Advertisement

Topics

Hydralazine and Valproate Plus Cisplatin Chemoradiation in Cervical Cancer

2014-08-27 03:41:25 | BioPortfolio

Summary

The current standard for locally advanced cervical cancer is concurrent cisplatin-based chemotherapy, however, the treatment results need to be improved. Epigenetic aberrations play an important role in cancer progression by silencing growth regulatory genes and there is now evidence that inhibitors of DNA methylation and HDAC inhibition synergize the radiation and chemotherapy effects.

Objective. To determine response rate, safety and biological effects of hydralazine and magnesium valproate when added to cisplatin chemoradiation.

Hypothesis. Hydralazine and magnesium valproate associated to chemoradiation will increase the clinical complete response rate to 95% as compared to 75% as seen in historical controls treated with cisplatin chemoradiation in FIGO stage IIIB patients.

Metodology. A total of 17 FIGO stage IIIB patients with histologically confirmed cervical carcinoma with no previous treatment will be included. Patients will be typed for acetylator status and and then receive either 182 or 83 mg of hydralazine, and magnesium valproate at 40mg/Kg from day -7 to the end of chemoradiation (external and brachytherapy). Clinical response rate, safety and transcriptome changes will be analyzed.

Description

Eligible patients after signing informed consent will undergo study evaluation and then typed for acetylator phenotype before receive either 182 or 83 mg of hydralazine, and magnesium valproate at 30mg/Kg from day -7 to the end of chemoradiation (external and brachytherapy. External beam radiation will be delivered by megavoltage equipment for a dose of 50gy (2Gy fraction from monday to friday) concurrently with cisplatin at 40mg/m2 for six weeks. Within one to two weeks, intracavitary brachytherapy (low-dose rate, Cesium sources) will be delivered to achieve at least 85Gy to point A. A punch biopsy from the primary tumor will be taken at entering the study and at day 8 of hydralazine and valproate treatment (before the first dose of cisplatin and radiation)to assess global gene expression profiling by microarray analysis. Blood samples will be taken to assess global DNA methylation, histone deacetylase activity and plasma levels of hydralazine and valproic acid.

Clinical response and toxicity will be assessed.

Study Design

Allocation: Non-Randomized, Control: Uncontrolled, Endpoint Classification: Safety/Efficacy Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment

Conditions

Cervical Cancer

Intervention

Hydralazine and magnesium valproate, Punch biopsy of the primary tumor

Location

National Institute of Cancerologia
Mexico City
Tlalpan
Mexico
14080

Status

Completed

Source

National Institute of Cancerología

Results (where available)

View Results

Links

Published on BioPortfolio: 2014-08-27T03:41:25-0400

Clinical Trials [1871 Associated Clinical Trials listed on BioPortfolio]

Hydralazine Valproate for Cervical Cancer

The current standard for recurrent, persistent or metastatic cervical cancer is palliative chemotherapy with cisplatin topotecan, however, the results need to be improved. Epigenetic aberr...

Hydralazine and Valproate Added to Chemotherapy for Breast Cancer

Aberrant DNA methylation and histone deacetylation participate in cancer development and progression, as epigenetic alterations are common to breast cancer, in this phase II study, the dem...

A Phase II Study of Epigenetic Therapy to Overcome Chemotherapy Resistance in Refractory Solid Tumors

Chemotherapy resistance, either innate or acquired requires for its development, expression changes on a large number of genes therefore, it has been hypothesized that epigenetic-mediated ...

Biopsy Incisional With Trepan in Periocular Lesions

The purpose of this study was to identify accuracy rates of 2mm punch biopsy technique in diagnosing periocular malignancy.

Hydralazine as a Demethylating Agent in Rectal Cancer

Clinically feasible dose of Hydralazine for ~ 3 months, by virtue of its demethylating effect, will: 1. Result in re-expression of epigenetically silenced TSGs in rectal cancer specimen...

PubMed Articles [14554 Associated PubMed Articles listed on BioPortfolio]

Association between grade of referral smear and high-grade disease among women with biopsy samples showing cervical intraepithelial neoplasia grade 2.

To determine whether the grade of referral smear reflects the frequency of cervical intraepithelial neoplasia (CIN) grade 3 (CIN3) or worse lesions among patients with CIN2 on punch biopsy.

18F-FDG PET/CT for detection of the primary tumor in adults with extracervical metastases from cancer of unknown primary: A systematic review and meta-analysis.

Cancer of unknown primary (CUP) is a heterogeneous group of cancers, so called when a biopsy from a patient reveals malignancy without giving a clue to where in the body the primary tumor is located. ...

Squamous cell carcinoma in situ of the cervix and placental site nodule: Case report.

An asymptomatic 24-year-old woman underwent a colposcopy, cervical biopsy, and subsequently, a conization for a cervical squamous cell carcinoma in situ with glandular extension. Simultaneously, an en...

Prediction of Primary Tumors in Cancers of Unknown Primary.

A cancer of unknown primary (CUP) is a metastatic cancer for which standard diagnostic tests fail to identify the location of the primary tumor. CUPs account for 3-5% of cancer cases. Using molecular ...

A unique case of malignant mixed müllerian tumor with metastasis to the thyroid: a case report.

We present a case of a 61-year-old postmenopausal woman with a known diagnosis of malignant mixed müllerian tumor (MMMT) originally treated with systemic chemotherapy and total abdominal hysterectomy...

Medical and Biotech [MESH] Definitions

First lymph node to receive drainage from the primary tumor. SENTINEL LYMPH NODE BIOPSY is performed to determine early METASTASIS status because cancer cells may appear first in the sentinel node.

Magnesium chloride. An inorganic compound consisting of one magnesium and two chloride ions. The compound is used in medicine as a source of magnesium ions, which are essential for many cellular activities. It has also been used as a cathartic and in alloys.

Magnesium oxide (MgO). An inorganic compound that occurs in nature as the mineral periclase. In aqueous media combines quickly with water to form magnesium hydroxide. It is used as an antacid and mild laxative and has many nonmedicinal uses.

A nutritional condition produced by a deficiency of magnesium in the diet, characterized by anorexia, nausea, vomiting, lethargy, and weakness. Symptoms are paresthesias, muscle cramps, irritability, decreased attention span, and mental confusion, possibly requiring months to appear. Deficiency of body magnesium can exist even when serum values are normal. In addition, magnesium deficiency may be organ-selective, since certain tissues become deficient before others. (Harrison's Principles of Internal Medicine, 12th ed, p1936)

Conducting a biopsy procedure with the aid of a MEDICAL IMAGING modality.

More From BioPortfolio on "Hydralazine and Valproate Plus Cisplatin Chemoradiation in Cervical Cancer"

Quick Search
Advertisement
 

Relevant Topics

Cancer
  Bladder Cancer Brain Cancer Breast Cancer Cancer Cervical Cancer Colorectal Head & Neck Cancers Hodgkin Lymphoma Leukemia Lung Cancer Melanoma Myeloma Ovarian Cancer Pancreatic Cancer ...

Epigenetics
The development and maintenance of an organism is orchestrated by a set of chemical reactions that switch parts of the genome off and on at strategic times and locations. Epigenetics is the study of these reactions and the factors that influence them. ...

Head and neck cancers
Cancer can occur in any of the tissues or organs in the head and neck. There are over 30 different places that cancer can develop in the head and neck area. Mouth cancers (oral cancers)  - Mouth cancer can develop on the lip, the tongue, the floor...


Searches Linking to this Trial