Overview

Hydralazine and Valproate Plus Cisplatin Chemoradiation in Cervical Cancer

Status:
Completed
Trial end date:
2006-11-01
Target enrollment:
0
Participant gender:
Female
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.
Phase:
Phase 2
Accepts Healthy Volunteers?
No
Details
Lead Sponsor:
National Institute of Cancerología
Collaborators:
National Council of Science and Technology, Mexico
Psicofarma S.A. de C.V.
Treatments:
Cisplatin
Hydralazine
Valproic Acid
Criteria
Inclusion Criteria:

- informed consent, histological diagnosis of cervical carcinoma (epidermoid,
adenoesquamous and adenocarcinoma), clinical stage III B, untreated, aged 18-70 years,
performance status 0-2 according to ECOG classification, and adequate liver,
hematological and renal function, as defined by: hemoglobin >10 g/L, leukocytes
>4000/mm3, platelets >100 000mm3; normal creatinine value and creatinine clearance >60
mL/min; total bilirubin < 1.5 upper normal limit value; no evidence of systemic
disease or para-aortic lymph node involvement.

Exclusion Criteria:

- History of allergy to hydralazine or valproate; past or present condition of rheumatic
disease, central nervous system disease, heart failure from aortic stenosis and
postural hypotension as diagnosed by a physician; previous use of the experimental
drugs (hydralazine and magnesium valproate) as well as if patients were pregnant or
breast-feeding. Other exclusion criteria included uncontrolled systemic disease or
infection.