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Sarah Peters
Northland Health
5-FLUOROURACIL CREAM (5%)
          (Efudix)
MECHANISM OF ACTION
Which Lesion? Which Patient?



      INDICATIONS:                             SELECTION:



    Solar keratoses                   •Superficial only (masking effect)
Bowen disease (SCC in situ)             •No diagnostic doubt/ biopsy
                                          •Not surgical candidate
Occasionally Superficial BCC                •Compliant with Rx
                                                •Not recurrent
   Other: Psoriasis, Viral
EFUDIX: INSTRUCTIONS FOR USE


•Locked up, instructed areas only
•Winter months for 2-8 weeks
•+/- tretinoin priming
•+/- pulsed (Crabb)                                   Avoid sun!
                                           Make up and UV protection after
•Wash & Dry Area                                      acute course
•Wash finger or use glove to apply                  No swimming
• BD application in general area (not           Can get wet in shower
just visible lesions), morning/ evening
(not night)                               2-4 weeks for healthy new skin after
                                                     stopping 5FU
•Wash hands after applying
PATIENT EDUCATION


•60% failure rate - compliance
“You will look worse before you get better”,
“Expect major changes”
•Expect inflammation  blistering, peeling,
cracking. Sores/pain. This means it is working.
•Expect:
•Wk 1: mild redness/ minimal reaction
•Wk 2: red, crusted, possibly uncomfortable
•End Wk 3: Follow up/Cessation
•Wk4-6: RECOVERY: pink 1- 10 weeks
SIDE EFFECTS

             MILD:
          Severe stinging
Redness + irritation/ raw areas at 5-
               10/7

                  COMPLICATIONS:
         Excessive inflammation  ulceration
             Persistent white marks/scarring
           Irritant contact dermatitis/ allergic
                     contact dermatitis
                   Secondary infection
            Undiagnosed skin cancers – may
         appear to heal but recur later requiring
                         surgery.
Efudix – before, during, after
COST



           Subsidised

      $3 Fully subsidised
  No special authority required

      Pharmac schedule:
   Fluorouracil sodium
          Crm 5%

Efudix 253065 $26.49 per 20 g OP
IMIQUIMOD 5%
     (Aldara)
MECHANISM OF ACTION
INDICATIONS




          Solar keratoses
  Basal cell carcinoma (especially
         superficial types)
Bowen disease (aka SqCC in situ)-
      unregistered indication
Viruses – genital warts, molluscum,
                HSV
Efficacy


                                  FOR sBCC:

•Schulze: 7x/week        Aldara             80% histological clearance
                Vehicle alone      6% clearance

•Geisse: 6 week course -   5x/week Aldara 82% clearance
                           7x/week Aldara 79% clearance
                           Vehicle only   3% clearance

                                FOR AKs:
          Median % decrease in AKs 3x/week 86%, 2x/week 83.3%
SYSTEMIC

•Flu like symptoms: fever,
fatigue, headache, nausea,
diarrhoea, mm pain.
ALDARA: INSTRUCTIONS FOR
                                      USE


                                                     Apply sparingly
                                       If problematic inflammation, pause for few
                                                           days.
          HOW TO USE:                       Apply evening. SPF creams mane.

Duration: 4-16 weeks                    Variable effect: dependent on skin lesion
Biopsy to confirm dx before starting      and genetic factors (TL7 expression)
BCC: 5x/wk for 6 weeks
SK: 2x/wk for 6 weeks, repeat if       WHERE/WHEN TO USE:
necessary after a 4 week break.
                                       Areas where surgery may be difficult or
                                       undesirable especially face + lower legs.
COST


   PHARMAC funded under special                   Without special authority:
         authority $3
                                                     $110/pack of 12

     Conditions of Special Authority:
             -Superficial BCC
 -Surgery contraindicated/inappropriate
-surgery is first line because higher cure,
           can assess clearance
    -Not evaluated for within 1cm of
   hairline, eyes, nose, mouth or ears
--not for recurrent, invasive, infiltrating,
               nodular BCC
TREATMENT DECISIONS


    Which patient?
    Which lesion?
    Which cream?



