Merkel cell cancer medical therapy

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Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1] ; Associate Editor(s)-in-Chief: Vamsikrishna Gunnam M.B.B.S [2]

Overview

The predominant therapy for merkel cell cancer is surgical resection. Adjunctive chemoradiation and adjuvant immunotherapy may also be required in more advanced disease.


Medical Therapy

  • Merkel cell cancer that has metastasized may respond, at least partially, to treatment with chemotherapy and/or radiation.

Radiation

  • Merkel cell cancer is radiosensitive carcinoma.
  • Radiation is an alternative treatment and used can be alone in patients with merkel cell cancer who are not suitable for surgery.[1]
  • Radiotherapy has a curative rate of 75 to 85 percent.[2]
  • Systemic relapse after radiotherapy is one f the cause of death in patients with merkel cell cancer.[3]
  • Adjuvant radiotherapy is effective in reducing the rate of recurrence and increasing the 5-year survival of patients with merkel cell cancer.
    • Preferred dosage: 60 to 66 Gy

Chemotherapy or chemoradiotherapy

  • Chemotherapy usually does not cure the disease, but it can be effective in shrinking the tumor size if the tumor is either too large to be resectable or is located within in critical or difficult regions.
  • Contraindications in using chemotherapy is immunosuppression which are of a great concern.
    • Preferred regimen (1): Carboplatin a weekly regimen IV: Target AUC 4.5 on day 1 of weeks 1, 4, 7, and 10.
    • Preferred regimen (2): Etoposide IV concentrations >0.4 mg/mL.

Adjuvant immunotherapy

  • Using new medications like monoclonal antibodies in patients with merkel cell cancer shows promising results especially if the patients have metastasis.[5][6][7][8][9][10][11]
    • Preferred regimen (1):Avelumab(PD-L1 inhibition ), IV: 800 mg once every 2 weeks until disease progression or unacceptable toxicity.
    • Preferred regimen (2):Nivolumab, IV 240 mg on Day 1 and Day 15.
    • Preferred regimen (3):Pembrolizumab, IV: 200 mg once every 3 weeks until disease progression, unacceptable toxicity.

References

  1. Pape E, Rezvoy N, Penel N, Salleron J, Martinot V, Guerreschi P, Dziwniel V, Darras S, Mirabel X, Mortier L (November 2011). "Radiotherapy alone for Merkel cell carcinoma: a comparative and retrospective study of 25 patients". J. Am. Acad. Dermatol. 65 (5): 983–90. doi:10.1016/j.jaad.2010.07.043. PMID 21641081.
  2. Harrington C, Kwan W (October 2014). "Outcomes of Merkel cell carcinoma treated with radiotherapy without radical surgical excision". Ann. Surg. Oncol. 21 (11): 3401–5. doi:10.1245/s10434-014-3757-8. PMID 25001091.
  3. Veness M, Foote M, Gebski V, Poulsen M (November 2010). "The role of radiotherapy alone in patients with merkel cell carcinoma: reporting the Australian experience of 43 patients". Int. J. Radiat. Oncol. Biol. Phys. 78 (3): 703–9. doi:10.1016/j.ijrobp.2009.08.011. PMID 19939581.
  4. Poulsen MG, Rischin D, Porter I, Walpole E, Harvey J, Hamilton C, Keller J, Tripcony L (January 2006). "Does chemotherapy improve survival in high-risk stage I and II Merkel cell carcinoma of the skin?". Int. J. Radiat. Oncol. Biol. Phys. 64 (1): 114–9. doi:10.1016/j.ijrobp.2005.04.042. PMID 16125873.
  5. Kaufman HL, Russell J, Hamid O, Bhatia S, Terheyden P, D'Angelo SP, Shih KC, Lebbé C, Linette GP, Milella M, Brownell I, Lewis KD, Lorch JH, Chin K, Mahnke L, von Heydebreck A, Cuillerot JM, Nghiem P (October 2016). "Avelumab in patients with chemotherapy-refractory metastatic Merkel cell carcinoma: a multicentre, single-group, open-label, phase 2 trial". Lancet Oncol. 17 (10): 1374–1385. doi:10.1016/S1470-2045(16)30364-3. PMC 5587154. PMID 27592805.
  6. Gaiser MR, Bongiorno M, Brownell I (April 2018). "PD-L1 inhibition with avelumab for metastatic Merkel cell carcinoma". Expert Rev Clin Pharmacol. 11 (4): 345–359. doi:10.1080/17512433.2018.1445966. PMID 29478343.
  7. Gaiser MR, Bongiorno M, Brownell I (April 2018). "PD-L1 inhibition with avelumab for metastatic Merkel cell carcinoma". Expert Rev Clin Pharmacol. 11 (4): 345–359. doi:10.1080/17512433.2018.1445966. PMID 29478343.
  8. Topalian, Suzanne Louise; Bhatia, Shailender; Kudchadkar, Ragini Reiney; Amin, Asim; Sharfman, William Howard; Lebbe, Celeste; Delord, Jean-Pierre; Shinohara, Michi M; Baxi, Shrujal S.; Chung, Christine H.; Martens, Uwe Marc; Ferris, Robert L.; Stein, Julie E; Soumaoro, Ibrahima; Zwirtes, Ricardo F.; Chen, Tian; Cao, Z. Alexander; Taube, Janis M.; Nghiem, Paul (2018). "Nivolumab (Nivo) as neoadjuvant therapy in patients with resectable Merkel cell carcinoma (MCC) in CheckMate 358". Journal of Clinical Oncology. 36 (15_suppl): 9505–9505. doi:10.1200/JCO.2018.36.15_suppl.9505. ISSN 0732-183X.
  9. Chan IS, Bhatia S, Kaufman HL, Lipson EJ (March 2018). "Immunotherapy for Merkel cell carcinoma: a turning point in patient care". J Immunother Cancer. 6 (1): 23. doi:10.1186/s40425-018-0335-9. PMC 5865292. PMID 29566749.
  10. Bhatia S, Afanasiev O, Nghiem P (December 2011). "Immunobiology of Merkel cell carcinoma: implications for immunotherapy of a polyomavirus-associated cancer". Curr Oncol Rep. 13 (6): 488–97. doi:10.1007/s11912-011-0197-5. PMC 4112947. PMID 21953511.
  11. Femia D, Prinzi N, Anichini A, Mortarini R, Nichetti F, Corti F, Torchio M, Peverelli G, Pagani F, Maurichi A, Mattavelli I, Milione M, Bedini N, Corti A, Di Bartolomeo M, de Braud F, Pusceddu S (October 2018). "Treatment of Advanced Merkel Cell Carcinoma: Current Therapeutic Options and Novel Immunotherapy Approaches". Target Oncol. 13 (5): 567–582. doi:10.1007/s11523-018-0585-y. PMID 30073632.


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