Cervical Cancer Treatment Regimens

Cervical Cancer Treatment Regimens

Clinical Trials: The NCCN recommends cancer patient participation in clinical trials as the gold standard for treatment.

Cancer therapy selection, dosing, administration, and the management of related adverse events can be a complex process that should be handled by an experienced healthcare team. Clinicians must choose and verify treatment options based on the individual patient; drug dose modifications and supportive care interventions should be administered accordingly. The cancer treatment regimens below may include both U.S. Food and Drug Administration-approved and unapproved indications/regimens. These regimens are only provided to supplement the latest treatment strategies.

These Guidelines are a work in progress that may be refined as often as new significant data becomes available. The National Comprehensive Cancer Network Guidelines® are a consensus statement of its authors regarding their views of currently accepted approaches to treatment. Any clinician seeking to apply or consult any NCCN Guidelines® is expected to use independent medical judgment in the context of individual clinical circumstances to determine any patient’s care or treatment. The NCCN makes no warranties of any kind whatsoever regarding their content, use, or application and disclaims any responsibility for their application or use in any way.

Note: All recommendations are Category 2A unless otherwise indicated.

▶Chemoradiation as Primary Therapy, Adjuvant Therapy, or Therapy for Recurrent Disease1

REGIMEN

DOSING

Preferred Regimens

Carboplatin (if patient is Cisplatin intolerant)2,a

Day 1: Carboplatin AUC 2 IV over 30 minutes.

Repeat cycle weekly for 6 weeks with concurrent radiation.

Cisplatin3,a,b

Day 1: Cisplatin 40mg/m2 IV over 60 minutes.

Repeat cycle weekly for 6 weeks with concurrent radiation.

Other Recommended Regimens

Cisplatin + Fluorouracil4-6,a,b

Day 1: Cisplatin 50-75mg/m2 IV over 60 minutesb

Days 1-4: Fluorouracil 1000mg/m2 IV continuous infusion over 24 hours daily.

Repeat cycle every 3 week for 3-4 cycles.

▶Systemic Therapy for Recurrent or Metastatic Disease1

First-line Combination Therapyc,d

Preferred Regimens

Carboplatin + Paclitaxel (Category 1 for patients who have received prior Cisplatin therapy)7,a

Day 1: Paclitaxel 175mg/m2 IV over 3 hours, followed by:

Day 1: Carboplatin AUC 5 IV over 30 minutes.

Repeat cycle every 3 weeks.

Carboplatin + Paclitaxel + Bevacizumab7-9,a,e

Day 1: Bevacizumab 15mg/kg IV

Day 1: Paclitaxel 175mg/m2 IV over 3 hours, followed by:

Day 1: Carboplatin AUC 5 IV over 30 minutes.

Repeat cycle 3 weeks.

Cisplatin + Paclitaxel (Category 1)3,10,11,a,b

Day 1: Paclitaxel 135mg/m2 IV continuous infusion, followed by:

Day 2: Cisplatin 50mg/m2 IV over 60 minutes

Repeat cycle every 3 weeks.

OR

Day 1: Paclitaxel 175mg/m2 IV over 3 hours, followed by:

Day 1: Cisplatin 50mg/m2 IV over 60 minutes.

Repeat cycle every 3 weeks.

Cisplatin + Paclitaxel + Bevacizumab (Category 1)12,a,b,e

Day 1: Bevacizumab 15mg/kg IV

Day 1: Paclitaxel 135mg/m2 IV continuous infusion over 24 hours, followed by:

Day 2: Cisplatin 50mg/m2 IV over 60 minutes.

Repeat cycle every 3 weeks.

OR

Day 1: Bevacizumab 15mg/kg IV

Day 1: Paclitaxel 175mg/m2 IV over 3 hours, followed by:

Day 1: Cisplatin 50mg/m2 IV over 60 minutes.

Repeat cycle every 3 weeks.

Topotecan + Paclitaxel12,a

Day 1: Paclitaxel 175mg/m2 IV over 3 hours

Days 1-3: Topotecan 0.75mg/m2 IV over 30 minutes.

Repeat cycle every 3 weeks.

Topotecan + Paclitaxel + Bevacizumab (Category 1)12,a,e

Day 1: Bevacizumab 15mg/kg IV

Day 1: Paclitaxel 175mg/m2 IV over 3 hours

Days 1-3: Topotecan 0.75mg/m2 IV over 30 minutes.