        GPs?
Comparison


             Efudix (5FU)                           Aldara (Imiquimod)
                 Winter                                    Summer
        Inhibits DNA synthesis                    Immune response modifier
          Consistent response                        Variable response

         Treats generalised area                   Used sparingly on points

               Subsidised                               More expensive

         Local side effects only                     Systemic Side effects

 Compliance – BD for 3 weeks or BD in           Compliance - od 5/7 on, 2/7 off
           pulsed rounds 3                                 6 weeks
Good option for Solar keratoses, Bowens,         Not registered for Bowens
      sometimes used for sBCC.             Not fully investigated for use on the face
GP Guidelines (NZGG)


       BCC Good practice points:                        -SCC Good practice points:


             Should have histology                  SCC are non healing keratinizing or
   BCCs are slow growing, usually without          crusted lesions larger than 1 cm with
     significant expansion over 8 weeks.            significant induration on palpation,
 A GP may treat a BCC topically without a          documented expansion over 8 weeks
 histological diagnosis but in that case f/u is   and typically face, scalp, back of hand.
                   mandatory
“A Practitioner should refer a person with a      -Obtain histology or refer to specialist
     clinically suspected or histologically
  confirmed BCC to a specialist where the
practitioner deems management of the lesion
            beyond their skill set”.



                            http://northlandent.blogspot.co.nz/2012/06/h
                            ow-to-do-punch-biopsy.html
CURRENT SITUATION IN
                      WHANGAREI



Plastics 1/4
Dermatology 1/6
GPSI x5 – Skin
Cancer Project
An Ounce of Prevention is Better than a Ton
                 Of Cure




                          Replenex
                          Extreme
References


        Basic pharmacology of topical imiquimod, 5-fluorouracil
        , and diclofenac for the dermatologic surgeon. [Review]
                    Desai T. Chen CL. Desai A. Kirby W.
                Dermatologic Surgery. 38(1):97-103, 2012 Jan.
                           [Journal Article. Review]
    Treatment of squamous cell carcinoma in situ: a review. [Review]
                Shimizu I. Cruz A. Chang KH. Dufresne RG.
              Dermatologic Surgery. 37(10):1394-411, 2011 Oct.
                           [Journal Article. Review]
[Non-surgical treatment of skin carcinomas and their precursors]. [French]
                         Lourari S. Paul C. Meyer N.
                 Presse Medicale. 40(7-8):690-6, 2011 Jul-Aug.
                      [English Abstract. Journal Article]
References


Agreement on the clinical diagnosis and management of cutaneous squamous neoplasms.
  Terushkin V. Braga JC. Dusza SW. Scope A. Busam K. Marghoob AA. Gill M. Halpern AC.
                       Dermatologic Surgery. 36(10):1514-20, 2010 Oct.
                                        [Journal Article]
                                          UI: 20698872
        Superficial basal cell carcinoma on face treated with 5% imiquimod cream.
                Malhotra AK. Bansal A. Mridha AR. Khaitan BK. Verma KK.
     Indian Journal of Dermatology, Venereology & Leprology. 72(5):373-5, 2006 Sep-Oct.
                                 [Case Reports. Journal Article]
 Treatment of an extensive superficial basal cell carcinoma of the face with imiquimod 5%
                                             cream.
                             Micali M. Nasca MR. Musumeci ML.
                 International Journal of Tissue Reactions. 27(3):111-4, 2005.
                                 [Case Reports. Journal Article]
                                          UI: 16372477
Smith, Walton. Treatment of Facial Basal Cell carcinoma: A review. [Review]
                         2011. Journal of Skin cancer.
 Amini, Viera, Valins, Berman. Non surgical Innovations in the Treatment of
Non melanoma Skin Cancer. 2010. Journal of Clinical Aesthetic Dermatology.
                                June 2010 (3):6


               Best Practice Guidelines. Bestpractice.bmj.com
                       Dermnet NZ. Dermnetnz.org
                   Medsafe Data Sheets. Medsafe.govt.nz
                         Pharmac. Pharmac.govt.nz
THE END
PDT


 Other Non surgical approahces – PDT (photodynamic therapy – slightly less
clearance rates c/t excision but better cosmetic results especially hard to get to.

