Systemic Therapy for Stage I–III Anal Squamous Cell Carcinoma

Publication Date: December 16, 2024
Last Updated: December 17, 2024

Treatment

General note: The following recommendations (strong or conditional) and terminology represent reasonable options for patients depending on clinical circumstances and in the context of individual patient preferences. Recommended care should be accessible to patients whenever possible.

Clinical Question 1: What are the recommended radiosensitizing chemotherapy agents for patients with stage I–III anal cancer?

1.1.

Mitomycin-C (MMC) with a fluoropyrimidine (5-fluorouracil [5FU] or capecitabine) is recommended as the radiosensitizing component of chemoradiation for anal cancer. (M, S)

Qualifying statements:

  • Due to an increased risk of myelosuppresion, patients who are immunosuppressed should avoid treatment with MMC. The preferable regimen is cisplatin and 5FU (Recommendation 1.2).
  • While there have been no randomized clinical trials (RCTs) of the MMC and capecitabine combination, the Expert Panel recognizes that this agent is often used as an orally administered alternative to 5FU and is currently being used in ongoing clinical trials. A prospective nonrandomized study of this intervention found that there was a higher rate of hematologic grade 3 or 4 toxicity at 6 weeks after completion of CRT with 5FU v capecitabine.
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1.2.

Cisplatin with 5FU is an additional chemotherapy combination that may be recommended as the radiosensitizing component of chemoradiation. (M, S)

Qualifying statements:

  • This recommendation is based on the noninferiority of cisplatin and 5FU compared to MMC and 5FU in the ACT-II RCT. In this trial there was a lower risk of myelosuppression with cisplatin and 5FU compared to MMC and a fluoropyrimidine.
  • Cisplatin is not recommended for patients with renal dysfunction, significant neuropathy, or hearing loss.
  • There is no evidence to support substituting carboplatin for cisplatin.
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Clinical Question 2: What are the recommended dose and schedule for the chemotherapy options included in Recommendations 1.1 and 1.2?

1.3.

Recommended dosing and schedules for the chemotherapy options included in Recommendations 1.1 and 1.2 include:

MMC and 5FU

  • MMC: 10 mg/m2 (max 20 mg) on day 1 and day 29*, or 12 mg/m2 (max 20 mg) on day 1.
  • 5FU: 1000 mg/m2 (continuous infusion) on days 1–4 (week 1) and 29–32 (week 5).
  • * Qualifying statement: The second dose of mitomycin, as used in week 5 (day 29) in Radiation Therapy Oncology Group (RTOG) 98–11, is associated with additional toxicity and should be used with caution.

MMC and capecitabine as an alternative to 5FU

  • In combination with MMC, the recommended dose of capecitabine is 825 mg/m2 twice daily, orally administered on days of radiation.

Cisplatin and 5FU

  • Cisplatin: 60 mg/m2 on days 1 and 29 with a maximum surface area of 2.0 m2 (i.e., max. single dose of 120 mg) with 5FU (1000 mg/m2 [continuous infusion]) on days 1–4 (week 1) and 29–32 (week 5).
  • Qualifying statements:
    • Patients who are immunosuppressed and treated with the recommended dose and frequency of cisplatin and 5FU should be monitored closely.
    • 20 mg/m2 intravenously once weekly with daily 5FU (300 mg/m2) infused continuously on days of radiation is also a recommended alternative, based on a lower level of evidence.
(M, C)
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1.4.

Where combination chemotherapy is not indicated, for example in patients with poor Eastern Cooperative Oncology Group (ECOG) performance status (PS), radiosensitizing with single agent 5FU may be offered. (L, C)
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Clinical Question 3: Is induction chemotherapy recommended for patients with stage I–III anal cancer?

2.1.

Routine induction chemotherapy prior to CRT is not recommended for patients with localized anal cancer. (M, S)
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Clinical Question 4: Is ongoing adjuvant chemotherapy recommended for patients with stage I–III anal cancer?

3.1.

Additional chemotherapy following CRT is not recommended for patients with localized anal cancer. (M, S)
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Recommendation Grading

Disclaimer

The information in this patient summary should not be used as a substitute for professional medical care or advice. Contact a health care provider if you have questions about your health.

Overview

Title

Systemic Therapy for Stage I–III Anal Squamous Cell Carcinoma

Authoring Organization

American Society of Clinical Oncology

Publication Month/Year

December 16, 2024

Last Updated Month/Year

December 17, 2024

Document Type

Guideline

Country of Publication

US

Document Objectives

To provide evidence-based guidance for clinicians who treat patients with stage I-III anal cancer.

Target Patient Population

Patients with stages I-III anal cancer

Target Provider Population

Medical oncologists, radiation oncologists, surgical oncologists, and other clinicians who treat patients with anal cancer

Inclusion Criteria

Male, Female, Adult, Older adult

Health Care Settings

Ambulatory, Hospital, Outpatient

Intended Users

Nurse, nurse practitioner, physician, physician assistant

Scope

Treatment

Diseases/Conditions (MeSH)

D002294 - Carcinoma, Squamous Cell, D011838 - Radiation-Sensitizing Agents, D001005 - Anus Neoplasms

Keywords

anal cancer, Anal Squamous Cell Carcinoma, radiosensitizing chemotherapy

Source Citation

Morris VK, Kennedy EB, Amin MA, et al. Systemic Therapy for Stage I–III Anal Squamous Cell Carcinoma: ASCO Guideline. J Clin Oncol. 2024 December  16. doi: 10.1200/JCO.24.02120