Dr. Mauro Orlando, with Eli Lilly Interamerica in Buenos Aires, Argentina, and colleagues explain that chemotherapy added to radiotherapy has been shown to improve outcomes of locally advanced cervical cancer. Furthermore, adjuvant therapy may be useful, since about a third of patients experience disease progression after chemotherapy.
Noting that gemcitabine potentiates radiotherapy and chemotherapy, the investigators “aimed to improve survival outcomes for patients with locally advanced cervical cancer, using the synergy between gemcitabine, cisplatin, and external-beam radiotherapy and the potential value of adjuvant chemotherapy.”
The trial enrolled 515 patients with stage IIB-IVA cervical carcinoma; 259 were assigned to cisplatin and gemcitabine weekly for 6 weeks with concurrent external-beam radiotherapy, followed by brachytherapy and then two adjuvant cycles of cisplatin plus gemcitabine, while 256 patients received standard treatment with cisplatin and concurrent external-beam radiotherapy followed by brachytherapy only.
Progression-free survival at 3 years was 74.4% among those given the gemcitabine regimen compared with 65.0% in the standard-therapy arm (p=0.029), and overall survival was also better in the gemcitabine group than the standard therapy group (hazard ratio 0.68; p=0.0224), the researchers report.
Rates of grade 3 and 4 toxicities in the two arms were 86.5% vs 46.3%, respectively (p=0.001), but were generally manageable, according to the report. Nonetheless, there were more discontinuations in the gemcitabine group than the standard treatment group, most often because of adverse events, including decreased creatinine clearance, neutropenia, and diarrhea.
“In conclusion, this study demonstrates that, within study limitations and despite increased but clinically manageable toxicity, the gemcitabine combination improves survival outcomes for patients with locally advanced cervical cancer compared with current standard of care,” Dr. Orlando and colleagues conclude.
They add, “Further studies are required to define optimal patient selection for this combination and to delineate the specific contributions of multiagent chemoradiotherapy and adjuvant chemotherapy phases to survival outcomes.”
Phase III, Open-Label, Randomized Study Comparing Concurrent Gemcitabine Plus Cisplatin and Radiation Followed by Adjuvant Gemcitabine and Cisplatin Versus Concurrent Cisplatin and Radiation in Patients With Stage IIB to IVA Carcinoma of the Cervix
J Clin Oncol 2011;29.