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by: Gil Lederman, MD
One of the great success stories in general over the last decade has been the
use of combined modality - chemotherapy and radiation - for those with anal
carcinoma.
In the past, this was a disease treated with radical surgery resulting in
colostomy. The advantage of chemotherapy/radiation success is control of the
disease and maintenance of the anal sphincter meaning no colostomy and a high
degree of freedom from disease recurrence.
New data using chemotherapy/radiation was recently presented by Doci et al
from the National Cancer Institute of Italy evaluating 35 patients with anal
carcinoma. In a descriptive article from The Journal of Clinical
Oncology, the authors describe their treatment approach and results.
Previous studies have shown that chemotherapy and radiation combined gives
results and outcomes comparable to those of radical surgery, however, function
of the anus and rectum is maintained. Surgery is only used for cancers that
progress despite therapy. The Italian National Cancer Institute's previous
studies had used 5FU (5 Fluorouracil) and Mitomycin with external beam radiation
therapy for treatment of anal carcinoma with complete responses of 87%.
Unfortunately, recurrence of cancer was noted in 24% of patients after an
average of eight months.
In an attempt to improve treatment outcome, a new chemotherapy protocol was
commenced using Cisplatin and 5FU. Cisplatin represented a replacement of
Mitomycin.
Between 1991 and 1995, 35 patients were enrolled in this approach. Cancer was
described as squamous cell in 30 and basaloid in 5. Treatment included two
chemotherapy cycles of 5FU and Cisplatin with concurrently administered pelvic
radiation. A 24 hour infusion of 5FU daily on Day 1, 2, 3 and 4 was administered
with Cisplatin administered on Day 1. This chemotherapy treatment was repeated
21 days later.
Radiation was started on the first day using the linear accelerator
delivering treatment to anal and perineum area as well as lower and middle
pelvic sites including the inguinal and external iliac lymph nodes. Total dosage
of 5400 to 5800 rad was administered. A third cycle of chemotherapy was given in
younger patients who had tolerated the previous treatments well.
Toxicity included transient nausea or vomiting and lowering of blood count in
some as well as local side effects including irritation to the skin and
surrounding anal/rectal area as well as diarrhea. Topical treatments were
administered and were successful in general.
Complete response of the anal cancer in metastatic lymph nodes was assessed
in 33 of 35 patients. There was complete regression generally evident at two
months. Nine patients with metastatic cancer to the lymph nodes also had a
complete response at the lymph node site. Two patients had a partial response.
Follow-up at 37 months on average showed that 94% of patients are alive without
cancer. Of the 33 patients who had complete responses, two patients or 6% had
local recurrence. One patient had abdominal perineal resection and is
disease-free 46 months after surgery. A second patient had developed HIV (human
immuno virus) and has liver metastasis.
One patient had a long-standing anal fistula and developed an abscess
requiring surgery. Overall, of 35 patients, 33 are alive without disease and 30
have normal anal function.
These results are obviously highly encouraging. The authors "stress the
feasibility of the treatment, the toxicity and the complication rates of which
none exceed those observed with 5FU plus Mitomycin. However it is possible that
further modification of the schedule could reduce toxicity; in particular, we
are changing the administration of Cisplatin from a single high dose to repeated
low doses with the aim to reduce nausea and vomiting."
In concluding, it is noted that "the overall results of the present
experience are highly encouraging. However, as suggested by others the activity
of this regimen should be tested in Phase III randomized studies before it can
be entered into the standard clinical practice. These data further support the
indication to treat epidermoid cancer of the anal canal with combination
chemotherapy and radiation as primary treatment. Surgery can be reserved as
salvage treatment when residual tumor or local recurrence is detected."
Thus, ongoing research is showing further benefit for those with invasive cancer. Anal cancer once a disease requiring extensive surgery is now treated successfully in the majority with combined chemotherapy and radiation, maintaining anal control and freedom of disease.
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