RACHEL SIMOES PIMENTA RIECHELMANN

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Projetos de Pesquisa
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LIM/24 - Laboratório de Oncologia Experimental, Hospital das Clínicas, Faculdade de Medicina

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  • article 47 Citação(ões) na Scopus
    Pregabalin for the Prevention of Oxaliplatin-Induced Painful Neuropathy: A Randomized, Double-Blind Trial
    (2017) ANDRADE, Daniel Ciampi De; TEIXEIRA, Manoel Jacobsen; GALHARDONI, Ricardo; FERREIRA, Karine S. L.; MILENO, Paula Braz; SCISCI, Nathalia; ZANDONAI, Alexandra; TEIXEIRA, William G. J.; SARAGIOTTO, Daniel F.; SILVA, Valquiria; RAICHER, Irina; CURY, Rubens Gisbert; MACARENCO, Ricardo; HEISE, Carlos Otto; BROTTO, Mario Wilson Iervolino; MELLO, Alberto Andrade De; MEGALE, Marcelo Zini; DOURADO, Luiz Henrique Curti; BAHIA, Luciana Mendes; RODRIGUES, Antonia Lilian; PARRAVANO, Daniella; FUKUSHIMA, Julia Tizue; LEFAUCHEUR, Jean-Pascal; BOUHASSIRA, Didier; SOBROZA, Evandro; RIECHELMANN, Rachel P.; HOFF, Paulo M.; SILVA, Fernanda Valerio Da; CHILE, Thais; DALE, Camila S.; NEBULONI, Daniela; SENNA, Luiz; BRENTANI, Helena; PAGANO, Rosana L.; SOUZA, Angela M. De
    Background. Patients with colorectal cancer (CRC) receiving oxaliplatin (OXA) develop acute and chronic painful oxaliplatin-induced peripheral neuropathy (OXAIPN). Acute and chronic OXA-related neuropathies have different pathophysiological bases, but both lead to a common phenomenon: central sensitization (CS) of nociceptive neuronal networks, leading to increased sensitivity (hyperlgesia, allodynia) in the somatosensory system, the common ground of chronic neuropathic pain. Because CS is related to increased risk of painful OXAIPN, we hypothesized that preemptive use of the anti-hyperalgesic drug pregabaline (known to decrease CS) during OXA infusions would decrease the incidence of chronic OXAIPN. Methods. Pain-free, chemotherapy-naive CRC patients receiving at least one cycle of modified-FLOX [5-FU(500 mg/m(2)) 1 leucovorin(20 mg/m(2))/week for] 6 weeks+oxaliplatin(85 mg/m2) at weeks 1-3-5 every 8 weeks] were randomized (1:1) into the study. Patients received either pregabalin or placebo for 3 days before and 3 days after each OXA infusion and were followed for up to 6 months. Clinical assessments were performed at baseline, at the end of chemotherapy, and after the follow-up period. The main outcome was average pain at the last visit assessed by the visual analogic scale (0-10) item of the Brief Pain Inventory (BPI). Secondary endpoints were presence of neuropathic pain according to the Douleur Neuropathique-4 (DN-4), pain dimensions (short-form McGill Pain Questionnaire [MPQ]), Neuropathic Pain Symptom Inventory (NPSI), and changes in nerve conduction studies (NCS) and side effect profile. Results. One hundred ninety-nine patients (57.0 +/- 10.7 years old, 98 female, 101 male) were randomized. Data from 56 patients were not included in the analyses (as they did not receive at least one full cycle of modified FLOX). Data from 78 patients in the pregabalin group and 65 patients in the placebo group were retained for analyses. At the last visit, pain intensity in the pregabalin group was 1.03 (95% confidence interval [CI] 50.79-1.26), and 0.85 (95% CI50.64-1.06) in the placebo group, which did not reach significance. Scores from the BPI, MPQ, DN-4, NPSI, and NCS and side-effect profiles and incidence of death did not differ between groups. Quality of life (QoL) score did not differ between groups (placebo = 576.9 +/- 23.1, pregabalin group 79.4 +/- 20.6). Mood scores were not significantly different between groups (placebo 9.7 [8.1-11.2]; pregabalin 6.8 [5.6-8.0]). Conclusion. The preemptive use of pregabalin during OXA infusions was safe, but did not decrease the incidence of chronic pain related to OXAIPN.
