The role of neoadjuvant chemotherapy in the management of locally advanced cervix cancer: a systematic review

Mohammed Osman, Mohammed Osman

Abstract

Cervical cancer is the second most common cancer in women. Neoadjuvant chemotherapy for patients with locally advanced cervix cancer has comparable benefits to concurrent chemoradiotherapy (CCRT), but with fewer side effects. This systematic review aims to provide a comprehensive summary of the benefits of neoadjuvant chemotherapy for the management of locally advanced cervix cancer from stage IB2 (tumor >4.0 cm) to IIIB (tumor extending to the pelvic wall and/or hydronephrosis). Our primary objective was to assess benefits in terms of survival. The data source included the USA national library of medicine, Medline search, and the National Cancer Institute PDQ Clinical Protocols. Inclusion criteria for consideration in the current systematic review included studies published between January 1997 and December 2012. In terms of histology, they had to be focused on squamous cell carcinoma, adenosquamous carcinoma, and/or adenocarcinoma. Patients should be either chemotherapy naïve or cervix cancer chemotherapy naïve, and have a performance status ≤2. The search in the above-mentioned scientific websites led to identify 49 publications, 19 of which were excluded, as they did not meet the inclusion criteria of this systematic review. Therefore only 30 studies were deemed eligible. Data was collected from 1760 patients enrolled in the current systematic review study. The mean age was 45.2 years. The mean tumor size was 4.7 cm. The most commonly used chemotherapies were cisplatin doublets. Paclitaxel was the most commonly used chemotherapeutic agent in the doublets. The mean chemotherapy cycles were 2.7. After chemotherapy, patients underwent surgery after a mean time of 2.5 weeks. The standard operation was radical hysterectomy with pelvic lymphadenectomy. Chemotherapy achieved an objective response rate of 84%. The 5-year progression-free survival and overall survival were 61.9% and 72.8% respectively. The treatment protocol was associated with a mild early toxicity profile. Leucopenia and neutropenia were the most common side effects. Late toxicity was also generally mild and mainly associated with bladder dysfunction and vaginal dehiscence. The quality of the studies was assessed using the Newcastle-Ottawa quality assessment scale. Neoadjuvant chemotherapy achieved comparable survival results to CCRT, and was associated with less toxicity.

Keywords: neoadjuvant cervix chemotherapy; systemic quality survival.

Conflict of interest statement

Conflict of interests: the author declares no potential conflict of interests.

Figures

Figure 1.
Figure 1.
Treatment response by stage. CR, complete remission; PR, partial remission; SD, stable disease; DP, disease progression.
Figure 2.
Figure 2.
Survival result of the systematic review. A) Progression free survival (PFS) of the study group; B) overall survival (OS) of the study group.
Figure 3.
Figure 3.
Comparison of the trials which favor neoadjuvant chemotherapy vs other treatment.

