The role of neoadjuvant chemotherapy followed by radical surgery in the treatment of locally advanced cervical cancer

In 1984 the first pilot study on neoadjuvant chemotherapy in cervical cancer was reported. Since then, many investigators have studied the possible role that this therapeutic strategy could achieve in patients. Different chemotherapic combinations are constantly being attempted in order to obtain the maximum tumour response. At the same time few randomised studies have demonstrated the superiority of this treatment when adopted before radical surgery, in terms of overall survival compared to radiotherapy alone. Recently a detailed meta-analysis has been performed and the results confirmed what previously was achieved by the randomised trials. Since the beginning of all the phase III trials, the standard treatment of locally advanced disease has been modified from radiotherapy alone to concomitant radio-chemotherapy. For this reason the EORTC group has launched a trial with the objective of comparing neoadjuvant chemotherapy followed by radical surgery versus concomitant chemo-radiotherapy.

Neoadjuvant chemotherapy; Cervical cancer; Radical surgery

[1] Friedlander M.L., Atkinson K., Coppleson J.V., Elliot P., Green D., Houghton R. et al.:'The integration of chemotherapy into the management of locally advanced cervical cancer: a pilot study". Gynecol. Oneal., 1984, 19 (1), 1.

[2] Sardi J.E., di Paola G.R., Cachau A., Ortiz O.C., Sananes C., Giaroli A. et al.: "A possible new trend in the management of the carcinoma of the cervix uteri". Gynecol. Oncol., 1986, 25 (2), 139.

[3] Benedetti-Panici P., Greggi S., Colombo A., Amoroso M., Smaniotto D., Giannarelli D. et al.: "Neoadjuvant chemotherapy and radical surgery versus exclusively radiotherapy in locally advanced squamous cell cervical cancer: results from the Italian multi-centre randomised study". J. Clin Oncol., 2002, 1, 20 (1), 179.

[41 Sardi J., Sananes C., Giaroli A, Maya G., di Paola G.: "Neoadjuvant chemotherapy in locally advanced carcinoma of the cervix uteri". Gynecol Oneal., 1990, 38 (3), 486.

[5] Souhami L., Gill R.A., Allan S.E., Canary P.C.V., Arauio C.M.M., Pinto L.H.J., Silveira T.R.T.: "A Randomized trial of chemotherapy followed by radiation therapy in stage IIIB carcinoma of the cervix". JCO, 1991, 9 (6), 970.

[6] Eddy G.L.: "Neoadjuvant chemotherapy before surgery in cervical cancer". J. Natl. Cancer Inst. Monogr., 1996, (21), 93.

[7] Douple E.B., Green C.J., Simic M.G.: "Potentiation of cellular radiosensitivity by nitroprusside and vitamin B 12". Int. J. Radiar. Oncol. Biol Phys., 1980.

[8] Muss H.B., Jobson V.W., Homesley H.D., Welander C., Ferree C.: "Neoadjuvant therapy for advanced squamous cell carcinoma of the cervix: cisplatin followed by radiation therapy-a pilot study of the Gynecologic Oncology Group". Gynecol. Oncol., 1987, 26 (1), 35.

[9] Tokuhashi Y., Kikkawa F., Ishikawa H., Tamakoshi K., Hattori S., Matsuzawa K. et al.: "Distribution of platinum in human gynecologic tissues and pelvic lymph nodes after administration of cisplatin". Gynecol. Obstet. Invest., 1997, 44 (4), 270.

[10] Friedlander M., Kate S.B., Sullivan A., Atkinson K., Elliott P., Coppleson M. et al.: "Cervical Carcinoma: A drug-responsive tumour-Expenence with combined cisplatin, vinblastine, and bleomycin therapy". Gynecol. Oneal., 1983, 16, 275.

[11] Valle J.C.,R ezenende M.R.,W erneck C.,C hu C.,F igueredo E.: "Neoadjuvant & adjuvant chemotherapy with adriamycin,b leomycin & cisplatin (ABC) and modified radical hysterectomy in the cancer of cervix, Stage III". Proc. ASCO, 1985 (4), 125, C-486.

[12] Benedetti-Panici P., Scambia G., Baiocchi G., Greggi S., Ragusa G., Gallo A. et al.: "Neoadjuvant chemotherapy and radical surgery in locally advanced cervical cancer. Prognostic factors for response and survival". Cancer, 1991, 15, 67 (2), 372.

[13] Kirsten F., Atkinson K.H., Coppleson J.V., Elliott P.M., Green D., Houghton R. et al.: "Combination chemotherapy followed by surgery or radiotherapy in patients with locally advanced cervical cancer". Br. J. Obstet. Gynaecol., 1987, 94 (6), 583.

