Infusion reactions

Monoclonal antibody treatment, which is one of the most promising molecular targeting cancer therapies, has recently become indispensable for the treatment of cancer due to its effectiveness and fewer side effects. Infusion reactions, which are similar to hypersensitivity or allergic reactions, are the generic term for the acute characteristic harmful reactions commonly associated with monoclonal antibody treatment. Those typically occur within the first 2 hours of the first infusion and are generally mild-to-moderate reactions which can be managed by either temporary interruption of infusion or administration of supportive care including corticosteroids, oxygen, or intravenous fluids. However, there are sometimes severe or life-threatening reactions, thus indicating the importance of closely observing the patient following the monoclonal antibody treatment. It is quite important that the entire medical staff understands the practical information regarding the timing and prevention or management of infusion reactions. In addition, it is also necessary to establish a system for prompt management of infusion reactions. Furthermore, sufficient information must be provided to the patient regarding infusion reactions.     

奥沙利铂致过敏反应6例回顾性分析

目的:探讨奥沙利铂致过敏反应的发生机制、临床表现及其预防和处理对策。方法:对6例奥沙利铂过敏患者的临床资料进行回顾性分析,并结合相关文献进行讨论。结果:1例患者自第2周期出现发热,体温最高38℃,无其他不适,1例患者在第10周期出现发热症状,并于第15周期出现Ⅱ度过敏反应,2例患者主要表现为全身瘙痒、皮疹,1例患者主要表现为腹痛,1例患者出现过敏性休克症状。结论:奥沙利铂过敏临床并不罕见,患者出现过敏反应的临床表现及严重程度个体差异性较大,部分患者出现严重过敏反应,临床上需引起足够重视。     

Hypersensitivity reactions from antineoplastic agents

Antitumor drugs, like any other therapeutic agent, have the ability to incite hypersensitivity reactions. Certain of such drugs (e.g., L-asparaginase and taxol) cause reactions with great enough frequency to be a major impediment to repetitive use of the drug. Very few antitumor drugs have not had at least one reported instance of causing a hypersensitivity reaction. Most reactions are of the type I category in the Gell and Coombs classification, but there also are instances of types II, III, and IV reactions caused by many of the antineoplastic agents.The mechanisms of such reactions have been poorly evaluated in many reports. In analyzing a hypersensitivity reaction in a patient being treated for cancer, one should document that the antitumor drug is indecd the offender, and not an ancillary drug or a formulation product that is being used. There are many tests that evaluate the source and mechanism of hypersensitivity reactions. This article reviews the current information on hypersensitivity reactions to antincoplastic drugs and provides a logical approach for their assessment.     

Amifostine-induced toxic epidermal necrolysis during radiotherapy: a case report

Amifostine is a phosphorylated aminothiol prodrug that can selectively protect normal tissues against the toxic effects of chemotherapy and radiotherapy. In clinical use amifostine is well tolerated and may rarely cause allergic reactions. Stevens-Johnson syndrome (SJS) and toxic epidermal necrolysis (TEN) are two closely related entities that present with severe acute mucocutaneous reactions most often triggered by drugs. There are only two case reports related to the use of amifostine during radiotherapy, one case with SJS and the other with SJS-TEN overlap. In this paper, a case with amifostine-induced TEN during radiotherapy is presented.     

Safety of cisplatin after severe hypersensitivity reactions to carboplatin in patients with recurrent ovarian carcinoma

BACKGROUND: Carboplatin is a milestone drug against ovarian carcinoma; it is used both in front-line and second-line chemotherapy. Hypersensitivity reactions to carboplatin may occur during the treatment as salvage therapy. The purpose of this study was to describe the feasibility of the replacing of carboplatin with cisplatin in patients presenting with severe hypersensitivity reactions to carboplatin. PATIENTS AND METHODS: Ten consecutive patients with platinum-sensitive, recurrent ovarian carcinoma, presenting with moderate/severe hypersensitivity reactions to carboplatin were treated with cisplatin 60 mg/m2 from January 2000 to December 2002. Hypersensitivity reactions consisted of respiratory distress (chest tightness, wheezing, dyspnea), urticaria/erythema with tachycardia, facial swelling and hypotension. RESULTS: The total number of cisplatin cycles given was 44 (range 2-5). The treatment with cisplatin was generally well tolerated. No serious allergic reactions occurred. A mild allergic reaction was recorded (urticaria) in only one case, after one cycle of cisplatin, and the patient was not rechallenged because of progressive disease. No reductions of chemotherapy doses were needed. CONCLUSION: To date, platinum-based regimens remain the most effective treatment in recurrent platinum-sensitive ovarian cancer with a high rate of objective responses. Although our experience is limited, we suggest that, under anesthesiologic surveillance and providing immunologic blockade, the replacement of carboplatin salvage therapy with cisplatin can be considered a safe therapeutic strategy in patients who cannot continue carboplatin due to allergic reactions.     

