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Profiles of Drug Substances,... 2016Dacarbazine is a cell cycle nonspecific antineoplastic alkylating agent used in the treatment of metastatic malignant melanoma. This chapter contains the descriptions of... (Review)
Review
Dacarbazine is a cell cycle nonspecific antineoplastic alkylating agent used in the treatment of metastatic malignant melanoma. This chapter contains the descriptions of the drug: nomenclature, formulae, chemical structure, elemental composition, and appearance. The uses and applications of dacarbazine and the methods that were used for its preparation are reported. The methods which were used for the physical characterization of the drug are ionization constant, solubility, X-ray powder diffraction pattern, crystal structure, melting point, and differential scanning calorimetry. The profile contains the spectra of the drug: ultraviolet spectrum, vibrational spectrum, nuclear magnetic resonance spectra, and mass spectrum. The compendial methods of analysis for dacarbazine include the United States Pharmacopeia methods, British Pharmacopeia methods, and International Pharmacopeia methods. Other reported methods that are used for the analysis of the drug are high-performance liquid chromatography, high-performance liquid chromatography-mass spectrometry, and polarography. Metabolism, pharmacokinetics, and stability studies on dacarbazine are also included. Reviews of some analytical methods and physicochemical properties of the drug as well as the most important enzymes that are involved in the prodrug activation are provided. Sixty-four references are listed at the end of this monograph.
Topics: Animals; Antineoplastic Agents; Chemistry, Pharmaceutical; Dacarbazine; Humans
PubMed: 26940170
DOI: 10.1016/bs.podrm.2015.12.002 -
Annales de Dermatologie Et de... Apr 2001
Review
Topics: Animals; Antineoplastic Agents, Alkylating; Dacarbazine; Disease Models, Animal; Drug Evaluation, Preclinical; Drug Interactions; France; Humans; Melanoma; Reproduction
PubMed: 11395650
DOI: No ID Found -
Report on Carcinogens : Carcinogen... 2011
Topics: Animals; Antineoplastic Agents, Alkylating; Carcinogens; Dacarbazine; Humans; Neoplasms
PubMed: 21850138
DOI: No ID Found -
IARC Monographs on the Evaluation of... May 1981
Topics: Animals; Carcinogens; Chemical Phenomena; Chemistry; Chromosome Aberrations; Dacarbazine; Female; Humans; Male; Mice; Mutagenicity Tests; Neoplasms, Experimental; Pregnancy; Rats; Reproduction; Teratogens
PubMed: 6944259
DOI: No ID Found -
International Journal of Dermatology 1976
Topics: Chemical Phenomena; Chemistry; Dacarbazine; Humans; Melanoma; Triazenes
PubMed: 1245371
DOI: 10.1111/j.1365-4362.1976.tb05098.x -
Report on Carcinogens : Carcinogen... 2004
Topics: Animals; Antineoplastic Agents, Alkylating; Carcinogenicity Tests; Carcinogens; Dacarbazine; Environmental Exposure; Female; Guidelines as Topic; Humans; Male; Mice; Models, Biological; Rats
PubMed: 21089844
DOI: No ID Found -
Postepy Higieny I Medycyny... Nov 2011Melanoma is a tumour derived from melanocytes, cells of neuroectodermal origin. Melanoma treatment represents a challenge to oncologists due to its aggressive course and... (Review)
Review
Melanoma is a tumour derived from melanocytes, cells of neuroectodermal origin. Melanoma treatment represents a challenge to oncologists due to its aggressive course and early and multiple metastases. Surgical excision of lesions is a highly effective intervention, but only in early stages. In contrast, median survival of patients with metastatic melanoma is still below one year. In 2011 the FDA and EMA have approved new drugs, ipilimumab and vemurafenib, that might be a major breakthrough in treating patients with advanced melanoma. However, time is needed to conclude whether they replace dacarbazine, a drug used for over 30 years in the therapy of metastatic melanoma, even if the response rate was only 10-15%. The mechanism of dacarbazine action is not clear but it is probably based on methylation of purine bases in DNA. The low therapeutic efficacy of dacarbazine might be the consequence of rapid removal of DNA lesions by repair systems. A high melanoma chemoresistance is also driven by the extent and nature of alterations in signal transductions in tumour cells. None of the previously conducted trials proved superiority of any treatment modality over monotherapy with dacarbazine. Higher response rates did not correlate with survival benefit, and more intense adverse effects were frequently observed. There are some expectations for targeted therapy and immunotherapy, which have already demonstrated some efficacy in clinical studies. This review aims at providing the current knowledge on dacarbazine and its analogue, temozolomide, including the latest results of clinical studies combining these drugs with other treatment protocols.
Topics: Antibodies, Monoclonal; Antineoplastic Agents, Alkylating; DNA Damage; Dacarbazine; Humans; Immunotherapy; Indoles; Ipilimumab; Melanoma; Randomized Controlled Trials as Topic; Sulfonamides; Temozolomide; Vemurafenib
PubMed: 22173438
DOI: 10.5604/17322693.966832 -
Melanoma Research Aug 2020We observed several cases of hypotension associated with high-dose dacarbazine. We conducted a retrospective observational analysis of all patients treated with...
