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Antineoplastic Drugs during Pregnancy
Published in “Bert” Bertis Britt Little, Drugs and Pregnancy, 2022
Vismodegib is an antineoplastic for which there is no human studies for use during pregnancy. The manufacturer reports that the drug is highly embryotoxic. In rat models, 100 percent of conceptuses were resorbed early during gestation after exposure to this drug.
Rare Cancer Presentations
Published in Debjani Sahni, Adam Lerner, Bilal Fawaz, Advanced Skin Cancer, 2022
Bilal Fawaz, Heather A. Edwards, Monica Rosales Santillan, Debjani Sahni, Connor O’Boyle, Daniel L. Faden
Given the widespread, advanced nature of the NMSCs with evidence of metastasis, a PD-1 inhibitor was started at the outset, pembrolizumab (200 mg IV every 3 weeks), as this agent has been approved in a tissue-type agnostic manner for tumors with a high somatic mutation burden (>10 mutations/megabase). A slow partial response was noted. Based on data on the use of hedgehog pathway inhibitors in basosquamous tumors, vismodegib was then added to the regimen (150 mg daily). Combination systemic therapy resulted in ~50% reduction in tumor size within months, most notably on the nose and left cheek. There was also visible regrowth of healthy granulation tissue on the nasal septum. Side effects of mild-to-moderate dysgeusia secondary to vismodegib developed after a couple of months. Weakness in the right shoulder and contractures involving the right fourth and fifth fingers also evolved with treatment. The latter was thought to occur due to an immune-mediated brachial plexus neuritis. The side effects were tolerable to the patient, and importantly, their quality of life improved significantly. Surgical excision was utilized to debulk a large pedunculated tumor on the left cheek (which subsequently resolved with continued systemic therapy). The tender left cervical node was also removed surgically and further serial imaging did not show evidence of regional disease recurrence or new distant metastases over the following year.
Small-Molecule Targeted Therapies
Published in David E. Thurston, Ilona Pysz, Chemistry and Pharmacology of Anticancer Drugs, 2021
Developed by Genentech Inc, vismodegib (ErivedgeTM) (Figure 6.68) is a first-in-class Hedgehog signaling pathway inhibitor which was approved by the FDA in 2012 for the treatment of basal cell carcinoma (BCC) which has either metastasized to other parts of the body, relapsed after surgery, or cannot be treated with radiation or surgery. BCC is usually treated with surgery and rarely recurs or spreads, although advanced tumors can eventually lose their responsiveness to conventional treatment options. It is recommended by NICE in the UK for the same purpose and is also undergoing clinical trials in other cancer types in which the Hedgehog signaling pathway is known to be relevant. The FDA approval for vismodegib was based on positive results from a Phase II clinical trial in which an objective response was observed in 18 out of 33 patients, with 2 complete and 16 partial responses. Of the remaining 15 patients, 11 had stable disease and 4 progressed. Structure of the first-in-class Hedgehog signaling inhibitor vismodegib (ErivedgeTM).
The current clinical approach to difficult-to-treat basal cell carcinomas
Published in Expert Review of Anticancer Therapy, 2023
Eugenia Veronica Di Brizzi, Giuseppe Argenziano, Gabriella Brancaccio, Camila Scharf, Andrea Ronchi, Elvira Moscarella
An open-label, non-comparative, multicentre Phase 2 study (VISMONEO) was performed for neoadjuvant therapy with vismodegib. Fifty-five patients with facial laBCC (confirmed histologically) considered inoperable or operable with risk of esthetic and/or functional sequelae were included in the study. Patients were given vismodegib 150 mg daily orally for 4–10 months prior to surgery (scheduled once best vismodegib response was observed). The primary endpoint was the percentage of BCC patients with tumor downstaging after surgical resection after neoadjuvant vismodegib. Forty-four patients (80%) experienced downstaging after vismodegib treatment. Of these, 27 had a complete response. The mean duration of treatment was 6.0 months. The overall response rate according to RECIST 1.1 criteria was 71%. At 3 years of follow-up, 16/44 patients had a known recurrence (36%) [121].
My patient refers smell/taste disturbance. It may not be COVID-19. Dermatological drugs associated with olfactory and/or gustative disorders
Published in Journal of Dermatological Treatment, 2022
Luiz Guilherme Martins Castro, Isabella Parente Almeida
Initially approved in 2012, vismodegib is used for locally advanced and metastatic basal cell carcinomas (BCC). Dysgeusia is observed in up to 55% of patients. Its use is limited to these specific BCC types, therefore it is a drug not so commonly used by the average dermatologist. According to Wang and Lipner (6), taste disturbance was 6 times more common than smell disturbance. Adalimumab was the most common dermatological medication associated with anosmia in clinical trials while terbinafine (TBF), an antifungal commonly used to treat dermatophytosis, presented taste disturbance in 2.8% of phase III clinical trial patients (5,6). To identify risk factors associated with taste loss to TBF, Strycker et al. performed a case-control study of 87 reports of probable TBF-induced taste loss. The mean latent period between the first intake of TBF and taste loss was 35 days. Most patients recovered within 4 months after discontinuation (5). Cases were significantly older than controls. A low body mass index, a history of taste loss, and aging were identified as risk factors for developing taste loss to TBF (5).
Treatment of basal cell carcinoma with vismodegib: future or present?
Published in Acta Chirurgica Belgica, 2021
Jos Velleman, Outi Kaarela, Jan J. Vranckx
The neoadjuvant use of Vismodegib can possibly turn unresectable BCC into operable tumours. A case report by Tang et al. described the use of 150 mg Vismodegib daily for six months prior to MS with no clinical evidence of recurrence during a 7-month follow-up [11]. Paulsen et al. described an extended use of Vismodegib over a 10-month period followed by surgery [19]. The pathology report showed the absence of BCC and after a 9-month follow-up, the patient was still in complete remission [19]. Ally et al. studied 13 BCCs, which were excised after a mean of 4 ± 2 months of Vismodegib [20]. An overall reduction of the surgical defect area by 27% was described [20]. One tumour recurred 17 months after MS [20]. Mean follow-up was 11.5 months [20]. A drug exposure of less than three months seemed to be ineffective [20].