Clinical toxicities encountered with paclitaxel (Taxol)
- PMID: 8102012
Clinical toxicities encountered with paclitaxel (Taxol)
Abstract
Although paclitaxel (TAXOL) appears to be one of the most promising antineoplastic agents of the last decade, with demonstrated activity in advanced and refractory ovarian, breast, lung, and head and neck cancers, most clinical oncologists have had little experience with the agent. This is largely the result of the initially limited supply of paclitaxel and other obstacles encountered during early clinical development that restricted the drug's availability to a few investigational centers. Although a high incidence of major hypersensitivity reactions due to the Cremophor EL vehicle used in formulation disrupted and almost terminated the clinical development of paclitaxel, hypersensitivity reactions are no longer a serious problem consequent to the advent of effective premedication regimens and longer administration schemes. Instead, neutropenia is the principal toxicity of paclitaxel. At clinically relevant doses, absolute neutrophil count nadirs are severely depressed in most patients. The duration of severe neutropenia, however, is usually brief; treatment delays for unresolved hematologic toxicity are rare, and absolute neutrophil count nadirs are constant with repetitive dosing, suggesting that neutropenia is not cumulative. Asymptomatic sinus bradycardia has occurred in up to 29% of patients in phase II trials, and other cardiac disturbances, including atrioventricular conduction and bundle branch blocks, ventricular tachycardia, and possible ischemic manifestations, have been reported in approximately 3% of patients. Cardiac disturbances have primarily been noted in studies that used cardiac monitoring to more effectively detect and manage major hypersensitivity reactions. Although sinus bradycardia and conduction blocks appear to represent true toxicities, ventricular tachycardia and ischemic manifestations, which have largely been observed in patients with preexisting cardiac disease, may not be due to paclitaxel. In view of the lack of clinical significance of the cardiac effects and their infrequent occurrence, cardiac monitoring during paclitaxel is not recommended for patients without cardiac risk factors. However, until precise risk factors can be defined, patients with a significant antecedent cardiac history are generally not considered to be good candidates for paclitaxel therapy. Neurotoxicity, characterized principally by peripheral neurosensory manifestations, has generally been of mild to moderate severity, even in heavily pretreated patients at paclitaxel doses < or = 200 mg/m2. However, some patients have developed a severe sensory-motor polyneuropathy at higher doses of paclitaxel (given as a single agent or in combination with cisplatin). Patients with an antecedent peripheral neuropathy or coexisting medical illnesses associated with peripheral neuropathy (such as diabetes mellitus and substantial prior alcohol use) appear to be especially prone to developing peripheral neuropathy.(ABSTRACT TRUNCATED AT 400 WORDS)
Similar articles
-
Sequences of taxol and cisplatin: a phase I and pharmacologic study.J Clin Oncol. 1991 Sep;9(9):1692-703. doi: 10.1200/JCO.1991.9.9.1692. J Clin Oncol. 1991. PMID: 1678780 Clinical Trial.
-
Patient care issues: the management of paclitaxel-related toxicities.Ann Pharmacother. 1994 May;28(5 Suppl):S27-30. doi: 10.1177/10600280940280S507. Ann Pharmacother. 1994. PMID: 7915156 Review.
-
Taxol (paclitaxel): a novel anti-microtubule agent with remarkable anti-neoplastic activity.Int J Clin Lab Res. 1994;24(1):6-14. doi: 10.1007/BF02592403. Int J Clin Lab Res. 1994. PMID: 7910054 Review.
-
Cardiac disturbances during the administration of taxol.J Clin Oncol. 1991 Sep;9(9):1704-12. doi: 10.1200/JCO.1991.9.9.1704. J Clin Oncol. 1991. PMID: 1678781
-
Taxol: a unique antineoplastic agent with significant activity in advanced ovarian epithelial neoplasms.Ann Intern Med. 1989 Aug 15;111(4):273-9. doi: 10.7326/0003-4819-111-4-273. Ann Intern Med. 1989. PMID: 2569287
Cited by
-
Breast Cancer and the Cardiovascular Disease: A Narrative Review.Cureus. 2022 Aug 12;14(8):e27917. doi: 10.7759/cureus.27917. eCollection 2022 Aug. Cureus. 2022. PMID: 36110451 Free PMC article. Review.
-
Peptide ligand and PEG-mediated long-circulating liposome targeted to FGFR overexpressing tumor in vivo.Int J Nanomedicine. 2012;7:4499-510. doi: 10.2147/IJN.S32817. Epub 2012 Aug 14. Int J Nanomedicine. 2012. PMID: 22923988 Free PMC article.
-
Overcoming ABCB1 mediated multidrug resistance in castration resistant prostate cancer.Cell Death Dis. 2024 Aug 1;15(8):558. doi: 10.1038/s41419-024-06949-3. Cell Death Dis. 2024. PMID: 39090086 Free PMC article.
-
A phase I study of intraperitoneal nanoparticulate paclitaxel (Nanotax®) in patients with peritoneal malignancies.Cancer Chemother Pharmacol. 2015 May;75(5):1075-87. doi: 10.1007/s00280-015-2737-4. Epub 2015 Apr 23. Cancer Chemother Pharmacol. 2015. PMID: 25898813 Free PMC article. Clinical Trial.
-
Overview of imaging findings associated with systemic therapies in advanced epithelial ovarian cancer.Abdom Radiol (NY). 2020 Mar;45(3):828-841. doi: 10.1007/s00261-019-02175-0. Abdom Radiol (NY). 2020. PMID: 31396642 Review.
Publication types
MeSH terms
Substances
LinkOut - more resources
Other Literature Sources