Repeat cycle every 3 weeks.

Other Recommended Regimens

Cisplatin + Topotecan13,a,b

Days 1-3: Topotecan 0.75mg/m2 IV over 30 minutes, followed by:

Day 1: Cisplatin 50mg/m2 IV over 60 minutes.

Repeat cycle every 3 weeks.

Possible First-line Single-Agent Therapyd

Preferred Regimens

Cisplatin14,a

Day 1: Cisplatin 50mg/m2 IV over 60 minutes.

Repeat cycle every 3 weeks.

Other Recommended Regimens

Carboplatin14,a

Day 1: Carboplatin AUC 5-6 IV over 30 minutes.

Repeat cycle every 3-4 weeks.

Paclitaxel15,16,a

Day 1: Paclitaxel 175mg/m2 IV over 3 hours.

Repeat cycle every 3-4 weeks.

OR

Day 1: Paclitaxel 155mg/m2 IV over 3 hours, if prior pelvic radiation.

Repeat cycle every 3-4 weeks.

OR

Day 1: Paclitaxel 170mg/m2 IV continuous infusion over 24 hours.

Repeat cycle every 3-4 weeks.

OR

Day 1: Paclitaxel 135mg/m2 IV continuous infusion over 24 hours, If prior pelvic radiation.

Repeat cycle every 3-4 weeks.

OR

Day 1: Paclitaxel 80mg/m2 IV over 60 minutes.

Repeat cycle weekly.

Second-line Therapy

Preferred Regimens

Pembrolizumab (for PD-L1-positive or MSI-H/dMMR tumors)17,f

Day 1: Pembrolizumab 200mg IV over 30 minutes.

Repeat cycle every 3 weeks.

Other Recommended Regimens (Category 2B)

Albumin-Bound Paclitaxel18,19

Days 1,8,15: Albumin-Bound Paclitaxel 125mg/m2 IV over 30 minutes.

Repeat cycle every 4 weeks.

OR

Day 1: Albumin-Bound Paclitaxel 260mg/m2 IV over 30 minutes.

Repeat cycle every 3 weeks.

Bevacizumab20,e

Day 1: Bevacizumab 15mg/kg IV.

Repeat cycle every 3 weeks.

Docetaxel21

Day 1: Docetaxel 100mg/m2 IV over 60 minutes.

Repeat cycle every 3 weeks.

Fluorouracil + Leucovorin22

Days 1-5: Leucovorin 200mg/m2 IV push daily, followed by:

Days 1-5: Fluorouracil 370mg/m2 IV push daily.

Repeat every 28 days for 2 cycles, then every 35 days.

Gemcitabine23,24

Days 1,8,15: Gemcitabine 800mg/m2 IV over 30 minutes.

Repeat cycle every 4 weeks.

Ifosfamide25,26,g

Days 1-5: Ifosfamide 1,500mg/m2 IV over 3 hours dailyg

Days 1-5: Mesna 300mg/m2 IV over 15 minutes before Ifosfamide, then at 4 and 8 hours from the start of each Ifosfamide dose.

Repeat cycle every 3 weeks.

Irinotecan27

Days 1,8,15,22: Irinotecan 125mg/m2 IV over 90 minutes.

Repeat cycle every 6 weeks (4 weeks on followed by 2 weeks off).

Mitomycin28,h

Day 1: Mitomycin 10mg/m2 IV push.

Repeat cycle every 4 weeks.

Pemetrexed29

Day 1: Pemetrexed 900mg/m2 IV over 10 minutes.

Repeat cycle every 3 weeks.

OR

Day 1: Pemetrexed 700mg/m2 IV over 10 minutes, if prior pelvic radiation.

Repeat cycle every 3 weeks.

Topotecan30,31

Days 1-5: Topotecan 1.5mg/m2 IV over 30 minutes.

Repeat cycle every 4 weeks.

OR

Days 1,8,15: Topotecan 3-4mg/m2 IV over 30 minutes.

Repeat cycle every 4 weeks.

Vinorelbine32

Days 1,8: Vinorelbine 30mg/m2 IV over 5-10 minutes.

