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Chemotherapy in pregnancy
Published in Hung N. Winn, Frank A. Chervenak, Roberto Romero, Clinical Maternal-Fetal Medicine Online, 2021
For patients with distant metastatic spread of melanoma, the use of chemotherapy has not met with impressive results. Agents administered during pregnancy include dacarbazine, temozolomide, cisplatin, vinblastine, and interferon alpha2b (28,29).
Nucleic Acids as Therapeutic Targets and Agents
Published in David E. Thurston, Ilona Pysz, 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.
The Role of Interferons in the Therapy of Melanoma
Published in Ronald H. Goldfarb, Theresa L. Whiteside, 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)
An overview on the advantages and limitations of 3D printing of microneedles
Published in Pharmaceutical Development and Technology, 2021
Emine Dilek Ozyilmaz, Aybuke Turan, Tansel Comoglu
In a study of Lu et al., microneedles containing polypropylene fumarate (PPF) and a chemotherapeutic agent have been developed using the stereolithographic process. In the study, diethyl fumarate (DEF) was mixed with polymer to increase PPF viscosity. In the study, dacarbazine, which is widely used in skin cancer treatment, was homogeneously mixed into a solution containing both polymers. Each microneedle has a 700 μm high cylindrical base and a 300 μm high cone-shaped tip. Based on the compression test results of the prepared microneedles, it has been shown that the force of failure is much greater than the theoretical force of penetration of the skin. The release kinetic studies showed that dacarbazine can be released at a controlled rate for five weeks. Results have shown that PPF-based drug-loaded microneedles are a potential method for treating skin carcinomas, and SLA is an attractive manufacturing technique for biomedical applications, especially for the production of microneedles (Lu et al. 2015).
Combination chemotherapy with temozolomide, lomustine, vincristine and interferon-alpha (TOL-IFN) plus vemurafenib or TOL-IFN as first-line treatment for patients with advanced melanoma
Published in Acta Oncologica, 2020
Kalle E. Mattila, Pia Vihinen, Susan Ramadan, Tanja Skyttä, Leena Tiainen, Meri-Sisko Vuoristo, Kristiina Tyynelä-Korhonen, Jussi Koivunen, Laura Kohtamäki, Siru Mäkelä, Micaela Hernberg
In the past decades, when dacarbazine-based chemotherapy was the treatment of choice, the median survival of patients with unresectable melanoma was only six to nine months and only 10–15% of the patients were alive after three years [1]. Dacarbazine as single agent demonstrated an objective response of 13% with a median overall survival (OS) ranging from 5.6 to 11 months according to eight randomized studies, and a one-year OS was 20–30% in five randomized studies [2]. Combination chemotherapy and interferon-alpha (IFN) increased response rate to 50–60% [3–5] but failed to prolong survival [1]. The median OS of 8.9 months was observed with dacarbazine, lomustine and vincristine ± IFN in a retrospective analysis of Finnish melanoma patients [6]. Immune checkpoint inhibitors, v-Raf murine sarcoma viral oncogene homolog B (BRAF), and mitogen-activated protein kinase (MEK) inhibitors have dramatically improved the survival of metastatic melanoma patients: three-year OS rate has reached 44–58% in recent trials with BRAF + MEK inhibitors and immune checkpoint inhibitors [7–9]. Brain metastases are still associated with poor survival, although remarkably long intracranial responses have been observed with combination therapies: 12-month progression-free survival (PFS) rate of 19–47% with dabrafenib + trametinib and 9-month PFS rate of 56.6% with ipilimumab + nivolumab [10,11].
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.