GIOVANNI MENDONCA BARIANI
Projetos de Pesquisa
Unidades Organizacionais
Instituto do Câncer do Estado de São Paulo, Hospital das Clínicas, Faculdade de Medicina - Médico
16 resultados
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conferenceObject Prospective study of biomarkers in squamous cell carcinoma of the anal canal (SCCAC) and their influence on treatment outcomes: Five-year long-term results.(2020) MONIZ, Camila Motta Venchiarutti; RIECHELMANN, Rachel Pimenta; BRAGHIROLI, Maria Ignez; RIBEIRO, Suilane Coelho; RIVELLI, Thomas Giollo; BARIANI, Giovanni M.; CHEN, Andre Tsin Chih; NAHAS, Caio; BONADIO, Renata Colombo; ORTEGA, Cinthia; FRANCO, Rejane; MEIRELES, Sibele; PEREIRA, Allan Andresson Lima; SABBAGA, Jorge; COUDRY, Renata A.; HOFF, Paulo Marcelo- A Prospective Cohort Study of Biomarkers in Squamous Cell Carcinoma of the Anal Canal (SCCAC) and their Influence on Treatment Outcomes(2021) MONIZ, C. M. V.; RIECHELMANN, R. P.; OLIVEIRA, S. C. R.; BARIANI, G. M.; RIVELLI, T. G.; ORTEGA, C.; PEREIRA, A. A. L.; MEIRELES, S. I.; FRANCO, R.; CHEN, A.; BONADIO, R. C.; NAHAS, C.; SABBAGA, J.; COUDRY, R. A.; BRAGHIROLI, M. I.; HOFF, P. M.Background: Although Chemoradiation (CRT) is the curative treatment for SCCAC, many patients present primary resistance. Since it is a rare tumor, response predictors remain unknown. Methods: We performed a prospective cohort study to evaluate biomarkers associated with CRT response, progression-free survival (PFS), and overall survival (OS). The primary endpoint was response at 6 months (m). Tumor DNA and HPV were analyzed by next-generation sequencing, while KI-67 and PD-L1 by immunohistochemistry in tumor tissue. Results: Seventy-eight patients were recruited between October/2011 and December/2015, and 75 were response evaluable. The median age was 57 years, 65% (n=49) were stage III and 12% (n=9) were HIV positive (HIV+). At 6m, 62.7% (n=47) presented CR. On multivariate analyses, stage II patients were 4.7 more likely to achieve response than stage III (OR, 4.70; 95%CI, 1.36-16.30; p=0.015). HIV+ was associated with a worse response (OR, 5.72; 95%CI, 2.5-13.0; p<0.001). 5-year PFS and OS rates were 63.3% and 76.4%, respectively, with a median follow up of 66m. On multivariate analyses, older age (HR 1.06, p=0.022, 95%IC 1.01-1.11) and absence of CR at 6m (HR 3.36, p=0.007, 95%IC 1.39-8.09) were associated with inferior OS. The 5-year OS rate was 62.5% in HIV+ group compared to 78% among HIVpts, although this difference was not statistically significant (p=0.4). PIK3CA, MET and TP53 mutations, HPV, Ki-67 expression, and PD-L1 expression, were not associated with PFS and OS. Conclusions: Clinical stage III and HIV+ were associated with worse response to CRT at 6m. The absence of CR was the main factor associated with poor 5-year OS. © The author(s).
