KARIME KALIL MACHADO

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3
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Instituto do Câncer do Estado de São Paulo, Hospital das Clínicas, Faculdade de Medicina - Médico

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  • conferenceObject
    Expression of ERCC1 protein (excision repair cross complementing group 1) in patients with invasive carcinoma of the uterine cervix (CC) undergoing definitive chemoradiation (CR)
    (2012) CAIRES, Inacelli Queiroz de Souza; CAIRES-LIMA, Rafael; COLOMBO, Renata; RAMOS, Clarissa C. A.; MACHADO, Karime Kalil; SIQUEIRA, Sheila Aparecida Coelho; CARVALHO, Heloisa de Andrade; FUKUSHIMA, Julia Tizue; ADRA, Thais Rodrigues; HOFF, Paulo M.; ESTEVEZ-DIZ, Maria Del Pilar
    Background: CC is the leading cause of cancer death among women in developing countries. ERCC1 protein participates in DNA repair through the nucleotide excision repair pathway, involved in resistance to platinum-based chemotherapy. Its value as a predictive marker of tumor response to treatment, progression or death is still unknown. We evaluated ERCC1 protein expression and clinical variables as a predictive marker of progression-free survival (PFS) and overall survival (OS) in patients (pts) with CC submitted to CR. Methods: Retrospective data analysis of pts with histological diagnosis of CC, treated with CR between 2004-2009. Platinum-based chemotherapy was administered weekly (x6) concurrent to external beam radiotherapy (EBRT) to the pelvis (39.6 – 45.0 Gy), parametrial boost (14.0 – 20.0 Gy) when indicated and high-dose rate brachytherapy (HDR) (28.0 – 30.0 Gy). ERCC1 expression was assessed by immunohistochemistry (IHC). Results: We analyzed 75 pts, median age was 55 years (range 24-76), the performance status (PS) was 0 or 1 at baseline in 50 pts (66%) and 63 had squamous histology (84%). Thirty-two were stage IIB (43%) and 19 were IIIB (25%). Sixty-five patients received cisplatin 40mg/m2/w (87%) and 9, carboplatin AUC2/w (12%), median of 6 cycles (range 2-9). Median RT and HDR doses were 59.4 Gy (range 40.4 to 60.3) and 28.0 Gy (range 14.0 – 37.5), respectively. Thirty-two pts were available by ERCC1 IHC and all expressed the marker. Median PFS and OS were 35.5 (95% CI – 13.8 - 57.6) and 81 (95% CI- 21.2 - 140.8) months, respectively. In multivariate analysis, receiving < 6 chemotherapy cycles and baseline Hb <10.0 were correlated with disease progression and death, HR 0.302; p 0.011 (95% CI- 0.012-0.762) and HR 0.6; p 0.00 (95% CI- 0.474 – 0.760), respectively. PS at baseline did not correlate with PFS or OS, HR 0.985; p 0.614 (95% CI 0.930 – 1.044). Conclusions: In this population, since all pts expressed the protein, ERCC1 expression couldn't discriminate patients who most benefit from CR. Interestingly, a minimum of 6 chemotherapy cycles and a baseline Hb ≥ 10.0 seem to have a prognostic value.
  • conferenceObject
    Use of bevacizumab to reduce the rate of oxaliplatin-induced thrombocytopenia and splenomegaly.
    (2012) OVERMAN, Michael J.; GEORGE, Binsah; KALIL, Karime; FERRAROTTO, Renata; ENG, Cathy; GARRETT, Chris R.; LOYER, Evelyn; HOFF, Paulo Marcelo; CHARNSANGAVEJ, Chusilp; KOPETZ, Scott
  • article 78 Citação(ões) na Scopus
    Role of angiogenesis in the pathogenesis of cancer
    (2012) HOFF, Paulo M.; MACHADO, Karime Kalil
    It has been recognized for decades that angiogenesis is an important event in tumor growth and metastasis; the concept of the ""angiogenic switch,"" whereby tumors acquire the ability to grow exponentially and disseminate beyond their primary site, is one of the central components in our understanding of cancer. A vast network of signaling molecules and receptors that are involved in the regulation of angiogenesis have been identified and characterized; most notably, the vascular endothelial growth factor (VEGF) family. Indeed, the VEGF family of growth factors and receptors has become a prototype for our understanding of angiogenesis during early development and in pathological conditions such as cancer. The specific inhibition of key regulatory molecules including VEGF-A (such as with bevacizumab treatment) has been recognized as a useful strategy to reduce tumor growth and progression in several tumor types. Nevertheless, the contribution of other members of the VEGF family, other signaling pathways, and also endogenous angiogenic inhibitors to tumor angiogenesis, is beginning to emerge. The diversity of pathways and molecules involved in the regulation of angiogenesis in both normal development and cancer will likely offer many more prospects for successful therapeutic intervention.
  • article 9 Citação(ões) na Scopus
    Autonomy Versus Paternalism in Latin America
    (2012) MACHADO, Karime K.; HOFF, Paulo M.
  • bookPart 0 Citação(ões) na Scopus
  • article 13 Citação(ões) na Scopus
    A multicenter, multinational analysis of mitomycin C in refractory metastatic colorectal cancer
    (2012) FERRAROTTO, Renata; MACHADO, Karime; MAK, Milena P.; SHAH, Neeraj; TAKAHASHI, Tiago K.; COSTA, Frederico P.; OVERMAN, Michael J.; KOPETZ, Scott; HOFF, Paulo M.
    Background: A considerable number of metastatic colorectal cancer (mCRC) patients who progress on standard treatment with 5-fluorouracil (5FU), oxaliplatin, irinotecan and monoclonal antibodies, still have adequate performance status and desire further treatment. Mitomycin C (MMC) has been widely used in this context, and despite good tolerability, there are doubts regarding its true benefit. Methods: In order to assess the activity of MMC in the refractory mCRC setting, we retrospectively evaluated 109 heavily pre-treated patients who received MMC as single agent or in combination for mCRC at three different institutions in two countries. Results: Median patient's age was 54 years old, 57% were male and 94% had performance status ECOG 0 or 1. MMC was used in second line in 11%, third line in 38% and fourth line or beyond in 51% of patients. 58% received MMC combinations, mainly with capecitabine. Grade 3 or 4 toxicity was observed in 5% of patients and 6% required dose reductions. Median time to treatment failure (TTF) was 1.7 months with MMC and 3.6 months on the regimen prior to MMC, with a ratio between these TTF below 1 in 82% of patients. Median survival was only 4.5 months (95% confidence interval (CI) of 3.48-5.56). Conclusions: This retrospective data represent the largest reported series of unselected refractory mCRC patients treated with MMC. The median survival of 4.5 months is similar to the survival expected for best supportive care. This lack of activity strongly suggests that MMC should not be routinely used in refractory mCRC.