BOSTONHIV-positive patients often cannot tolerate treatment for
anal squamous cell carcinoma and have a worse prognosis than other
patients, according to two studies presented at the American Society
of Colon and Rectal Surgeons (ASCRS) annual meeting.
Groups in Texas and Washington, DC, reported that review of recent
charts of HIV-positive patients showed they were a distinct group
that could not handle the toxicity of standard therapy. The trend was
so strong that presenters from the University of Texas Southwestern
Medical Center at Dallas said that anal squamous cell carcinoma
should become an AIDS-defining illness, triggering intense
antiretroviral treatment before cancer therapy is attempted.
They tend not to die from their cancer. Even if they die with
cancer, they do not die from cancer; they die from AIDS. The cancer
is a marker that AIDS is very severe, Clifford L. Simmang, MD,
told ONI . He is associate professor of surgery and program
director for Colon and Rectal Surgery at UT-Southwestern.
Bruce A. Orkin, MD, led the study at George Washington University
Medical School. He told ONI, We have to reassess our
treatment of HIV-positive patients with anal cancerlooking at
methods for prevention and earlier detection as well as modification
of the traditional treatment. Dr. Orkin is associate professor
of surgery and director of the Division of Colon and Rectal Surgery,
where he has already begun to experiment with a different regimen.
Although they acted separately, Drs. Orkin and Simmang both said they
had noticed they were treating an unusual number of middle-aged
HIV-positive men for a relatively rare disease that typically occurs
in older women.
The Dallas Study
For the UT-Southwestern study, Ronald J. Place, MD, performed a
retrospective chart review from 1980 to 1999 and identified 29
HIV-positive patients with anal cancer. Of these, 14 had invasive
anal squamous cell carcinoma, 9 had in situ squamous cell carcinoma,
and 6 had non-Hodgkins lymphoma. The mean age was 39.9 years,
all but one was male, and 24 had AIDS.
Therapy was adjusted because of toxicity for nine of the patients
with invasive anal squamous cell carcinoma and four of the lymphoma
Five of the lymphoma patients died with a mean survival rate of 10
months; the only survivor was newly diagnosed. Eight of the invasive
carcinoma patients died at a mean of 17 months; again, four of the
six survivors had been newly diagnosed. Two of the patients with in
situ carcinoma died. Both had CD4 counts of less than 20 cells/mm3.
The rest are currently without anal disease.
CD4 counts showed a correlation with outcome. At diagnosis, the
average counts were 93 for the lymphoma patients, 200 for those with
the in situ carcinomas, and 210 for those with the invasive
carcinomas. The mean CD4 cell count at diagnosis was 121 for those
who died, compared with 248 for those surviving.
A CD4 count under 200 cells/mm³ predicts a poor prognosis for
HIV-positive patients, according to the researchers, who attributed
the deaths to HIV status rather than cancer. Patients with AIDS
cannot tolerate the treatment because of their severe AIDS, Dr.
Simmang said. We have to modify treatment, since it is the AIDS
that kills them. We need to treat them first with antiviral therapy,
so they can tolerate the cancer treatment.
Dr. Place, now chief of colorectal surgery, Madigan Army Medical
Center, Fort Lewis, Washington, told ONI he believes that patients
need to be identified before they develop invasive carcinoma.
People who are HIV positive and who practice anal intercourse
should have regular examinations, just like women have Pap
smears, he said.
George Washington Study
The group at George Washington University treated 98 patients for
anal neoplasms from 1985 to 1999. The researchers analyzed charts on
a cohort of 73 patients who had invasive squamous cell carcinoma,
including cloacogenic carcinoma. Of these patients, 13 were HIV
positive and 60 were HIV negative.
The HIV-positive patients were younger, having a mean age of 42 vs 62
for the HIV-negative group. They were more likely to be male (92% vs
42%) and homosexual (54% vs 15%).
While stage and radiation dose did not differ between the groups,
there were major differences in acute and late treatment toxicity:
62% of the HIV-positive patients vs 31% of HIV-negative patients had
acute treatment toxicity, and 33% and 15%, respectively, had late toxicity.
After initial therapy, 62% of the HIV-positive patients were disease
free vs 85% of the HIV-negative patients. Among those who died, the
mean time to cancer-related death was 2.1 years for the HIV-positive
patients vs 4.6 years for those who were HIV negative (P < .05).
The study concluded that the HIV-positive patients were a distinct
population that had poor tolerance of combined chemotherapy and
radiation, died in a shorter time, and demonstrated a strong trend
toward poorer initial response.
In the 18 months since the study, Dr. Orkin told ONI that he
has changed the regimen for HIV-positive patients from mitomycin C
(Mutamycin) plus fluorouracil to cisplatin (Platinol) plus
fluorouracil, with promising results. He estimates that he has seen
20 more patients with anal cancer since the studyan unusually
high number, he stressed, for a disease that was rare 10 years ago.
The Washington group has solicited doctors at other centers for a
larger study, he said.