[14] Kim D.S., Moon H., Kang K.J.: "Primary chemotherapy and postoperative adjuvant chemotherapy in the treatment of squamous cell carcinoma of the uterine cervix". Gynecol. Oncol., 1985.

[15] Kirn D.S., Moon H., Hwang Y.Y., Cho S.H.: "Preoperative adjuvant chemotherapy in the treatment of cervical cancer stage lb, Ila, and IIb with bulky tumor". Gynecol. Oncol., 1988, 29 (3), 321.

[16] Kim D.S., Moon H., Kim K.T., Hwang Y.Y., Cho S.H., Kim S.R.:'Two-year survival: preoperative adjuvant chemotherapy in the treatment of cervical cancer Stages lb and II with bulky tumor". Gynecol. Oncol., 1989, 33 (2), 225.

[17] Benedetti-Panici P.,S cambia G.,G reggi S.,D i Roberto P.,B aiocchi G.,M ancuso S.: "Neoadjuvant chemotherapy and radical surgery inlocally advanced cervical carcinoma: a pilot study". Obstet. Gynecol., 1988, 71 (3 Pt 1), 344.

[18] Giaroli A., Sananes C., Sardi J.E., Maya A.G., Bastardas M.L., Snaidas L. et al.: "Lymph node metastases in carcinoma of the cervix uten: response to neoadjuvant chemotherapy and its impact on survival". Gynecol. Oncol., 1990, 39 (1), 34.

[19] Dottino P.R., Plaxe S.C., Beddoe A.M., Johnston C., Cohen CJ.: "Induction chemotherapy followed by radical surgery in cervical cancer" Gynecol. Oncol., 1991, 40 (1), 7.

[20] Chang H.C., Lai C.H., Chou P.C., T seng C.J., Chang T.C., Hsueh S. et al.: "Neoadjuvant chemotherapy with cisplatin, vincristine, and bleomycin and radical surgery in early-stage bulky cervical carcinoma". Cancer Chernother. Pharrnacol., 1992, 30 (4), 281.

[21] Benedetti-Panici P., Maneschi F., Cutillo G., Greggi S., Salerno M.G., Amoroso M.: "Modified type IV-V radical hysterectomy with systematic pelvic and aortic lymphadenectomy in the treatment of patients with Stage III cervical carcinom. Feasibility,t echnique,a nd clinical results" Cancer, 1996, 1, 78 (11), 2359.

[22] Zanetta G., Dissoni A., Gabriele A., Bandoni F., Colombo A., Perego P., Mangioni C.: "Intense neoadjuvant chemotherapy with cisplatin and epirubicina for advanced or bulky cervical and vaginal adenocarcinoma". Gynecol. Oncol., 1997, 64, 431.

[23] Leone B., Vallejo C., Perez J., Cuevas M. A., Machiavelli M., Lacava J. et al.: "Ifosfamide and cisplatin as neoadjuvant chemotherapy for advanced cervical cancer". Arn. J. Clin. Oncol., 1996, 19 (2), 132.

[24] Kumar L., Kaushal R., Nandy M., Biswual B.M., Kumar S., Kriplani A et al.: "Chemotherapy followed by radiotherapy versus radiotherapy alone in locally advanced cervical cancer: A randomised study". Gynecol. Oncol., 1994, 54, 307.

[25] Benedetti-Panici P.L. et al.: "Neoadjuvant chemotherapy in cervical cancer". In: "Chemotherapy in Gynecologic Oncology" (in press).

[26] Chang T.C., Lai C.H., Hong J.H., Hsueh S., Huang K.G., Chou H.H. 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. Oneal., 2000, 18 (8), 1740.

[27] Sardi J.E., Giaroli A., Sananes C., Ferreira M., Soderini A., Bermudez A. et al.: "Long-term follow-up of the first randomized trial using neoadjuvant chemotherapy in stage lb squamous carcinoma of the cervix: the final results". Gynecol. Oncol., 1997, 67 (1), 61.

[28] Sardi J., Sananes C.E., Giaroli A., Bermudez A., Ferreira M.H., Soderini A.H. et al.: "Neoadjuvant chemotherapy in cervical carcinoma Stage IIB: a randomised controlled trial". Int. J. Gynecol. Cancer, 1998, 8, 441.

[29] Sardi J., Giaroli A., Sananes C., Rueda N.G., Vicgi S., Fereira M. et al.: "Randomized trial with neoadjuvant chemotherapy in Stage IIIB squamous carcinoma cervix uteri: an unexpected therapeutic management". Int. J. Gynecol. Cancer, 1996, 6, 85.

[30] Tierney J.F.: "Neoadjuvant chemotherapy for locally advanced cervical cancer: A systematic review and meta-analysis of individual patient data from 21 randomised trials". Eur. J. Cancer (in press).