SAN FRANCISCOA major intergroup phase III study reported at the
30th Annual Meeting of the Society of Gynecologic Oncologists has
shown that adding chemotherapy to radiation therapy improves the
overall survival rate for women with high-risk early-stage cervical
cancer. William A. Peters III, MD, of the Puget Sound Oncology
Consortium, Seattle, reported the results on behalf of researchers
from the Southwest Oncology Group, Gynecologic Oncology Group, and
Radiation Therapy Oncology Group.
We were looking at patients who had early, operable cervical
cancer but with high-risk features. About 40% of such patients will
have disease recurrence, Dr. Peters said in an interview.
We were trying to determine whether the addition of systemic
chemotherapy would decrease that failure rate. Previous studies
had shown that radiation therapy decreased recurrence rates but did
not improve long-term survival.
Radical hysterectomy with pelvic lymphadenectomy is the recommended
surgical treatment for women diagnosed with early-stage cervical
carcinoma. Radiation therapy is usually added for those who have
positive lymph nodes or parame-trial involvement. Five-year survival
is 80% to 90% in patients without any lymph node or parametrial
involvement but drops to 50% to 70% when these risk factors are present.
The study enrolled 260 patients with clinical stage IA2, IB, and IIA
carcinoma of the cervix. All were initially treated with radical
hysterectomy and pelvic lymphadenectomy and had positive pelvic lymph
nodes and/or positive margins and/or microscopic involvement of the
parametrium. Of these patients, 241 were evaluable at the time of
Patients were randomized to receive radiation therapy or radiation
therapy plus chemotherapy. Patients in each group received 4,930 cGy
in 29 fractions to a standard pelvic field.
Chemotherapy consisted of bolus cisplatin (Platinol), 70 mg/m²,
and a 96-hour infusion of fluorouracil (5-FU), 1,000 mg/m²/day
for 4 days every 3 weeks for four cycles, with the first and second
cycles given concurrently with radiation. Both agents are active in
cervical cancer, and both are radiation sensitizers.
Progression-free and overall survival were significantly improved in
the patients given chemotherapy (P = .01 for each). The hazard ratio
for overall survival was 2.02 for the radiation-only arm compared
with the radiation/chemotherapy arm. Projected progression-free
survival at 4 years was 63% with radiation and 81% with
Grade 3-4 hematologic and gastrointestinal toxicity were more
frequent in the radiation therapy plus chemotherapy group, Dr. Peters
said, but there were no toxicity-related deaths in either group.
For high-risk patients who have positive nodes after radical
hysterectomy and/or parametrial involvement and/or positive margins,
this study clearly showed a reduction of about 50% in the treatment
failure rate. It would be hard to justify treating such patients any
other way, based on current knowledge, he said.
The study was one of five cited by the NCI in its recommendation that
oncol-ogists use chemotherapy and radiation therapy rather than
radiation alone to treat invasive cervical cancer.
Dr. Peters emphasized that the majority of patients who have surgery
for cervical cancer do not need adjuvant therapy, only those with
risk factors. The regimen is well tolerated and could potentially be
used in any high-risk patient who is a candidate for surgery. He
noted that this approach could be used in virtually any center that
offers radiation therapy and chemotherapy, since it does not require brachytherapy.
The mechanism of action underlying the benefit produced by adding
chemotherapy requires further study. Dr. Peters said it could be due
to radiation sensitization, a systemic antitumor effect, or a
combination of the two.