AB 12. Chronomodulated chemotherapy in chemo naïve NSCLC patients
Background: Lung cancer treatment efficiency has reached a plateau
during the last decade. Although targeted therapies according to tumors
biology and genome expression (pharmacogenomics) have been
introduced in the standard care or are under investigation. Therefore
new methods of chemotherapy treatment have been investigated in
order to augment the efficiency of the already well-established cytotoxic
regimens.
Patients and methods: Twenty non-small cell lung cancer (NSCLC)
chemo naïve patients stage IV were included in the protocol. Sleep
disorders were measured with questionnaires (FSS, MRC, Pittsburgh,
and ESS), polysomnography and actigraphy for 3 consecutive days.
The actigraphy (actiwatch spectrum, Philips, Respironics) was initiated
1 day before treatment when the patient was still at home, the second day when the patient received the platinum analogue doublet and
during the 3 day where the patient was still hospitalized for follow up.
Laboratory values of ACTH, adrenaline, nor-adrenaline, saliva cortisol
(4 measurements/day), morning cortisol and DPD enzyme were
collected and measured for 3 consecutive days. The measurements were
reevaluated after 3 cycles of chemotherapy.
Results: Twenty NSCLC patients entered the protocol and received a
doublet of platinum analogue and docetaxel. Two patients were excluded
from the protocol since they did not wear the actigraph spectrum
watch the proper hours indicated by the treating physicians. No severe
hematological toxicity grades 3 or 4 (according to the National Cancer
Institute of Canada Common Toxicity Criteria version 3) were observed.
An objective tumor response according to the RECIST revised criteria
version 1.1 was observed in 10/18 patients. Chronomodulated
administration according to the circadian rhythm (rest of cell division
of normal cells) is strongly associated with chemo-efficiency (P<0.001).
A strong association was observed between circulating hormones and
disease status (P<0.006). In addition, sleep disorders were associated
with disease status (P<0.005) and normalized with efficient treatment
(P<0.003).
Conclusions: Chronomodulate chemotherapy administration is a
method to augment the treatment efficiency, however expensive and
difficult to perform. Key parameters such as expensive equipment and
sleep expert pulmonary physicians are required.