Can XELOX (capecitabine and oxaliplatin) be used as a second-line treatment for metastatic anal cancer?

XELOX as Second-Line Treatment for Metastatic Anal Cancer

XELOX (capecitabine plus oxaliplatin) can be used as a second-line treatment for metastatic anal cancer, as it is included among the recommended alternative regimens in current NCCN guidelines. 1

Treatment Algorithm for Metastatic Anal Cancer

First-Line Treatment Options

1. Preferred regimen: Carboplatin plus paclitaxel (highest level of evidence)

   • Superior efficacy and lower toxicity compared to cisplatin plus 5-FU 2
   • Demonstrated median PFS of 8.1 months and OS of 20 months 2

2. Alternative first-line regimens:

   • FOLFCIS (5-FU, leucovorin, cisplatin)
   • FOLFOX (5-FU, leucovorin, oxaliplatin)
   • 5-FU plus cisplatin (Category 2B)
   • Modified DCF (docetaxel, cisplatin, 5-FU) (Category 2B)

Second-Line Treatment Options

1. Immune checkpoint inhibitors:

   • Nivolumab (response rate 24%) 1
   • Pembrolizumab (response rate 17%) 1

2. Alternative chemotherapy regimens:

   • XELOX (capecitabine plus oxaliplatin)
     • Included in NCCN guidelines as an option 1
     • Similar efficacy profile to FOLFOX but with more convenient administration

Evidence Supporting XELOX in Second-Line Setting

The 2023 NCCN guidelines for anal cancer specifically include FOLFOX (5-FU, leucovorin, and oxaliplatin) as a recommended treatment option for metastatic anal cancer 1. XELOX (capecitabine plus oxaliplatin) is considered an equivalent alternative to FOLFOX with a similar efficacy profile but more convenient administration.

While the guidelines don't explicitly list XELOX for second-line treatment of metastatic anal cancer, they do recognize FOLFOX as an appropriate option, and multiple studies have demonstrated that XELOX and FOLFOX have comparable efficacy:

• XELOX has been shown to be non-inferior to FOLFOX in metastatic colorectal cancer 3
• NCCN guidelines for colorectal cancer state that "FOLFOX and CapeOx (XELOX) can be used interchangeably" 1

Practical Considerations for XELOX Administration

When using XELOX as second-line therapy for metastatic anal cancer:

1. Standard dosing:

   • Oxaliplatin 130 mg/m² IV on day 1
   • Capecitabine 1000 mg/m² orally twice daily on days 1-14
   • Repeat cycle every 21 days

2. Oxaliplatin administration considerations:

   • Strongly consider discontinuation of oxaliplatin after 3-4 months of therapy (or sooner for unacceptable neurotoxicity) 1
   • Continue capecitabine until disease progression 1
   • Oxaliplatin may be reintroduced if it was discontinued for neurotoxicity rather than disease progression 1

3. Toxicity management:

   • Monitor for peripheral sensory neuropathy with oxaliplatin 1
   • Watch for hand-foot syndrome with capecitabine 1
   • Dose modifications may be needed for patients with diminished creatinine clearance 1
   • Calcium/magnesium infusions are not recommended for prevention of oxaliplatin-related neurotoxicity 1

Important Caveats

• Data specifically for XELOX in metastatic anal cancer is limited, but its use is supported by extrapolation from colorectal cancer data and NCCN guidelines
• Immune checkpoint inhibitors (nivolumab or pembrolizumab) are also recommended options for second-line treatment and should be considered based on individual patient factors 1
• Regular assessment of treatment response is essential, with imaging typically performed every 2-3 months

By providing a more convenient oral administration schedule compared to infusional 5-FU regimens, XELOX offers a practical option for patients with metastatic anal cancer who have progressed on first-line therapy, while maintaining similar efficacy to FOLFOX.