- Regorafenib in Patients with Antiangiogenic-Naive and Chemotherapy-Refractory Advanced Colorectal Cancer: Results from a Phase IIb Trial(2019) RIECHELMANN, Rachel P.; LEITE, Luiz S.; BARIANI, Giovanni M.; GLASBERG, Joao; RIVELLI, Thomas G.; FONSECA, Leonardo Gomes da; NEBULONI, Daniela R.; I, Maria Braghiroli; QUEIROZ, Marcelo A.; ISEJIMA, Alice M.; KAPPELER, Christian; KIKUCHI, Luciana; HOFF, Paulo M.Background Regorafenib is a multikinase inhibitor with antiangiogenic effects that improves overall survival (OS) in metastatic colorectal cancer (mCRC) after failure of standard therapies. We investigated the efficacy and safety of regorafenib in antiangiogenic therapy-naive chemotherapy-refractory advanced colorectal cancer. Patients and Methods This single-center, single-arm, phase IIb study (NCT02465502) enrolled adults with mCRC whose disease had progressed on, or who were intolerant to, standard therapy, but who were antiangiogenic therapy-naive. Patients received regorafenib 160 mg once daily for 3 weeks per 4-week cycle. The primary endpoint was progression-free survival (PFS) rate at week 8. Results Of 59 treated patients, almost half had received at least four prior lines of therapy. Patients received a median of 86% of the planned dose. The week 8 PFS rate was 53% (95% confidence interval [CI], 39.1-64.3); median PFS was 3.5 months (95% CI, 1.8-3.6). Median OS was 7.4 months (95% CI, 5.3-8.9). Tumor response (RECIST version 1.1) was 2%, and metabolic response rate (criteria from the European Organisation for Research and Treatment of Cancer) was 41%. The most frequently reported regorafenib-related grade >= 3 adverse events were hypertension (36%), hand-foot skin reaction (HFSR, 25%), and hypophosphatemia (24%). There were no regorafenib-related deaths. An exploratory analysis showed that patients with grade >= 2 HFSR had longer OS (10.2 months) with regorafenib treatment versus those with grades 0-1 (5.4 months). Conclusion These findings support the antitumor activity of regorafenib in antiangiogenic-naive patients with chemotherapy-refractory mCRC. Implications for Practice The multikinase inhibitor regorafenib improved overall survival in the phase III CORRECT and CONCUR trials in heavily pretreated patients with treatment-refractory metastatic colorectal cancer (mCRC). Exploratory subgroup analysis from CONCUR suggested that regorafenib treatment prior to targeted therapy (including bevacizumab) may improve outcomes. In this single-center, single-arm phase IIb study, regorafenib demonstrated antitumor activity in 59 antiangiogenic-naive patients with chemotherapy-refractory mCRC. Further studies should assess the efficacy of regorafenib in this patient population, as well as explore the reasons behind improved outcomes among patients who had a metabolic response and those who developed hand-foot skin reaction.
- 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.
- Self-Reported Conflicts of Interest of Authors, Trial Sponsorship, and the Interpretation of Editorials and Related Phase III Trials in Oncology(2013) BARIANI, Giovanni M.; FERRARI, Anezka C. R. de Celis; HOFF, Paulo M.; KRZYZANOWSKA, Monika K.; RIECHELMANN, Rachel P.Purpose Growing participation by industry in cancer research has resulted in increased reporting of conflicts of interest (COI). We aimed to test any association between authors' conclusions and self-reported COI or trial sponsorship in cancer studies. Methods Editorials and related phase III trials published in six clinical oncology journals in the last 3.5 years were analyzed independently by two investigators who classified study conclusions according to authors' endorsement of the experimental therapy. Logistic regression multivariable models were used to assess predictors of favorable conclusions of editorialists and of phase III authors. Results From January 2008 to October 2011, 1,485 articles were retrieved: 150 phase III trials and 150 editorials were eligible. Among the phase III trials, 82 (54.7%) had positive results, and 78 (52.0%) were entirely or partially funded by industry. Any COI were disclosed in 103 phase III trials (68.7%) and in 71 editorials (47.3%). Multivariable analysis showed that phase III trial results were the only significant predictor for a positive conclusion by trial authors (odds ratio [OR], 92.2; 95% CI, 19.7 to 431.6; P < .001). Sponsorship did not predict for positive conclusion by phase III authors (OR, 0.86; 95% CI, 0.3 to 2.5; P = .788). The only factor associated with positive conclusions by editorial authors was a positive conclusion by phase III trial authors (OR, 36.3; 95% CI, 6.8 to 194.2; P < .001). Conclusion The interpretation of recently published phase III cancer trials by their authors or by editorialists was not influenced by financial relationships or industry sponsorship. Increased awareness of COI policies may have led to more integrity in cancer research reporting. (C) 2013 by American Society of Clinical Oncology
