Intravenous-to-Oral Switch in Anticancer Chemotherapy: A Focus on Docetaxel and Paclitaxel

Koolen, Stijn L.W.; Beijnen, Jos H.; Schellens, Jan H.M.

doi:10.1038/clpt.2009.233

Cited by 47 publications

(48 citation statements)

References 32 publications

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“…Another randomized study assessing the strategy of inhibiting P-gp was ineffective but provided some glimpse at Pgp contribution to protecting against taxane central nervous system toxicity (43)(44)(45)(46)(47).…”

Section: Resultsmentioning

confidence: 99%

Defining Risks of Taxane Neuropathy: Insights from Randomized Clinical Trials

Kudlowitz

2013

Clinical Cancer Research

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Sensory neuropathy is a common but difficult to quantify complication encountered during treatment of various cancers with taxane-containing regimens. Docetaxel, paclitaxel, and its nanoparticle albuminbound formulation have been extensively studied in randomized clinical trials comparing various dose and schedules for the treatment of breast, lung, and ovarian cancers. This review highlights differences in extent of severe neuropathies encountered in such randomized trials and seeks to draw conclusions in terms of known pharmacologic factors that may lead to neuropathy. This basic knowledge provides an essential background for exploring pharmacogenomic differences among patients in relation to their susceptibility of developing severe manifestations. In addition, the differences highlighted may lead to greater insight into drug and basic host factors (such as age, sex, and ethnicity) contributing to axonal injury from taxanes.

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Section: Resultsmentioning

confidence: 99%

Defining Risks of Taxane Neuropathy: Insights from Randomized Clinical Trials

Kudlowitz

2013

Clinical Cancer Research

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“…The efficacy of a once-weekly small dose regimen is comparable to a large dose given once every 3 weeks yet with a lower hematologic toxicity profile (1,2). However, docetaxel administration is associated with unpredictable and hypersensitive reactions, due, in part, to polysorbate 80, the nonionic surfactant needed for solubilization (3).…”

Section: Introductionmentioning

confidence: 99%

High Plasma Levels and Effective Lymphatic Uptake of Docetaxel in an Orally Available Nanotransporter Formulation

et al. 2011

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Docetaxel, an efficient chemotherapeutic drug, exhibits low and variable oral bioavailability due to the active efflux by P-glycoprotein (P-gp) and more so to CYP3A4 gut metabolism. Using a spray-drying technique, docetaxel was incorporated in PLGA [poly(lactic-co-glycolic acid)] nanocapsules (NC) which were embedded in entero-coated microparticles. An oral administration of the NC formulation elicited a higher absolute bioavailability than both a docetaxel solution (276%) and a free docetaxel NC formulation (400%) injected intravenously, a 5-mg/kg dose. The batches (B) I and II NC formulations elicited C max values that were 1,735% and 2,254%, respectively; higher than the C max value of the oral docetaxel solution combined with blank microparticles, a 10-mg/kg dose. No significant difference in AUC (area under curve) was observed between the batches. These unexpected results can be explained only if the pharmacokinetics of docetaxel had been modified. It was shown that NCs released from the microparticles penetrated the enterocytes, bypassing P-gp; apparently circumventing gut metabolism and accumulating within the lymphatic system from where both intact or biodegraded NCs and free docetaxel were progressively released into the circulation as plausibly supported by the fluorescent imaging results. Furthermore, the circulating docetaxel in plasma was unencapsulated and circulated either in free form or bound to albumin. Both free docetaxel NCs and microparticles exhibited in vitro efficacy on WRC 256 cells suggesting that the activity of docetaxel was not altered. This delivery concept has potential for clinical translation, perhaps allowing docetaxel chemotherapy to be switched from intravenous to oral delivery. Cancer Res; 71(8); 3018-28. Ó2011 AACR.

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“…Different inhibitors were used such as OC144-093 (a P-gpinhibitor), cyclosporine (a dual inhibitor of P-gp and CYP3A4) and ritonavir (CYP3A4 inhibitor), which have shown increased oral bioavailability of docetaxel [170] . In line with this observation, which indicates that CYP3A4 is the major determinant of the low oral bioavailability of docetaxel, it seems rational that future trials will continue with oral docetaxel in combination with ritonavir [167,170] .…”

Section: Increase Oral Bioavailability By Increasing Gut Epithelial Umentioning

confidence: 70%

“…These studies have shown promising results, but long-term oral use of cyclosporine might be complicated by immunosuppressive effects. Therefore, other inhibitors might replace cyclosporine such as elacridar (GF120918) or HM30181, respectively [167,168] . Being a P-gp substrate in addition to the encouraging results of oral paclitaxel, preclinical studies were also initiated with another taxane, namely docetaxel [169] .…”

Section: Increase Oral Bioavailability By Increasing Gut Epithelial Umentioning

confidence: 99%

How to overcome ATP-binding cassette drug efflux transporter-mediated drug resistance?

Jaramillo¹,

Saig²,

Cloos³

et al. 2018

CDR

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P-glycoprotein (ABCB1), multidrug resistance protein-1 (ABCC1) and breast cancer resistance protein (ABCG2) belong to the ATP-binding cassette (ABC) superfamily of proteins that play an important physiological role in protection of the body from toxic xenobiotics and endogenous metabolites. Beyond this, these transporters determine the toxicity profile of many drugs, and confer multidrug resistance (MDR) in cancer cells associated with a poor treatment outcome of cancer patients.It has long been hypothesized that inhibition of ABC drug efflux transporters will increase drug accumulation and thereby overcome MDR, but until now no approved inhibitor of these transporters is available in the clinic. In this review we present molecular strategies to overcome this type of drug resistance and discuss for each of these strategies their promising value or indicate underlying reasons for their limited success.

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Intravenous-to-Oral Switch in Anticancer Chemotherapy: A Focus on Docetaxel and Paclitaxel

Cited by 47 publications

References 32 publications

Defining Risks of Taxane Neuropathy: Insights from Randomized Clinical Trials

Defining Risks of Taxane Neuropathy: Insights from Randomized Clinical Trials

High Plasma Levels and Effective Lymphatic Uptake of Docetaxel in an Orally Available Nanotransporter Formulation

How to overcome ATP-binding cassette drug efflux transporter-mediated drug resistance?

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