taxane and Drug-Hypersensitivity

Taxanes are an important class of antineoplastic agents used in the treatment of a wide variety of cancers. However, paclitaxel and docetaxel, which are the most commonly used taxanes, elicit immediate hypersensitivity reactions (HSRs) in 5% to 10% of patients. Almost all patients that experience these reactions can be safely re-exposed to taxanes either through desensitization or challenge. This article describes the clinical presentation, diagnosis, and management of HSRs to taxanes and discusses the different options for their safe readministration.

Topics: Allergens; Animals; Antineoplastic Agents; Bridged-Ring Compounds; Desensitization, Immunologic; Docetaxel; Drug Hypersensitivity; Humans; Paclitaxel; Skin Tests; Taxoids

Hypersensitivity reactions to chemotherapy drugs pose significant difficulties in management, especially when no suitable alternative is available or acceptable and delay in continuation of treatment may be life-threatening. Such reactions may be IgE- or non-IgE-mediated and have varied manifestations. Timely recognition and treatment of life-threatening hypersensitivity reactions are essential. Identification of patients at high risk of developing hypersensitivity reactions allows risk stratification to guide clinical decision-making. Skin testing for carboplatin hypersensitivity has good predictive value but is not yet established for oxaliplatin and taxane hypersensitivity. Rapid desensitisation may be considered if no suitable alternative drug is available. Available protocols have shown good safety and efficacy but must be performed in an appropriate setting with adequate monitoring. There are many avenues for research into the utility of skin testing for other chemotherapy agents as well as in vitro tests.

Topics: Antineoplastic Agents; Bridged-Ring Compounds; Cisplatin; Desensitization, Immunologic; Dose-Response Relationship, Immunologic; Drug Hypersensitivity; Humans; Referral and Consultation; Risk Factors; Skin Tests; Taxoids; Treatment Outcome

The two commercially available taxanes (paclitaxel and docetaxel) are widely employed in standard oncologic practice. Toxicity of the agents includes bone marrow suppression (principally neutropenia), complete alopecia, and hypersensitivity reactions. While both drugs can cause neurotoxicity and myalgias/arthralgias, this is a greater clinical concern with paclitaxel. Docetaxel can be associated with the development of significant fluid retention (e.g., edema, ascites, pleural effusions), the incidence and severity of which appear to be limited by prophylactic treatment with corticosteroids both before and after each treatment. If patients are monitored closely (e.g., for hypersensitivity reactions, bone marrow suppression) the taxanes have a favorable side effect profile, and it is currently uncommon for treatment to be discontinued because of the development of excessive toxicity.

Topics: Antineoplastic Agents, Phytogenic; Arthralgia; Bridged-Ring Compounds; Docetaxel; Drug Hypersensitivity; Humans; Neutropenia; Paclitaxel; Peripheral Nervous System Diseases; Taxoids; Thrombocytopenia

Patients receiving taxanes are at risk for developing hypersensitivity reactions (HSRs) primarily during first and second lifetime exposures. Immediate HSRs require emergency care and can interfere with the continuation of preferred treatment. Although different approaches to slow titration have been used successfully for desensitization after HSR occurrence, there are no standardized recommendations for taxane titration to prevent HSRs.. To determine if a gradual, three-step infusion rate titration decreases the rate and severity of immediate HSRs during first and second lifetime exposures to paclitaxel and docetaxel.. We used a prospective, interventional design with historical comparisons to evaluate a sample of 222 first and second lifetime exposure paclitaxel and docetaxel infusions. The intervention was a three-step infusion rate titration provided at the initiation of first and second lifetime exposures. Ninety-nine titrated infusions were compared with 123 historical records of nontitrated infusions.. Compared with the nontitrated group (n = 123), the titrated group (n = 99) had significantly less HSRs (19%. A standardized, three-step infusion rate titration prevented HSR occurrence. Significant issues affecting practice feasibility and sustainability were addressed.

Topics: Docetaxel; Drug Hypersensitivity; Epinephrine; Humans; Paclitaxel; Prospective Studies; Taxoids

We aimed to investigate the role of skin tests (ST) in the diagnosis of hypersensitivity reactions (HSRs) with platinum salts (PS) and taxane (TX) groups drugs and their reliability in patient management.. Patients' data who developed immediate HSR with PS and TX were recorded and ST was performed. The gradual challenge was applied to all patients with ST negative and grade 1-2 with the suspect drug.. In total, the data of 104 patients (74 with PS, 30 with TX) who developed HSR against PS and TX were shared. The gradual challenge was applied to 72 ST negative and grade 1-2 patients (46 PS group, 26 TX group). The gradual challenge was negative in 39 patients in the PS group and 23 patients in the Tx group. The negative predictive value (NPV) for PS was 83% and NPV for TX was 88%. We found significantly higher skin test positivity in patients with PS and TX and grade 3 HSR (. We found very high NPV values for PS and TX. We found that the gradual challenge applied to patients with negative skin tests is reliable if Grade 3 HSR is not observed and with this approach, unnecessary desensitization processes and/or drug alterations can be avoided.

