Excretion of Acetylamantadine (AA) by Lung Cancer Patients During a Chemotherapy Regimen
This study is designed to determine if changes in acetyl amantadine (AA) metabolism with
systemic chemotherapy - reflective of SSAT1 activity - are predictive of response to
systemic therapy in patients with lung cancer. Ten patients with adenocarcinoma and 10 with
small-cell cancer who are at American Joint Committee on Cancer (AJCC) stages 3 or 4 at the
time of diagnosis will participate. AA metabolites will be examined by ELISA prior to
initiation of systemic chemotherapy and after the second cycle of therapy. Changes in the
pattern of metabolites will be correlated with convention clinical and radiographic response
- Pattern of AA metabolite excretion/secretion relative to response to therapy.
- Pattern of AA metabolite excretion/secretion relative to time to recurrence or progression.
Evaluation of response to systemic therapy is dependant on clinical and radiographic changes
assessed prior to and after several cycles of systemic therapy. The response rate for lung
cancer to systemic therapy ranges from 30 - 85%, depending on histology and other clinical
factors, but difficult to predict in individual patients. Spermine-spermidine acetyl
transferase (SSAT1) activity is up-regulated in many cancers and may be a marker of response
to therapy. Metabolism of acetyl amantadine (AA) is reflective of SSAT1 activity. In order
to determine if change in SSAT1 activity is predictive of response to systemic chemotherapy,
we propose the following pilot clinical trial. A total of 20 volunteer patients - 10
patients with adenocarcinoma of the lung and 10 patients with small-cell histology will be
included. Eligibility includes patients with adenocarcinoma and small-cell lung cancer who
are at AJCC stage III or IV at diagnosis. Volunteers will be informed that this study is
examining the possibility that we can detect a therapeutic response by a change in their
excretion of AA before it can be detected by conventional patient assessment methods. The
chemotherapy regimen will be selected by the treating physician and will not be influenced
by participation in this clinical trial. The usual treatment regimen for the entities
described above is a platinum-based doublet, often cis-platin with etoposide or gemcitabine
administered for 4 to 6 cycles. The therapeutic response rates with these drug regimens is
about 40% for adenocarcinoma and 70% for small-cell carcinoma. Clinical response is usually
assessed between the second and third cycles of chemotherapy.
Biological Sampling Details
Patient volunteers will be asked to fast overnight prior to the day of their first scheduled
chemotherapy and to ingest an oral dose of 200 mg of amantadine hydrochloride (HCl) in the
morning within an hour of arriving in clinic. The following biological specimens will be
collected: blood (2 x 10 ml) at 2 and 4 hours after amantadine ingestion, saliva (2 x 5ml)
immediately after the blood samples, and a total urine specimen between the time of the 2
blood samples. Patient will be instructed to empty the bladder immediately before the first
blood sample and then collect the total urine produced until the end of the second blood
sample (4 hours). Subsequently, the patient will be allowed lunch (if they so choose) prior
to their scheduled chemotherapy.
The sampling protocol will be repeated 3 weeks later with the second cycle of chemotherapy.
Data to be collected: tumour type (histology), stage of cancer, age, sex, weight, height,
smoking history, concurrent medications, systemic chemotherapy treatment prescribed and
history of recent alcohol intake. Data will be used for correlation and to determine the
relationship of plasma, salivary or urinary AA to the particular cancer diagnosis and
response to treatment.
Documentation of acetylamantadine metabolite excretion/secretion.
Response to therapy (complete response, partial response, stable disease, progressive
Time to disease recurrence or progression.
View this trial on ClinicalTrials.gov