CHICAGOCisplatin-based chemoradiotherapy has greater
efficacy than previous regimens in treating cervical cancer, but toxicity
needs to be reduced, stated William Small, Jr., MD. He is assistant
professor of radiology, Division of Radiation Oncology, at Northwestern
University’s Robert H. Lurie Comprehensive Cancer Center in Chicago.
"There is some preliminary evidence that amifostine
(Ethyol) may be beneficial in cervical cancer patients," he said.
"The Radiation Therapy Oncology Group (RTOG) is about to test this
hypothesis in a group of cervical cancer patients at high risk for
The RTOG study is expected to be a two-stage design. Stage I
will include about 25 patients to establish the toxicity of weekly cisplatin
(Platinol) plus extended field radiotherapy. If the expected toxicity is
seen in stage I, additional patients will be treated with the addition of
Bulky stage IIB, IIIB, and IVA cervical cancers are
traditionally treated with high dose radiotherapy, which is associated with
significant long-term toxicity. "Recently, the results of five
randomized trials have been published comparing cisplatin-based
chemoradiotherapy to other chemoradiotherapy regimens or to radiotherapy
alone. All of these trials noted survival advantages of the cisplatin-based
combined-modality arms, but toxicity in the combination therapy groups was
greater than in the radiotherapy alone groups," Dr. Small said.
For example, RTOG 90-01 showed a significant early toxicity
rate, including 14% grade 3 and 3% grade 4 nausea and vomiting, 12% grade 3
and 5% grade 4 bowel and rectal toxicity, and 57% grade 3 and 16% grade 4
GOG 120 was a randomized trial of pelvic radiotherapy
combined with cisplatin vs cisplatin/5-fluorouracil/hydroxyurea vs
hydroxyurea alone. "Both cisplatin-containing arms improved
survival," Dr. Small said. Toxicity included 21% grade 3 leukopenia, 2%
grade 4 leukopenia, 10% grade 3 GI toxicity, and 5% grade 4 GI toxicity.
Studies With Amifostine
Although only limited clinical trials have been done of
amifostine in cervical cancer, according to Dr. Small, these studies have
shown the feasibility of combining amifostine with cisplatin and
radiotherapy in the treatment of this disease.
Recently researchers have also studied subcutaneous
amifostine vs traditional intravenous amifostine in various malignancies. In
one trial of 40 patients with pelvic malignancies, three had cervical
cancer, Dr. Small reported. Amifostine was interrupted due to a fever/rash
syndrome or asthenia in 14.2% of the patients. The mucosal toxicity with
radiotherapy alone was 35% grade 2 and 15% grade 3 to 4. With the subcutaneous amifostine there was only 13% grade 2 and no grade 3
to 4 toxicity, "so there seemed to be a significant benefit," Dr.
The upcoming RTOG trial will be developed to include IV
amifostine, since little data on the SC formulation were available at the
time the protocol was designed. Dr. Small said that this may be
reconsidered, as the trial has not yet opened. Treatment will consist of
extended field external beam radiotherapy followed by brachytherapy
concurrent with weekly cisplatin.
"A number of the chemoradiotherapy trials delivered
amifostine only on the days when the chemotherapy was given. The RTOG trial
will give a flat 500 mg of amifostine on the days when cisplatin is
delivered and a flat 200 mg when radiotherapy alone is delivered," Dr.