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VISM

Cancer Type: Skin, Basal Cell  Intent: Curative, Palliative
Regimen Category: Evidence-Informed
Funding:
Exceptional Access Program
    vismodegib - Treatment for metastatic basal cell carcinoma (BCC) or with locally advanced BCC (including patients with basal cell nevus syndrome, i.e. Gorlin syndrome), according to specific criteria
A - Regimen Name

VISM Regimen
Vismodegib


Disease Site
Skin - Basal Cell

Intent
Curative
Palliative

Regimen Category
Evidence-Informed :

Regimen is considered appropriate as part of the standard care of patients; meaningfully improves outcomes (survival, quality of life), tolerability or costs compared to alternatives (recommended by the Disease Site Team and national consensus body e.g. pan-Canadian Oncology Drug Review, pCODR).  Recommendation is based on an appropriately conducted phase III clinical trial relevant to the Canadian context OR (where phase III trials are not feasible) an appropriately sized phase II trial. Regimens where one or more drugs are not approved by Health Canada for any indication will be identified under Rationale and Use.


Rationale and Uses

Treatment of histologically confirmed metastatic basal cell carcinoma or locally advanced basal cell carcinoma inappropriate for surgery or radiotherapy

 


Supplementary Public Funding

vismodegib
Exceptional Access Program (vismodegib - Treatment for metastatic basal cell carcinoma (BCC) or with locally advanced BCC (including patients with basal cell nevus syndrome, i.e. Gorlin syndrome), according to specific criteria) (EAP Website)

 
B - Drug Regimen

vismodegib
150 mg PO Daily

(Outpatient prescription available in 150 mg capsules)

 

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C - Cycle Frequency

CONTINUOUS TREATMENT

Until disease progression or unacceptable toxicity. The majority of responses occurred in the first 16 weeks; the benefit of continued treatment after this period should be re-evaluated.

 
D - Premedication and Supportive Measures

Antiemetic Regimen:

Minimal – No routine prophylaxis; PRN recommended

Other Supportive Care:

Also refer to CCO Antiemetic Recommendations.

 
E - Dose Modifications

Doses should be modified according to the protocol by which the patient is being treated. The following recommendations have been adapted from clinical trials or product monographs and could be considered.

 

Dosage with toxicity

 

There are no dose reductions for vismodegib. Interruptions up to 8 weeks are allowed for intolerable side effects* or for a planned surgical procedure. New onset of cutaneous squamous cell carcinoma should be managed according to the standard of care.

*intolerable side effects: Grade 3 or 4 related toxicities that are likely to be clinically significant, life-threatening or irreversible.

 

The following were excluded in the phase II clinical trial:

  • Hematologic or metabolic/chemistry abnormalities not considered clinically significant
  • Nausea, vomiting, or diarrhea that are adequately controlled after optimization of medical management.
  • Transient and manageable grade 3 infection
  • Asymptomatic thromboembolism found incidentally on imaging and managed with anti-coagulation therapy) 

Toxicity

Action

Pancreatitis Consider hold or discontinuation

Grade 3 or 4 treatment-related

Hold up to 8 weeks

Planned surgery

Hold up to 8 weeks

Grade 3 or 4 hepatotoxicity

Hold or discontinue



Hepatic Impairment

Hepatic Impairment

Total bilirubin / AST

 

AST

Vismodegib dose

Mild

 

≤ ULN

And

>ULN

No change; exercise caution

>ULN to 1.5x ULN

And

any

No change; exercise caution

Moderate

>1.5 to < 3x ULN

And

any

No change; exercise caution

Severe

3 to <10x ULN

And

any

Not recommended for use

 


Renal Impairment

The safety and efficacy of vismodegib have not been established in patients with severe renal impairment.  

Creatinine clearance (ml/min)

Vismodegib dose

≥ 50

No change

30 to 49

No change

< 30

No data


Dosage in the Elderly

No specific dose adjustment is necessary. However, monitor with caution.

