About Oral Systemic Therapy
Hedgehog pathway inhibitors for basal cell carcinoma
Vismodegib has been approved for treatment of unresectable metastatic basal cell carcinomas. It comes as oral medication taken once again. It has been shown to be significantly effective in reducing and occasionally curing basal cell carcinomas. Its side effects are significant. They include loss of sense of taste, muscle cramps in upper and lower extremities, gastrointestinal side effects such as nausea, diarrhea, constipation, fatigue, and hair loss. Most of the side effects are reversible with stopping medication. Significant shortcoming of this medication is resistance of some basal cell carcinomas to the drug.
The length of treatment with Vismodegib can be variable and has not been well-established. Shortest courses can be as long as three months terminating due to the patient's intolerance of the side effects. Most courses run 7-9 months limited by the patient's intolerance of the drug. Surprisingly, some patients are able to tolerate the drug for over a year. The cost of the drug is significant up to $10,000 a month. Insurance companies cover the cost of the drug consistently. In cases of lack of insurance coverage, the manufacturers often provide the medication at no cost to the patient.
The mechanism of action is its effect on Sonic Hedgehog pathway. Vismodegib is the first SMO inhibitor molecule in its class. It binds and hinders SMO (transmembrane protein).
Sonidegib is also known by its chemical name erismodegib. It is also used for locally advanced basal cell carcinomas or metastatic basal cell carcinomas not amenable to surgery or radiation therapy. The mechanism of action is inhibition of smoothened protein. Its side effect profiles are similar to Vismodegib. It also suffers from development of resistances of the carcinomas. This drug is priced similarly to Vismodegib at approximately $10,000 per month.
Itraconazole is known as an antifungal drug. Due to its ability to inhibit Hedgehog pathway activity, it inhibits basal cell carcinoma growth. It has not been as widely evaluated for treatment of basal cell carcinoma as other Hedgehog inhibitors, although it is an older drug. Its feasibility in treating basal cell carcinomas and its dosing regimen are still being evaluated. It acts on SMO protein. It has also been called a Cilial translocation inhibitor. It is a powerful Hedgehog pathway inhibitor. It has similar side effect profile to the other Hedgehog inhibitors. This drug is also associated with resistance development by cancers.
Oral therapy for squamous cell carcinoma
This chemotherapy agent is available as an oral medication. It is used primarily for squamous cell carcinomas. Its more common use is in gastrointestinal squamous cell carcinomas. The drug is converted intercellularly into 5-Fluorouracil. It is considered to be better tolerated form of 5-Fluorouracil than the IV 5-FU. Xeloda has been used for suppression of new squamous cell carcinomas in organ transplant recipients on chronic immunosuppressants.
Acitretin is a vitamin A derivative, a retinoid normally prescribed for psoriasis. It had been found to be effective in treatment of extensive actinic keratosis. It decreases the frequency and thickness of actinic keratoses. Although some theorize it could decrease the frequency of squamous cell carcinomas, this has not been proven.
Acceptance of residual melanoma-in-situ (lentigo maligna) after an excision can avoid cosmetic and functional deformation. Is the residual risk of recurrence and transformation into invasive melanoma low enough to warrant observation? Melanoma-in-situ (MIS) is a high risk lesion due to three primary reasons. The first is that a partially biopsied melanocytic lesion with a diagnosis…Read More
HISTORY 69-year-old man presents with melanoma in situ of the upper back. A biopsy on 6/15/2017 showed malignant melanoma at least in-situ and at least Clark’s level I with margins involved. Excision and skin graft closure performed on 8/9/2017. Pathology showed residual malignant melanoma in situ with involved margin at 2-4 o’clock. DISCUSSION Management of…Read More
HISTORY 86-year-old man presented in June 2017 with a 2 month history of squamous cell carcinoma of the left cheek. The lesion was partially treated with Mohs surgery on 6/12/2017. Due to the size of the defect and depth of extension into the ear and the parotid gland, Mohs surgery was stopped after 3 levels.…Read More
HISTORY 82 year old man presented in 02/2017 with a 3 year history of a crusty forehead lesion treated with cryoablation and 5-FU. Incisional biopsy in 2016 revealed poorly differentiated sclerosing squamous cell carcinoma, with perineural invasion. Excision a few months later was performed with residual circumferentially involved margins. CT with contrast showed only local…Read More
Discussion Here we present three cases of extended lateral nasal island flap. These flaps are based on the branches of angular artery that include alar artery and the lateral nasal arteries. The flap is an excellent way of reconstructing nasal tip, dorsum and ala defects up to 1.5 cm in diameter. The release of the…Read More
Metatypical basosquamous cell carcinoma is a subset of cutaneous cancers that poses an increased risk of metastases to the patient due to its aggressive behavior. The classic histology of metatypical basosquamous cell carcinoma includes features of both basal cell carcinoma and squamous cell carcinoma, as well as areas of intermediate differentiation. The cells are larger and…Read More
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