Neoadjuvant Chemotherapy Followed by Surgery in Locally Advanced Cervical Carcinoma
Authors: Alfonso Duenas-Gonzalez, Carlos M. Lopez-Graniel, Aida Mota, Alejandro Mohar, P. Benedetti-Panici, S. Greggi
Journal: Journal of Clinical Oncology (2002)

Article Tools SPECIAL DEPARTMENTS Article Tools OPTIONS & TOOLS Export Citation Track Citation Add To Favorites Rights & Permissions COMPANION ARTICLES No companion articles ARTICLE CITATION DOI: 10.1200/JCO.2002.20.12.2908 Journal of Clinical Oncology - published online before print September 21, 2016 PMID: 12065571 Neoadjuvant Chemotherapy Followed by Surgery in Locally Advanced Cervical Carcinoma Alfonso Duenas-GonzalezxAlfonso Duenas-GonzalezSearch for articles by this author , Carlos M. Lopez-GranielxCarlos M. Lopez-GranielSearch for articles by this author , Aida MotaxAida MotaSearch for articles by this author , Alejandro MoharxAlejandro MoharSearch for articles by this author P. Benedetti-PanicixP. Benedetti-PaniciSearch for articles by this author , S. GreggixS. GreggiSearch for articles by this author Show More Instituto Nacional de Cancerología, Instituto de Investigaciones Biomedicas, Universidad Nacional Autonoma de Mexico, Mexico City, MexicoUniversity of Rome “Campus Bio Medico”, Rome, Italy https://doi.org/10.1200/JCO.2002.20.12.2908 First Page Full Text PDF Figures and Tables © 2002 by American Society of Clinical OncologyjcoJ Clin OncolJournal of Clinical OncologyJCO0732-183X1527-7755American Society of Clinical OncologyResponse15062002In Reply:The Italian multicenter randomized trial was designed in the late 1980s, when neoadjuvant chemotherapy (NACT) followed by radical surgery (RS) emerged as a valid alternative to standard therapy in the treatment of locally advanced cervical cancer. In fact, several pilot studies had reported encouraging results in terms of response and survival.1-6 Only recently have other strategies involving integrated therapies, particularly with regard to concomitant chemoradiotherapy, been investigated.7-9 On the basis of the promising results of these studies, a European prospective randomized study comparing NACT followed by RS with concomitant chemoradiation has been designed.With regard to the chemotherapy regimen, given our previous experience and data from several phase II trials,1-6,10-12 cisplatin-based NACT was used in our study.13 These data had clearly indicated cisplatin as the leading agent in the treatment of advanced cervical cancer. Moreover, in an excellent review, Vermorken14 noted that cisplatin combinations were superior to cisplatin alone (approximately 40% v 25%) with no evidence for a steep dose-response relationship. Only in the last years have preliminary results of phase II studies on the use of combinations including new drugs (paclitaxel, irinotecan, and so on) been reported.15-16 In particular, cisplatin/paclitaxel–containing regimens seem to be able to induce higher rates of pathologic “optimal” (complete + microscopic partial) response, with a likely impact on survival. Unexpectedly, our study, using a cisplatin-based NACT regimen, showed similar rates of distant relapse in both arms. Therefore, it could be speculated that the incorporation of paclitaxel (or of another active “second-generation” drug) into a cisplatin NACT regimen may decrease the incidence of systemic failures after the chemotherapy-surgery sequence. However, the lack of complete sterilization of distant micrometastases may be not only drug dependent but also related to the duration of NACT.The number of different centers (n = 14) participating in our study could have negatively affected the treatment. Nevertheless, in a multicenter setting, the 75% rate of treatment compliance is usually considered an acceptable rate. As better underlined in our article’s Discussion,1 the 70-Gy total dose at point A delivered in 62 days seems to be lower than that considered optimal radiotherapy in advanced cervical cancer. Nevertheless, based on the pattern of the radiotherapy centers participating in the trial, our opinion is that the administered doses were those usually given in Italy and in other European centers, at least during the study period.Our study is one of the few phase III trials to compare NACT followed by RS with radiotherapy alone, and it demonstrated a significant improvement of both overall and progression-free survival for the experimental arm, although significant only for the stages IB2 to IIB.It is now consequential to compare the chemosurgical approach with that based on the concomitant use of chemotherapy and radiation. Therefore, data reported by Duenas-Gonzales et al, although generated from a nonrandomized, partly retrospective study, are of interest. Indeed, several questions concerning the chemosurgical as well as chemoradiation approaches are still open. First, the treatment of patients with tumors not responsive to chemotherapy (and/or radiation) remains an unsolved problem and calls for alternative strategies. Second, if the role of adjuvant surgery after chemoradiation seems to be very limited, adjuvant (chemo)radiotherapy may be of value in selected patient subsets. Finally, the possible additional benefit of paclitaxel in both the NACT and chemoradiation setting should be ascertained.1. Kim DS, Moon H, Kim KT, et al: Two-year survival: Pre-operative adjuvant chemotherapy in the treatment of cervical cancer stages IB and II with bulky tumor. Gynecol Oncol 33:: 225,1989-230, Crossref, Medline, Google Scholar2. 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