Anal Cancer Treatment Regimens

Anal Carcinoma 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 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.

▶Localized Cancer1

REGIMEN

DOSING

Fluorouracil + Mitomycin + Radiotherapy
[XRT]2-5 [preferred]

Days 1-4; 29-32: Fluorouracil 1,000mg/m2 IV continuous infusion over 24 hours

Days 1 and 29: Mitomycin 10mg/m2 (max 20mg) IV push, with:

Concurrent XRT

OR

Days 1-4; 29-32: Fluorouracil 1,000mg/m2 IV continuous infusion over 24 hours

Day 1: Mitomycin 12mg/m2 (max 20mg) IV push, with:

Concurrent XRT.

Capecitabine + Mitomycin + XRT3,6-8 [preferred]

Days 1-5; 8-12; 15-19; 22-26; 29-33; 36-38: Capecitabine 825mg/m2 orally twice daily

Days 1 and 29: Mitomycin 10mg/m2 IV (max 20 mg) push, with:

Concurrent XRT

OR

Days 1-5; 8-12; 15-19; 22-26: 29-33; 36-38: Capecitabine 825 mg/m2 orally twice daily

Day 1: Mitomycin 12mg/m2 (max 20mg) IV push, with:

Concurrent XRT

Fluorouracil + Cisplatin +
XRT2,4,9,10 (Category 2B)

Days 1-4; 29-32: Fluorouraciil 1,000mg/m2 IV continuous infusion over 24 hours

Days 1 and 29: Cisplatin 75mg/m2 IV over 60 minutes

Administer for one 56-day cycle without XRT, then one 56-day cycle with XRT.

▶Metastatic Cancer1

Fluorouracil + Cisplatin2,9,11,12

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

Days 1-4: Fluorouracil 1,000mg/m2 IV continuous infusion over 24 hours daily

Repeat cycle every 3 weeks

OR

Day 1: Cisplatin 75mg/m2 IV over 60 minutes

Days 1-5: Fluorouracil 750mg/m2 IV continuous infusion over 24 hours daily

Repeat cycle every 4 weeks.

mFOLFOX62,13-15

Day 1: Oxaliplatin 85mg/m2 IV over 2 hours, with:

Day 1: Leucovorin 400mg/m2 IV over 2 hours, followed by:

Day 1: Fluorouracil 400mg/m2 IV push, followed by:

Days 1-2: Fluorouracil 1,200 mg/m2 IV continuous infusion daily (2,400 mg/m2 IV over 46-48 hours)

Repeat cycle every 2 weeks.

Carboplatin + Paclitaxel11,16-18

[preferred]

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

Day 1: Carboplatin AUC 5 IV over 30 minutes

Repeat cycle every 3 weeks.

FOLCIS (Fluorouracil
Continuous Infusion/
Leucovorin/Cisplatin)2,9,14,19

Day 1: Cisplatin 40mg/m2 IV over 30 minutes, with:

Day 1: Leucovorin 400mg/m2 IV over 30 minutes, followed by:

Day 1: Fluorouracil 400mg/m2 IV push, followed by:

Days 1-2: Fluorouracil 1000mg/m2 IV continuous infusion daily (2,000mg/m2 IV over 46-48 hours)

Repeat cycle every 2 weeks.

▶Subsequent Therapy

Nivolumab20,21
[preferred]

Day 1: Nivolumab 240mg IV over 30 minutes

Repeat cycle every 2 weeks.

OR

Day 1: Nivolumab 3mg/m2 IV over 30 minutes

Repeat cycle every 2 weeks.

OR

Day 1: Nivolumab 480mg IV over 30 minutes

Repeat cycle every 4 weeks.

Pembrolizumab22,23
[preferred]

Day 1: Pembrolizumab 200mg IV over 30 minutes

Repeat cycle every 3 weeks.

OR

Day 1: Pembrolizumab 2mg/m2 IV over 30 minutes

Repeat cycle every 3 weeks.

Note: Modification to cancer treatment should not be made solely on the basis of HIV status.

References

  1. Referenced with permission from the NCCN Clinical Practice Guidelines in Oncology™. Anal Carcinoma v2.2019. https://www.nccn.org/professionals/physician_gls/pdf/anal.pdf. Accessed September 26, 2019.

  2. 5-Fluorouracil (Fluorouracil injection) [package insert]. Irvine, CA: Spectrum Pharmaceuticals; 2016.

  3. Mitomycin (Mitomycin for Injection) [package insert]. Durham, NC: Accord Healthcare, Inc.; 2013.

  4. Ajani JA, Winter KA, Gunderson LL, et al. Fluorouracil, mitomycin, and radiotherapy vs fluorouracil, cisplatin, and radiotherapy for carcinoma of the anal canal: a randomized controlled trial. JAMA. 2008;299:1914–1921.

