Treatment

  Treatment Guidelines / Melanoma Overview / Treatment

Treatment

SURGERY

  • Surgical excision w/ histologically negative margins is the primary treatment for cutaneous melanoma of any thickness
    • Mainstay of curative treatment for primary melanoma
  • Surgical margins, as determined by the Breslow depth, ensure complete removal of the lesion to definitively treat it & reduce chance of recurrence
    • A Cochrane review in 2009 showed no significant difference in survival between narrow & wide margins thus permitting narrow surgical margins to be recommended due to its lesser morbidity rate
    • Surgical margins for in situ lesions are 0.5-1 cm, invasive melanoma 1-2 cm, & for lentigo maligna lesions >0.5 cm due to wide subclinical extension
    • Permanent paraffin sections & not frozen sections are deemed to be the gold standard for surgical margins’ histologic evaluation for in situ & invasive lesions
  • Surgical removal is also indicated for treatment of lymph node metastases (complete lymph node dissection) & distant metastatic spread to organs (if feasible) to achieve palliation
  • Though no literature is available for the optimal time from diagnosis to treatment, final operative management should be done w/in 3-6 wk after biopsy

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OBSERVATION

  •  An acceptable option when surgery is not possible
    • Though therapies directed toward reducing tumor burden may improve disease outcome, these treatment modalities have not been demonstrated to be superior to observation