We observed several cases of hypotension associated with high-dose dacarbazine. We conducted a retrospective observational analysis of all patients treated with high-dose dacarbazine from January 2018 to August 2019 in Oscar Lambret Center, Lille, France. In our study, a total of 23 patients in outpatient care were analyzed, they underwent 57 treatment cycles. We observed 8 episodes of hypotension in 7 of the 23 consecutive treated patients (30.4%). We discuss herein several hypotheses explaining dacarbazine-induced hypotension. Dacarbazine high dose and administration methods seem to be the main causes of hypotension adverse events. Administration methods include administration duration, which should be above 2 hours, concomitant hydration with 500 ml 0.9% sodium chloride, and UV-resistant pump tube downstream the administration tree.
Topics: Acute Disease; Antineoplastic Agents, Alkylating; Dacarbazine; Female; Humans; Hypotension; Male; Retrospective Studies
PubMed: 32141965
DOI: 10.1097/CMR.0000000000000659 -
Melanoma Research Oct 2013The widespread prevalence of melanoma, one of the most malignant forms of skin cancer, is increasing rapidly. Two chemotherapeutic regimens are commonly used for the... (Meta-Analysis)
Meta-Analysis Review
The widespread prevalence of melanoma, one of the most malignant forms of skin cancer, is increasing rapidly. Two chemotherapeutic regimens are commonly used for the palliative treatment of malignant melanoma: intravenous administration of single-agent dacarbazine or oral administration of temozolomide. The aim of this study was to compare the effectiveness and side effects of dacarbazine with those of temozolomide through a meta-analysis. A thorough literature bibliography search was conducted up to 2012 to gather and review all randomized clinical trials comparing the use of dacarbazine with that of temozolomide in the treatment of malignant melanoma. Three head-to-head randomized clinical trials comprising 1314 patients met the criteria and were included. Comparison of temozolomide with dacarbazine yielded a nonsignificant relative risk (RR) of 0.83 [95% confidence interval (CI) = 0.26-2.64, P = 0.76] for complete response, a nonsignificant RR of 1.05 (95% CI = 0.85-1.3, P = 0.65) for stable disease, and a nonsignificant RR of 2.64 (95% CI = 0.97-1.36, P = 0.11) for disease control rate. The RR for nonhematologic side effects and hematologic side effects, such as anemia, neutropenia, and thrombocytopenia, of temozolomide compared with dacarbazine in patients with malignant melanoma was nonsignificant in all cases, but the RR for lymphopenia of temozolomide compared with dacarbazine was 3.79 (95% CI = 1.38-10.39, P = 0.01), which was significant. Although it is easier to administer oral medication, according to the results, there is no significant difference in the efficacy and side effects of these two drugs. Owing to the higher cost of treatment with temozolomide and the increased prevalence of lymphopenia on using temozolomide, use of dacarbazine as the first choice treatment for malignant melanoma is suggested.
Topics: Administration, Intravenous; Administration, Oral; Antineoplastic Agents, Alkylating; Dacarbazine; Disease Progression; Humans; Melanoma; Odds Ratio; Randomized Controlled Trials as Topic; Remission Induction; Risk Factors; Skin Neoplasms; Temozolomide; Time Factors; Treatment Outcome
PubMed: 23880781
DOI: 10.1097/CMR.0b013e3283649a97 -
Bioorganic Chemistry Mar 2022Caffeine has been studied as a potentiating agent in chemotherapy against some types of cancer, but there are few reports on its effects on melanoma. This study aimed to...
OBJECTIVE
Caffeine has been studied as a potentiating agent in chemotherapy against some types of cancer, but there are few reports on its effects on melanoma. This study aimed to investigate caffeine's ability to enhance the effects of dacarbazine in vitro.
MATERIALS AND METHODS
Murine melanoma B16F10 cells were treated 24 h with 1-40 µM caffeine. We evaluated cytotoxicity, DNA damage, apoptosis, and oxidative lesion induced by dacarbazine associated with caffeine. The metabolization of these drugs, as well as immunocytochemical labeling, were also evaluated.
CONCLUSIONS
The pre-treatment with caffeine showed to be more effective. Caffeine potentiated dacarbazine-induced cytotoxic effects by increasing dacarbazine biotransformation, apoptosis, DNA damage, and malondialdehyde levels; also, caffeine reduced Ki67 and ERK1/2 nuclear labeling and increased p53 labeling in B16F10 cells. In our experiment, caffeine promoted modifications associated with dacarbazine metabolism by viable cells potentiating this antineoplastic drug. These promising results should be further evaluated in experimental models in vivo.
Topics: Animals; Antineoplastic Agents; Apoptosis; Caffeine; Cell Line, Tumor; Dacarbazine; Melanoma; Mice
PubMed: 34979447
DOI: 10.1016/j.bioorg.2021.105576