conferenceObject THE QUALITY OF SAMPLE SIZE CALCULATION (SSC) REPORTING IN CANCER CLINICAL TRIALS(2012) BARIANI, G. M.; FERRARI, A. C. R. C.; HOFF, P. M.; ARAI, R.; PRECIVALE, M.; RIECHELMANN, R. P.Background SSC is a pivotal step in clinical trial concept and design. It determines the chance of detecting a significant result, ensures appropriate power, and helps sponsors to allocate adequate resources into trials. Here we describe the frequency with which randomized cancer clinical trials (RCT) report the data required for SSC. Methods We systematically searched for phase III RCT published in top clinical oncology journals which were accompanied by editorials from Jan 2008 to Oct 2011. We assumed that RCT discussed by editorialists were clinically important. Two blinded investigators extracted data on SSC. Table 1 describes the information required for SSC according to variable type used for primary endpoint. Results 140 out of 150 RCT were eligible. Median sample size was 596 subjects (50-40,000) per RCT. In 65.7% of RCT, the number of enrolled subjects was at least 90% of the planned sample size. The primary endpoint was a categorical variable in 10.0%, continuous in 27.9%, and time-to-event in 62.1%. In general, 80.7% reported a planned sample size, 57.9% described their null hypothesis (H0), with 20.7% giving a scientific rationale for H0. 57.9% informed their alternative hypothesis (H1). Alpha (α) and beta (β) errors were explicit in 92.9% and 90.7%, respectively. Expected difference between arms was reported in 88.6%. Only 2.9% of RCT provided all information for proper SSC (required and optional, Table). Excluding “optional information”, SSC could be reproducible in 18.6% of RCT. Conclusion Regardless of the CONSORT 2010 statement, the quality of SSC reporting in phase III cancer RCT seems inadequate. This may compromise future study designs, pooling of data and interpretation of results. Lack of transparency in SSC reporting may also have ethical implications. Variable Type Required information Optional information Categorical H1H0 Expected difference between arms (delta) α and β errors Dropout rate Statistical test used for SSC Scientific rationale for H0 and H1 Continuous H1H0 Delta Standard deviation for both arms α and β errors Same as above Time-to-event H1H0 Delta (hazard ratio) Length of recruitment Length of follow up for each patient α and β errors Same as above Information necessary for SSC- A Prospective Cohort Study of Biomarkers in Squamous Cell Carcinoma of the Anal Canal (SCCAC) and their Influence on Treatment Outcomes(2021) MONIZ, Camila Motta Venchiarutti; RIECHELMANN, Rachel Pimenta; OLIVEIRA, Suilane Coelho Ribeiro; BARIANI, Giovanni Mendonca; RIVELLI, Thomas Giollo; ORTEGA, Cintia; PEREIRA, Allan Andresson Lima; MEIRELES, Sibele Inacio; FRANCO, Rejane; CHEN, Andre; BONADIO, Renata Colombo; NAHAS, Caio; SABBAGA, Jorge; COUDRY, Renata Almeida; BRAGHIROLI, Maria Ignez; HOFF, Paulo MarceloBackground: Although Chemoradiation (CRT) is the curative treatment for SCCAC, many patients present primary resistance. Since it is a rare tumor, response predictors remain unknown. Methods: We performed a prospective cohort study to evaluate biomarkers associated with CRT response, progression-free survival (PFS), and overall survival (OS). The primary endpoint was response at 6 months (m). Tumor DNA and HPV were analyzed by next-generation sequencing, while KI-67 and PD-L1 by immunohistochemistry in tumor tissue. Results: Seventy-eight patients were recruited between October/2011 and December/2015, and 75 were response evaluable. The median age was 57 years, 65% (n=49) were stage III and 12% (n=9) were HIV positive (HIV+). At 6m, 62.7% (n=47) presented CR. On multivariate analyses, stage II patients were 4.7 more likely to achieve response than stage III (OR, 4.70; 95%CI, 1.36-16.30; p=0.015). HIV+ was associated with a worse response (OR, 5.72; 95%CI, 2.5-13.0; p<0.001). 5-year PFS and OS rates were 63.3% and 76.4%, respectively, with a median follow up of 66m. On multivariate analyses, older age (HR 1.06, p=0.022, 95%IC 1.01-1.11) and absence of CR at 6m (HR 3.36, p=0.007, 95%IC 1.39-8.09) were associated with inferior OS. The 5-year OS rate was 62.5% in HIV+ group compared to 78% among HIVpts, although this difference was not statistically significant (p=0.4). PIK3CA, MET and TP53 mutations, HPV, Ki-67 expression, and PD-L1 expression, were not associated with PFS and OS. Conclusions: Clinical stage III and HIV+ were associated with worse response to CRT at 6m. The absence of CR was the main factor associated with poor 5-year OS.
