KOLKATA, India - They lie in long rows of beds in a hospital women's ward - weak and forlorn as they battle cervical cancer.
plight of such women inspired a team of doctors from Louisville, Ky.,
and Kolkata in 2007 to explore a new treatment for the potentially
But that team is now reaching a disappointing
conclusion: An experimental radiation and immunotherapy regimen appears
less effective against advanced cancer than the traditional Western
treatment, which remains out of reach for many poor, Indian women.
data show that chemo and radiation, which is the consensus way to treat
advanced cervical cancer in the States," seems to work better than the
experimental treatment among the Indian patients, said University of
Louisville researcher Dr. A. Bennett Jenson.
"I was (initially) under the notion it was as effective as chemo. And I don't think it is," said Jenson, of the James Graham Brown Cancer Center.
"I'm disappointed. It wasn't the answer we wanted. ... (But)
seventy-five percent of clinical trials don't yield the results you want
them to yield."
Initial results from the five-year study at India's Chittaranjan National Cancer Institute
looked promising, with the experimental regimen accounting for slightly
more recoveries than the conventional treatment two years into the
Hopes were high that the experimental regimen might help
impoverished women around the world, including in rural, low-income
But now, nearly a year after the last woman enrolled, the results have become discouraging.
103 women in the experimental arm of the trial, 42 are free of disease,
six are alive with recurrent disease, and 55 have died. Of the 106
women in the control arm - those treated with conventional treatment -
61 are free of disease, 10 are alive with a recurrence, and 35 have
Cervical cancer at late stages is uniformly fatal if left
untreated, and even with chemo-radiation treatment, the five-year
survival rate is 50 percent or less.
As of now, "the study shows
the immunotherapy does not have any advantage over the conventional
chemo-radiation," said Dr. Partha Basu, head of the department of
gynecological oncology at Chittaranjan and principal investigator in the
"I wish the immunotherapy arm would have done a little
better. I really wanted it to work better for the patients," said
Debapriya Banerjee, clinical trials manager for gynecological oncology
stressed that they are still following up with patients, and questions
remain - including some that raise doubt about whether the difference in
deaths is statistically significant and will hold up over the long
For example, he said, more women who joined the study early
were placed into the experimental arm, meaning they've had more time for
relapses and death to occur than those in the control arm. Also, he
said, it's been difficult to determine what has happened to every
participant, since some women never returned from remote villages for
No matter what they find, Basu and Jenson said there's
an undeniable upside to the study: a commitment to providing more
patients with chemotherapy.
Before 2007, Basu said most
Chittaranjan patients with advanced cervical cancer received only
radiation because there weren't enough hospital beds for chemotherapy.
we started providing chemotherapy through the trial, more patients
started demanding chemotherapy," Basu said, resulting in a day
chemotherapy center opening at the hospital.
Deadly in India
Basu and Jenson said the study also underscores the need for cervical cancer prevention.
Jenson, one of the inventors of the Gardasil
shots that protect against the human papillomavirus that causes most
cervical cancer, is now working on an inexpensive version for the
developing world that would cost as little as $3.
Basu, meanwhile, has become more involved in improving cervical
cancer detection and awareness, partly through "screening camps" in
remote areas. He recently operated on 50-year-old Neburjan Bibi, who
lives in a village seven hours from Kolkata and whose early-stage cancer
was discovered at a screening camp.
"The chance of recurrence is very low," Basu said, touching Bibi's arm as she lay in a hospital bed. "She'll be OK."
cancer is both preventable and curable at early stages. Yet it remains
the biggest cancer killer of Indian women, striking 130,000 each year
and killing 75,000.
Poverty, combined with a lack of cervical
cancer screening and access to health care, means the vast majority of
cases are diagnosed late.
In the United States, women are
routinely screened for cervical cancer with Pap smears and often have
precancerous lesions removed before they turn into cancer. About 12,000
American women are diagnosed with cervical cancer each year, and about
A study released in 2009 by the World Health
Organization found that Indian women have a lower rate of infection from
human papillomavirus, or HPV, than Americans.
But Indians face
risk factors Americans don't. For example, village women often marry in
their teens and get pregnant soon afterward, which suppresses immune
systems weakened by malnutrition and increases the likelihood that an
HPV infection will progress to cancer.
And once cancer strikes,
getting care can be difficult for the poor, rural women who are hardest
hit. There are fewer than a third as many hospital beds per person in
India as in the United States, and many rural villages are hours from
A new approach
trial, which began enrolling women in the fall of 2007, randomly
assigned participants with advanced cancer to the chemotherapy-radiation
control group or the study group.
Those in the study group got
radiation plus immunotherapy consisting of pills of retinoic acid, a
derivative of Vitamin A; and shots of the protein interferon-alpha. When
recruiting subjects, doctors said they emphasized the experimental
nature of the regimen.
This wasn't the first trial to test the
treatment; it had shown promise in three of four pilot studies
elsewhere. But researchers said it is the first time it was tested in
untreated women with cancer as advanced as the majority of cases in
Doctors said both treatments cost about the same. Treatment
medications and hospital care are free to participants, and Jenson
personally donated $5,000 for other medicines that patients in the trial
Basu said there were fewer side effects among women
in the experimental arm of the trial. And two years into the trial, 69
of the 114 who had enrolled were disease-free, with the experimental arm
accounting for a greater number of disease-free patients than the
But over the next few years, cancer returned among
more patients taking the immunotherapy treatment than in those receiving
coordinator of the Cervical Cancer Prevention & Control Initiative,
a partnership among Chittaranjan, the medical testing company Qiagen of
Germany, and the ministry of health in West Bengal, the state where
Kolkata is located, Basu said he is focused now on trying to head off
cervical cancer before it starts.
His efforts include working with
several nongovernmental organizations, training field workers to raise
awareness in their communities and using a Qiagen HPV test to screen for
pre-cancers among women in remote areas.
Meanwhile, research on a new HPV vaccine continues in Louisville.
and colleagues are looking at using Kentucky tobacco to develop the
inexpensive vaccine and hope to have a federally approvable version
within two years.
"What we want more than anything is to deliver
an economically viable vaccine that can be used in places like India,"
Jenson said. "If we are successful with this, Partha would be the first
person to vaccinate women. And I would hope to go there to see the first
person be vaccinated."
Laura Ungar, The (Louisville, Ky.) Courier-Journal