Publications by authors named "Álvaro Henrique Ingles Garces"

6 Publications

  • Page 1 of 1

Efficacy of doxorubicin after progression on carboplatin and paclitaxel in advanced or recurrent endometrial cancer: a retrospective analysis of patients treated at the Brazilian National Cancer Institute (INCA).

Med Oncol 2018 Jan 31;35(3):20. Epub 2018 Jan 31.

Instituto Nacional do Câncer, Hospital do Câncer II, Equador St, 831, 3rd Floor - Santo Cristo, Rio de Janeiro, RJ, 22220-410, Brazil.

The treatment of endometrial cancer (EC) is challenging. There is no standard of care for patients who progressed after carboplatin and paclitaxel (CT) and all available drugs show a small response and poor long-term survival in this scenario. The objective of this study was to evaluate the efficacy and toxicity profile of palliative doxorubicin after progression to CT therapy in advanced or recurrent EC. A retrospective review of the Brazilian National Cancer Institute database between 2009 and 2013 was performed, and all patients with recurrent and advanced EC treated with palliative doxorubicin after progression on CT were included. Progression-free survival (PFS), overall survival (OS), objective response rates as well as toxicity were evaluated. A total of 33 patients were enrolled, with a median age of 65.7 years. Objective responses were documented in 12.1% (3.0% of complete responses and 9.1% of partial responses). The median PFS was 4.4 months, and the median OS was 8.1 months for patients exposed to doxorubicin. The most common adverse event was anemia observed in 60.6% of patients. This retrospective study suggests that doxorubicin has a modest activity in patients with advanced or recurrent EC after treatment with CT.
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http://dx.doi.org/10.1007/s12032-018-1086-7DOI Listing
January 2018

A Review of mTOR Pathway Inhibitors in Gynecologic Cancer.

Oxid Med Cell Longev 2017 13;2017:4809751. Epub 2017 Feb 13.

Brazilian National Cancer Institute (INCA), Rio de Janeiro, RJ, Brazil.

The treatment of advanced gynecologic cancers remains palliative in most of cases. Although systemic treatment has entered into the era of targeted drugs the antitumor efficacies of current therapies are still limited. In this context there is a great need for more active treatment and rationally designed targeted therapies. The PI3K/AKT/mTOR is a signaling pathway in mammal cells that coordinates important cell activities. It has a critical function in the survival, growth, and proliferation of malignant cells and was object of important research in the last two decades. The mTOR pathway emerges as an attractive therapeutic target in cancer because it serves as a convergence point for many growth stimuli and, through its downstream substrates, controls cellular processes that contribute to the initiation and maintenance of cancer. Aberrant PI3K-dependent signaling occurs frequently in a wide range of tumor types, including endometrial, cervical, and ovarian cancers. The present study reviewed the available evidence regarding the potential impact of some mTOR pathway inhibitors in the treatment of gynecological cancer. Few advances in medical management have occurred in recent years in the treatment of advanced or recurrent gynecological malignancies, and a poor prognosis remains. Rationally designed molecularly targeted therapy is an emerging and important option in this setting; then more investigation in PI3K/AKT/mTOR pathway-targeted therapies is warranted.
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http://dx.doi.org/10.1155/2017/4809751DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5327776PMC
March 2017

Patterns of Care and Outcome of Elderly Women Diagnosed With Cervical Cancer in the Developing World.

Int J Gynecol Cancer 2016 09;26(7):1246-51

*National Cancer Institute, Rio de Janeiro; †EVA, Brazilian Group of Gynecologic Oncology; and ‡University of Itauna, Minas Gerais, Brazil.

Scarce data exist about the impact of age in cervical cancer (CC) patients in the developing world. The objective of the current study was to examine the patterns of care and outcome of elderly patients treated in a developing country. Medical records of patients treated from 2006-2009 at the Brazilian National Cancer Institute were reviewed. Patients were divided between women 70 years or older and women younger than 70 years. The χ tests were used and odds ratios were calculated. Survival was examined using the Kaplan-Meier method. Single and multivariate Cox proportional hazards modeling were used. A total of 1482 patients were analyzed: 1339 patients younger than 70 years and 143 patients 70 years or older. A marked difference in treatment was noted, even after stratifying by disease stage. Only 21% of the older patients underwent surgical treatment compared with 27.6% of the younger. After adjusting for confounding variables, the hazard ratio for death from CC in the elderly was 1.05 (95% confidence interval, 0.81-1.36; P = 0.11). These results corroborate previous data from developed countries: elderly patients have more advanced disease at diagnosis, and age is an important factor in the allocation of treatment for patients with CC. Worse outcome seemed to be mainly the result of more advanced stage and treatment allocation rather than age itself.
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http://dx.doi.org/10.1097/IGC.0000000000000756DOI Listing
September 2016

A phase I study of mTOR inhibitor everolimus in association with cisplatin and radiotherapy for the treatment of locally advanced cervix cancer: PHOENIX I.

Cancer Chemother Pharmacol 2016 Jul 20;78(1):101-9. Epub 2016 May 20.

Brazilian Clinical Cancer Research Network (RNPCC) - INCA/Decit/MS, D'or Institute of Research and Education (IDOR), Rio de Janeiro, Brazil.