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PHARMACOLOGICAL THERAPY

Clinical Trial
  • Considered candidates for ongoing clinical trials are patients w/ all stages of melanoma
  • Highly considered for patients due to the advances in the development of new drugs & combination of agents w/c help in reversing or interrupting aberrant molecular pathways that aid in the growth of the tumor
Systemic Therapy
  • Additional treatment modalities for patients w/ either resectable or unresectable disease
  • Preferred regimens for advanced or metastatic disease include Ipilimumab, Vemurafenib, Dabrafenib, Dabrafenib w/ Trametinib, clinical trial, & high-dose Interleukin-2
1. Cancer Immunotherapy 
1.1. Immunotherapy
  • Checkpoint inhibitors, eg Pembrolizumab (Lambrolizumab) & Nivolumab
    • Investigational antibodies which inhibit programmed death (PD-1) receptors that diminish effector responses of T-cell against cancer
    • Pembrolizumab had been approved for the treatment of advanced or unresectable melanoma unresponsive to other drugs & disease progression after therapy w/ Ipilimumab & BRAF inhibitor, if BRAF V600 positive
    • A large phase I trial had shown long-lasting clinical responses w/ low toxicity
    • Phase II & III trials have shown that Pembrolizumab has higher response rates & lesser toxicity compared to Ipilimumab
    • a. Nivolumab
    • Adverse Reactions
      • GI effects (abdominal pain, constipation, nausea); Resp effects (cough, dyspnea); Other effects (hyponatremia, inc AST/lipase, rash, fatigue, musculoskeletal pain)
    • Special Instructions
      • Monitor liver enzymes, serum creatinine & thyroid function
    • Dosage Guidelines
      • 3 mg/kg IV infusion over 60 min 2 wkly
      b. Pembrolizumab
      • Adverse Reactions
        • GI effects (nausea, constipation, dec appetite, diarrhea); Resp effects (cough, pneumonitis, dyspnea, pneumonia); Dermatologic effects (pruritus, rash, cellulitis); Other effects (fatigue, arthralgia, renal failure, pain)
      • Special Instructions
        • Withhold treatment if any of the following occurs: grade 2 pneumonitis grade 2 or 3 colitis; symptomatic hypophysitis, grade 2 nephritis; grade 3 hyperthyroidism, AST or ALT >3-5x ULN or total bilirubin >1.5-3x ULN, or any other severe or grade 3 treatment-related adverse reaction
        • Discontinue if life-threatening adverse events occur: grade 3 or 4 pneumonitis, grade 3 or 4 nephritis, AST or ALT >5x ULN or total bilirubin >3x ULN; grade 3 or 4 infusion-related reactions, inability to reduce corticosteroid dose to ≤10 mg of prednisone or equiv per day w/in 12 wk, persistent grade 2 or 3 adverse reactions (excluding endocrinopathies controlled w/ hormone replacement therapy) that do not recover to grade 0-1 w/in 12 wk after last dose, or any severe or grade 3 treatment-related adverse reaction that recurs
        • Use w/ caution in patients w/ hypothyroidism, type 1 DM, immune-mediated hepatitis/nephritis, renal failure
      • Dosage Guidelines
        • 2 mg/kg IV infusion over 30 min 3 wkly
    1.2. Interferon alfa
    • High-dose Interferon alfa-2b is an immunomodulating cytokine used for adjuvant treatment of melanoma stage IIB-III
    • Pegylated Interferon alfa-2b (peginterferon alfa-2b) is an interferon formulation conjugated to polyethylene glycol for improved circulation & decreased immunogenicity
      • An alternative to high-dose non-pegylated interferon for adjuvant treatment of stage III disease that has been resected with microscopic or gross LN involvement
    • High-dose & pegylated Interferon alfa may be given to patients who had complete surgical resection but had a high risk for relapse
      • High-dose alfa interferon is given for up to 1 yr or pegylated interferon alfa-2b for up to 5 yr
    • Prospective, randomized, controlled trials w/ high-dose & pegylated Interferon alfa have not demonstrated increase in OS when compared w/ observation
    • Close patient monitoring should be done due to significant toxic side effects from both agents
    • Adverse Reactions
      • Influenza-like symptoms (fatigue, fever, headache, myalgia, arthralgia); Neuropsychiatric symptoms (depression, mood swings, irritability, somnolence); Hematologic effects (granulocytopenia, thrombocytopenia); CV effects (chest pain, edema, hypertension); Others (pain at inj site, dyspepsia, alopecia, thyroid function abnormalities)
      • May cause or aggravate fatal or life-threatening infectious or ischemic disorders
    • Special Instructions
      • Contraindicated in patients w/ decompensated liver disease, autoimmune hepatitis
      • Use w/ caution in patients w/ hepatic or renal impairment, depression or psychiatric disorders, cardiovascular disease, arrhythmias, hypertension, pre-existing thyroid disease
      • Maintain adequate hydration during treatment
      • Withdraw drug if jaundice occurs
      • Monitor LFTs
    • Dosage Guidelines
      a. Interferon alfa-2a
      • Resected malignant melanoma: 3 MIU SC 3x/wk x 18 mth
      • Metastatic malignant melanoma: 18 MIU SC 3x/wk x 3 mth
      b. Interferon alfa-2b
      • Monotherapy: 20 MIU/m2 IV 5x/wk x 4 wk followed by 10 MIU/m2 SC 3x/wk x 48 wk
      • Combination therapy: 15 MIU/m2 IV 5x/wk x 3 wk followed by 10 MIU/m2 SC 3x/wk until physician feels it is no longer needed
      • Resected malignant melanoma: 3 MIU SC 3x/wk x 18 mth
      • Metastatic malignant melanoma: 18 MIU SC 3x/wk x 3 mth
    1.3. Interleukin-2 (IL-2)
    • May be given to patients w/ brain metastases that are small and no significant peritumoral edema
    • Demonstrated durable complete response in few patients w/ metastatic melanoma that have been previously treated; however, randomized trials failed to show improvement in OS
    • High-dose IL-2 can cause serious cardiac & pulmonary side effects, thus is generally given for young healthy patients
    • Adverse Reactions
      • Capillary leak syndrome (hypotension, edema, decreased organ perfusion w/ cardiac & respiratory effects, renal abnormalities, & mental status changes); Others (flu-like symptoms, GI disturbances, rashes, decreased blood counts, elevated liver enzymes, increased risk of bacterial infection)
    • Special Instructions
      • Maintain adequate hydration
      • If patient develops severe somnolence, therapy should be stopped
      • Prophylactic antibiotics may be needed due to risk of bacterial infection
    • Dosage Guidelines
      • a. Aldesleukin (Modified human recombinant Interleukin-2)
    • 600,000 U/kg IV 8 hrly for up to 14 doses x 5 days; after 9 days, repeat cycle for another 14 doses
    1.4. Ipilimumab
    • A monoclonal antibody to cytotoxic T lymphocyte-associated antigen 4 (CTLA-4) that is considered the treatment of choice for unresectable or metastatic disease
      • Blocks CTLA-4 function in down regulating T-cell activation, thus allowing the immune system to attack tumor cells
    • Response rate is <20%; though it may take months for a clinical response to become discernible, this response, however, is durable
    • Has shown improvement in progression-free survival & OS in trials of patients w/ advanced or unresectable disease
    • Indications for Ipilimumab reinduction are the following: Absence of remarkable systemic toxicity during previous therapy, relapse occurring after first clinical response, or progression following disease stability >3 mth
    • Close monitoring is needed as immune-mediated reactions may be severe eg colitis, hepatitis, skin inflammation
    • Adverse Reactions
      • GI effects (diarrhea, colitis, hepatitis); Dermatologic effects (rash, pruritus, toxic epidermal necrolysis); Others (fatigue, blurred vision, neuropathy, hypopituitarism, adrenal insufficiency)
    • Special Instructions
      • Monitor for signs & symptoms of immune-mediated reactions
      • Treatment w/ Ipilimumab may be temporarily stopped & steroid therapy started if moderate reactions occur; however, treatment should be permanently stopped if moderate disease persists or severe reactions occur
      • Check liver & thyroid function tests at baseline & prior each treatment
    • Dosage Guidelines
      • 3 mg/kg IV every 3 wk for a total of 4 doses
    2. Targeted Cancer Therapy  

