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EDITORIAL
Year : 2018  |  Volume : 1  |  Issue : 2  |  Page : 116-117

Modified dose dexamethasone premedication for paclitaxel use


Department of Medical Oncology, Tata Memorial Hospital, Mumbai, Maharashtra, India

Date of Web Publication17-May-2019

Correspondence Address:
Sharada Mailankody
Department of Medical Oncology, Tata Memorial Hospital, Parel, Mumbai - 400 012, Maharashtra
India
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Source of Support: None, Conflict of Interest: None


DOI: 10.4103/CRST.CRST_13_19

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How to cite this article:
Mailankody S. Modified dose dexamethasone premedication for paclitaxel use. Cancer Res Stat Treat 2018;1:116-7

How to cite this URL:
Mailankody S. Modified dose dexamethasone premedication for paclitaxel use. Cancer Res Stat Treat [serial online] 2018 [cited 2019 Aug 24];1:116-7. Available from: http://www.crstonline.com/text.asp?2018/1/2/116/258531



Paclitaxel is an antimicrotubule agent that promotes the assembly of microtubules from tubulin dimers and stabilizes microtubules by preventing depolymerization, thus acting as an antimitotic agent. Paclitaxel is one of the most widely used chemotherapeutic agents in oncological practice. It is utilized in gynecological, breast, head and neck, and lung malignancies. Conventional paclitaxel is formulated in a 50% ethanol and 50% polyethoxylated castor oil solution, Cremophor EL.[1] Without premedication, infusion of paclitaxel results in 30% incidence of infusion-related reactions and severe anaphylactic reactions in 2%–4%.[2] The current recommendation for premedication before paclitaxel use consists of dexamethasone 20 mg orally (PO) administered approximately 12 and 6 hours before paclitaxel, diphenhydramine (or its equivalent) 50 mg intravenous (I.V.) 30–60 min before paclitaxel, and cimetidine (300 mg) or ranitidine (50 mg) I.V. 30–60 min before paclitaxel.[1] Although this is the recommended schedule, trials have attempted to bring down the doses and change to a more convenient dosing schedule.[3],[4] The use of a single premedication dose of dexamethasone 20 mg I.V. has also been studied in patients receiving taxanes.[5],[6] This dosing schedule is more convenient and decreases the pill burden for the patient.

The study published in this edition of the journal by Noronha et al. on paclitaxel hypersensitivity reactions (HSRs) represents a real-world report of the use of the modified dexamethasone premedication regimen in Indian patients.[7] This was a prospective, observational cohort study from a tertiary care center in India which reported the outcomes of the modified dexamethasone premedication regimen in 310 patients who received 495 cycles of paclitaxel-based chemotherapy, including 256 patients who were paclitaxel-naive. This cohort included patients with different malignancies such as carcinoma breast, carcinoma ovary/endometrium, carcinoma cervix, carcinoma esophagus, carcinoma lung, carcinoma head and neck, and urologic malignancies. The original brand paclitaxel was used in 268 cycles (54.1%). The doses of dexamethasone, however, varied across the patients with 8 mg I.V. and 20 mg I.V. being the most common dosing schedules. The reported incidence of HSR was 1.6%, with severe HSR in 1.2%. This is comparable to the reported HSR rates with conventional premedication.

Although the modified dexamethasone premedication schedule is widely practiced in India, we do not have reports of the incidence of HSR with this regimen. This observational study helps confirm that the modified single-dose dexamethasone I.V. regimen is a feasible treatment option with no increase in the rates of HSR. This is particularly important in a country like India where many of the patients may not comply with the 'night-before' dose of dexamethasone which may lead to unnecessary postponement of scheduled chemotherapy. Dexamethasone may also cause adverse effects such as hyperglycemia and insomnia. In this era of immunotherapy co-administration with chemotherapy, this modified premedication schedule might be more relevant. There are alternative preparations of paclitaxel such as nab-paclitaxel and Nanoxel™ where the steroid premedication can be avoided.[8] However, due to various constraints, it may not be possible to use these preparations routinely. Also notable is the fact that in this study, nearly half of the patients received only 8 mg I.V. dexamethasone premedication. HSRs may lead to an increased duration of hospitalization, need for change in the formulation of paclitaxel, or interruption in chemotherapy schedules. This may adversely impact cancer outcomes and cost of treatment. This study hence represents confirmation of the feasibility of reduced dose dexamethasone regimen with paclitaxel. Further studies are required to know the optimum premedication schedule and the possibility of further dose reductions.



 
  References Top

1.
Paclitaxel injection. Available from: https://www.accessdata.fda.gov/drugsatfda_docs/label/2011/020262s049lbl.pdf. [Last accessed on 31 Jan 2019].  Back to cited text no. 1
    
2.
Shepherd GM. Hypersensitivity reactions to chemotherapeutic drugs. Clin Rev Allergy Immunol 2003;24:253-62.  Back to cited text no. 2
    
3.
Kwon JS, Elit L, Finn M, Hirte H, Mazurka J, Moens F, et al. Acomparison of two prophylactic regimens for hypersensitivity reactions to paclitaxel. Gynecol Oncol 2002;84:420-5.  Back to cited text no. 3
    
4.
Rosenberg P, Andersson H, Boman K, Ridderheim M, Sorbe B, Puistola U, et al. Randomized trial of single agent paclitaxel given weekly versus every three weeks and with peroral versus intravenous steroid premedication to patients with ovarian cancer previously treated with platinum. Acta Oncol 2002;41:418-24.  Back to cited text no. 4
    
5.
Chouhan JD, Herrington JD. Single premedication dose of dexamethasone 20 mg IV before docetaxel administration. J Oncol Pharm Pract 2011;17:155-9.  Back to cited text no. 5
    
6.
Picard M, Castells MC. Re-visiting hypersensitivity reactions to taxanes: A Comprehensive review. Clin Rev Allergy Immunol 2015;49:177-91.  Back to cited text no. 6
    
7.
Noronha V, Enting D, Ravi T, Joshi A, Patil VM, Prabhash K. Hypersensitivity reactions to paclitaxel with a modified dexamethasone intravenous premedication regimen. Cancer Res Stat Treat 2018;1:78-83.  Back to cited text no. 7
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8.
Rajappa S, Joshi A, Doval DC, Batra U, Rajendranath R, Deo A, et al. Novel formulations of docetaxel, paclitaxel and doxorubicin in the management of metastatic breast cancer. Oncol Lett 2018;16:3757-69.  Back to cited text no. 8
    




 

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