ALEXANDRA KHICHFY ALEX
Projetos de Pesquisa
Unidades Organizacionais
Instituto do Câncer do Estado de São Paulo, Hospital das Clínicas, Faculdade de Medicina - Médico
9 resultados
Resultados de Busca
Agora exibindo 1 - 9 de 9
- Phase 2 Trial of Metformin Combined With 5-Fluorouracil in Patients With Refractory Metastatic Colorectal Cancer(2016) MIRANDA, Vanessa C.; BRAGHIROLI, Maria Ignez; FARIA, Luiza Dib; BARIANI, Giovanni; ALEX, Alexandra; BEZERRA NETO, Joao Evangelista; CAPARELI, Fernanda C.; SABBAGA, Jorge; SANTOS, Juliana Ferreira Lobo dos; HOFF, Paulo M.; RIECHELMANN, Rachel P.Effects of metformin in colorectal cancer have not been tested in clinical trials. In this phase 2 trial with 50 patients, metformin and 5-fluorouracil (5-FU) showed median progression-free survival of 2 months and overall survival of 7.9 months. However, among patients who experienced stable disease at 8 weeks, disease stabilization lasted for 5.6 months and patients survived for 16 months. Obese patients and those with longer periods off 5-FU seemed to derive more benefit. Background: Observational and preclinical studies have suggested that metformin has antitumor effects in solid tumors, including colorectal cancer (CRC). However, the effects of metformin in CRC have not been tested in clinical trials. Patients and Methods: This was a single-center, single-arm phase 2 clinical trial where histologically confirmed CRC patients with measurable and progressing metastatic disease previously treated with 5-fluorouracil (5-FU), irinotecan, oxaliplatin, and an antieepidermal growth factor receptor (if the tumor was RAS wild type) were enrolled to receive metformin 850 mg orally continuously 2 times a day plus 5-FU 425 mg/m(2) and leucovorin 50 mg intravenously weekly until disease progression, unacceptable toxicity, or withdrawal of consent. The primary end point was disease control rate at 8 weeks. Results: Among 50 patients included, 11 (22%) met the primary end point. The median progression-free survival was 1.8 months and the median overall survival 7.9 months. Analyzing only the 11 patients who experienced disease control at 8 weeks, their median progression-free survival was 5.6 months and their median overall survival was 16.2 months. There was a trend for prolonged median survival for obese patients (12.4 vs. 5.8 months) and those longer off 5-FU. The treatment was well tolerated; the main adverse effects were diarrhea, nausea, vomiting, and myelotoxicity. Conclusion: Metformin and 5-FU showed an overall modest but intriguing activity in patients with refractory CRC in this phase 2 study. Some patients experienced long-term disease control. Further trials are needed to confirm these results, particularly in obese patients with CRC.
conferenceObject Should patients with advanced colorectal cancer and ECOG 3/4 be treated with chemotherapy?(2013) CROSARA, M. A. T.; MARQUES, D. F.; FERRARI, A. C.; ALVES, M. F. S.; ALEX, A. K.; SABBAGA, J.; HOFF, P. M.; RICHELMANN, R. P.conferenceObject Phase II trial of inetforrnin and paclitaxel for patients with gemcitabine-refractory advanced adenocarcinoma of the pancreas(2014) FERRARI, Anezlca Carvalho Rubin De Celia; PFIFFER, Tulio Eduardo Flesch; ALEX, Alexandra Khichfy; NEBULONL, Danielle R.; CARNELRO, Allyne Q.; CAPARELL, Fernanda Cunha; LEITE, Luiz Antonio Senna; BRAGHIROLI, Maria Ignez Freitas Meiro; LOBO, Juliana; HOFF, Paulo Marcelo; RIECHELMANN, Rachel PimentaconferenceObject Response to chemotherapy and prognosis in metastatic colorectal cancer with deficient mismatch repair(2016) ALEX, A.; SIQUEIRA, S.; COUDRY, R.; SANTOS, J.; ALVES, M.; HOFF, P.; RIECHELMANN, R.