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 health care 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 provided only to supplement the latest treatment strategies.

These Guidelines are a work in progress that may be refined as often as new significant data become available. The NCCN 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.

▶Squamous Cell Carcinoma, Adenocarcinoma, or Adenosquamous Carcinoma1

REGIMEN

DOSING

Chemoradiation

Preferred Regimens

Carboplatin (if patient is Cisplatin intolerant)2-5

Day 1: Carboplatin AUC 2 IV over 30 minutes.
Repeat cycle weekly for 6 weeks with concurrent radiation.

Cisplatin6-8,b

Day 1: Cisplatin 40mg/m2 IV over 1 hour.

Repeat cycle weekly for 6 weeks with concurrent radiation.

Recurrent or Metastatic Disease

First-Line Combination Therapyj

Preferred Regimens

Carboplatin/Paclitaxel + Bevacizumab2,9-13;c,d

Paclitaxel requires premedication.

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 + Bevacizumab (Category 1)6,9,14,15,b-e
Paclitaxel requires premedication.

Day 1: Bevacizumab 15mg/kg IV

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

Day 1: Cisplatin 50mg/m2 IV over 1 hour.

Repeat cycle every 3 weeks.

Pembrolizumab + Carboplatin/Paclitaxel (for PD-L1-positive tumors) (Category 1)2,10,16,17, a,c,f

Paclitaxel requires premedication.

Day 1: Pembrolizumab 200mg IV over 30 minutes

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

Day 1: Carboplatin AUC 5 IV over 30 minutes.

Repeat cycle every 3 weeks for up to 35 cycles.

Pembrolizumab + Carboplatin/Paclitaxel + Bevacizumab (for PD-L1-positive tumors) (Category 1)2,9,10,16,17,a,c,d,f
Paclitaxel requires premedication.

Day 1: Pembrolizumab 200mg IV over 30 minutes

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

Day 1: Carboplatin AUC 5 IV over 30 minutes

Day 1: Bevacizumab 15mg/kg IV.

Repeat cycle every 3 weeks for up to 35 cycles.

Pembrolizumab + Cisplatin/Paclitaxel for PD-L1-positive tumors (Category 1)6,10,16,17,a-c,f
Paclitaxel requires premedication.

Day 1: Pembrolizumab 200mg IV over 30 minutes

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

Day 1: Cisplatin 50mg/m2 IV over 1 hour.

Repeat cycle every 3 weeks for up to 35 cycles.

Pembrolizumab + Cisplatin/Paxlitaxel + Bevacizumab (for PD-L1-positive tumors) (Category 1)6,9,10,16,17,a-d,f

Paclitaxel requires premedication.

Day 1: Pembrolizumab 200mg IV over 30 minutes

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

Day 1: Cisplatin 50mg/m2 IV over 1 hour

Day 1: Bevacizumab 15mg/kg IV.

Repeat cycle every 3 weeks for up to 35 cycles.

Other Recommendations Regimens

Carboplatin/Paclitaxel (Category 1 for patients who have received prior Cisplatin therapy)2,10,18,19,c

Paclitaxel requires premedication.

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.

Cisplatin/Paclitaxel (Category 1)6,10,20-22,b,c,e

Paclitaxel requires premedication.

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

Day 1 OR Day 2: Cisplatin 50mg/m2 IV over 1 hour.

Repeat cycle every 3 weeks.

Cisplatin/Topotecan6,23,24,b

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

Day 1: Cisplatin 50mg/m2 IV over 1 hour.

Repeat cycle every 3 weeks.

Topotecan/Paclitaxel + Bevacizumab (Category 1)9,10,14,15,23,c,d

Paclitaxel requires premedication.

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.

Topotecan/Paclitaxel10,14,15,23,c

Paclitaxel requires premedication.

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.

Possible First-line Single-agent therapyj

Preferred Regimens

Cisplatin6,21,b

Day 1: Cisplatin 50mg/m2 IV over 1 hour.

Repeat cycle weekly for 3 weeks.

Other Recommended Regimens

Carboplatin2,25

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

Repeat cycle every 3-4 weeks.

Paclitaxel10, 26,27,c
Paclitaxel requires premedication.

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

Repeat cycle every 3-4 weeks.

OR

Day 1: Paclitaxel 175mg/m2 IV over 3 hours, if no prior pelvic radiation.