    2.1. Targeted Therapy (Signal Transduction Inhibitors)

    • BRAF inhibitors, eg Vemurafenib & Dabrafenib
      • Inhibition of BRAF activity slows or stops proliferation of tumor cells & promotes apoptosis
      • Not to be used for wild-type BRAF melanoma but may instead give Ipilimumab
      • Vemurafenib is considered to be the treatment of choice for metastatic or unresectable melanoma that is BRAF V600E mutation positive
        • Response rate is 40-50% & may be seen days to weeks following therapy; however, median duration is 5-6 mth only
        • Monitoring for significant dermatologic reactions is advised
      • Dabrafenib may also be given for unresectable stage III disease, may develop episodic & recurrent fevers which are treated by drug discontinuation & use of antipyretic; monitoring for significant dermatologic reactions is also advised
      • Vemurafenib & Ipilimumab combination is currently being tested in clinical trials to prevent resistance
      • Both Vemurafenib & Ipilimumab are available to patients w/ newly diagnosed & previously treated melanoma
      a. Dabrafenib
      • Adverse Reactions
        • Arthralgia, cough, uveitis, iritis, fever, headache, hyperglycemia, new primary skin neoplasm
      • Special Instructions
        • Should be taken on an empty stomach & swallowed whole
        • Doses may have to be reduced or withheld if toxicity occurs, but treatment is continued until disease progresses or intolerable toxicity occurs
        • Contraindicated in pregnancy; advise contraception during & 4 wk following treatment
      • Dosage Guidelines
        • 150 mg PO 12 hrly
      b. Vemurafenib
      • Adverse Reactions
        • Dermatologic effects (pruritus, rash, photosensitivity reaction, alopecia, cutaneous neoplasm); Others (nausea, fatigue, joint pain & swelling)
      • Special Instructions
        • May be taken w/ or w/o food & swallowed whole
        • Use w/ caution in pregnant & lactating patients, in hepatic & renal impairment
        • Ophthalmological reactions, QT prolongation, skin neoplasms, previous or concurrent cancer w/ RAS mutation
        • Monitor hepatic enzymes & bilirubin before or during therapy
        • Contraindicated in patients w/ hypersensitivity to Vemurafenib
      • Dosage Guidelines
        • 960 mg (4 tab of 240 mg) PO 12 hrly

    2.2. MEK (mitogen-activated protein kinase) inhibitor

    • A MEK1 & MEK 2 selective inhibitor that can control growth & induce cell death in some melanoma tumors w/ BRAF mutation; can be given in patients intolerant to BRAF inhibitor single-agent therapy
    • Trametinib/Dabrafenib combination therapy may be given for advanced or metastatic melanoma, may be associated w/ fewer cutaneous toxicity than monotherapy
    • Adverse Reactions
      • Dermatologic effects (rash, pruritus, dry skin, severe skin toxicity); Cardiac effects (hypertension, cardiomyopathy); Others (diarrhea, lymphedema, hemorrhage, interstitial lung disease, retinal vein occlusion & retinal pigment epithelial detachment)
    • Special Instructions
      • Should be taken on an empty stomach & swallowed whole
      • Doses may have to be reduced or withheld if toxicity occurs, but treatment is continued until disease progresses or intolerable toxicity occurs
      • Contraindicated in pregnancy; advise contraception during & 4 wk following treatment
    • Dosage Guidelines
      • a. Trametinib
      • 2 mg PO 24 hrly