  • conferenceObject
    Acromegaly Due to Ectopic Secretion of GHRH Mimicking a GH-Secreting Pituitary Adenoma: The Role of Imaging and GHRH Assay
    (2014) SANTANA, Nathalie Oliveira; JALLAD, Raquel S.; DUARTE, Felipe H. G.; RIECHELMANN, Rachel Simoes Pimenta; RAVEROT, Veronique; TROUILLAS, Jacqueline; RAVEROT, Gerald; BRONSTEIN, Marcello D.
  • article 7 Citação(ões) na Scopus
    International Practice Patterns and Resource Utilization in the Treatment of Neuroendocrine Tumors
    (2013) CASCIANO, Roman; WANG, Xufang; STERN, Lee; PARIKH, Rohan; CHULIKAVIT, Maruit; WILLET, Jacob; LIU, Zhimei; STROSBERG, Jonathan; CADIOT, Guillaume; RIECHELMANN, Rachel
    Objectives: This study compared resource use and practice patterns in patients with advanced neuroendocrine tumors (NETs) on disease progression, across countries, and by tumor type. Methods: Physicians in the United States, United Kingdom, Germany, France, Brazil, and Italy completed data extraction forms to extract chart data of patients with NET relating to health care resource utilization and treatment practice. Data were assessed in a cross-sectional manner, by country, and by NET subtype. Univariate and multivariate analyses were performed to compare categories of resource use by disease progression status. Results: A total of 197 physicians provided data on 394 patients. Overall resource utilization was high across tumor types, countries, and progression. Nearly half of all patients received chemotherapy (49%); moreover, high rates of hospitalization (65%), surgery (47%), and use of somatostatin analog (77%) were observed, with lower rates of peptide receptor radionuclide therapy (10%) and targeted therapies (6%). These patterns were consistent across gastrointestinal tract/lung NET and pancreatic NET. However, a certain variation in resource utilization was observed across countries. Disease progression was associated with increasing utilization of chemotherapy, hospitalization, and targeted therapy. Conclusions: Advanced NET is associated with significant resource use across subtypes and countries, and resource utilization is likely to increase on disease progression. There remains an unmet need for therapeutic options after disease progression.
  • article 16 Citação(ões) na Scopus
    Aflibercept Plus FOLFIRI for Second-line Treatment of Metastatic Colorectal Cancer: Observations from the Global Aflibercept Safety and Health-Related Quality-of-Life Program (ASQoP)
    (2019) RIECHELMANN, Rachel P.; SRIMUNINNIMIT, Vichien; BORDONARO, Roberto; KAVAN, Petr; BARTOLOMEO, Maria Di; MAIELLO, Evaristo; CICIN, Irfan; GARCIA-ALFONSO, Pilar; CHAU, Ian; FEDYANIN, Mikhail Y.; MARTOS, Carlos Fernandez; TER-OVANESOV, Mikhail; PEETERS, Marc; KO, Yoo-Joung; YALCIN, Suayib; KARTHAUS, Meinolf; APARICIO, Jorge; HEINEMANN, Volker; PICARD, Pascaline; BURY, Denise; DREA, Edward; SOBRERO, Alberto
    This study evaluated safety and quality of life in patients with metastatic colorectal cancer undergoing treatment with aflibercept and FOLFIRI (fluorouracil, leucovorin, irinotecan). Most patients treated with this combination experienced either improvement or stability in quality of life scores. Aflibercept plus FOLFIRI is tolerable in the treatment of patients with metastatic colorectal cancer with a safety profile similar to that seen in previous studies of these individual medications. Background: The objectives of this study were to evaluate the safety profile of aflibercept and health-related quality of life (HRQL) in patients with metastatic colorectal cancer (mCRC) provided with aflibercept access before marketing authorization. Patients and Methods: Patients received aflibercept followed by FOLFIRI (fluorouracil, leucovorin, irinotecan) on day 1 of a 2-week cycle until disease progression, unacceptable toxicity, death, or patient/investigator decision to discontinue. Treatment-emergent adverse events (TEAEs) were evaluated, and HRQL was assessed at baseline, cycle 3, and every other cycle using the European Organisation for Research and Treatment of Cancer (EORTC) QLQ-C30, EORTC QLQ-CR29, and EuroQol 5-Dimensions 3-Levels questionnaires (NCT01571284). Results: Overall, 779 adult patients with mCRC, who received >= 1 prior oxaliplatin-based regimen and had disease progression during or following their last administration of oxaliplatin-based chemotherapy, were enrolled. At data cutoff, all patients had discontinued treatment, mainly owing to disease progression (51.7%). The most common TEAEs of any grade were diarrhea (61.6%), hypertension (48.4%), and nausea (43.3%). The most common grade 3/4 TEAEs were hypertension (24.1%), neutropenia (23.1%), and diarrhea (15.3%). Clinically meaningful changes in HRQL were reported for all measures. Most patients either had an improvement in their HRQL scores or remained stable during the treatment period based on patient-reported outcomes. Conclusion: The data from this study support the tolerability of the combination of aflibercept and FOLFIRI in a setting that more closely approximates real life in patients with mCRC who failed to respond to oxaliplatin-based chemotherapy, and also suggest an improvement in HRQL.