Repeat cycle every 3-4 weeks.

OR

Day 1: Paclitaxel 80mg/m2 IV over 1 hour.

Repeat cycle weekly.

Second-line or Subsequent Therapy

Preferred Regimens

Nivolumab (for PD-L1-postive tumors)28,29,a,f

Day 1: Nivolumab 240mg IV over 30 minutes.

Repeat every 2 weeks.

Pembrolizumab (for PD-L1-positive or MSI-H/dMMR tumors)16,30-32,a,f

Day 1: Pembrolizumab 200mg IV over 30 minutes.

Repeat cycle every 3 weeks.

OR

Day 1: Pembrolizumab 400mg IV over 30 minutes.

Repeat cycle every 6 weeks.

Other Recommended Regimens

Albumin-Bound Paclitaxel (Category 2B)33-35

Days 1,8,15: Albumin-Bound Paclitaxel 100-125mg/m2 IV over 30 minutes.

Repeat cycle every 4 weeks.

Bevacizumab (Category 2B)9,36,d

Day 1: Bevacizumab 15mg/kg IV.

Repeat cycle every 3 weeks.

Docetaxel (Category 2B)37, 38,g
Docetaxel requires premedication.

Day 1: Docetaxel 100mg/m2 IV over 1 hour.

Repeat cycle every 3 weeks.

Fluorouracil + Leucovorin (Category 2B)39-41

Days 1-5: Leucovorin 200mg/m2 IV over 15 minutes daily, followed by:

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

Repeat every 4 weeks for 2 cycles, then every 5 weeks.

Gemcitabine (Category 2B)42-44

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

Repeat cycle every 4 weeks.

Ifosfamide (Category 2B)45-47,h

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

Days 1-5: Mesna 300mg/m2 IV over 15 minutes (one dose before ifosfamide then three times daily at 4 and 8 hours from the start of ifosfamide dose).

Repeat cycle every 3 weeks.

Irinotecan (Category 2B)48,49

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 treatment).

Mitomycin (Category 2B)50,51

Day 1: Mitomycin 10mg/m2 IV push.

Repeat cycle every 4 weeks.

Pemetrexed (Category 2B)52,53,i
Pemetrexed requires premedication.

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.

Tisotumab vedotin-tftv54,55

Day 1: Tisotumab vedotin 2mg/kg IV (max 200mg)

Repeat every 3 weeks.

Topotecan (Category 2B)23, 56-58,e

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.

Vinorelbine (Category 2B)59,60

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

Repeat cycle every 3 weeks.

Useful in Certain Circumstances

Entrectinib (for NTRK gene fusion-positive tumors) (Category 2B)61,62

Day 1-28: Entrectinib 600mg orally once daily.

Repeat cycle every 4 weeks.

Larotrectinib (for NTRK gene fusion-positive tumors) (Category 2B)63,64

Day 1-28: Larotectinib 100mg PO twice daily.

Repeat cycle every 4 weeks

Pembrolizumab (for TMB-H tumors)16,30-32,a,f,k

Day 1: Pembrolizumab 200mg IV over 30 minutes.

Repeat cycle every 3 weeks.

OR

Day 1: Pembrolizumab 400mg IV over 30 minutes.

Repeat cycle every 6 weeks.

▶Small Cell Neuroendocrine Carcinoma of the Cervix (NECC)1

Chemoradiation

Preferred Regimen

Cisplatin/Etoposide6,65-70,b,e

Day 1-3: Cisplatin 25mg/m2 IV over 1 hour daily

Day 1-3: Etoposide 100mg/m2 IV over 1 hour daily.

Repeat cycle every 3 or 4 weeks for 4-6 cycles.

OR

Day 1: Cisplatin 75mg/m2 IV over 2 hours

Day 1-3: Etoposide 100mg/m2 IV over 1 hour daily.

Repeat cycle every 3 or 4 weeks for 4-6 cycles.

OR

Day 1: Cisplatin 80mg/m2 IV over 2 hours

Day 1-3: Etoposide 80mg/m2 IV over 1 hour daily.

Repeat cycle every 3 or 4 weeks for 4-6 cycles.

Other Recommended Regimens

Carboplatin/Etoposide (if patient is Cisplatin intolerant)2, 65, 69-74,

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

Day 1-3: Etoposide 100mg/m2 IV over 1 hour.

