © Springer-Verlag 2014.

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