Cervical carcinoma is one of the most common gynecologic cancers worldwide. The prognosis
of cervical cancer is favorable, with around 80-90% 5-year survival rate in early stage
disease. However, advanced disease carries a poor prognosis. Current standard treatment
for locally advanced cervical cancer, which is not eligible for surgical treatment, is
cisplatin-based concurrent chemoradiation (CRT). Based on the results of five randomized
clinical trials, which consistently showed improved survival in patients treated with
cisplatin-based CRT, the National Cancer Institute (NCI) of the United States announced
that 'Strong consideration should be given to the incorporation of concurrent
cisplatin-based chemotherapy with RT in women who require radiation therapy for treatment
of cervical cancer' in 1999.
Although recently reported meta-analysis studies also demonstrated improved local control
rates and survival with cisplatin-based chemotherapy concurrent to radiation therapy
(RT), the optimal cisplatin dose and dosing schedule are still undetermined. Among the
previous five randomized clinical trials, two trials performed by the Gynecologic
Oncology Group (GOG) used weekly cisplatin 40 mg/m2 while the other three trials used
tri-weekly cisplatin at a dosage range of 50 mg/m2 to 75 mg/m2 combined with
5-fluorouracil (5-FU). Despite the diversity in cisplatin dose and dosing schedules,
weekly cisplatin at a dose of 40 mg/m2 concurrent to RT is widely accepted as the
standard regimen of CRT because of its convenience, equal effectiveness, and favorable
toxicity in comparison to other 5-FU combined regimens.
However, as a result of the GOG 165 study, which was closed prematurely because an
interim analysis found that patients in the 5-FU treatment group were not likely to
achieve a better outcome, the role of 5-FU (previously popularly included in clinical
trials) as a radiosensitizer became subject to debate. Furthermore, a clinical trial
performed by the NCI in Canada comparing pelvic RT alone with weekly cisplatin 40 mg/m2
concurrent to RT failed to show improvement of progression free and 5-year survival.
While the authors suggested several possible reasons for why their study failed to
demonstrate a survival benefit with concurrent weekly cisplatin 40 mg/m2 chemotherapy,
other investigators have tried to find another optimal dose and dosing schedule for
cisplatin administration.
In light of the results of the previous clinical trial that indicated 5-FU may not be an
active radiosensitizer, weekly cisplatin 40 mg/m2 and tri-weekly cisplatin 75 mg/m2
remain the most popular cisplatin doses and dosing schedules. However, despite the
possible advantages of tri-weekly cisplatin 75 mg/m2, which offer an increased peak
concentration of cisplatin and cisplatin administration during brachytherapy, no clinical
trials thus far have directly compared weekly and tri-weekly cisplatin-based chemotherapy
concurrent to RT.
Recently the investigators reported a randomized phase II trial to compare the compliance
to and toxicity of weekly cisplatin 40 mg/m2 and tri-weekly cisplatin 75 mg/m2
administration concurrent to RT. The study showed that tri-weekly cisplatin 75 mg/m2
concurrent to RT is feasible and increase 5-year survival rate significantly compared to
weekly cisplatin 40 mg/m2 in patients with locally advanced cervical cancer (66.5% in the
weekly arm, 88.7% in the tri-weekly arm; HR=0.375, 95% CI: 0.154-0.914, p= .03).
Therefore, in this randomized phase III trial, The investigators intend to confirm the
survival difference between weekly cisplatin 40 mg/m2 and tri-weekly cisplatin 75 mg/m2
administration concurrent to RT in this patient population.