    2.3. KIT inhibitor

    • C-KIT inhibitors are available in phase II & phase III trials for patients w/ unresectable stage III or IV mucosal or acral melanomas positive for the C-KIT mutation
    • A 23% response rate w/ Imatinib was seen in a phase II study of patients w/ metastatic melanoma positive for KIT mutation; however, limited duration of responses was shown
    • Adverse Reactions
      • GI effects (N/V, dyspepsia, diarrhea, abdominal pain); Dermatologic effects (rash, eczema, dermatitis); Musculoskeletal effects (headache, myalgia, arthralgia, muscle spasm & cramps); Others (decreased blood counts, fluid retention, edema,cardiac failure, pneumonia)
    • Special Instructions
      • Should be taken w/ food
      • Monitor LFTs, CBC, & wt regularly
      • Use w/ caution in patients w/ history of cardiac disease, renal or hepatic impairment, severe fluid retention & in women of childbearing age
      • Contraindicated in patients who are pregnant & lactating & in those w/ hypersensitivity to Imatinib
    • Dosage Guidelines 
      a. Imatinib
      • 400 mg PO 12 hrly

    2.4 Multikinase inhibitor

    • Active against the Raf/MEK/ERK pathway & the vascular endothelial growth-factor signaling
    • Sorafenib has minimal activity in melanoma as a single agent but combination studies continue as results of usage with Carboplatin plus Paclitaxel were encouraging