References

    1. Ferlay J, Shin HR, Bray F, et al. Cancer incidence and mortality worldwide: IARC Cancer Base No. 10. Lyon: International Agency for Research on Cancer; 2010.
    1. Pecorelli S. Revised FIGO staging for carcinoma of the vulva, cervix, and endometrium. Int J Gynaecol Obstet 2009;105:103-4.
    1. Monk BJ, Tewari KS, Koh WJ. Multimodality therapy for locally advanced cervical carcinoma: state of the art and future directions. J Clin Oncol 2007;25:2952-65.
    1. Thomas GM. Improved treatment for cervical cancer-concurrent chemotherapy and radiotherapy. N Engl J Med 1999;340:1198-200.
    1. Green JA, Kirwan JM, Tierney JF, et al. Survival and recurrence after concomitant cehmotherapy and radiotherapy for cancer of the uterine cervix: a systematic review and meta-analysis. Lancet 2001;358:781-6.
    1. Tan LT, Zahra M. Long-term survival and late toxicity after chemoradiotherapy for cervical cancer - The Addenbrooke’s experience. Clin Oncol (R Coll Radiol) 2008;20:358-64.
    1. Huang HJ, Chang TC, Hong JH, et al. Prognostic value of age and histologic type in neoadjuvant chemotherapy plus radical surgery for bulky (>/=4 cm) stage IB and IIA cervical carcinoma. Int J Gynecol Cancer 2003;13:204-11.
    1. Panici PB, Scambia G, Baiocchi G, et al. Neoadjuvant chemotherapy and radical surgery in locally advanced cervical cancer. Prognostic factors for response and survival. Cancer 1998;67:372-9.
    1. Stang A. Critical evaluation of the Newcastle-Ottawa scale for the assessment of the quality of nonrandomized studies in meta-analyses. Eur J Epidemiol 2010;25:603-5.
    1. Shoji T, Takatori E, Saito T, et al. Neoadjuvant chemotherapy using platinum- and taxane-based regimens for bulky stage Ib2 to IIb non-squamous cell carcinoma of the uterine cervix. Cancer Chemother Pharmacol 2013;71:657-62.
    1. Shen Y, Yang L, Wang Z. Treatment of early bulky cervical cancer with neoadjuvant paclitaxel, carboplatin and cisplatin prior to laparoscopical radical hysterectomy and pelvic lymphadenectomy. Oncol Lett 2012;3:641-5.
    1. Yamaguchi S, Nishimura R, Yaegashi N, et al. Phase II study of neoadjuvant chemotherapy with irinotecan hydrochloride and nedaplatin followed by radical hysterectomy for bulky stage Ib2 to IIb, cervical squamous cell carcinoma: Japanese Gynecologic Oncology Group study (JGOG 1065). Oncol Rep 2012;28:487-93.
    1. Pinheiro W, Pereira AK, Soares JM, Jr, et al. Is the combination of mitomycin C, bleomycin and methotrexate effective as aneoadjuvant treatment for cervical cancer in women. Eur J Gynaecol Oncol 2011;32:37-9.
    1. Vizza E, Pellegrino A, Milani R, et al. Total laparoscopic radical hysterectomy and pelvic lymphadenectomy in locally advanced stage IB2-IIB cervical cancer patients after neoadjuvant chemotherapy. Eur J Surg Oncol 2011;37:364-9.
    1. Mossa B, Mossa S, Corosu L, et al. Follow-up in a long-term randomized trial with neoadjuvant chemotherapy for squamous cell cervical carcinoma. Eur J Gynaecol Oncol 2010;31:497-503.
    1. Shoji T, Takatori E, Hatayama S, et al. Phase II study of tri-weekly cisplatin and irinotecan as neoadjuvant chemotherapyfor locally advanced cervical cancer. Oncol Lett 2010;1:515-9.
    1. Kumar JV, Doval DC, Rao R, et al. A retrospective study of patients with locally advanced cancer of the cervix treated with neoadjuvant chemotherapyfollowed by radical surgery. Int J Gynecol Cancer 2009;19:417-22.
    1. Cho Y, Kim D, Kim J, et al. Comparative study of neoadjuvant chemotherapy before radical hysterectomy and radical surgery alone in stage IB2-IIA bulky cervical cancer. J Gynecol Oncol 2009;20:22-7.
    1. Kokawa K, Nishimura R, Fujii T, et al. Neoadjuvant chemotherapy with irinotecan and mitomycin-C for locally advanced squamous cell carcinoma of the uterine cervix. Anticancer Res 2007;27:2721-7.
    1. Sláma J, Cibula D, Freitag P, et al. Contribution of neoadjuvant chemotherapy for operability of cancers of the uterine cervix. Ceska Gynekol 2007;72:116-9.
    1. Eddy G, Bundy B, Creasman W, et al. Treatment of (“bulky”) stage IB cervical cancer with or without neoadjuvant vincristine and cisplatin prior to radical hysterectomy and pelvic/para-aortic lymphadenectomy: a phase III trial of the gynecologic oncology group. Gynecol Oncol 2007;106:362-9.
    1. Choi YS, Sin J, Kim J, et al. Survival benefits of neoadjuvant chemotherapy followed by radical surgery versus radiotherapy in locally advanced chemoresistant cervical cancer. J Korean Med Sci 2006;21:683-9.