- Regorafenib in antiangiogenic-naive, chemotherapy-refractory advanced colorectal cancer: A phase IIb trial.(2018) RIECHELMANN, Rachel Pimenta; LEITE, Luiz Antonio Senna; GLASBERG, Joao; BARIANI, Giovanni Mendonca; RIVELLI, Thomas Giollo; NEBULONI, Daniela R.; PUTY, Fabiola; KAPPELER, Christian; PEREIRA, Kaline M. C.; QUEIROZ, Marcelo A.; HOFF, Paulo Marcelo
conferenceObject METRONOMIC ORAL CYCLOPHOSPHAMIDE IN THE TREATMENT OF METASTATIC SOFT TISSUE SARCOMA: IS THERE A ROLE FOR MAINTENANCE THERAPY?(2012) FERRARI, A. C. R.; CAMARGO, V. P.; BARIANI, G. M.; GONCALVES, M. S.; HOFF, P. M.; CASTRO JR., G. DeBackground Metronomic chemotherapy has been demonstrated to improve DFS in advanced STS. Here we aimed to analyze the efficacy and safety of metronomic oral cyclophosphamide (M-CTX) as maintenance or salvage therapy in these patients (pts). Methods It is a retrospective study of all advanced/metastatic STS pts (RMS, GIST, bone sarcomas excluded) treated in our institution between Feb/2009 and Jan/2012 with M-CTX 100 mg PO daily 21 out of 28 days, until disease progression (DP). Tumor response (RECIST 1.1) was assessed every 2 cycles. The primary endpoint of the study was time to treatment failure (TTF). Toxicity was graded according to the NCI-CTC v.3.0. criteria. Results 27 pts were consecutively included in this analysis. Thirteen pts received M-CTX as maintenance chemotherapy after presenting best response: median age 60 y, 9 female; 5 LMS, 3 HGUPS, 2 PNET, 3 others. Median number of previous chemotherapy regimens 2; 9 previously treated with doxorubicin and 4 with ifosfamide; 4 presented PR as best response. Median TTF (mTTF) was 9.2 mo, 4 pts (2 PNET, 1 LMS, 1 HGUPS) had mTTFs ≥ 6 mo and no deaths were observed in a median follow-up of 7 mo. 14 pts received M-CTX as salvage chemotherapy after DP: median age 45.5 y, 8 female; 3 LMS, 3 HGUPS, 3 synovial, 2 ASPS, 3 others. Median number of previous chemotherapy regimens 1.5; 11 previously treated with doxorubicin and 6 with ifosfamide; 1 PR as best response. mTTF 3.3 mo, 1 ASPS had mTTFs ≥ 6 mo, and 9 deaths (HR 1.403, 95%CI 0.608-3.236, p = 0.409, in comparison with maintenance strategy). In general, M-CTX was well tolerated, and the most common toxicity (>10%) included nausea G1 (5 pts), renal failure (3 pts), anemia G1 (4 pts), anemia G2 (3 pts), lymphopenia G1 (12 pts). Conclusions Metronomic oral cyclophosphamide seems to be a valid option as maintenance chemotherapy after presenting best response in advanced/metastatic STS, with acceptable toxicity. This compares favorably with historical controls (mPFS around 4 months). However, after disease progression, it is a futile chemotherapy regimen. Disclosure A.C.R. Ferrari: Travel expenses covered: Roche.- Prospective study of biomarkers in squamous cell carcinoma of the anal canal (SCCAC) and their influence on treatment outcomes: Final results.(2017) MONIZ, Camila Motta Venchiarutti; RIECHELMANN, Rachel Pimenta; RIBEIRO, Suilane Coelho; RIVELLI, Thomas Giollo; BARIANI, Giovanni Mendonca; CHEN, Andre; FRANCO, Rejane; NAHAS, Caio; PEREIRA, Allan Andresson Lima; ORTEGA, Cintia; SABBAGA, Jorge; MEIRELES, Sibele; COUDRY, Renata A.; HOFF, Paulo Marcelo