Esophageal carcinoma is a rare cancer of the gastro-intestinal
tract, but the incidence is increasing annually. This is because
of continued smoking (Epidermoid Carcinoma) and the high
incidence of acid reflux disorder as in Western Hemisphere
(Adenocarcinoma). The later in part may be due to abuse of
alcohol, and being overweight. In the seventies the primary
treatment of localized disease of the esophagus was surgery alone
for mid and lower third operable and resectable early lesion.
Post operative radiotherapy (RT) was recommended and given to
those with close margin(s) and/or found to have regional lymph
node(s) involvement. The patients with cancers of the upper third,
regardless of their pathology, and those with locally advanced
disease where treated with radiation only [1-6].
In spite of the above, the overall five year survival was very poor
and unacceptable. With the introduction of Cisplatin chemotherapy
in patients with advanced head and neck cancers, and possible
activities in patients with esophageal carcinoma, led to the early
combined modality therapy in these patients. Induction Cisplatin
followed by RT, concurrent or post total RT where the early of
these trials, and results where somewhat encouraging. With our
introduction of Platinol and 5FU (PF) as active combination in
previously untreated head and neck cancers, this led to the use of PF
in locally advanced esophageal carcinoma with or without surgical
removal or total RT in these patients. The total RT was reduced to
5,000 cGr when was combined and concurrent with this effective
CT because of the overall tolerance and toxicities.
A phase II trial was conducted in the RTOG using two courses
of modified PF combined with RT was tolerable, effective and
acceptable. This led to the well known intergroup trial, headed by
the RTOG of total RT compared to two courses of PF concurrent with
RT, followed by additional two courses of the same doses PF post
RT. The results of this important trial, was outstanding, and even
more than anticipated. This led by a second intergroup randomized
trial, comparing total RT to same CT dose and sequence, but the
concurrent with increased dose of total RT to 6,000 cGr against the
original authors concern. As predicted, the trial ended early with
about 10% treatment death in the combined arm. So, the standard arm reverse back to concurrent two courses of PF with 5,000 cGr,
and adjuvant two courses of PF and unfortunately remained the
“gold” standard treatment for these patients until today.
The total treatment of locally advanced head and neck cancers,
have changed during the last twenty years. Instead, of PF we are
given TPF (Taxotere, Platinol, 5FU) which found to be superior in
randomized intergroup trial. Unfortunate, TPF was rather toxic,
resulted in treatment interruption and even hospitalization to some
patients. This led us to modify TPF giving same dose of Taxotere, but
instead of Cisplatin, we changed to Carboplatin and instead of 5FU
120 hours infusion, we recommended 5FU 2,600mg/m2 24 hour
infusion day 1, 8 and 15. All the three active agents to be repeated
on days 22, and 43.
The following is the full modified TPF treatment:
a. Taxotere 75mg/m2 IV day one and every three weeks
b. Carboplatin AUC 5.00 IV day one and every three weeks
c. 5FU 2,600mg/m2 given as 24 hour IV infusion days 1, 8,
and 15 Repeat all agents of days 22 and 43
This resulted in the most active, and the least toxic combination
for these patients. Less or eliminated side effects of nausea
and vomiting, fluid and electrolytes imbalance, stomatitis/
mucositis, renal, hearing, and peripheral neuropathy. Eliminated
hospitalization, and increased the overall response rates and the
cure rate at five years.
Following the induction CT, concurrent weekly Carboplatin
with total RT was administered. Carboplatin AUC 1.5 IV was given
on the first day of RT and then weekly during RT and for 2-3 weeks
after. This is because the biological effects of RT are still on. Same
total and combination where used by us in limited patients with
locally advanced esophageal cancers, with the same success rate.
It is time to change the course, and the cure rate and survival of
these patients with locally advanced esophageal cancers (both
of Adenocarcinoma or epidermoid carcinoma) at any third of the
esophagus into induction three courses of modified TPF, followed
by RT 5,000 cGr concurrent with weekly Carboplatin.
ISSN: 2574 -1241