  • conferenceObject
    Aflibercept plus FOLFIRI for 2nd line treatment of metastatic colorectal cancer (mCRC): Long-term safety observation from the global aflibercept safety and quality-of-life (QoL) program (ASQoP)
    (2016) RIECHELMANN, R.; SRIMUNINNIMIT, V.; KAVAN, P.; BARTOLOMEO, M. Di; MAIELLO, E.; CICIN, I.; KROENING, H.; GARCIA-ALFONSO, P.; CHAU, I.; FERNANDEZ-MARTOS, C.; TER-OVANESOV, M.; PEETERS, M.; PICARD, P.; BORDONARO, R.
  • article 87 Citação(ões) na Scopus
    A randomized, open-label, phase 2 study of everolimus in combination with pasireotide LAR or everolimus alone in advanced, well-differentiated, progressive pancreatic neuroendocrine tumors: COOPERATE-2 trial
    (2017) KULKE, M. H.; RUSZNIEWSKI, P.; CUTSEM, E. Van; LOMBARD-BOHAS, C.; VALLE, J. W.; HERDER, W. W. De; PAVEL, M.; DEGTYAREV, E.; BRASE, J. C.; BUBUTEISHVILI-PACAUD, L.; VOI, M.; SALAZAR, R.; BORBATH, I.; FAZIO, N.; SMITH, D.; CAPDEVILA, J.; RIECHELMANN, R. P.; YAO, J. C.
    Background: Several studies have demonstrated the antitumor activity of first-generation somatostatin analogs (SSAs), primarily targeting somatostatin receptor (sstr) subtypes 2 and 5, in neuroendocrine tumors (NET). Pasireotide, a second-generation SSA, targets multiple sstr subtypes. We compared the efficacy and safety of pasireotide plus everolimus to everolimus alone in patients with advanced, well-differentiated, progressive pancreatic NET. Patients and methods: Patients were randomized 1 : 1 to receive a combination of everolimus (10 mg/day, orally) and pasireotide long-acting release (60 mg/28 days, intramuscularly) or everolimus alone (10 mg/day, orally); stratified by prior SSA use, and baseline serum chromogranin A and neuron-specific enolase. The primary end point was progression-free survival (PFS). Secondary end points included overall survival, objective response rate, disease control rate, and safety. Biomarker response was evaluated in an exploratory analysis. Results: Of 160 patients enrolled, 79 were randomized to the combination arm and 81 to the everolimus arm. Baseline demographics and disease characteristics were similar between the treatment arms. No significant difference was observed in PFS: 16.8months in combination arm versus 16.6months in everolimus arm (hazard ratio, 0.99; 95% confidence interval, 0.64-1.54). Partial responses were observed in 20.3% versus 6.2% of patients in combination arm versus everolimus arm; however, overall disease control rate was similar (77.2% versus 82.7%, respectively). No significant improvement was observed inmedian overall survival. Adverse events were consistent with the known safety profile of both the drugs; grade 3 or 4 fasting hyperglycemia was seen in 37% versus 11% of patients, respectively. Conclusions: The addition of pasireotide to everolimus was not associated with the improvement in PFS compared with everolimus alone in this study. Further studies to delineate mechanisms by which SSAs slow tumor growth in NET are warranted.