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Topical chemo therapeutic treatments for non melanoma skin cancer

  • 2.
  • 5. Which Lesion? Which Patient? INDICATIONS: SELECTION: Solar keratoses •Superficial only (masking effect) Bowen disease (SCC in situ) •No diagnostic doubt/ biopsy •Not surgical candidate Occasionally Superficial BCC •Compliant with Rx •Not recurrent Other: Psoriasis, Viral
  • 6. EFUDIX: INSTRUCTIONS FOR USE •Locked up, instructed areas only •Winter months for 2-8 weeks •+/- tretinoin priming •+/- pulsed (Crabb) Avoid sun! Make up and UV protection after •Wash & Dry Area acute course •Wash finger or use glove to apply No swimming • BD application in general area (not Can get wet in shower just visible lesions), morning/ evening (not night) 2-4 weeks for healthy new skin after stopping 5FU •Wash hands after applying
  • 7. PATIENT EDUCATION •60% failure rate - compliance “You will look worse before you get better”, “Expect major changes” •Expect inflammation  blistering, peeling, cracking. Sores/pain. This means it is working. •Expect: •Wk 1: mild redness/ minimal reaction •Wk 2: red, crusted, possibly uncomfortable •End Wk 3: Follow up/Cessation •Wk4-6: RECOVERY: pink 1- 10 weeks
  • 8. SIDE EFFECTS MILD: Severe stinging Redness + irritation/ raw areas at 5- 10/7 COMPLICATIONS: Excessive inflammation  ulceration Persistent white marks/scarring Irritant contact dermatitis/ allergic contact dermatitis Secondary infection Undiagnosed skin cancers – may appear to heal but recur later requiring surgery.
  • 9. Efudix – before, during, after
  • 10. COST Subsidised $3 Fully subsidised No special authority required Pharmac schedule: Fluorouracil sodium Crm 5% Efudix 253065 $26.49 per 20 g OP
  • 11. IMIQUIMOD 5% (Aldara)
  • 13. INDICATIONS Solar keratoses Basal cell carcinoma (especially superficial types) Bowen disease (aka SqCC in situ)- unregistered indication Viruses – genital warts, molluscum, HSV
  • 14. Efficacy FOR sBCC: •Schulze: 7x/week Aldara 80% histological clearance Vehicle alone 6% clearance •Geisse: 6 week course - 5x/week Aldara 82% clearance 7x/week Aldara 79% clearance Vehicle only 3% clearance FOR AKs: Median % decrease in AKs 3x/week 86%, 2x/week 83.3%
  • 15. SYSTEMIC •Flu like symptoms: fever, fatigue, headache, nausea, diarrhoea, mm pain.
  • 16. ALDARA: INSTRUCTIONS FOR USE Apply sparingly If problematic inflammation, pause for few days. HOW TO USE: Apply evening. SPF creams mane. Duration: 4-16 weeks Variable effect: dependent on skin lesion Biopsy to confirm dx before starting and genetic factors (TL7 expression) BCC: 5x/wk for 6 weeks SK: 2x/wk for 6 weeks, repeat if WHERE/WHEN TO USE: necessary after a 4 week break. Areas where surgery may be difficult or undesirable especially face + lower legs.
  • 17. COST PHARMAC funded under special Without special authority: authority $3 $110/pack of 12 Conditions of Special Authority: -Superficial BCC -Surgery contraindicated/inappropriate -surgery is first line because higher cure, can assess clearance -Not evaluated for within 1cm of hairline, eyes, nose, mouth or ears --not for recurrent, invasive, infiltrating, nodular BCC
  • 18. TREATMENT DECISIONS Which patient? Which lesion? Which cream? GPs?
  • 19. Comparison Efudix (5FU) Aldara (Imiquimod) Winter Summer Inhibits DNA synthesis Immune response modifier Consistent response Variable response Treats generalised area Used sparingly on points Subsidised More expensive Local side effects only Systemic Side effects Compliance – BD for 3 weeks or BD in Compliance - od 5/7 on, 2/7 off pulsed rounds 3 6 weeks Good option for Solar keratoses, Bowens, Not registered for Bowens sometimes used for sBCC. Not fully investigated for use on the face
