A phase III, open-label, randomized trial found that adding gemcitabine to concurrent cisplatin chemoradiotherapy and using gemcitabine as adjuvant chemotherapy with cisplatin improved survival outcomes in women with locally advanced cervical cancer. Toxicity was increased compared to standard treatment but clinically manageable.
The 515 study patients, aged 18 to 70, with stage IIB to IVA cervical cancer not previously treated with chemotherapy or radiotherapy, were randomly assigned to one of two treatment arms. Patients in arm A received treatment consisting of gemcitabine plus cisplatin chemoradiotherapy followed by brachytherapy and adjuvant gemcitabine and cisplatin. Patients in arm B received treatment consisting of cisplatin chemoradiotherapy followed by brachytherapy only. At a median follow-up of 46.9 months, the investigators found a statistically significant improvement for arm A over arm B in the three main survival endpoints: 3-year progression-free survival (74.4% in arm A vs 65.0% in arm B; P = .029), overall progression-free survival, and overall survival.
“To our knowledge, the data from this trial represent the first finding of significantly improved survival outcomes” for patients with locally advanced cervical cancer “with combination multimodality therapy compared with single-agent cisplatin chemotherapy,” the authors wrote. The results were reported in the Journal of Clinical Oncology.
Grade 3 and 4 toxicities were seen more frequently in arm A than in arm B (86.5% vs 46.3%, respectively; P < .001), including two deaths possibly related to treatment toxicity in arm A, the investigators reported. There were also more discontinuations in arm A than arm B, mostly a result of the adverse events.
An accompanying editorial noted that the study was “remarkable for many reasons,” including being conducted at sites in the developing world, where the majority of patients with advanced disease live and where access to basic medical care is limited or absent. “This study represents clear evidence that large phase III randomized controlled trials can be conducted in a rapid fashion in the developing world if sufficient commitment, expertise, and financial support are available in countries where the disease is so rampant,” the editorial stated. “This study highlights the importance of the use of therapies accessible and affordable to the developing world.”