What is the role of carboplatin (CBP) and paclitaxel (PTX) in the treatment of anal canal cancer?

From the Guidelines

Carboplatin and paclitaxel is the preferred regimen for first-line treatment of metastatic anal cancer, as it has shown lower toxicity and improved overall survival compared to other regimens, such as cisplatin and 5-FU. The role of carboplatin (CBP) and paclitaxel (PTX) in the treatment of anal canal cancer is well established, particularly in the context of metastatic disease. According to the NCCN guidelines, version 2.2023, CBP and PTX have been noted as the preferred regimen for first-line treatment of metastatic anal cancer, based on results from the phase II International Multi-centre InterAACT study 1. This study demonstrated that CBP and PTX had similar response rates to cisplatin and 5-FU, but with lower toxicity, including grade ≥3 toxicity and serious adverse events.

Key Points

• The CBP and PTX regimen has been shown to have a median PFS of 8.1 months and OS of 20 months, compared to 5.7 months and 12.3 months for cisplatin and 5-FU, respectively 1.
• Other treatment options, such as 5-FU, leucovorin, and cisplatin (FOLFCIS), 5-FU, leucovorin, and oxaliplatin (FOLFOX), and modified docetaxel, cisplatin, and 5-FU (DCF), are also available, but CBP and PTX remains the preferred regimen due to its favorable toxicity profile and efficacy 1.
• Ongoing clinical trials, such as NCT04444921 and POD1UM-303/InterAACT2, are investigating the role of checkpoint inhibitors in the first-line treatment of metastatic anal cancer, but CBP and PTX remains the standard of care until these trials are completed 1.

Treatment Considerations

• CBP and PTX can be administered concurrently with radiation therapy in a weekly schedule for 5-6 weeks, with CBP dosed at AUC 2 and PTX at 45-50 mg/m².
• The combination is particularly valuable for patients who cannot tolerate mitomycin C due to hematologic toxicities or renal dysfunction.
• CBP/PTX offers a more favorable toxicity profile while maintaining efficacy in treating squamous cell carcinoma of the anal canal.
• Regular blood count monitoring and supportive care are necessary to manage side effects, including myelosuppression, peripheral neuropathy, and fatigue.

From the Research

Treatment of Anal Canal Cancer

• The treatment of anal canal cancer typically involves chemoradiation therapy, with 5-fluorouracil (5-FU) and mitomycin-C (MMC) being the standard chemotherapy regimen 2, 3, 4, 5.
• However, the role of carboplatin (CBP) and paclitaxel (PTX) in the treatment of anal canal cancer is not well established, as the provided studies do not mention these specific chemotherapy agents.
• The studies focus on the efficacy and toxicity of 5-FU and MMC, with or without radiotherapy, in the treatment of anal canal cancer 2, 3, 6, 4, 5.

Efficacy of 5-FU and MMC

• The combination of 5-FU and MMC has been shown to be effective in the treatment of anal canal cancer, with disease-free survival rates ranging from 60% to 80% 3, 6, 4, 5.
• However, the treatment is associated with significant acute and late toxicity, including hematologic, dermatologic, and gastrointestinal toxicities 2, 3, 4, 5.

Alternative Treatment Regimens

• Some studies have explored alternative treatment regimens, such as protracted infusion 5-FU and mitomycin C, which may be less toxic or more efficacious 5.
• Additionally, the use of proton radiation therapy has been investigated as a way to reduce toxicity while maintaining disease control 4.

Conclusion Not Provided as per Request

• As per the request, no conclusion will be provided. The information provided is based on the available evidence and is intended to inform and educate.