Cowden syndrome medical therapy

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

Overview

Due to different phenotypes cowden syndrome is likely to be an underdiagnosed condition. Pharmacologic medical therapy is recommended among patients with cutaneous manifestations in cowden syndrome.

Medical Therapy

Pharmacologic medical therapy is recommended among patients with cutaneous manifestations in cowden syndrome patients.^[1]
- Preferred regimen (1): Acitretin 30 mg/day for cutaneous manifestations.^[2]^[3]^[4]
  - Side effects:
    - Teratogenicity
    - Dryness of the eyes
    - Dryness of the nose
    - Dryness of the lips
    - Dryness of the mouth
    - Dryness of the skin
- Acitretin should be discontinued once the recurrence of skin lesions are noted.
- Preferred regimen (2): Sirolimus/ rapamycin Oral: Initial loading dose: 5 mg once, followed by a maintenance dose of 3 mg once daily^[5]^[6]^[7]
  - MOA: Inhibiting cell proliferation by inhibiting mTOR
  - Sirolimus helps in decreasing mucocutaneous lesions and helps in decreasing the occurrence of mucocutaneous lesions.
Screening for multiple cancers should be effectively done in the patients with cowden syndrome.

References

↑ Jornayvaz FR, Philippe J (March 2008). “Mucocutaneous papillomatous papules in Cowden’s syndrome”. Clin. Exp. Dermatol. 33 (2): 151–3. doi:10.1111/j.1365-2230.2007.02602.x. PMID 18021272.
↑ Kadakia KC, Barton DL, Loprinzi CL, Sloan JA, Otley CC, Diekmann BB, Novotny PJ, Alberts SR, Limburg PJ, Pittelkow MR (April 2012). “Randomized controlled trial of acitretin versus placebo in patients at high-risk for basal cell or squamous cell carcinoma of the skin (North Central Cancer Treatment Group Study 969251)”. Cancer. 118 (8): 2128–37. doi:10.1002/cncr.26374. PMC 3365547. PMID 21882176.
↑ Chen K, Craig JC, Shumack S (March 2005). “Oral retinoids for the prevention of skin cancers in solid organ transplant recipients: a systematic review of randomized controlled trials”. Br. J. Dermatol. 152 (3): 518–23. doi:10.1111/j.1365-2133.2005.06347.x. PMID 15787821.
↑ Bavinck JN, Tieben LM, Van der Woude FJ, Tegzess AM, Hermans J, ter Schegget J, Vermeer BJ (August 1995). “Prevention of skin cancer and reduction of keratotic skin lesions during acitretin therapy in renal transplant recipients: a double-blind, placebo-controlled study”. J. Clin. Oncol. 13 (8): 1933–8. doi:10.1200/JCO.1995.13.8.1933. PMID 7636533.
↑ Marsh DJ, Trahair TN, Martin JL, Chee WY, Walker J, Kirk EP, Baxter RC, Marshall GM (June 2008). “Rapamycin treatment for a child with germline PTEN mutation”. Nat Clin Pract Oncol. 5 (6): 357–61. doi:10.1038/ncponc1112. PMID 18431376.
↑ Squarize CH, Castilho RM, Gutkind JS (September 2008). “Chemoprevention and treatment of experimental Cowden’s disease by mTOR inhibition with rapamycin”. Cancer Res. 68 (17): 7066–72. doi:10.1158/0008-5472.CAN-08-0922. PMID 18757421.
↑ Schmid GL, Kässner F, Uhlig HH, Körner A, Kratzsch J, Händel N, Zepp FP, Kowalzik F, Laner A, Starke S, Wilhelm FK, Schuster S, Viehweger A, Hirsch W, Kiess W, Garten A (April 2014). “Sirolimus treatment of severe PTEN hamartoma tumor syndrome: case report and in vitro studies”. Pediatr. Res. 75 (4): 527–34. doi:10.1038/pr.2013.246. PMID 24366516.

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[pmid18021272-1] Jornayvaz FR, Philippe J (March 2008). “Mucocutaneous papillomatous papules in Cowden’s syndrome”. Clin. Exp. Dermatol. 33 (2): 151–3. doi:10.1111/j.1365-2230.2007.02602.x. PMID 18021272.

[pmid21882176-2] Kadakia KC, Barton DL, Loprinzi CL, Sloan JA, Otley CC, Diekmann BB, Novotny PJ, Alberts SR, Limburg PJ, Pittelkow MR (April 2012). “Randomized controlled trial of acitretin versus placebo in patients at high-risk for basal cell or squamous cell carcinoma of the skin (North Central Cancer Treatment Group Study 969251)”. Cancer. 118 (8): 2128–37. doi:10.1002/cncr.26374. PMC 3365547. PMID 21882176.

[pmid15787821-3] Chen K, Craig JC, Shumack S (March 2005). “Oral retinoids for the prevention of skin cancers in solid organ transplant recipients: a systematic review of randomized controlled trials”. Br. J. Dermatol. 152 (3): 518–23. doi:10.1111/j.1365-2133.2005.06347.x. PMID 15787821.

[pmid7636533-4] Bavinck JN, Tieben LM, Van der Woude FJ, Tegzess AM, Hermans J, ter Schegget J, Vermeer BJ (August 1995). “Prevention of skin cancer and reduction of keratotic skin lesions during acitretin therapy in renal transplant recipients: a double-blind, placebo-controlled study”. J. Clin. Oncol. 13 (8): 1933–8. doi:10.1200/JCO.1995.13.8.1933. PMID 7636533.

[pmid18431376-5] Marsh DJ, Trahair TN, Martin JL, Chee WY, Walker J, Kirk EP, Baxter RC, Marshall GM (June 2008). “Rapamycin treatment for a child with germline PTEN mutation”. Nat Clin Pract Oncol. 5 (6): 357–61. doi:10.1038/ncponc1112. PMID 18431376.

[pmid18757421-6] Squarize CH, Castilho RM, Gutkind JS (September 2008). “Chemoprevention and treatment of experimental Cowden’s disease by mTOR inhibition with rapamycin”. Cancer Res. 68 (17): 7066–72. doi:10.1158/0008-5472.CAN-08-0922. PMID 18757421.

[pmid24366516-7] Schmid GL, Kässner F, Uhlig HH, Körner A, Kratzsch J, Händel N, Zepp FP, Kowalzik F, Laner A, Starke S, Wilhelm FK, Schuster S, Viehweger A, Hirsch W, Kiess W, Garten A (April 2014). “Sirolimus treatment of severe PTEN hamartoma tumor syndrome: case report and in vitro studies”. Pediatr. Res. 75 (4): 527–34. doi:10.1038/pr.2013.246. PMID 24366516.

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