Topics: Desensitization, Immunologic; Drug Hypersensitivity; Humans; Platinum; Reproducibility of Results; Salts; Skin Tests; Taxoids

Hypersensitivity reactions to antineoplastic agents may lead to discontinuation of first-line treatments. Rapid drug desensitization (RDD) allows for a safe reintroduction in patients who are allergic to them.. To evaluate the safety and efficacy of the Brigham and Women's Hospital's 12-step RDD in a Portuguese patient population with cancer and to identify markers associated with breakthrough reactions (BTRs) to platins.. We conducted a retrospective review of desensitizations undertaken at the Immunoallergology Day-Care Unit of the Santa Maria Hospital in Lisbon, Portugal, from July 2008 to July 2019. Adult patients with cancer and with immediate hypersensitivity reactions were included. Skin testing was performed to platins, trastuzumab, and cetuximab. The 12-step protocol was used for most patients, and a shorter protocol was used in 9 patients who were taxane-reactive to resume regular infusions.. A total of 1471 RDDs were performed in 272 patients to 136 platins, 124 taxanes, 13 monoclonal antibodies, and 10 other drugs. Skin test results were positive in 127 of patients who were platin-reactive (95.3%) and negative in patients who were cetuximab- and trastuzumab-reactive. There were 141 BTRs during RDD (9.6% of infusions), 79.4% induced by platins with the majority having mild reactions (68.8%). There were 8 patients who were paclitaxel-reactive, and who completed a shorter protocol and resumed regular infusions successfully. Multiple platin infusions (cutoff: ≥10) and total immunoglobulin E greater than or equal to 100 U/mL were identified as independent risk factors for BTRs in patients who were platin-reactive.. This large single-center study confirmed the safety and efficacy of the 12-step RDD protocol in a diverse cancer population, providing evidence of its universal applications. Total immunoglobulin E is a potentially useful biomarker to identify high-risk patients who are platin-reactive.

Topics: Adult; Aged; Aged, 80 and over; Antibodies, Monoclonal; Antineoplastic Agents; Bridged-Ring Compounds; Cetuximab; Desensitization, Immunologic; Drug Hypersensitivity; Female; Humans; Immunoglobulin E; Male; Middle Aged; Neoplasms; Outpatients; Paclitaxel; Portugal; Retrospective Studies; Risk Factors; Skin Tests; Taxoids; Trastuzumab; Young Adult

Premedication with dexamethasone is an essential part of the prevention of hypersensitivity reaction (HSR) associated with taxane administration. However, the possibility of stopping dexamethasone premedication has been investigated in previous studies to reduce the steroid's adverse events; however, either the result or the particular protocol was limited. Thus, our study aimed to evaluate the incidence of HSR after dexamethasone premedication discontinuation after lack of HSR in two previous weekly paclitaxel infusions.. Early breast cancer patients who received adjuvant weekly paclitaxel in a retrospective cohort from January 2012 through February 2016 at the King Chulalongkorn Memorial Hospital were reviewed. All patients received a standard premedication protocol prior to the first and second paclitaxel infusion. Dexamethasone was omitted in later cycles in all patients who did not undergo infusion HSR. Patients who developed HSR during the first or second cycles of paclitaxel infusion were excluded. The incidence of HSR during the later cycle of paclitaxel administration and factors associated with this adverse reaction were collected.. Eighty-one of 85 patients who did not undergo infusion HSR after 2 cycles of weekly paclitaxel administration were retrospectively reviewed. The median age was 51 years (range 27-74 years). Only 16% of the patients had a BMI greater than 30 kg/m. Withholding dexamethasone premedication in non-experiencing HSR patients after two previous cycles of weekly paclitaxel administration was safe and did not impact the higher incidence of HSR. A discontinuing dexamethasone protocol should be recommended generally in these patients, especially those with a high risk for steroid-induced side effects.

Topics: Adult; Aged; Breast Neoplasms; Bridged-Ring Compounds; Cohort Studies; Dexamethasone; Drug Hypersensitivity; Drug-Related Side Effects and Adverse Reactions; Female; Humans; Incidence; Middle Aged; Paclitaxel; Premedication; Retrospective Studies; Taxoids

Chemotherapy-related hypersensitivity reaction seems to be problematic in the safe management of chemotherapy. In this study we investigated chemotherapy-related hypersensitivity reaction in patients with gynecologic malignancy.. Between January 2009 and December 2010, we examined hypersensitivity reaction (> or = grade2) using the Common Terminology Criteria for Adverse Events (CTCAE) v.4.0. We analyzed the incidence, clinical features, management, and outcome.. We administered over 1,057 infusions (24 regimens) to 205 patients. We found a total of four hypersensitivity reactions (> or = grade 2) cases (carboplatin: 2; nedaplatin: 1; docetaxel: 1). Signs and symptoms were varied. In two cases, the same regimen was rechallenged by using anti-allergic drugs. The docetaxel case was successful. The carboplatin case was not successful.. Chemotherapy-related hypersensitivity reaction (> or = grade2) does not occur frequently. In the case of platinum, especially, carboplatin, re-administering after hypersensitivity reaction should be done carefully though platinum is a key drug in patients with gynecologic malignancies.

Topics: Adult; Aged; Aged, 80 and over; Antineoplastic Agents; Bridged-Ring Compounds; Carboplatin; Drug Hypersensitivity; Female; Genital Neoplasms, Female; Humans; Japan; Middle Aged; Organoplatinum Compounds; Retrospective Studies; Taxoids; Young Adult