Pharmacodynamics of non-break weekly paclitaxel (Taxol) and pharmacokinetics of Cremophor-EL vehicle: results of a dose-escalation study

Briasoulis, Evangelos; Karavasilis, Vasilios; Tzamakou, Eleftheria; Haidou, Constantina; Piperidou, Christina; Pavlidis, Nicholas

doi:10.1097/00001813-200206000-00006

Cited by 18 publications

(9 citation statements)

References 24 publications

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“…However, high doses and prolonged infusion can markedly increase the terminal half-life. 9 Cremophor EL itself is considered a neurotoxic agent and, therefore, could cause a delayed seizure disorder. It has been associated with clonic seizures and burst-suppression patterns, as seen on electroencephalograms in rats.…”

Section: Discussionmentioning

confidence: 99%

Delayed Seizure Associated with Paclitaxel‐Cremophor EL in a Patient with Early‐Stage Breast Cancer

O’Connor

Kossoff

2009

Pharmacotherapy

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Paclitaxel, a microtubule stabilizer, is an effective agent for treating cancer of the breast, ovary, head and neck, and lung. Because paclitaxel is insoluble in water, it is formulated with the micelle-forming Cremophor EL. Neurologic toxicity is well described with both the drug and this carrier, with most toxicities manifesting as peripheral neuropathy, motor neuropathy, autonomic neuropathy, and myopathy. Toxic effects on the central nervous system, such as seizures or encephalopathy, have been rarely reported; however, the seizures reported were closely related to the time of infusion. We describe a 41-year-old woman with no history of seizures who was treated with paclitaxel for breast cancer. Four days after the drug was infused, she developed a generalized tonic-clonic seizure that could not be attributed to other causes. The patient was treated with phenytoin and was able to complete her adjuvant chemotherapy with nab-paclitaxel without further events. Her condition was neurologically stable without phenytoin for the next 6 months. Use of the Naranjo adverse drug reaction probability scale indicated a possible association (score of 3) between the delayed seizure and paclitaxel or its solvent, Cremophor EL. Clinicians should be aware of the potential for seizure activity in patients who receive paclitaxel formulated with Cremophor EL.

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Section: Discussionmentioning

confidence: 99%

Delayed Seizure Associated with Paclitaxel‐Cremophor EL in a Patient with Early‐Stage Breast Cancer

O’Connor

Kossoff

2009

Pharmacotherapy

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“…By contrast, the toxicity of dose-dense taxane seemed to be well tolerated because of absence of relevant toxicity [94]. A pharmacokinetic study revealed that paclitaxel can be administered weekly at doses of 110 mg/m 2 without interruption, while neutropenia precluded scheduled administration of doses ≥ 130 mg/m 2 [94,117]. In theory, weekly dose-dense paclitaxel provided the better cytotoxicity to tumors, through more sustained exposure, limiting the emergence of tumors resistant to chemotherapy, enhancing the apoptotic and antiangiogenic effect, and improving the therapeutic index [94,[118][119][120], although the single use of dose-dense paclitaxel for the first-line chemotherapy treatment of patients with ETOC seemed to be not approved by clinical trials [109,110].…”

Section: Rationale Of Dose-dense Therapymentioning

confidence: 99%

Comparing Paclitaxel–Carboplatin with Paclitaxel–Cisplatin as the Front-Line Chemotherapy for Patients with FIGO IIIC Serous-Type Tubo-Ovarian Cancer

