Basal Cell Nevus Syndrome
Dongyou Liu in Handbook of Tumor Syndromes, 2020
Due to the multisystem presentation of BCNS, patients with this disorder must be treated by numerous specialists. Prevention of BCC includes decreased sun exposure, and wearing UV sunblock, sunglasses, and sun-protective clothing. Also, oral retinoids may thwart or delay the growth and recurrence of BCCs [46]. When BCCs do occur, the mainstay of treatment is surgical excision. For initial small and well-defined lesions, curettage and cautery/electrodessication is preferred, as well as cryosurgery [47–50]. For larger, thick, concave lesions, microscopic excision with ultrapulse CO2 laser therapy can be used [51,52]. Photodynamic therapy with topical application of delta-aminolaevulinic acid is an option for superficial and flat lesions [52–55]. For recurrent lesions in risky locations such as the periorbital, nasolabial, and nasal skin, a more aggressive approach must be taken, which includes Mohs micrographic surgery [48,56–58]. Local radiotherapy is not recommended due to the risk of tumor enlargement and recurrence [22,39]. Nonsurgical approaches also depend on tumor characteristics. For low-risk, superficial, non-hair follicle−involving BCC, topical 0.1% 5–fluorouracil can be used [59]. For small papular tumors, intralesional injection of interferon alfa-2b can be used [52]. Paclitaxel can be used to treat multiple aggressive BCCs [60]. Topical imiquimod may treat small, low-risk superficial or nodular BCC [61]. It acts as a Toll-like receptor-7 agonist and causes apoptosis of BCCs [62]. In addition, vismodegib (Erivedge) and sonidegib (Odomzo) targeting the “hedgehog pathway,” which is affected by the PTCH mutation, have been approved to treat people with basal cell cancers that have spread in the body or that cannot be treated with surgery or radiation.
The Role of Interferons in the Therapy of Melanoma
Ronald H. Goldfarb, Theresa L. Whiteside in Tumor Immunology and Cancer Therapy, 2020
Dosages from 12 Mu/M2 to 50 Mu/M2, as well as 50 Mu/M2 plus Cimetidine, gave comparable results at the Mayo Clinic with recombinant interferon alfa-2a in 96 patients with metastatic melanoma (45). A large experience has been reported with recombinant interferon alfa-2b given at 10 Mu/M2 administered subcutaneously three times a week, with overall response rates and durable complete response rates comparable to higher dose IV, and IM experiences (42). These are summarized in Table 1.
Acquired Bleeding Disorders Associated with Disease and Medications
Harold R. Schumacher, William A. Rock, Sanford A. Stass in Handbook of Hematologic Pathology, 2019
Interferon alfa-2a is associated with GI hemorrhage during therapy; infrequently, the GI hemorrhage is severe or fatal. In CML patients treated with interferon alfa-2a, a severe life-threatening leukopenia and thrombocytopenia were seen in 27% of patients. Retinal hemorrhages have been observed rarely in patients being treated with interferon alfa-2b after use of the drug for several months (134).
Chimeric antigen receptor T-cell therapy for melanoma
Published in Expert Review of Clinical Immunology, 2021
Azadehsadat Razavi, Mahsa Keshavarz-Fathi, John Pawelek, Nima Rezaei
Surgical excision of tumor is the treatment applied to all stages of melanoma [30,50]. However, surgical excision is ineffective in relapsed patients and those with stage III and IV melanoma [28,51,52]. For these patients, surgery is combined with other treatments. In addition, patients may be given other therapies either before or after removal of malignant lesions as neoadjuvant or adjuvant therapy, respectively [28]. Neoadjuvant therapy such as biochemotherapy (BCT), which is administered before surgery, is an efficient therapy to reduce local invasion [53]. As its name implies, adjuvant therapy is administered to the patient after surgery to maximize the overall survival and help prevent relapse. Studies have shown that radiotherapy, chemotherapy or immunotherapy combined with surgery can prolong survival of stage IV melanoma [54,55]. Interferon alfa-2b (IFNα-2b) was the first adjuvant therapy for patients who underwent surgical resection [28].
Safety of pembrolizumab for resected stage III melanoma
Published in Expert Opinion on Drug Safety, 2020
Overall, around 1500 patients with resected stage III melanoma have been treated with ipilimumab 10 mg/kg Q3W for 4 doses then every 12 weeks up to 4 additional doses in three phase III clinical trials to date: EORTC 18071, Checkmate-238 and E1609 comparing ipilimumab to placebo, nivolumab and high-dose interferon alfa-2b, respectively [14–16]. The overall incidence of treatment-related AEs was 90–98.8% with a rate of grade ≥3 AEs of 42.5–56.7%. The most frequently reported AEs were diarrhea/colitis (45.9–55.5%), fatigue/asthenia (41–44.6%), skin rash (29.4–58.6%) and alanine aminotransferase elevation (ALT, 14.6–32.4%). There was a total of 13 deaths related to ipilimumab (0–1.6%). Those AEs lead to discontinuation of ipilimumab in 42.6–54% of patients which is higher than has been observed in advanced melanoma [33]. In the phase III trial E1609, ipilimumab 3 mg/kg Q3W for 4 doses then every 12 weeks up to 4 additional doses has also been compared to high-dose interferon alfa-2b in 516 patients with a rate of grade ≥3 treatment-related AEs of 38.2% for an overall incidence of treatment-related AEs of 90% in the ipilimumab arm [15]. The most common AEs were diarrhea/colitis (50.6%), skin rash (46.7%) and ALT elevation (18.6%). There were 3 deaths related to ipilimumab (0.6%). The rate of discontinuation owing to AEs was 35%.
CTLA4 antagonists in phase I and phase II clinical trials, current status and future perspectives for cancer therapy
Published in Expert Opinion on Investigational Drugs, 2019
Bartosz Szostak, Filip Machaj, Jakub Rosik, Andrzej Pawlik
An open label, phase I/II study, KEYNOTE 029 (NCT02089685), enrolled 293 patients with advanced melanoma or renal cell carcinoma from twelve medical centres in three countries. In the Ib phase, 153 patients were followed for 17 months [median follow-up was 17 months; interquartile range (IQR), 14.8–18.8]. The toxicity of combination of standard-dose pembrolizumab and reduced-dose ipilimumab was found to be manageable. Forty-five per cent of patients had ≥1 grade 3–4 treatment-related adverse events, 14% of patients had to discontinue the treatment with both drugs and 17% of patients discontinued the treatment with one drug and continued only with the other one. However, the treatment did not result in any lethality [66]. The KEYNOTE 029 dose finding results are quite promising. The pembrolizumab plus ipilimumab dose that demonstrates antitumor activity is tolerable. In a cohort of 22 patients, 19 were evaluable for dose-limiting toxicity (DLT), 27% of patients experienced one or more DLT and 59% of patients experienced one or more grade 3 to 4 treatment-related adverse events. Forty-two per cent (5/12) of patients with melanoma and 30% (3/10) of patients with renal cell carcinoma responded to the therapy. In the same study, efficacy and toxicity of pembrolizumab plus pegylated interferon alfa-2b were assessed, but the results were not as positive as with the combination of anti-CTLA-4 and anti-PD-1 drugs [67].
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