Repeat cycle every 3 weeks.

a. Cisplatin, Carboplatin, Docetaxel, and Paclitaxel may cause drug reactions. See NCCN Guidelines for Ovarian Cancer – Management of Drug Reactions.

b. Hydration is required with supplemental electrolytes pre- and post-administration of Cisplatin.

c. Cost and toxicity should be carefully considered when selecting an appropriate regimen for treatment.

d. If not used previously, these agents can be used as second-line therapy as clinically appropriate.

e. An FDA-approved biosimilar is an appropriate substitute for Bevacizumab.

f. Recommended for disease progression on or after chemotherapy in patients whose tumors express PD-L1 (combined positive score [CPS] ≥1) as determined by an FDA-approved test.

g. Hydration is required pre- and post-administration of Ifosfamide.

h. Continue until disease progression or unacceptable toxicity including reaching a lifetime cumulative mitomycin dose.

References

  1. NCCN Clinical Practice Guidelines in Oncology™ Cervical Cancer, v5.2019. https://www.nccn.org/professionals/physician_gls/pdf/cervical.pdf. Accessed November 7, 2019.

  2. Katanyoo K, Tangjitgamol S, Chongthanakorn M, et al. Treatment outcomes of concurrent weekly carboplatin with radiation therapy in locally advanced cervical cancer patients. Gynecol Oncol. 2011;123:571-576.

  3. Moore DH, Blessing JA, McQuellon RP, et al. Phase III study of cisplatin with or without paclitaxel in stage IVB, recurrent, or persistent squamous cell carcinoma of the cervix: a gynecologic oncology group study. J Clin Oncol. 2004;22:3113-3119.

  4. Peters WA 3rd, Liu PY, Barrett RJ 2nd, et al. Concurrent chemotherapy and pelvic radiation therapy compared with pelvic radiation therapy alone as adjuvant therapy after radical surgery in high-risk early-stage cancer of the cervix. J Clin Oncol. 2000;18:1606-1613.

  5. Whitney CW, Sause W, Bundy BN, et al. Randomized comparison of fluorouracil plus cisplatin versus hydroxyurea as an adjunct to radiation therapy in stage IIB-IVA carcinoma of the cervix with negative para-aortic lymph nodes: a Gynecologic Oncology Group and Southwest Oncology Group study. J Clin Oncol. 1999;17:1339-1348.

  6. Morris M, Eifel PJ, Lu J, et al. Pelvic radiation with concurrent chemotherapy compared with pelvic and para-aortic radiation for high-risk cervical cancer. N Engl J Med. 1999;340:1137-1143.

  7. Kitagawa R, Katsumata N, Shibata T, et al. Paclitaxel Plus carboplatin versus paclitaxel plus cisplatin in metastatic or recurrent cervical cancer: The open-label randomized phase III trial JCOG0505. J Clin Oncol. 2015;33:2129-2135.

  8. Zarba JJ, Pastrana VA, Espinoza DE, et al. Analysis of safety and outcome of the combination of carboplatin (C) paclitaxel (P) and bevacizumab (B) in advanced/recurrent cervical cancer (ACC). J Clin Oncol. 2016;34(15_suppl):Abstract e17015.

  9. 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;133:117-123.

10. Eisenhauer EA, ten Bokkel Huinink WW, Swenerton KD, et al. European-Canadian randomized trial of paclitaxel in relapsed ovarian cancer: high-dose versus low-dose and long versus short infusion. J Clin Oncol. 1994;12:2654-2666.

11. Monk BJ, Sill MW, McMeekin DS, et al. Phase III trial of four cisplatin-containing doublet combinations in stage IVB, recurrent, or persistent cervical carcinoma: a Gynecologic Oncology Group study. J Clin Oncol. 2009;27:4649-4655.

12. Tewari KS, Sill MW, Long HJ 3rd, et al. Improved survival with bevacizumab in advanced cervical cancer. N Engl J Med. 2014;370:734-743.

13. Long HJ 3rd, Bundy BN, Grendys EC Jr, et al. Randomized phase III trial of cisplatin with or without topotecan in carcinoma of the uterine cervix: a Gynecologic Oncology Group Study. J Clin Oncol. 2005;23:4626-4633.

14. Weiss GR, Green S, Hannigan EV, et al. A phase II trial of carboplatin for recurrent or metastatic squamous carcinoma of the uterine cervix: a Southwest Oncology Group study. Gynecol Oncol. 1990;39:332-336.

15. Tinker AV, Bhagat K, Swenerton KD, Hoskins PJ. Carboplatin and paclitaxel for advanced and recurrent cervical carcinoma: the British Columbia Cancer Agency experience. Gynecol Oncol. 2005;98:54-58.