    3. Cytotoxic Chemotherapy

    • Halts or slows down growth of cancer cells by interfering w/ the cells’ ability to reproduce
    • Generally not used as initial therapy for advanced disease as it is less effective than Ipilimumab & Vemurafenib
    • Eg Dacarbazine (DTIC), a reference drug if clinical trial or new targeted drug is unavailable, & Temozolomide, an oral alkylating agent that hydrolyzes to the same moiety as DTIC but has better CNS penetration
    • Other chemotherapeutic agent that has shown modest response rates for advanced or metastatic melanoma is Paclitaxel w/ or w/o Carboplatin
    • Polychemotherapy has shown no survival benefit when compared w/ monochemotherapy & is not considered first-line therapy
      • Tamoxifen addition to chemotherapy (CDBT regimen: Cisplatin, Dacarbazine, Carmustine, Tamoxifen) is ineffective & has shown no improvement in OS
    • Biochemotherapy is a combination of chemotherapy w/ IL-2 &/or Interferon alfa
      • When compared w/ chemotherapy, no impact on OS was demonstrated
      • Associated w/ increased toxic side effects
    • Recommended combination therapies for advanced or metastatic melanoma
      • Dacarbazine on days 1-3 plus Carmustine on day 1 plus Cisplatin on days 1-3; cycle is repeated w/ Dacarbazine & Cisplatin every 3 wk; repeat Carmustine cycle every 6 wk
      • Interferon alfa-2b (induction therapy w/ IV infusion on days 1-5, 8-12, & 15-19 followed by SC injection 3x wkly) plus Dacarbazine on days 22-26
    3.1. Alkylating Agents
      a. Carmustine
      • Adverse Reactions
        • Bone marrow depression w/ leucopenia & neutropenia, pulmonary fibrosis, neuroretinitis, N/V, hepatic & renal impairment, headache, hypotension, chest pain, hypersensitivity; may result in permanent infertility
      • Special Instructions
        • Use w/ caution in patients w/ decreased lung function
        • Monitor lung function before & frequently during treatment, blood counts wkly & 6 wk after final dose, & hepatic & renal function periodically
        • Contraindicated in pregnant & lactating women
      • Dosage Guidelines1
        • Combination therapy: 150-200 mg/m2 IV or 75-100 mg/m2 IV x 2 days
      b. Dacarbazine (DTIC)
      • Adverse Reactions
        • GI effects (N/V, anorexia); Neurologic effects (headache, lethargy, confusion, convulsions, facial paresthesia); Hematologic effects (anemia, leucopenia, thrombocytopenia); flu-like symptoms
      • Special Instructions
        • Use w/ caution in patients w/ impaired renal & hepatic function
        • Contraindicated in patients w/ decreased WBC & platelet counts, in pregnancy & lactation
      • Dosage Guidelines1
        • Monotherapy: 2-4.5 mg/kg/day IV x 10 days every 4 wk or 200-250 mg/m2 IV x 5 days every 3 wk
        • Combination therapy: 800-850 mg/m2 IV every 3 wk
      c. Fotemustine
      • Adverse Reactions
        • Bone marrow depression w/ leucopenia & neutropenia, pulmonary fibrosis, neuroretinitis, N/V, hepatic & renal impairment, headache, hypotension, chest pain, hypersensitivity; may result in permanent infertility
      • Special Instructions
        • Use w/ caution in patients w/ decreased lung function
        • Monitor lung function before & frequently during treatment, blood counts wkly & 6 wk after final dose, & hepatic & renal function periodically
        • Contraindicated in pregnant & lactating women
      • Dosage Guidelines1
        • 100 mg/m2 IV wkly x 3 wk
        • Maintenance dose (after 4-5 wk): 100 mg/m2 IV every 3 wk
      d. Melphalan
      • Adverse Reactions
        • Dermatologic effects (rashes, hypersensitivity, skin ulceration, necrosis); GI disturbances, pulmonary fibrosis, hemolytic anemia, ovarian suppression, temporary or permanent male infertility; flu-like symptoms
      • Special Instructions
        • Use w/ caution in pregnancy, in patients w/ renal impairment, & in those who have just received radiotherapy or cytotoxic agents
        • Contraindicated in lactating women
      • Dosage Guidelines1
        • Upper extremity: 0.6-1 mg/kg IA
        • Lower extremity: 0.8-1.5 mg/kg IA
      e. Temozolomide
      • Adverse Reactions
        • GI effects (N/V, anorexia, constipation, diarrhea); Hematologic effects (myelosuppression, anemia); Others (fatigue, headache, rashes, fever)
      • Special Instructions
        • Taken on empty stomach & swallowed whole
        • Dose changes should be based on toxicities related to decreases in ANC & platelet count
        • Use w/ caution in severe renal or hepatic dysfunction, in males due to possible irreversible infertility following therapy
        • Contraindicated in patients w/ hypersensitivity to DTIC, severe myelosuppression, & pregnant & lactating women
      • Dosage Guidelines1
        • W/o previous chemotherapy: 200 mg/m2 PO 24 hrly x 5 days/28-day cycle
        • W/ previous chemotherapy: 150 mg/m2 PO 24 hrly x 5 days; 2nd cycle: 200 mg/m2 PO daily x 5 days if ANC >1.5 x 109/L & platelet count >100 x 109/L on day 1 of next cycle
    3.2. Cytotoxic Antibiotic
    • Adverse Reactions
      • CNS effects (changes in sensorium, fever); Dermatologic effects (inj site reaction, alopecia, anaphylaxis, rash); GI effects (N/V, diarrhea, loss of appetite); Hematologic effects (leukopenia, anemia, thrombocytopenia); Other effects (menstrual dysfunction, hot flushes, tachycardia, arrhythmia)
    • Special Instructions
      • Avoid in patients w/ cardiac impairment & marked myelosuppression
      • Use w/ caution in patients w/ myelosuppression, preexisting cardiac disease, hepatic & renal dysfunction & in patients who have previously received anthracyclines
    • Dosage Guidelines1
      • a. Epirubicin
      • 60-90 mg/m2 IV inj over 3-5 min every 21 days
    3.3. Plant Akaloids & Other Natural Products, Vinca Alkaloids & Analogues
    • Adverse Reactions
      • Neurological effects (depression, agitation, insomnia, hallucination); Dermatologic effects (alopecia, allergic reactions); Decreased blood counts; GI effects (constipation, abdominal cramps); Others (increased uric acid levels, urinary disturbances, fever, headache, hypotension)
    • Special Instructions
      • Use w/ caution in pregnancy & lactation, elderly, patients w/ prior radiation. Gout or urate stones, hepatic dysfunction, neuromuscular disease
      • Contraindicated in patients w/ hypersensitivity to vinca alkaloids, w/ Charcot-Marie-tooth syndrome (demyelinating type), & those on radiation therapy via ports which include the liver
    • Dosage Guidelines1
      • a. Vincristine
      • Combination therapy: 0.4-1.4 mg/m2 IV wkly
    3.4. Platinum-containing Antineoplastic Agent
    • Adverse Reactions
      • Reactions are dose dependent; Hematologic effects (severe bone marrow depression, low blood counts); Others (mild renal impairment, immunosuppression, GI & hearing disturbances, neuropathy w/ paresthesia)
    • Special Instructions
      • Use w/ caution in patients w/ mild hematologic, renal, or hearing impairment
      • Monitor blood counts, hepatic & renal function, plasma electrolytes, & audiometric testing before & during treatment
      • Practice birth control during & at least 6 mth following treatment
      • Contraindicated in patients w/ hypersensitivity to Cisplatin & other platinum compounds, recent infections, severe kidney disease, depressed bone marrow function, in pregnancy & lactation
    • Dosage Guidelines1
      • a. Cisplatin
      • Combination therapy: 50-120 mg/m2 IV single dose every 4 wk or 15-20 mg/m2 IV 24 hrly x 5 days or 50 mg/m2 IV days 1-8 x 3-4 wk
    3.5. Other Antineoplastic Agent
    • Adverse Reactions
      • GI effects (N/V, diarrhea, anorexia); Others (decreased blood counts, alopecia, headache)
    • Special Instructions
      • May be taken w/ or w/o food
      • Use w/ caution in the elderly
      • Monitor blood counts
      • Bone marrow depression, severe anemia, renal dysfunction, prior chemotherapy or radiation therapy
      • Contraindicated in pregnancy & lactation, hypersensitivity to Hydroxyurea, marked bone marrow depression
    • Dosage Guidelines1
      • a. Hydroxyurea (Hydroxycarbamide)
      • Intermittent therapy: 60-80 mg/kg PO single dose every 3rd day
      • Continuous therapy: 20-30 mg/kg PO single dose daily
      • Concomitant therapy: 80 mg/kg PO single dose every 3rd day
    4. Vaccines, Antisera & Immunologicals  
    4.1. Vaccination Therapy
    • A treatment option for patients w/ stage IV & recurrent melanoma that is currently under clinical evaluation
      • Adverse Reactions
        • Discomfort at injection site, redness, polyarthralgia w/ hand edema & rash
      • Special Instructions
        • Use w/ caution in pregnant & lactating women
        • Monitor liver functions regularly
        • Contraindicated in patients w/ hypersensitivity to Thymosin alpha-1 & those immunosuppressed following transplantation
      • Dosage Guidelines
        • a. Thymosin alpha-1 (Thymalfasin)
        • Adjuvant therapy: 1.6 mg (900 mg/m2) SC utilizing different schedules x 6 mth or given between chemotherapy cycles for the treatment duration