Children:
CONTRAINDICATED in patients aged below 18 years


 
F - Adverse Effects

Refer to vismodegib drug monograph(s) for additional details of adverse effects

 


Very common (≥ 50%)

Common (25-49%)

Less common (10-24%)

Uncommon (< 10%),

but may be severe or life-threatening

  • Musculoskeletal pain* (may be severe)
  • Alopecia
  • Dysgeusia*
  • Anorexia, weight loss*
  • Fatigue
  • Amenorrhea
  • Nausea, vomiting
  • Abnormal electrolytes
  • Diarrhea
  • Increase LFTs (may be severe)
  • Constipation
  • Cough, dyspnea
  • Creatinine increased (may be severe)
  • Headache
  • Insomnia
  • Infection
  • Arterial thromboembolism
  • Venous thromboembolism
  • GI obstruction, perforation, bleeding
  • Psychiatric (e.g. paranoia)
  • Arrhythmia
  • Cardiotoxicity
  • Hypertension
  • Rhabdomyolysis
  • Secondary malignancy (squamous cell carcinoma)
  • Pancreatitis

*may persist at least 12 months post-treatment discontinuation 

 
G - Interactions

Refer to vismodegib drug monograph(s) for additional details


  • Vismodegib is a possible inhibitor of BCRP, CYP2C9 and CYP2C19. Use caution when administering vismodegib and these respective substrates with a narrow therapeutic range.
 
H - Drug Administration and Special Precautions

Refer to vismodegib drug monograph(s) for additional details


Administration:

  • Oral administration by self or caregiver
  • Capsules must be swallowed whole with a glass of water and not crushed or opened; can be taken with or without food.
  • If dose is missed, skip this dose and give the next scheduled dose. Do not double the dose to make up for the missed one.
  • Store at room temperature (15 - 30°C), in original package away from moisture and heat.
  • Drug available to patients, physicians/pharmacists who are registered with The Erivedge® Pregnancy Prevention Program (EPPP). Call 1-888-748-8926 or log onto www.erivedge.ca  

Contraindications:

  • Patients who have a hypersensitivity to this drug or any of its components
  • In patients aged below 18 years
  • Females patients of childbearing potential and male patients who do not comply with the EPPP requirements
  • Breastfeeding female patients
  • Not recommended for use in patients with severe hepatic impairment

Warnings/Precautions:

  • Use with caution in patients with mild to moderate hepatic impairment.
  • Use with caution in patients with a history of pancreatitis and gallbladder disease.
  • Patients should not donate blood or semen while taking vismodegib, during dose interruptions and for 24 months (2 months for semen) after stopping therapy.
  • Contains lactose; carefully consider use in patients with hereditary galactose intolerance, severe lactase deficiency or glucose-galactose malabsorption.
  • Patients with history of significant cardiovascular disease or risk factors for syncope:  Severe related adverse events have been reported in these patients groups. There was no effect of vismodegib on the QT interval.

Pregnancy and Lactation:

  • REFER TO THE ERIVEDGE PREGNANCY PREVENTION PROGRAM (EPPP) for COMPLETE DETAILS. 
  • Vismodegib can cross the placenta and cause fetal malformations.
  • Females of childbearing potential as defined by EPPP (including those who are either menstruating, amenorrheic but have not entered menopause or are perimenopausal) must be capable of understanding and complying with the patient registration, education, and safety requirements of the ERIVEDGE® program, regular pregnancy testing (7 days prior to initiating vismodegib treatment, monthly during treatment and interruptions and for 24 months after the last dose) and the use of two simultaneous contraception methods (including 1 acceptable barrier method with spermicide) for at least one month prior to starting treatment, during treatment, during dose interruptions, and for 24 months following the last dose of vismodegib.
  • If pregnancy occurs or is suspected during treatment, vismodegib must be discontinued and patients referred to a gynaecologist/obstetrician for evaluation and counselling. 
  • Male patients must be capable of understanding and complying with the patient registration, education, and safety requirements of the EPPP, including mandatory contraceptive measures for men (condoms withe spermicide should be used even with vasectomized males) while taking vismodegib, during dose interruptions and for 2 months after stopping therapy. Also, male patients should not donate semen during the above period of time. If the female sexual partner becomes pregnant, the female partner should be referred to a gynecologist/obstetrician for evaluation and counselling. 
  • Any suspected exposure to vismodegib during pregnancy must be reported immediately to EPPP at 1-888-748-8926 or through forms available for healthcare professionals onwww.erivedge.ca 
  • Patients should not breastfeed during treatment and dose interruptions, and for 24 months after the last dose.
  • Fertility effects may be irreversible. Fertility preservation strategies should be discussed prior to starting treatment.
 