Background: Cervix cancer (CC) represents the fourth most common cancer in women. Treatment involving cisplatin and radiotherapy has been the standard for locally advanced disease. Everolimus inhibits the aberrant activity of mTOR that is part of carcinogenesis in CC. Further everolimus inactivates the HPV E7 oncoprotein and inhibits its proliferation. Preclinical models have suggested that everolimus sensitizes tumoral cells and vasculature to cisplatin and radiotherapy.

Methods: In a 3 + 3 design, the trial aimed to treat three dose levels of at least three patients with daily doses of everolimus (2.5, 5 and 10 mg/day), cisplatin and radiotherapy delivered in a 9-week interval in CC patients, stage IIB, IIIA or IIIB. Patients received everolimus from day -7 up to the last day of brachytherapy. Primary objective was to evaluate safety, toxicity and the maximum-tolerated dose (MTD) of everolimus in association with cisplatin and radiotherapy. Pharmacokinetic (PK) parameters and response rates were analyzed as secondary objectives.

Results: Thirteen patients were enrolled, 6 at 2.5 mg, 3 at 5 mg and 4 at 10 mg. Four patients did not complete the planned schedule, 1 at 2.5 mg presented grade 4 acute renal failure interpreted as dose-limiting toxicity (DLT) and 3 at 10 mg: 1 with disease progression, and 2 with DLTs-1 grade 3 rash and 1 grade 4 neutropenia. PK results were characterized by dose-dependent increases in AUC and C max.

Conclusions: The MTD of everolimus in combination with cisplatin and radiotherapy has been defined as 5 mg/day. The data regarding safety and response rates support further studies.
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http://dx.doi.org/10.1007/s00280-016-3064-0DOI Listing
July 2016

Treatment of ovarian cancer beyond chemotherapy: are we hitting the target?

Cancer Chemother Pharmacol 2015 Feb 12;75(2):221-34. Epub 2014 Sep 12.

Instituto Nacional do Câncer, Hospital do Câncer - II, Equador Street, 831, 3º floor - Santo Cristo, Rio de Janeiro, RJ, 22220-410, Brazil,

Ovarian cancer (OC) is the sixth most common cancer worldwide among women, and, in developed countries, it is the leading cause of mortality among gynecological malignancies. With an overall cure rate of <40% across all stages, it comprises a variety of tumors with different histopathological features and biological behavior. Nowadays, OC is considered a general term that designates a group of molecularly and etiologically distinct diseases that share an anatomical location. Approximately 70-80% of patients with OC will relapse after first-line chemotherapy, and the majority of them will eventually die of chemotherapy-resistant disease. Until now, the management of relapsed OC remains an unmet medical need. Therapy rather depends on tumor stage and grade than on histological type, but there is growing evidence that, as epithelial OC is a heterogeneous disease, it needs a tailored approach based on the underlying molecular genetic changes. Several phase III studies investigating targeted therapies are underway, and a more individual approach for treating OC will be selected in the future. The purpose of this paper was to review the literature in order to highlight available data emerging from trials and to evaluate efficacy and safety of molecularly targeted drugs in OC.
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http://dx.doi.org/10.1007/s00280-014-2581-yDOI Listing
February 2015

First-line paclitaxel and carboplatin in persistent/recurrent or advanced cervical cancer: a retrospective analysis of patients treated at Brazilian National Cancer Institute.

Int J Gynecol Cancer 2013 May;23(4):743-8

Hospital do Câncer II-INCA, GTG-Grupo de Tumores Ginecológicos do INCA, Rio de Janeiro, Brazil.

Objective: Cervical cancer represents the third most commonly diagnosed cancer and the fourth cause of cancer death in women worldwide. In the palliative scenario, the combination of paclitaxel and cisplatin is widely used. Carboplatin is also an active agent in cervical cancer, and its association with paclitaxel could represent a well-tolerated, less toxic, and effective therapeutic option. The objective of this study was to evaluate response rate, progression-free survival, overall survival, and toxicity of carboplatin and paclitaxel in first palliative line for cervical cancer.

Methods: A retrospective search of database at Brazilian National Cancer Institute was performed, and all patients with persistent/recurrent and advanced cervical cancer treated with paclitaxel and carboplatin in first palliative line, between August 2008 and January 2010, were included.

Results: A total of 153 women were enrolled. Objective responses were documented in 34.6% (5.2% of complete responses and 29.4% of partial responses). With a median follow-up of 27.8 months, the median progression-free survival was 5.2 months, and the median overall survival was 10.63 months. The most common toxicity was myelosuppression: grades 3 and 4 anemia, neutropenia, and thrombocytopenia observed in 43.0%, 17.8%, and 9.2% of the cases, respectively. Neurotoxicity was presented by 30.7% of the patients. Renal toxicity was detected in 21.9% of the patients, but only 4.0% were grade 3, and none were grade 4.

Conclusions: This retrospective study has demonstrated that paclitaxel-carboplatin is an active and well-tolerated regimen for the treatment of advanced cervical cancer.
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http://dx.doi.org/10.1097/IGC.0b013e31828c141dDOI Listing
May 2013
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