We agree with Drs. Malik and Mejia in their letter regarding our article[1] that improvements in survival among patients with locally advanced cervical cancer, an area of unmet need, are essential. On the top of that, we would add a crucial fact: advances in this disease will only be achieved by drawing the attention of pharmaceutical companies and designing innovative trials, issues that were major challenges nearly a decade ago when we initiated our phase 1 trial.

Addressing their comments, we highlight that the data in our study[1] had been compared with trials conducted more than a decade ago due to a drought of advances in the treatment of locally advanced cervical cancer since the late 1990s. Even when correlated to the recently presented data regarding treatment with bevacizumab combined with chemoradiation, the results of our study are promising in relation to progression-free survival and overall survival.

With regard to the concern of Drs. Malik and Mejia regarding patient selection and stage migration biases, it is important to emphasize some aspects: 42.1% of the patients in our trial had International Federation of Gynecology and Obstetrics stage III disease and 26.6% of them had bilateral disease, a scenario that predicts a poor outcome. Patients with positive paraaortic lymph nodes were not included because tumor beyond the true pelvis is considered metastasis according to the TNM and International Federation of Gynecology and Obstetrics classifications, and therefore was beyond the scope of this clinical investigation. It is interesting to note that both patients who did not complete the protocol and were excluded achieved a complete response, the primary endpoint of the trial. With regard to histology, there is controversy as to whether adenocarcinoma is an independent prognostic factor in patients with cervical cancer,[2] but there is growing evidence of molecular differences between adenocarcinoma and squamous cell carcinoma.[3] This panorama reinforces the necessity of developing specific and more efficient treatments for each subtype.

In this era of molecular oncology, we should clearly look beyond conventional chemoradiation. Indubitably, a scenario filled with a better understanding of the human papillomavirus carcinogenic process and the biological mechanisms underlying the disease may provide a more rational future direction for the design of clinical trials among patients with locally advanced cervical cancer. However, considering that to our knowledge, no driver mutations to date have been described in cervical cancer, we also agree with Drs. Malik and Mejia that progress will most likely occur through small steps such as the data we have generated.


  1. Top of page

The authors made no disclosures.

  • Angelica Nogueira-Rodrigues, MD, PhD

  • Carlos G. Ferreira, MD, PhD

  • Coordination of Clinical Research

  • National Cancer Institute

  • Rio de Janeiro, Brazil


  1. Top of page