  • 20. GP Guidelines (NZGG) BCC Good practice points: -SCC Good practice points: Should have histology SCC are non healing keratinizing or BCCs are slow growing, usually without crusted lesions larger than 1 cm with significant expansion over 8 weeks. significant induration on palpation, A GP may treat a BCC topically without a documented expansion over 8 weeks histological diagnosis but in that case f/u is and typically face, scalp, back of hand. mandatory “A Practitioner should refer a person with a -Obtain histology or refer to specialist clinically suspected or histologically confirmed BCC to a specialist where the practitioner deems management of the lesion beyond their skill set”. http://northlandent.blogspot.co.nz/2012/06/h ow-to-do-punch-biopsy.html
  • 21. CURRENT SITUATION IN WHANGAREI Plastics 1/4 Dermatology 1/6 GPSI x5 – Skin Cancer Project
  • 22. An Ounce of Prevention is Better than a Ton Of Cure Replenex Extreme
  • 23. References Basic pharmacology of topical imiquimod, 5-fluorouracil , and diclofenac for the dermatologic surgeon. [Review] Desai T. Chen CL. Desai A. Kirby W. Dermatologic Surgery. 38(1):97-103, 2012 Jan. [Journal Article. Review] Treatment of squamous cell carcinoma in situ: a review. [Review] Shimizu I. Cruz A. Chang KH. Dufresne RG. Dermatologic Surgery. 37(10):1394-411, 2011 Oct. [Journal Article. Review] [Non-surgical treatment of skin carcinomas and their precursors]. [French] Lourari S. Paul C. Meyer N. Presse Medicale. 40(7-8):690-6, 2011 Jul-Aug. [English Abstract. Journal Article]
  • 24. References Agreement on the clinical diagnosis and management of cutaneous squamous neoplasms. Terushkin V. Braga JC. Dusza SW. Scope A. Busam K. Marghoob AA. Gill M. Halpern AC. Dermatologic Surgery. 36(10):1514-20, 2010 Oct. [Journal Article] UI: 20698872 Superficial basal cell carcinoma on face treated with 5% imiquimod cream. Malhotra AK. Bansal A. Mridha AR. Khaitan BK. Verma KK. Indian Journal of Dermatology, Venereology & Leprology. 72(5):373-5, 2006 Sep-Oct. [Case Reports. Journal Article] Treatment of an extensive superficial basal cell carcinoma of the face with imiquimod 5% cream. Micali M. Nasca MR. Musumeci ML. International Journal of Tissue Reactions. 27(3):111-4, 2005. [Case Reports. Journal Article] UI: 16372477
  • 25. Smith, Walton. Treatment of Facial Basal Cell carcinoma: A review. [Review] 2011. Journal of Skin cancer. Amini, Viera, Valins, Berman. Non surgical Innovations in the Treatment of Non melanoma Skin Cancer. 2010. Journal of Clinical Aesthetic Dermatology. June 2010 (3):6 Best Practice Guidelines. Bestpractice.bmj.com Dermnet NZ. Dermnetnz.org Medsafe Data Sheets. Medsafe.govt.nz Pharmac. Pharmac.govt.nz
  • 27.
  • 28. PDT Other Non surgical approahces – PDT (photodynamic therapy – slightly less clearance rates c/t excision but better cosmetic results especially hard to get to.

Editor's Notes

  1. A-actinic keratosis B-Bowens D- sCC
  2. Mechanism: Competetive antagonist for uracil in the formation of RNA and inhibits incorporation of uracil into RNA. DNA inhibited indirectly because of its dependence for synthesis on RNA.
  3. Need patient info leaflets! Need education!!
  4. 60% tx failure secondary to low adherence due to se
  5. Immune response modifier Stimulates IS to release cytokines Inflammation destroys the lesio
  6. Mod- severe local site reaction 87%, erosions 36%, ulceration 22%, not sudies with facial BCcc
  7. Weekdays and weekends off Show patient information calendar Once inflammation settled there is generally a good/excellent cosmetic result.