Phase II trial of neoadjuvant chemotherapy followed by chemoradiation in locally advanced cervical cancer

Cervical cancer is a global public health challenge. Since 1999, platin based chemoradiation (CRT) is the standard treatment for those patients with locally advanced disease. However, this population still has a dismal prognosis and, alternatives approaches such as adjuvant chemotherapy are controversial, especially because of increased toxicity. Neoadjuvant chemotherapy (NACT) could be an option for more intensive treatment with manageable toxicity.

A phase II, prospective, non-randomized trial was conducted at a reference center in Recife, Brazil. Locally advanced cervical cancer patients (Ib2-IVa) were treated with neoadjuvant cisplatin 35mg/m² and gemcitabine 1000mg/m² D1 and D8, for 2cycles. Then, they received CRT (50.4Gy) with weekly cisplatin 40mg/m² followed by brachytherapy. Response rate (RR) and toxicity were the primary endpoints. Progression-free survival (PFS) and overall survival (OS) were secondary endpoints.

Between Sep/2013 and Oct/2015, 50 patients were initiated on NACT and CRT. RR was 81% at the end of treatment. Hematological and gastrointestinal toxicity were most common. Grade 3/4 toxicity was 20% during NACT and 44% during CRT. Late adverse events were present in 20% of patients. PFS at 1 and 3-years were 73.4% (IC 58.7-83.6) and 53.9% (IC 36.9-68.3), respectively; and, OS at 1 and 3-years were 93.9% (IC 82.4-98.0) and 71.3% (IC 53.3-83.3), respectively.

In our hands NACT in locally advanced cervical cancer patients did not show a meaningful improvement in ORR. Nevertheless, we believe it should be further explored in prospective trials.