The Role of Interferons in the Therapy of Melanoma
Ronald H. Goldfarb, Theresa L. Whiteside in Tumor Immunology and Cancer Therapy, 2020
The medical therapy of melanoma has not improved significantly for the past 30 years, despite the experimental application of a multitude of new cytotoxic drugs. Dacarbazine is the single cytotoxic drug approved for the indication of melanoma by the US FDA. Dacarbazine has consistently achieved response rates in the range of 20%, but has not yet demonstrated improved survival in patients with either inoperable metastatic melanoma, or patients with resectable disease at high risk of recurrence. Thus, biological and immunological therapies for melanoma have received increasing emphasis, which dating from the first half of this century and the exploration of a range of microbial immunostimulants that are still relevant, and the more recent pursuit of recombinant DNA-produced or highly purified cytokines. A considerable body of evidence suggests that melanoma may be susceptible to a variety of mediators of the host immune system. The clinical occurrence of spontaneous regression and paraneoplastic syndromes of depigmentation associated with prolonged survival of melanoma have represented a topic of investigation by our group for more than a decade (1–3). These clinical observations, together with the frequent histological appearance of host lymphocytes in the bed of the primary tumor, and correlation with prognosis of the primary tumor (4) and the demonstration of humoral and cellular immunity to melanoma in certain patients with melanoma in multiple laboratories, suggest that the immune response may be harnessed to improve the therapy of human melanoma. (5–8)
Endocrine and neuroendocrine tumours
Pat Price, Karol Sikora in Treatment of Cancer, 2014
The management of parathyroid carcinomas is surgical resection, and its completeness (excision en bloc and involved structures) assessed by post-operative serum PTH levels at the initial intervention determines the outcome. The operation may need to comprise a radical thyroidectomy and formal dissection of neck nodes, but this is not de rigueur and individual assessment as to the correct operative procedure is necessary. In a pooled series, Schantz and Castleman260 found a 30% recurrence rate, with less than one-half of patients dying within 5 years of the disease, indicating the very slow growth pattern of this tumour in most cases. Recurrence of the tumour is associated with refractory hypercalcaemia, which is often a considerable problem in these patients but may respond to oestrogen therapy. More recently, mithramycin and certain diphosphonate derivatives such as pamidronate (APD) have also been used to control persistent hypercalcaemia. While pamidronate is less effective in hyperparathyroidism than in malignant hypercalcaemia, either it or one of its congeners (e.g., clodronate and zoledronate) should always be considered in such patients. Chemotherapy and radiotherapy have little efficacy, although the rarity of this cancer has prevented large trials; dacarbazine has some activity.261,262 Cinecalcet, an inhibitor of the calcium feedback receptor, may also be useful in controlling hypercalcaemia in patients when surgery has been unsuccessful or is contraindicated.
Nucleic Acids as Therapeutic Targets and Agents
David E. Thurston, Ilona Pysz in Chemistry and Pharmacology of Anticancer Drugs, 2021
Given intravenously, the irritant properties of dacarbazine preclude contact with skin and mucus membranes. Also, because triazenes are prone to photochemical decomposition, an intravenous infusion bag containing dacarbazine must be protected from light. In the UK dacarbazine is used as a single agent to treat metastatic melanoma, and in combination with other agents for soft-tissue sarcomas and Hodgkin’s disease. In particular, it has been used as a component of a combination therapy for Hodgkin’s disease known as ABVD (doxorubicin [AdriamycinTM], Bleomycin, Vinblastine and Dacarbazine). Worldwide, it has also been used in a number of other cancer types including islet cell carcinoma of the pancreas. The predominant side effects are myelosuppression and intense nausea and vomiting.
