J Gynecol Oncol.  2015 Apr;26(2):118-124. 10.3802/jgo.2015.26.2.118.

Efficacy and tolerability of paclitaxel, ifosfamide, and cisplatin as a neoadjuvant chemotherapy in locally advanced cervical carcinoma

• Scandurra
• Scibilia G
• Banna GL
• D'Agate G
• Lipari H
• Gieri S
• Scollo P

• KMID: 2160794
• DOI: http://doi.org/10.3802/jgo.2015.26.2.118

Abstract

OBJECTIVE
To evaluate the efficacy and tolerability of a neoadjuvant paclitaxel, ifosfamide, and cisplatin chemotherapy in patients with locally advanced cervical carcinoma.
METHODS
Patients with histologically confirmed locally advanced cervical carcinoma, aged > or =18 years, were treated with intravenous ifosfamide 5,000 mg/m2 and mesna 5,000 mg/m2, on day 1; intravenous paclitaxel 175 mg/m2 and cisplatin 75 mg/m2, on day 2; every 3 weeks for three cycles. Following chemotherapy, operable patients underwent radical hysterectomy and pelvic lymphadenectomy, and, if necessary, adjuvant radiotherapy.
RESULTS
One hundred fifty-two patients with median age 53 years (range, 24 to 79 years), FIGO stage IIB in 126 (89%), were treated with chemotherapy for median 3 cycles (range, 1 to 3). Treatment was delayed or withdrawn in 23 patients (15%). One hundred thirty-nine patients (91%) underwent surgery. Postchemotherapy pathological complete response rate was 18% (25 patients). Postoperative radiotherapy was administered in 100 patients (72%). The 5-year overall survival and progression-free survival were 87.3% (95% confidence interval [CI], 84.5 to 90.3) and 76.4% (95% CI, 73.5 to 79.5), respectively.
CONCLUSION
Neoadjuvant paclitaxel, ifosfamide, and cisplatin chemotherapy was feasible and effective in the treatment of locally advanced cervical carcinoma patients with older age and more advanced disease stage than reported in previous studies. Hematological and renal toxicity could be carefully prevented.

Keyword

Antineoplastic Combined Chemotherapy Protocols; Disease-Free Survival; Retrospective Studies; Uterine Cervical Neoplasms

MeSH Terms

Adult
Aged
Antineoplastic Combined Chemotherapy Protocols/*therapeutic use
Carcinoma, Squamous Cell/*drug therapy/mortality/pathology
Cisplatin/*administration & dosage/adverse effects
Disease Progression
Feasibility Studies
Female
Humans
Ifosfamide/*administration & dosage/adverse effects
Middle Aged
Neoadjuvant Therapy
Paclitaxel/*administration & dosage/adverse effects
Retrospective Studies
Treatment Outcome
Uterine Cervical Neoplasms/*drug therapy/mortality/pathology
Young Adult
Cisplatin
Ifosfamide
Paclitaxel

Figure

• 

  Fig. 1 (A) Probability of overall survival. (B) Probability of progression-free survival.

Reference

1. National Cancer Institute. Concurrent Chemoradiation for Cervical Cancer Clinical: Announcement [Internet]. Washington DC: NCI;1999. cited 2015 Feb 3. Available from: http://www.cancer.gov/newscenter/cervicalcancer.

2. Eddy GL, Manetta A, Alvarez RD, Williams L, Creasman WT. Neoadjuvant chemotherapy with vincristine and cisplatin followed by radical hysterectomy and pelvic lymphadenectomy for FIGO stage IB bulky cervical cancer: a Gynecologic Oncology Group pilot study. Gynecol Oncol. 1995; 57:412–416.

3. Leone B, Vallejo C, Perez J, Cuevas MA, Machiavelli M, Lacava J, et al. Ifosfamide and cisplatin as neoadjuvant chemotherapy for advanced cervical carcinoma. Am J Clin Oncol. 1996; 19:132–135.

4. Benedetti-Panici P, Greggi S, Scambia G, Amoroso M, Salerno MG, Maneschi F, et al. Long-term survival following neoadjuvant chemotherapy and radical surgery in locally advanced cervical cancer. Eur J Cancer. 1998; 34:341–346.