  5. James RD, Glynne-Jones R, Meadows HM, et al. Mitomycin or cisplatin chemoradiation with or without maintenance chemotherapy for treatment of squamous-cell carcinoma of the anus (ACT II): a randomised, phase 3, open-label, 2×2 factorial trial. Lancet Oncol. 2013;14:516–524.

  6. Capecitabine (Xeloda) [package insert]. South San Francisco, CA: Genentech, Inc.; 2019.

  7. Goodman KA, Rothenstein D, Cambridge L, et al. Capecitabine plus mitomycin in patients undergoing definitive chemoradiation for anal squamous cell carcinoma. Int J Radiat Oncol Biol Phys. 2014;90:S32–S33.

  8. Thind G, Johal B, Follwell M, Kennecke HF. Chemoradiation with capecitabine and mitomycin-C for stage I-III anal squamous cell carcinoma. Radiation Oncology. 2014;9:124.

  9. Cisplatin (Cisplatin Injection). [package insert]. Lake Zurich, IL: Fresenius Kabi; 2015.

10. Gunderson LL, Winter KA, Ajani JA, et al. Long-term update of US GI intergroup RTOG 98-11 phase III trial for anal carcinoma: survival, relapse, and colostomy failure with concurrent chemoradiation involving fluorouracil/mitomycin versus fluorouracil/cisplatin. J Clin Oncol. 2012;30:4344-4351.

11. Eng C, Chang GJ, You YN, et al. The role of systemic chemotherapy and multidisciplinary management in improving the overall survival of patients with metastatic squamous cell carcinoma of the anal canal. Oncotarget. 2014;5: 11133-11142.

12. Sclafani F, Adams RA, Eng C, et al. InterAACT: An international multicenter open label randomized phase II advanced anal cancer trial comparing cisplatin (CDDP) plus 5-fluorouracil (5-FU) versus carboplatin (CBDCA) plus weekly paclitaxel (PTX) in patients with inoperable locally recurrent (ILR) or metastatic disease. J Clin Oncol. 2015; 33(3_suppl_abstr TPS792).

13. Oxaliplatin (Eloxatin) [package insert]. Bridgewater, NJ: sanofi-aventis U.S. LLC; 2011

14. Leucovorin (Leucovorin calcium injection) [package insert]. Bedford, OH: Bedford Laboratories; 2011.

15. Matsunaga M, Miwa K, Oka Y, et al. Successful treatment of metastatic anal canal adenocarcinoma with mFOLFOX + bevacizumab. Case Rep Oncol. 2016;9:249-254.

16. Carboplatin (Carboplatin Injection) [package insert]. North Wales, PA: Teva Pharmaceuticals USA Inc; 2011.

17. Paclitaxel (Paclitaxel Injection) [package insert]. Paramus, NJ: WG Critical Care, LLC; 2013.

18. Kim R, Byer J, Fulp WJ, et al. Carboplatin and paclitaxel treatment is effective in advanced anal cancer. Oncology. 2014;87:125-132.

19. Mondaca S, Chatila WK, Bates D, et al. FOLFCIS Treatment and genomic correlates of response in advanced anal squamous cell cancer. Clin Colorectal Cancer. 2019;18:e39-e52.

20. Nivolumab (Opdivo) [package insert]. Princeton, NJ: Bristol-Myers Squibb, Inc; 2019.

21. Morris VK, Salem ME, Nimeiri H, et al. Nivolumab for previously treated unresectable metastatic anal cancer (NCI9673):a multicenter, single-arm, phase 2 study. Lancet Oncol. 2017;18:446-453.

22. Pembrolizumab (Keytruda) [package insert]. Whitehouse Station, NJ: Merck & Co, Inc.; 2019.

23. Ott PA, Piha-Paul SA, Munster P, et al. Safety and antitumor activity of the anti–PD-1 antibody pembrolizumab in patients with recurrent carcinomma of the anal canal. Ann Oncol. 2017;28:1036-1041.

(Revised 10/2019) © 2019 by Haymarket Media, Inc.

Gastrointestinal Cancer Drug Monographs

Colorectal and Other GI Cancers

AVASTIN CAMPTOSAR CYRAMZA
Doxorubicin HCl Doxorubicin HCl Solution ELOXATIN
ERBITUX Floxuridine Fluorouracil
FUSILEV GLEEVEC HERCEPTIN
Leucovorin LONSURF Mitomycin
NEXAVAR PHOTOFRIN STIVARGA
SUTENT TAXOTERE VECTIBIX
XELODA ZALTRAP

Pancreatic, Thyroid, And Other Endocrine Cancers

ABRAXANE AFINITOR CAPRELSA
COMETRIQ Doxorubicin HCl Doxorubicin HCl Solution
Fluorouracil GEMZAR LENVIMA
LYSODREN Mitomycin NEXAVAR
ONIVYDE SOMATULINE DEPOT SUTENT
TARCEVA THYROGEN ZANOSAR
Data provided by the Monthly Prescribing Reference (MPR) Hematology/Oncology Edition.