Repeat cycle every 3 or 4 weeks for 4-6 cycles.

Neoadjuvant Therapy, Adjuvant Therapy, Recurrent or Metastatic Disease

First-line Therapy

Preferred Regimens

Carboplatin/Etoposide2, 65, 69-74,e

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

Day 1-3: Etoposide 100mg/m2 IV over 1 hour.

Repeat cycle every 3 or 4 weeks for 4-6 cycles.

Cisplatin/Etoposide6,55,66-70,c

Day 1-3: Cisplatin 25mg/m2 IV over 1 hour daily

Day 1-3: Etoposide 100mg/m2 IV over 1 hour daily.

Repeat cycle every 3 or 4 weeks for 4-6 cycles.

OR

Day 1: Cisplatin 75mg/m2 IV over 2 hours

Day 1-3: Etoposide 100mg/m2 IV over 1 hour daily.

Repeat cycle every 3 or 4 weeks for 4-6 cycles.

OR

Day 1: Cisplatin 80mg/m2 IV over 2 hours

Day 1-3: Etoposide 80mg/m2 IV over 1 hour daily.

Repeat cycle every 3 or 4 weeks for 4-6 cycles.

Second-line or Subsequent Therapy

See first-line or second line therapyl

  a CSF, colony stimulating factors; dMMR, mismatch repair deficient; MSI, microsatellite instability; NECC, neuroendocrine carcinoma of the cervix ; PD-L1, programmed cell death-ligand 1; TMB-H, tumor mutational burden-high.

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

  c For Paclitaxel: Premedication for hypersensitivity is required. The recommended dosing is:
• H2 antagonist
   — Famotidine 20mg IV or orally (or equivalent H2 blocker) 30-60 minutes pre-Paclitaxel AND
• H1 antagonist
   —Diphenhydramine 12.5-50mg IV or orally 30-60 minutes pre-Paclitaxel AND
• Dexamethasone (for 21-day regimen):
   — Dexamethasone 20mg orally approximately 12 and 6 hours pre-Paclitaxel OR
   — Dexamethasone 20mg IV 30 minutes pre-Paclitaxel
• Dexamethasone (for weekly regimens):
   — Dexamethasone 10mg IV 30 minutes pre-Paclitaxel

  d A biosimilar agent may be substituted for Bevacizumab if clinically appropriate.

  e CSFs may be considered for primary prophylaxis based on the febrile neutropenia (FN) risk of the chemotherapy regimen.

  f Early- and late-onset immune-related adverse events affecting multiple organ systems can occur in patients receiving immune checkpoint inhibitors. Patients with neurologic or life-threatening autoimmune disorders as well as those receiving high levels of immunosuppression for their underlying disease should be approached with caution when considering immunotherapy. All patients will require extensive resources including ongoing intensive monitoring and supportive care.

  g For Docetaxel: Premedication with Dexamethasone for fluid retention is required. One recommended strategy is:
• Dexamethasone 8mg orally twice daily for three consecutive days starting 1 day prior to Docetaxel administration.

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

  i For Pemetrexed: Premedication and supplemental medications to reduce the incidence and severity of hematologic, gastrointestinal, and cutaneous toxicities is required. The recommended dosing is:
• Vitamin B12 (cyanocobalamin) 1,000mcg IM during the week preceding the first cycle of Pemetrexed and every 3 cycles thereafter AND
• Folic acid400-1,000mcg orally daily starting 7 days before the first cycle and continuing for 21 days after the last dose of Pemetrexed AND
• Dexamethasone 4mg orally twice daily for 3 days starting the day prior to Pemetrexed.

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

  k For the treatment of patients with unresectable or metastatic tumor mutational burden-high (TMB_H) ≥[10 mutations/megabase (mut/Mb)] tumors, as determined by a validated and/or FDA-approved test, that have progressed following prior treatment and who have no satisfactory alternative treatment options.

  l Any of the regimens recommended for first-line or second-line treatment of recurrent/metastatic disease may be used as second-line or subsequent therapy for small cell neuroendocrine carcinoma if not used previously.

References

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(Revised 9/2022 NCCN Cervical Cancer Guidelines v1.2022) ©2022 by Haymarket Media, Inc

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Cervical Cancer Gynecologic Cancers Treatment Regimens