    4.2. Others
    • For in-transit &/or satellite lesions of extremity melanoma, palliative local therapy w/ hyperthermic isolated limb perfusion w/ Melphalan w/ or w/o tumor necrosis factor-alpha has shown high rates of tumor response & palliation
      • However, impact on OS has not been shown in controlled studies
    • Intralesional injection w/ BCG, Interferon alfa or IL-2 & carbon dioxide laser ablation therapy may be options for local recurrence & in-transit metastasis
    • Topical Imiquimod is an immune response modifier that may also be used as an adjunct after excisional surgery
      • May be given for local, satellite &/or in-transit recurrence
      • Studies are limited by different treatment regimens & absence of long-term follow-up
      • The risk of an inflammatory reaction & a low threshold for a repeat biopsy to check for residual or recurrent disease should always be considered

    1Various dosage recommendations are available. Please refer to specialist for specific treatment option

    All dosage recommendations are for non-pregnant & non-breastfeeding women, non-elderly adults w/ normal renal & hepatic function unless otherwise stated.

    Not all products are available or approved for above use in all countries. 

    Products listed above may not be mentioned in the disease management chart but have been placed here based on indications listed in regional manufacturers’ product information.

    Specific prescribing information may be found in the latest MIMS & MIMS.com

    Brands available in: Hong Kong       Indonesia       Malaysia       Philippines       Singapore       Thailand       Vietnam

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    RADIATION THERAPY

    • Palliative radiotherapy is especially helpful in alleviating symptoms particularly that of brain or bone metastases & of nerve compression
      • Shrinks tumor size, prevents development of additional tumors, & destroys any residual cancer cells following surgery
    • May be considered in primary disease desmoplastic melanoma w/ narrow margins or extensive neurotropism & in regional disease as adjuvant therapy in patients status post resection of clinically positive nodes & as palliative therapy for unresectable satellite, nodal or in-transit melanoma

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