I - Recommended Clinical Monitoring

Treating physicians may decide to monitor more or less frequently for individual patients but should always consider recommendations from the product monograph.

Recommended Clinical Monitoring

  • Liver function tests; baseline, before each cycle and as clinically indicated
  • Amylase and lipase; baseline and as clinically indicated
  • Renal function tests; baseline and before each cycle
  • Pregnancy test requirements based on the Erivedge® Pregnancy Prevention Program; before starting treatment and as indicated
  • Clinical toxicity assessment for musculoskeletal pain, fatigue, syncope, hypersensitivity, diarrhea, anorexia and other GI, cardiovascular effects, thromboembolism and psychiatric effects; at each visit
  • Grade toxicity using the current NCI-CTCAE (Common Terminology Criteria for Adverse Events) version

Suggested Clinical Monitoring

  • Electrolytes, including magnesium; baseline and as clinically indicated

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J - Administrative Information

Outpatient prescription for home administration


 
K - References

Sekulic A, Migden MR, Oro AE, et al.  Efficacy and safety of vismodegib in advanced basal-cell carcinoma. N Engl J Med 2012;366:2171-9.

Vismodegib drug monograph, Cancer Care Ontario.

June 2019 Updated emetic risk category


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M - Disclaimer

Regimen Abstracts
A Regimen Abstract is an abbreviated version of a Regimen Monograph and contains only top level information on usage, dosing, schedule, cycle length and special notes (if available). It is intended for healthcare providers and is to be used for informational purposes only. It is not intended to constitute or be a substitute for medical advice, and all uses of the Regimen Abstract are subject to clinical judgment. Such information is provided on an “as-is” basis, without any representation, warranty, or condition, whether express, or implied, statutory or otherwise, as to the information’s quality, accuracy, currency, completeness, or reliability, and Cancer Care Ontario disclaims all liability for the use of this information, and for any claims, actions, demands or suits that arise from such use.
Information in regimen abstracts is accurate to the extent of the ST-QBP regimen master listings, and has not undergone the full review process of a regimen monograph.  Full regimen monographs will be published for each ST-QBP regimen as they are developed.
Regimen Monographs
Refer to the New Drug Funding Program or Ontario Public Drug Programs websites for the most up-to-date public funding information.
The information set out in the drug monographs, regimen monographs, appendices and symptom management information (for health professionals) contained in the Drug Formulary (the "Formulary") is intended for healthcare providers and is to be used for informational purposes only. The information is not intended to cover all possible uses, directions, precautions, drug interactions or adverse effects of a particular drug, nor should it be construed to indicate that use of a particular drug is safe, appropriate or effective for a given condition. The information in the Formulary is not intended to constitute or be a substitute for medical advice and should not be relied upon in any such regard. All uses of the Formulary are subject to clinical judgment and actual prescribing patterns may not follow the information provided in the Formulary.
The format and content of the drug monographs, regimen monographs, appendices and symptom management information contained in the Formulary will change as they are reviewed and revised on a periodic basis. The date of last revision will be visible on each page of the monograph and regimen. Since standards of usage are constantly evolving, it is advised that the Formulary not be used as the sole source of information. It is strongly recommended that original references or product monograph be consulted prior to using a chemotherapy regimen for the first time.
Some Formulary documents, such as the medication information sheets, regimen information sheets and symptom management information (for patients), are intended for patients. Patients should always consult with their healthcare provider if they have questions regarding any information set out in the Formulary documents.
While care has been taken in the preparation of the information contained in the Formulary, such information is provided on an “as-is” basis, without any representation, warranty, or condition, whether express, or implied, statutory or otherwise, as to the information’s quality, accuracy, currency, completeness, or reliability.
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