In a Brazilian single-center phase II trial reported in the Journal of Clinical Oncology, da Costa et al found that neoadjuvant cisplatin/gemcitabine followed by standard chemoradiation therapy with cisplatin did not improve outcomes vs chemoradiation therapy alone in locally advanced cervical cancer.

Photo credit: Getty

Study Details

The open-label trial included 107 eligible patients with locally advanced cervical cancer (International Federation of Gynecology and Obstetrics stage IIB to IVA or with positive lymph nodes) at the Instituto do Câncer do Estado de São Paulo. Patients were randomly assigned between July 2012 to July 2017 to receive either three cycles of neoadjuvant chemotherapy with cisplatin/gemcitabine followed by standard chemoradiation therapy with weekly cisplatin plus pelvic radiotherapy (n = 55) or standard chemoradiation therapy alone (n = 55). Neoadjuvant chemotherapy consisted of cisplatin 50 mg/m² on day 1 and gemcitabine 1,000 mg/m² on day 1 and day 8 every 3 weeks for three cycles. Standard chemoradiation therapy consisted of weekly cisplatin 40 mg/m² for 6 weeks concurrent with radiotherapy. Pelvic external beam radiation therapy was given at 45–50.4 Gy in 25–28 fractions. Most patients (88%) had squamous cell carcinoma.

The primary endpoint was 3-year progression-free survival.

Progression-Free Survival

Median follow-up was 31.7 months. Progression-free survival at 3 years was poorer in the neoadjuvant chemotherapy vs chemoradiation therapy group (40.9% vs 60.4%, hazard ratio [HR] = 1.84, P = .033). The neoadjuvant chemotherapy group also had poorer 3-year overall survival (60.7% vs 86.8%, HR = 2.79, P = .006). After completion of treatment, complete response rates were 56.3% in the neoadjuvant chemotherapy group vs 80.3% in the chemoradiation therapy group (P = .008). Locoregional control rates at 3 years were 63.4% vs 69.9% (HR = 1.56, P = .227). Exploratory analysis indicated a greater frequency of para-aortic lymph node recurrence in the neoadjuvant chemotherapy group (nine vs two patients, P = .033).

Toxicity

The most common early adverse events were similar in both groups, consisting of myelosuppression, gastrointestinal symptoms, and dysuria. The neoadjuvant chemotherapy group had higher incidence of any-grade hypomagnesemia (27.2% vs 7.6%) and neuropathy (25.4% vs 1.9%). Late adverse events did not differ between the two groups.

The investigators concluded, “This study shows that the addition of neoadjuvant chemotherapy consisting of cisplatin and gemcitabine to standard chemoradiation therapy is not superior and is possibly inferior to chemoradiation therapy alone for the treatment of locally advanced cervical cancer.”

Samantha Cabral S. da Costa, MD, of the Instituto do Câncer do Estado de São Paulo, is the corresponding author for the Journal of Clinical Oncology article.

Disclosure: For full disclosures of the study authors, visit jco.ascopubs.org.