    1. Cai HB, Chen HZ, Yin HH. Randomized study of preoperative chemotherapy versus primary surgery for stage IB cervical cancer. J Obstet Gynaecol Res 2006;32:315-23.
    1. Termrungruanglert W, Tresukosol D, Vasuratna A, et al. Neoadjuvant gemcitabine and cisplatin followed by radical surgery in (bulky) squamous cell carcinoma of cervix stage IB2. Gynecol Oncol 2005;97:576-81.
    1. Taneja A, Rajaram S, Agarwal S, et al. ‘Quick Cycle’ neoadjuvant chemotherapy in squamous cell carcinoma of cervix. Indian J Pharmacol 2005;37:320-4.
    1. DeSouza NM, Soutter WP, Rustin G, et al. Use of neoadjuvant chemotherapy prior to radical hysterectomy in cervical cancer: monitoring tumour shrinkage and molecular profile on magnetic resonance and assessment of 3-year outcome. Br J Cancer 2004;90:2326-31.
    1. Hwang YY, Moon H, Cho SH, et al. Ten-year survival of patients with locally advanced, stage ib-iib cervical cancer after neoadjuvant chemotherapy and radical hysterectomy. Gynecol Oncol 2001;82:88-93.
    1. Napolitano U, Imperato F, Mossa B, et al. The role of neoadjuvant chemotherapy for squamous cell cervical cancer (Ib-IIIb): a long-term randomized trial. Eur J Gynaecol Oncol 2003;24:51-9.
    1. D’Agostino G, Distefano M, Greggi S, et al. Neoadjuvant treatment of locally advanced carcinoma of the uterine cervix with epirubicin, paclitaxel and cisplatin. Cancer Chemother Pharmacol 2002; 49:256-60.
    1. Benedetti-Panici P, Greggi S, Colombo A, et al. Neoadjuvant chemotherapy and radical surgery versus exclusive radiotherapy in locally advanced squamous cell cervical cancer: results from the Italian Multicenter Randomized Study. J Clin Oncol 2002;20:179-88.
    1. Dueñas-Gonzalez A, López-Graniel C, González-Enciso A, et al. A phase II study of multimodality treatment for locally advanced cervical cancer: neoadjuvant carboplatin and paclitaxel followed by radical hysterectomy and adjuvant cisplatin chemoradiation. Ann Oncol 2003;14:1278-84.
    1. Duenas-Gonzalez A, Lopez-Graniel C, Gonzalez-Enciso A, et al. Concomitant chemoradiation versus neoadjuvant chemotherapy in locally advanced cervical carcinoma: results from two consecutive phase II studies. Ann Oncol 2002;13:1212-19.
    1. Costa S, Terzano P, Santini D, et al. Neoadjuvant chemotherapy in cervical carcinoma. Regulators of cell cycle, apoptosis, and proliferation as determinants of response to therapy and disease outcome. Am J Clin Pathol 2001;116:729-37.
    1. MacLeod C, O’Donnell A, Tattersall MH, et al. Locally advanced cervix cancer: chemotherapy prior to definitive surgery or radiotherapy. A single institutional experience. Australas Radiol 2001;45:491-5.
    1. Aoki Y, Tomita M, Sato T, et al. Neoadjuvant chemotherapy for patients younger than 50 years with high-risk squamous cell carcinoma of the cervix. Gynecol Oncol 2001;83:263-7.
    1. Hwang Y, Moon H, Cho S, et al. Ten-year survival of patients with locally advanced, stage ib-iib cervical cancer after neoadjuvant chemotherapy and radical hysterectomy. Gynecol Oncol 2001;82:88-93.
    1. Chang TC, Lai CH, Hong JH, et al. Randomized trial of neoadjuvant cisplatin, vincristine, bleomycin, and radical hysterectomy versus radiation therapy for bulky stage IB and IIA cervical cancer. J Clin Oncol 2000;18:1740-7.
    1. Zanetta G, Lissoni A, Pellegrino A, et al. Neoadjuvant chemotherapy with cisplatin, ifosfamide and paclitaxel for locally advanced squamous-cell cervical cancer. Ann Oncol 1998;9:977-80.
    1. Sardi J, Giaroli A, Sananes C, et al. Long-term follow-up of the first randomized trial using neoadjuvant chemotherapyin stage Ib squamous carcinoma of the cervix: the final results. Gynecol Oncol 1997;67:61-9.
    1. Lacava JA, Leone BA, Machiavelli M, et al. Vinorelbine as neoadjuvant chemotherapy in advanced cervical carcinoma. J Clin Oncol 1997;15:604-9.
    1. Moher D, Liberati A, Tetzlaff J, et al. Preferred reporting items for systematic reviews and meta-analyses: the PRISMA statement. BMJ 2009;339:b2535.
    1. Garg A, Hackam D, Tonelli M. Systematic review and meta-analysis: when one study is just not enough. Clin J Am Soc Nephrol 2008;3: 253-60.
    1. Morris M, Eifel PJ, Lu J, et al. Pelvic radiation with concurrent chemotherapy versus pelvic and para-aortic radiation for high-risk cervical cancer: a randomized Radiation Therapy Oncology Group clinical trial. N Engl J Med 1999;340:1137-43.
    1. Lorusso D, Petrelli F, Coinu A, et al. A systematic review comparing cisplatin and carboplatin plus paclitaxel-based chemotherapy for recurrent or metastatic cervical cancer. Gynecol Oncol 2014; 133:117-23.

Source: PubMed

3
Suscribir