Evaluation of short-time premedication with d-chlorpheniramine maleate injection for paclitaxel-induced hypersensitivity reaction

Paclitaxel(referred to hereinafter as PTX )is used in ovarian cancer, non-small cell lung cancer, breast cancer, gastric cancer, and endometrial cancer with positive treatment result reports. However, severe allergic reactions such as decreases in blood pressure and impaired breathing occur with relatively high frequency. For the prevention of such allergic reactions, administration of a premedication composed of the three components, dexamethasone sodium phosphate injection, diphenhydramine hydrochloride tablet, and ranitidine hydrochloride injection solution(or injectable famodine), is advised in the appended documentation. Administration is difficult because, among these three components, only diphenhydramine hydrochloride is administered orally and thus must be provided through the internal medicine department. Particularly when this combined dosage is administered as outpatient chemotherapy, the doctor must prescribe diphenhydramine hydrochloride tablets, and the patient must not forget to bring them on the day in which chemotherapy is administered. Also, checks by the medical staff such as pharmacists and nurses are required, complicating the administration of this therapy further. Taking this situation into consideration, our hospital uses a short-time premedication method wherein d-Chlorpheniramine Maleate injections are substituted for diphenhydramine hydrochloride tablets, and the time required for premedication is reduced to 15 minutes. This study investigated the allergic reaction ratio to consider the safety and usefulness of the short-time premedication method used at our hospital. The chemotherapy regimens conducted for the subject patients were 9 cases of PTX+CBDCA, 6 cases of biweekly- PTX, and 5 cases of weekly-PTX. A total of 67 PTX injections were given, 15 of them being first-time administrations. The ratio of allergic/hypersensitivity reactions was 10.0%(2 cases in 20). The short-time premedication method using d-Chlorpheniramine Maleate injections did not display a significant difference from the conventional method used for prevention of allergic and hypersensitivity reactions. Also, since this method of medication proves useful for is easy for the patient, reduces treatment time, is safe, economical, and helps reduce the workload of doctors, pharmacists, and nurses.     

Cutaneous toxicities of cancer therapy

This review highlights the cutaneous side effects associated with the administration of chemotherapy and discusses the management of these conditions. Rapidly growing cells are the targets of chemotherapy, so the skin, hair follicles, and nail matrix are frequently affected by chemotherapy. Chemotherapy skin reactions are more likely toxic than allergic reactions. The most common cutaneous reactions are alopecia, hyperpigmentation, hand--foot syndrome, radiation recall, hypersensitivity, extravasation injuries, and nail dystrophies. While these side effects are generally not life threatening, they can be a source of significant distress to patients, especially alopecia.     

A case of Hodgkin's disease exhibiting erythrodermia probably due to allergic reaction to vinca alkaloids

A 58-year-old man with Hodgkin's disease exhibited erythrodermia due to allergic reaction to vincristine sulfate (VCR) and vindesine sulfate (VDS). However, chemotherapy could be continued by changing VCR and VDS to etoposide without allergic symptom. Clinical observation strongly suggested that erythrodermia was due to the use of vinca alkaloids in this patient. Hematological and neurological side effects have been well known for VDS and VCR, but erythrodermia has not yet been reported as being caused by these agents. It is often difficult to differentiate drugs as a cause of an allergic reaction when several drugs are used together. Therefore, it is important to collect all the cases showing the effects of drugs.     

Carboplatin hypersensitivity reactions: a single institution experience

Carboplatin-related hypersensitivity reactions, frequently encountered in the heavily pretreated subpopulation of patients with gynecologic malignancies, can be severe and even potentially lethal-precluding these patients from an effective salvage treatment. We describe our experience in the management of such reactions and the application of a pretreatment protocol with corticosteroids, antihistamines and a slow infusion rate in order to safely re-administer carboplatin to the above patients. From 1998 to 2004, twenty patients developed an allergic reaction to carboplatin. Sixteen of them (80%) suffered from ovarian cancer. Upon resolution of the acute reaction, thirteen patients were pretreated according to our protocol and were re-exposed to carboplatin. Fifteen patients experienced the reaction during second-line carboplatin-based treatment and 5 patients after 3 or more regimens. Fifteen of the reactions (75%) were severe. Thirteen patients were re-treated with carboplatin after the application of our protocol, all of them successfully, even though 10 patients (77%) experienced minor symptoms during subsequent courses. On the contrary, only one of the 6 patients who were re-treated without the application of the protocol was able to receive further platinum-based treatment. In conclusion, pretreatment with corticosteroids, antihistamines and a slower infusion rate may make re-treatment possible in patients having experienced hypersensitivity to carboplatin.     