Huang

Chen

Lee

et al. 2020

IJERPH

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The use of weekly chemotherapy for the treatment of patients with advanced-stage serous-type epithelial Tubo-ovarian cancer (ETOC), and primary peritoneal serous carcinoma (PPSC) is acceptable as the front-line postoperative chemotherapy after primary cytoreductive surgery (PCS). The main component of dose-dense chemotherapy is weekly paclitaxel (80 mg/m2), but it would be interesting to know what is the difference between combination of triweekly cisplatin (20 mg/m2) or triweekly carboplatin (carboplatin area under the curve 5-7 mg/mL per min [AUC 5-7]) in the dose-dense paclitaxel regimen. Therefore, we compared the outcomes of women with Gynecology and Obstetrics (FIGO) stage IIIC ETOC and PPSC treated with PCS and a subsequent combination of dose-dense weekly paclitaxel and triweekly cisplatin (paclitaxel–cisplatin) or triweekly carboplatin using AUC 5 (paclitaxel–carboplatin). Between January 2010 and December 2016, 40 women with International Federation of Gynecology and Obstetrics (FIGO) stage IIIC EOC, FTC, or PPSC were enrolled, including 18 treated with paclitaxel–cisplatin and the remaining 22 treated with paclitaxel–carboplatin. There were no statistically significant differences in disease characteristics of patients between two groups. Outcomes in paclitaxel–cisplatin group seemed to be little better than those in paclitaxel–carboplatin (median progression-free survival [PFS] 30 versus 25 months as well as median overall survival [OS] 58.5 versus 55.0 months); however, neither reached a statistically significant difference. In terms of adverse events (AEs), patients in paclitaxel–carboplatin group had more AEs, with a higher risk of neutropenia and grade 3/4 neutropenia, and the need for a longer period to complete the front-line chemotherapy, and the latter was associated with worse outcome for patients. We found that a period between the first-time chemotherapy to the last dose (6 cycles) of chemotherapy >21 weeks was associated with a worse prognosis in patients compared to that ≤21 weeks, with hazard ratio (HR) of 81.24 for PFS and 9.57 for OS. As predicted, suboptimal debulking surgery (>1 cm) also contributed to a worse outcome than optimal debulking surgery (≤1 cm) with HR of 14.38 for PFS and 11.83 for OS. Based on the aforementioned findings, both regimens were feasible and effective, but maximal efforts should be made to achieve optimal debulking surgery and following the on-schedule administration of dose-dense weekly paclitaxel plus triweekly platinum compounds. Randomized trials validating the findings are warranted.

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“…This neuropathy is characterized by intense pain in the extremities, tingling, numbness (paraesthesia), a paradoxical burning pain in response to cold temperatures, and loss of proprioception (Briasoulis et al, 2002, Dina et al, 2001, Dougherty et al, 2004, Forsyth et al, 1997, Lipton et al, 1989, Wiernik et al, 1987). Neurophysiologic examination of patients with paclitaxel-induced peripheral neuropathy reveals a decrease in sensory nerve conduction velocity and compound action potential amplitude (Augusto et al, 2008, Dougherty et al, 2004, Sahenk et al, 1994).…”

Section: Introductionmentioning

confidence: 99%

Vasodilatation in the rat dorsal hindpaw induced by activation of sensory neurons is reduced by paclitaxel

et al. 2011

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Peripheral neuropathy is a major side effect following treatment with the cancer chemotherapeutic drug paclitaxel. Whether paclitaxel-induced peripheral neuropathy is secondary to altered function of small diameter sensory neurons remains controversial. To ascertain whether the function of the small diameter sensory neurons was altered following systemic administration of paclitaxel, we injected male Sprague Dawley rats with 1 mg/kg paclitaxel every other day for a total of four doses and examined vasodilatation in the hindpaw at day 14 as an indirect measure of calcitonin gene related peptide (CGRP) release. In paclitaxel-treated rats, the vasodilatation induced by either intradermal injection of capsaicin into the hindpaw or electrical stimulation of the sciatic nerve was significantly attenuated in comparison to vehicle-injected animals. Paclitaxel treatment, however, did not affect direct vasodilatation induced by intradermal injection of methacholine or CGRP, demonstrating that the blood vessels' ability to dilate was intact. Paclitaxel treatment did not alter the compound action potentials or conduction velocity of C-fibers. The stimulated release of CGRP from the central terminals in the spinal cord was not altered in paclitaxel-injected animals. These results suggest that paclitaxel affects the peripheral endings of sensory neurons to alter transmitter release, and this may contribute to the symptoms seen in neuropathy.

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Pharmacodynamics of non-break weekly paclitaxel (Taxol) and pharmacokinetics of Cremophor-EL vehicle: results of a dose-escalation study

Cited by 18 publications

References 24 publications

Delayed Seizure Associated with Paclitaxel‐Cremophor EL in a Patient with Early‐Stage Breast Cancer

Delayed Seizure Associated with Paclitaxel‐Cremophor EL in a Patient with Early‐Stage Breast Cancer

Comparing Paclitaxel–Carboplatin with Paclitaxel–Cisplatin as the Front-Line Chemotherapy for Patients with FIGO IIIC Serous-Type Tubo-Ovarian Cancer

Vasodilatation in the rat dorsal hindpaw induced by activation of sensory neurons is reduced by paclitaxel

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