- Response to Chemotherapy and Prognosis in Metastatic Colorectal Cancer With DNA Deficient Mismatch Repair(2017) ALEX, Alexandra Khichfy; SIQUEIRA, Sheila; COUDRY, Renata; SANTOS, Juliana; ALVES, Michel; HOFF, Paulo M.; RIECHELMANN, Rachel P.This study suggests that the DNA deficient mismatch repair (dMMR) phenotype is predictive of resistance to oxaliplatin-based chemotherapy in metastatic colorectal cancer. Patients with dMMR had numerically lower response rate compared with patients with proficient MMR (11.7% vs. 28.6%; P = .088). Furthermore, dMMR was associated with BRAF mutations and was factor of poor prognostic, particularly in sporadic versus Lynch-related tumors. Background: DNA deficient mismatch repair (dMMR) genes are associated with microsatellite instability and good prognosis in early-stage colorectal cancer (CRC). However dMMR is rare in metastatic CRC (mCRC) and little is known about its influence on treatment response rate (RR). The primary objective of this study was to compare the RR of patients with mCRC according to dMMR status. Methods: This was a retrospective study that compared the RR by Response Evaluation Criteria In Solid Tumors 1.1 criteria in patients with mCRC treated with chemotherapy according to dMMR status. All digital images were retrieved for RR evaluation by a single radiologist blinded to dMMR results. dMMR was defined as loss of immunohistochemistry expression of at least 1 of the MMR genes (MLH1, MSH2, MSH6, or PMS2). Cases were dMMR patients, and controls were proficient MMR (pMMR) patients (1: 2 fashion). Based on clinical and molecular features, dMMR patients were classified as probable Lynch or sporadic. Results: From January 2009 to January 2013, 762 out of 1270 patients were eligible and screened for dMMR: n = 27 (3.5%) had dMMR mCRC and n = 735 (96.5%) had pMMR mCRC. Given the rarity, 14 dMMR cases outside the inclusion period were included (total 41 dMMR cases) and 84 controls (pMMR). By intention-to-treat analysis, considering all patients who received at least 1 dose of oxaliplatin-based chemotherapy (N dMMR = 34), those with dMMR had lower RR compared with those with pMMR (RR, 11.7% vs. 28.6%; odds ratio, 0.33; 95% confidence interval, 0.08-1.40; P = .088); patients with probable Lynch-related mCRC presented higher RR than subjects with probable sporadic dMMR (22.2% vs. 0%). dMMR was associated with BRAF mutations and poor prognosis, particularly in the sporadic subgroup (median survival, 29.8 vs. 5.9 months; P = .025). Conclusion: This study suggests that the dMMR phenotype is predictive of resistance to oxaliplatin-based chemotherapy. Apparently, such resistance is more pronounced in the sporadic dMMR phenotype, suggesting biological heterogeneity within the dMMR mCRC subgroup.
- The Effects of Palliative Chemotherapy in Metastatic Colorectal Cancer Patients With an ECOG Performance Status of 3 and 4(2015) TEIXEIRA, Marcela Crosara; MARQUES, Daniel Fernandes; FERRARI, Anezka Celis; ALVES, Michel Fabiano Silva; ALEX, Alexandra Khichfy; SABBAGA, Jorge; HOFF, Paulo M.; RIECHELMANN, Rachel P.There are no data supporting the effect of systemic chemotherapy on the survival of patients with Eastern Cooperative Oncology Group (ECOG) performance status (PS) score of 3 and 4. Among our ECOG PS 3/4 patients with metastatic colorectal cancer (mCRC), patients who received chemotherapy had a survival advantage compared with those given best supportive care (BSC) only. Background: Although chemotherapy is standard for patients with mCRC and ECOG PS of 0/1, the real benefit for patients with ECOG PS > 2 remains uncertain, because they are generally excluded from clinical trials. Our objectives were to compare the survival and safety of ECOG PS 3/4 patients who were administered chemotherapy with those who received BSC only. Patients and Methods: We retrospectively analyzed all consecutive mCRC patients who started first-line chemotherapy at our institution in a 4-year period. A multivariable Cox regression model was used to adjust for