16. Homesley HD, Meltzer NP, Nieves L, et al. A phase II trial of weekly 1-hour paclitaxel as second-line therapy for endometrial and cervical cancer. Int J Clin Oncol. 2008;13:62-65.

17. Chung HC, Ros W, Delord JP, et al. Efficacy and safety of pembrolizumab in previously treated advanced cervical cancer: Results from the phase II KEYNOTE-158 study. J Clin Oncol. 2019;37:1470-1478.

18. Alberts DS, Blessing JA, Landrum LM, et al. Phase II trial of nab-paclitaxel in the treatment of recurrent or persistent advanced cervix cancer: A gynecologic oncology group study. Gynecol Oncol. 2012;127:451-455.

19. Gradishar WJ, Tjulandin S, Davidson N, et al. Phase III trial of nanoparticle albumin- bound paclitaxel compared with polyethylated castor oil-based paclitaxel in women with breast cancer. J Clin Oncol. 2005;23:7794-7803.

20. Monk BJ, Sill MW, Burger RA, et al. Phase II trial of bevacizumab in the treatment of persistent or recurrent squamous cell carcinoma of the cervix: a gynecologic oncology group study. J Clin Oncol. 2009;27:1069-1074.

21. Garcia AA, Blessing JA, Vaccarello L, et al. Phase II clinical trial of docetaxel in refractory squamous cell carcinoma of the cervix: a Gynecologic Oncology Group Study. Am J Clin Oncol. 2007;30:428-431.

22. Look KY, Blessing JA, Gallup DG, Lentz SS. A phase II trial of 5-fluorouracil and high-dose leucovorin in patients with recurrent squamous cell carcinoma of the cervix: a Gynecologic Oncology Group study. Am J Clin Oncol. 1996;19:439-441.

23. Schilder RJ, Blessing J, Cohn DE. Evaluation of gemcitabine in previously treated patients with non-squamous cell carcinoma of the cervix: a phase II study of the Gynecologic Oncology Group. Gynecol Oncol. 2005;96:103-107.

24. Schilder RJ, Blessing JA, Morgan M, et al. Evaluation of gemcitabine in patients with squamous cell carcinoma of the cervix: a Phase II study of the gynecologic Oncology Group. Gynecol Oncol. 2000;76:204-207.

25. Coleman RE, Harper PG, Gallagher C, et al. A phase II study of ifosfamide in advanced and relapsed carcinoma of the cervix. Cancer Chemother Pharmacol. 1986;18:280-283.

26. Sutton GP, Blessing JA, McGuire WP, et al. Phase II trial of ifosfamide and mesna in patients with advanced or recurrent squamous carcinoma of the cervix who had never received chemotherapy: a Gynecologic Oncology Group study. Am J Obstet Gynecol. 1993;168:805-807.

27. Verschraegen CF, Levy T, Kudelka AP, et al. Phase II study of irinotecan in prior chemotherapy-treated squamous cell carcinoma of the cervix. J Clin Oncol. 1997;15:625-631.

28. Umesaki N, Fujii T, Nishimura R, et al. Phase II study of irinotecan combined with mitomycin-C for advanced or recurrent squamous cell carcinoma of the uterine cervix: the JGOG study. Gynecol Oncol. 2004;95:127-132.

29. Miller DS, Blessing JA, Bodurka DC, et al. Evaluation of pemetrexed (Alimta, LY231514) as second line chemotherapy in persistent or recurrent carcinoma of the cervix: a phase II study of the Gynecologic Oncology Group. Gynecol Oncol. 2008;110:65-70.

30. Muderspach LI, Blessing JA, Levenback C, Moore JL Jr. A Phase II study of topotecan in patients with squamous cell carcinoma of the cervix: a gynecologic oncology group study. Gynecol Oncol. 2001;81:213-215.

31. Fiorica JV, Blessing JA, Puneky LV, et al. A Phase II evaluation of weekly topotecan as a single agent second line therapy in persistent or recurrent carcinoma of the cervix: a Gynecologic Oncology Group study. Gynecol Oncol. 2009;115:285-289.

32. Muggia FM, Blessing JA, Method M, et al. Evaluation of vinorelbine in persistent or recurrent squamous cell carcinoma of the cervix: a Gynecologic Oncology Group study. Gynecol Oncol. 2004;92:639-643.

(Revised 12/2019; NCCN Cervical Cancer Guidelines v5.2019) © 2019 by Haymarket Media, Inc.