5. Sananes C, Giaroli A, Soderini A, Guardado N, Snaidas L, Bermudez A, et al. Neoadjuvant chemotherapy followed by radical hysterectomy and postoperative adjuvant chemotherapy in the treatment of carcinoma of the cervix uteri: long-term follow-up of a pilot study. Eur J Gynaecol Oncol. 1998; 19:368–373.

6. Zanetta G, Lissoni A, Pellegrino A, Sessa C, Colombo N, Gueli-Alletti D, et al. Neoadjuvant chemotherapy with cisplatin, ifosfamide and paclitaxel for locally advanced squamous-cell cervical cancer. Ann Oncol. 1998; 9:977–980.

7. Neoadjuvant Chemotherapy for Cervical Cancer Meta-Analysis Collaboration (NACCCMA) Collaboration. Neoadjuvant chemotherapy for locally advanced cervix cancer. Cochrane Database Syst Rev. 2004; 2:CD001774.

8. Park DC, Kim JH, Lew YO, Kim DH, Namkoong SE. Phase II trial of neoadjuvant paclitaxel and cisplatin in uterine cervical cancer. Gynecol Oncol. 2004; 92:59–63.

9. Angioli R, Plotti F, Montera R, Aloisi A, Luvero D, Capriglione S, et al. Neoadjuvant chemotherapy plus radical surgery followed by chemotherapy in locally advanced cervical cancer. Gynecol Oncol. 2012; 127:290–296.

10. Lissoni AA, Colombo N, Pellegrino A, Parma G, Zola P, Katsaros D, et al. A phase II, randomized trial of neo-adjuvant chemotherapy comparing a three-drug combination of paclitaxel, ifosfamide, and cisplatin (TIP) versus paclitaxel and cisplatin (TP) followed by radical surgery in patients with locally advanced squamous cell cervical carcinoma: the Snap-02 Italian Collaborative Study. Ann Oncol. 2009; 20:660–665.

11. Benedet JL, Bender H, Jones H 3rd, Ngan HY, Pecorelli S. FIGO staging classifications and clinical practice guidelines in the management of gynecologic cancers. FIGO Committee on Gynecologic Oncology. Int J Gynaecol Obstet. 2000; 70:209–262.

12. National Cancer Institute. Cancer therapy evaluation programme: common toxicity criteria manual: common toxicity criteria, version 2.0, 1999 June 1. Bethesda: Cancer Therapy Evaluation Program;1999.

13. Therasse P, Arbuck SG, Eisenhauer EA, Wanders J, Kaplan RS, Rubinstein L, et al. New guidelines to evaluate the response to treatment in solid tumors. European Organization for Research and Treatment of Cancer, National Cancer Institute of the United States, National Cancer Institute of Canada. J Natl Cancer Inst. 2000; 92:205–216.

14. Kaplan EL, Meier P. Nonparametric estimation from incomplete observations. J Am Stat Assoc. 1958; 53:457–481.

15. Cox DR. Regression models and life tables. J R Stat Soc Series B Methodol. 1972; 34:187–220.

16. Buda A, Fossati R, Colombo N, Fei F, Floriani I, Gueli Alletti D, et al. Randomized trial of neoadjuvant chemotherapy comparing paclitaxel, ifosfamide, and cisplatin with ifosfamide and cisplatin followed by radical surgery in patients with locally advanced squamous cell cervical carcinoma: the SNAP01 (Studio Neo-Adjuvante Portio) Italian Collaborative Study. J Clin Oncol. 2005; 23:4137–4145.

17. Minig L, Colombo N, Zanagnolo V, Landoni F, Bocciolone L, Cardenas-Rebollo JM, et al. Platinum-based neoadjuvant chemotherapy followed by radical surgery for cervical carcinoma international federation of gynecology and obstetrics stage IB2-IIB. Int J Gynecol Cancer. 2013; 23:1647–1654.

18. Bae JH, Lee SJ, Lee A, Park YG, Bae SN, Park JS, et al. Neoadjuvant cisplatin and etoposide followed by radical hysterectomy for stage 1B-2B cervical cancer. Gynecol Oncol. 2008; 111:444–448.