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 cervical cancer.
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 its recommendation.
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(Drug information on 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 hydroxyurea.
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.