A novel immunization strategy using cytokine/chemokines induces new effective systemic immune responses, and frequent complete regressions of human metastatic melanoma
Published in OncoImmunology, 2018
Fred T. Valentine, Frederick M. Golomb, Matthew Harris, Daniel F. Roses
87 patients meeting eligibility criteria were referred and monitored by oncologists. They all had clinically palpable cutaneous or subcutaneous in-transit metastases of an extremity or multiple metastases on the trunk or head. All had developed 2 to 100 metastases during the 2 months prior to entry, and 30 had failed to respond to chemotherapy including perfusions ending at least 2 months prior to entry. A majority had positive nodes on elective resection. They were stages IIIB 2 pts; IIIC 76 pts; and IV-M1a 9 pts60Table 3 tabulates the clinical stages of patients on entry, and the frequency of CRs in different entry groups. Patients with detectable visceral disease on entry were not eligible. There were no other exclusions. 48 patients progressed to Stage IV (2 M1a, 3 M1b; 44 M1c) during the study. 51 patients had excisional biopsies for monitoring, 5 of whom had several nodules resected, but all except one, who had experienced many regressions, had residual disease after biopsies. Patients were studied between 1979 and 1992 when standard chemotherapy was relatively ineffective dacarbazine.
Tebentafusp for the treatment of HLA-A*02:01–positive adult patients with unresectable or metastatic uveal melanoma
Published in Expert Review of Anticancer Therapy, 2022
Lanyi Nora Chen, Richard D. Carvajal
For patients who develop metastatic uveal melanoma, prognosis is poor and median survival is estimated at 12 months [12–16]. A meta-analysis of 29 trials for metastatic uveal melanoma between 2000 and 2016 identified a 1-year overall survival (OS) of 43% regardless of prior treatment [16]. For some patients with oligometastatic liver disease, surgical resection, and other regional approaches such as intra-arterial chemotherapy, hepatic artery chemoembolization, immunoembolization, radioembolization, isolated hepatic perfusion, and percutaneous hepatic perfusion can improve disease control, though careful patient selection is critical and survival benefit is largely unclear [17–24]. Until recently, advances in systemic treatments have not been shown to meaningfully improve survival [13]. Chemotherapeutic agents such as dacarbazine, temozolomide, and cisplatin have not demonstrated significant clinical activity [25]. Unlike its cutaneous counterpart, metastatic uveal melanoma is also largely refractory to immune checkpoint inhibitors. Single-agent checkpoint inhibitors have had disappointing clinical trial results. In one phase II trial, single-agent ipilimumab led to a 1-year OS of 22%, which was the primary endpoint; it did not lead to any partial or complete responses, and median OS was 6.8 months [26]. A phase II trial of single-agent tremelimumab, which had a primary endpoint of progression-free survival (PFS) at 6 months, led to a 9.1% 6-month PFS rate, no responses, and an OS of 12.8 months [27]. A retrospective review of patients treated with PD-1 or PD-L1 blockade yielded an objective response rate (ORR) of 3.6% and median OS of 7.6 months [28].
Redox-sensitive TRP channels: a promising pharmacological target in chemotherapy-induced peripheral neuropathy
Published in Expert Opinion on Therapeutic Targets, 2021
Ramandeep Singh, Pratik Adhya, Shyam Sunder Sharma
Dacarbazine is an anticancer agent used for the treatment of metastatic malignant melanoma, Hodgkin’s lymphoma and soft tissue sarcoma [72]. It belongs to the alkylating agent class of chemotherapeutics and is considered the main chemotherapeutic agent in the treatment of metastatic melanoma [73]. Dacarbazine is also associated with numerous adverse effects in patients such as nausea, vomiting flu-like symptoms and peripheral neuropathy. The exact cumulative dose of the drug that causes peripheral neuropathy in is not reported, but studies in mice have shown that an intraperitoneal dose of 1 mg/kg on four alternative days induces mechanical and cold allodynia [74].
Related Knowledge Centers
- Bleomycin
- Doxorubicin
- Liver Disease
- Melanoma
- Vinblastine
- Hodgkin Lymphoma
- Chemotherapy
- Intravenous Therapy
- Leukopenia
- Thrombocytopenia