BETHESDA, MdThe National Cancer Institute (NCI) has recommended
that oncologists use a combination of chemotherapy and radiation
instead of radiation alone to treat invasive cervical cancer.
In a clinical announcement mailed to cancer specialists, the
Institute cited results from five randomized, phase III studies that
showed clinical benefit for women who received chemotherapy and
radiation given in combination. Until now, surgery or radiation alone
has been the standard treatment for cervical cancer that has spread
locally or regionally.
Standard of Care
The findings of these five trials are remarkably
consistent, said NCI director Richard D. Klausner, MD.
They are likely to change the standard of care for invasive
Three of the studies compared chemotherapy-radiation combination
regimens against radiation alone. In all three trials, the
proportion of women alive after about 3 years follow-up was higher in
the groups receiving chemotherapy plus radiation than in those
receiving only radiation therapy, the NCI said in announcing
In the two other studies, all patients received concomitant
chemotherapy and radiation. However, the chemotherapy drugs differed
between the arms. In one arm of each of these trials, the
chemotherapy used was hydroxyurea (Hydrea) while in the other arms,
the chemotherapy included cisplatin (Platinol). In both trials, the
groups who received cisplatin had better survival rates.
Significant Results With Cisplatin
Although the best chemotherapy regimen for cervical cancer has not
been determined, significant results were seen using cisplatin
alone or cisplatin in combination with 5-FU [5-fluorouracil] and
other agents, the NCI said in its mailing to physicians.
A total of 1,894 cervical cancer patients participated in the five
studies, which were carried out around the country by three of
NCIs clinical trials cooperative groups.
None of the five studies had been published in peer-reviewed journals
at the time the NCI dispatched its letter. Three were in press at the New
England Journal of Medicine but available on its website (www.nejm.org);
one was in review at the Journal of Clinical Oncology; and
data from the fifth was scheduled for presentation at the Society of
Gynecologic Oncology (SGO) annual meeting in late March of this year.
NCI said its recommendation applied to women diagnosed with
International Federation of Gynecologists and Obstetricians (FIGO)
stages IB-IVA cervical cancer, as well as women with stage IA and IIA
cancer who have metastatic disease in the pelvic lymph nodes,
positive parametrial disease, or positive surgical margins.
Side effectsmostly leukopenia, nausea, and vomitingwere
more frequent and more severe in women who received the combination
therapy than in women who were treated with radiation only, the NCI
said. In general, these adverse effects were temporary and manageable.
The five studies and their results, as described by NCI, are:
GOG 85: 368 patients with stages IIB, III, and IVA disease, enrolled
1986-1990. Principal investigator: Charles W. Whitney, MD, director
of gynecologic oncology, Christiana Hospital, Newark, Del. Treatment
consisted of radiation therapy combined with cisplatin and 5-FU vs
radiation therapy with hydrox-yurea. Three years from the time
of diagnosis, 67% of women receiving radiation with cisplatin and
5-FU were alive, compared to 57% of those receiving radiation therapy
and hydroxyurea, the NCI said.
RTOG 9001: 389 patients with stages IIB, III, IVA disease, enrolled
1990-1997. Principal investigator: Mitchell Morris, MD, M.D. Anderson
Cancer Center. Radiation therapy with 5-FU and cisplatin vs radiation
therapy alone. The 3-year survival rate for women receiving
cisplatin and 5-FU is 75%, compared to 63% for women receiving
radiation therapy alone.
GOG 120: 526 patients with stages IIB, III, IVA disease, enrolled
1992-1997. Principal investigator: Peter Rose, MD, Case Western
Reserve University and University Hospitals of Cleveland. Radiation
therapy with cisplatin vs radiation therapy with cisplatin, 5-FU, and
hydroxyurea vs radiation therapy with hydroxyurea. In both
groups receiving radiation and cisplatin, the 3-year survival rate is
65%, compared to 47% for women receiving radiation and
SWOG 8797: 243 patients with stages IA2, IB, IIA disease with adverse
pathology found at surgery, enrolled 1992-1996. Principal
investigator: William Peters III, MD, Puget Sound Oncology Consortium
and the University of Washington, Seattle. Radiation therapy with
5-FU and cisplatin vs radiation therapy alone. The 3-year
survival rate for women receiving radiation, cisplatin, and 5-FU is
87%, compared to 77% for women receiving radiation alone.
GOG 123: 386 patients with stage IB bulky disease, enrolled
1992-1997. Principal investigator: Henry M. Keys, MD, Albany Medical
College. Radiation therapy with cisplatin vs radiation therapy alone.
With half of the patients followed for 35.7 months or more, 83%
of those who received concurrent chemotherapy and radiation therapy
are alive, compared to 74% of those treated with radiation therapy alone.