According to the hospital
based cancer registry (HBCR) data, cancers of the head and neck region are the
commonest among male and 6th most common among female cancer patients
attending our hospital1.About 75-80% of these patients present with
stage 3 &4 disease and have less than 33.7% of cure even after radical
treatment2. The scope of salvage of residual or recurrent disease is
limited as many patients are deemed inoperable. Systemic chemotherapy has been
used in such patients but the response rate is low. In addition, the toxicities
of systemic chemotherapy often worsen the distressing symptoms of cancer and
negatively impact the quality of life.
Metronomic chemotherapy is
an alternative way of delivering chemotherapeutic agents. Instead of giving the
maximum tolerated dose, 1/10th to 1/3rddose is
administered in order to maintain a constant low blood level of the drug. This
form of therapy achieves anti-tumour efficacy with low toxicity and also
targets the tumour endothelial cells.
Much of the available literature about metronomic chemotherapy comes
from experimental animals clinical trials using a variety of drugs have been
reported in solid tumours in adults and paediatric population. However the use
of metronomic chemotherapy in head and neck cancer is still very limited. Though some early trials from India have
shown promising results, the initial experience at this institute has shown
that the progression free survival could be significantly improved in patients
with residual and recurrent disease as compared to best supportive care3.
Most of the patients of head and neck cancer
in this institute come from a rural background with financial constraints. Repeatedvisits
to the hospital for a treatment which is unlikely to cure the disease burdens the
patients and their care givers. In addition management of chemotherapy induced
compounds the “out of pocket” expenditure of these patients. Metronomic
chemotherapy with methotrexate significantly reduces the visits to the hospital
and treatment expenses. If the disease control by metronomic chemotherapy is
comparable to the conventional form, using it in selected patients would reduce
toxicities and economic burden of our patients.
REVIEW OF LITERATURE:
Head and neck cancer is
the 6thmost commonly diagnosed cancer worldwide. Epidemiological
studies have estimated the global incidence of all head and neck cancers to be
between 6,00,000 cases per year and the mortality rate between 2,23,000 and 3,00,000
deaths each year4.
The incidence of head and
neck cancers globally is not uniform with a higher incidence in Asia
constituting about 57.5% of global head and neck cancers burden for both sexes5.
Over 2 lakh cases of head
and neck cancer occur each year in India.In Indian males around 30% of all
cancers are head and neck cancers. In females they constitute 11-16% of all
A 5 year (2011 -2015)
consolidated report from hospital based cancer registry(HBCR) at our Regional
cancer centre PGIMER Chandigarh showed that a total of 5284 head and neck
cancers were registered. Head and neck cancers were the most commonly diagnosed
malignancy in males and 6th most commonly diagnosed cancers in
females.Oro-pharyngeal cancer was the most common sub-site to be encountered (1736
cases) among both the sexes1.
% head and neck cancers are diagnosed in locally advanced stage(III/IV). A
similar proportion of cases(75%)were identified in the patients that present to
us with head and neck cancer. Locally advanced stage precludes surgery as a
treatment option. For the 60% of the patients who present with locally advanced
disease at diagnosis, combined modality therapy is generally recommended. For
patients with un-resectable disease the current standard treatment is
concurrent cisplatin-based chemo-radiation. However it has been seen that
despite the combination of chemotherapy and radiation therapy the 5-year
survival rates in locally advanced head and neck cancers is still 30-35%2.
The French cooperative
group trial, GORTEC 94-01 compared radiotherapy alone with concurrent
chemo-radiation where carboplatin and 5-FU were given along with 70 Gy of
conventional radiotherapy. Chemo-radiation therapy resulted in significant 5
year loco-regional control (48% vs. 25%;p=0.002), 5 year disease free survival
(27% vs. 15 %;p=0.01) and 5year survival(23 vs.16 %;p=0.05) at the cost of
increases in acute mucositis grade 2 or higher (79% vs. 39%)6.
Wendt et all conducted a
multi-institutional trial where they compared CRT vs. RT alone and found that
CRT doubled the 3-year local control(35% vs 17%;p