prognostic factors and logistic regression, to identify predictive factors of Grade 3/4 toxicity. Results: From June 2008 to June 2012, 240 consecutive patients were included: 100 (41.7%) had an ECOG PS of 0/1, 75 (31.3%) ECOG PS of 2, and 65 (27%) ECOG PS of 3/4. Median survival for patients treated with chemotherapy was 18.4 months for patients with ECOG PS of 0/1, 10.8 months for those with ECOG PS of 2, and 6.8 months for patients with ECOG PS of 3/4. Among those with ECOG PS of 3/4, chemotherapy use led to a nonsignificant survival gain (median, 6.8 vs. 2.3 months for BSC; P = .13). Factors significantly associated with worse survival in an adjusted analysis were right-sided tumors (hazard ratio [HR], 2.97; P = .005) and ECOG PS status (ECOG PS 2 vs. 0/1; HR, 1.67; P = .025, and ECOG PS 3/4 vs. 0/1; HR, 2.67; P < .0001). The rate of Grade >= 3 toxicities during the first cycle did not differ significantly across ECOG groups; likely because 40% of ECOG PS 3/4 patients received upfront dose-reduced therapy. The rates of treatment-related hospitalization were similar across all ECOG groups. All deaths were disease-associated. Conclusion: Our retrospective study suggests that chemotherapy might benefit selected mCRC patients with poor PS. With up-front dose reduction and close monitoring for toxicity, the risk of serious adverse events is minimized.
- Non-inferiority cancer clinical trials: scope and purposes underlying their design(2013) RIECHELMANN, R. P.; ALEX, A.; CRUZ, L.; BARIANI, G. M.; HOFF, P. M.Background: Non-inferiority clinical trials (NIFCTs) aim to demonstrate that the experimental therapy has advantages over the standard of care, with acceptable loss of efficacy. We evaluated the purposes underlying the selection of a non-inferiority design in oncology and the size of their non-inferiority margins (NIFm's). Patients and methods: All NIFCTs of cancer-directed therapies and supportive care agents published in a 10-year period were eligible. Two investigators extracted the data and independently classified the trials by their purpose to choose a non-inferiority design. Results: Seventy-five were included: 43% received funds from industry, overall survival was the most common primary end point and 73% reported positive results. The most frequent purposes underlying the selection of a non-inferiority design were to test more conveniently administered schedules and/or less toxic treatments. In 13 (17%) trials, a clear purpose was not identified. Among the trials that reported a pre-specified NIFm, the median value was 12.5% (range 4%-25%) for trials with binary primary end points and Hazard Ratio of 1.25 (range 1.10-1.50) for trials that used time-to-event primary outcomes. Conclusion: Cancer NIFCT harbor serious methodological and ethical issues. Many use large NIFm and nearly one-fifth did not state a clear purpose for selecting a non-inferiority design.
- A randomized, open-label, parallel-design phase III study to compare adjuvant 5-FU plus oxaliplatin (mFLOX) versus observation in locally advanced rectal cancer after neoadjuvant chemoradiation(2020) BRAGHIROLI, M. I.; MONIZ, C. M. V.; RIECHELMANN, R. S. P.; DORNELLAS, A. F. L.; CAPARELLI, F.; ALBAN, L.; ALEX, A.; BARIANI, G. M.; LEITE, L. A. Senna; RIVELLI, T. Giollo; NEBULONI, D.; ORTEGA, C.; BRAGHIROLI, O. F. M.; MOUTINHO, K.; NAHAS, S.; NAHAS, C.; COTTI, G.; SABBAGA, J.; CECONELLO, I.; HOFF, P. M.
conferenceObject Phase II study of capecitabine in substitution of 5-FU in the chemoradiotherapy regimen for patients with squamous cell carcinoma of the anal canal(2014) RIBEIRO, Suilane Coelho; MONIZ, Camila Motta Venchiarutti; RIECHELMANN, Rachel; BARIANI, Giovanni Mendonca; BRAGHIROLI, Maria Ignez; NAHAS, Caio; COUDRY, Renata; ALEX, Alexandra Khichfy; CARNEIRO, Allyne Q.; NEBULONI, Daniela R.; GLASBERG, Joao; HOFF, Paulo