Hypersensitivity reactions related to oxaliplatin (OHP)

Patients treated with platinum compounds are subject to hypersensitivity reactions. Our study has highlighted the reactions related to oxaliplatin (OHP) infusion. One hundred and twenty-four patients affected by advanced colorectal cancer were treated with different schedules containing OHP, at the Institute of Haematology and Medical Oncology 'L. and A. Seragnoli' of Bologna and at the Medical Oncology Division of Livorno Hospital. Seventeen patients (13%) showed hypersensitivity reactions after a few minutes from the start of the OHP infusion. Usually, these reactions were seen after 2-17 exposures to OHP (Mean+/-s.e.: 9.4+/-1.07). No patient experienced allergic reactions at his/her first OHP infusion. Eight patients developed a mild reaction consisting of flushing and swelling of the face and hands, itching, sweating and lachrymation. The remaining nine patients showed a moderate-severe reaction with dyspnoea, wheezing, laryngospasm, psycho-motor agitation, tachycardia, precordial pain, diffuse erythema, itching and sweating. Six patients out of 17 were re-exposed to the drug with premedication of steroids and all except one developed the hypersensitivity reaction again. The cumulative dose, the time of exposure to OHP and the clinical features are variable and unpredictable. The risk of developing hypersensitivity reactions in patients treated with a short infusion of OHP cannot be underestimated.     

奥沙利铂过敏反应临床特征的研究

  目的  通过分析结直肠癌患者使用含奥沙利铂方案化疗前常规行地塞米松5 mg预处理后过敏反应发生的临床特征,为降低奥沙利铂过敏风险提供参考依据。  方法  回顾性分析2014年1月至2017年10月苏州大学附属常州肿瘤医院收治的242例含奥沙利铂方案化疗的结直肠癌患者临床资料,统计过敏反应发生率,对多项因素与过敏反应关系进行单因素分析,采用Logistic多因素回归模型分析影响过敏反应发生的独立因素,并探讨奥沙利铂过敏患者再次使用奥沙利铂治疗的结局。  结果  242例结直肠癌患者使用含奥沙利铂方案化疗前行地塞米松5 mg静推,发生过敏反应12例（4.9%）,均为Ⅰ型过敏反应,中位发生时间6（5.5~ 10.5）个周期,中位累积剂量895（716.5~1 075.0）mg。多因素分析提示存在无奥沙利铂间隔期为过敏反应的独立预测因素（P= 0.04）。其中3例奥沙利铂过敏患者接受药物预处理后再次使用奥沙利铂,1例（33.3%）成功完成治疗。  结论  奥沙利铂使用前常规行小剂量地塞米松预处理,过敏反应发生率低于文献报道,安全性高,无奥沙利铂间隔期患者再次使用该药过敏反应发生率明显提高,奥沙利铂过敏患者再次使用需谨慎。      

Hypersensitivity reactions to oxaliplatin: experience in a single institute.

BACKGROUND: A rising incidence of hypersensitivity reactions to oxaliplatin has been observed as a result of increasing clinical use. Epidemiological and clinical features of these reactions are reviewed. PATIENTS AND METHODS: Records of patients treated with a modified FOLFOX regimen from March 1999 to March 2004 were reviewed. RESULTS: One hundred and eighty patients were identified. Twenty-seven patients (15%) have been labelled as allergic to oxaliplatin, the proportion being higher among those receiving oxaliplatin in palliative second-line or above settings (19.6%) than in adjuvant or palliative first-line settings (10.2%). Some 2.2% of them developed grade 3-4 reactions. The reactions occurred after a mean (+/-SD) of 8.5 (+/-4.2) cycles (range 1-18). Among the 14 patients re-exposed to oxaliplatin, four (28.6%) developed hypersensitivity reaction, in two of whom (14.3%) reactions were grade 3-4 in severity. CONCLUSIONS: The risk of developing hypersensitivity reactions in patients receiving oxaliplatin should not be underestimated. The risk of developing potentially life-threatening hypersensitivity reactions should be explained to patients in the context of the potential benefits of such therapy. Patients receiving oxaliplatin infusion should be closely monitored. Once a patient develops hypersensitivity reaction to oxaliplatin, re-exposure should only be considered if the reaction is mild and there has been documented clinical benefit from previous doses of this agent.     

Hypersensitivity reactions to deoxycoformycin

Summary Deoxycoformycin (dCF) is a promising new antineoplastic agent in the treatment of lymphoid malignancies, particularly hairy cell leukemia (HCL). Skin toxicity in the form of a maculopapular eruption has previously been reported but has not clearly been associated with idiosyncratic reactions. We present five cases of dCF-related hypersensitivity reactions in which additional systemic manifestations indicated an allergic etiology. The value of dCF in treating lymphoid neoplasms suggests that further study of the treatment of these reactions is indicated.     

Cisplatin may be a valid alternative approach in ovarian carcinoma with carboplatin hypersensitivity. Report of three cases

Platinum-based therapy is considered the standard treatment for patients with advanced ovarian cancer. Carboplatin has a more favorable toxicity profile than cisplatin; however, hypersensitivity reactions to carboplatin have been reported occasionally. We reviewed 112 cases of ovarian cancer treated with carboplatin at our institute to identify the hypersensitivity reactions to this chemotherapeutic agent. Hypersensitivity reactions were documented in nine cases (8%). No deaths occurred, but the reactions were judged severe in three of the 112 patients (2.6%). In our own experience with patients showing idiosyncrasy to carboplatin we observed successful resolution after retreatment with cisplatin. Since patients who relapse after initial treatment with carboplatin often respond to it a second time, it is important to continue this treatment.     

An experimental biological test to diagnose hypersensitivity reactions to carboplatin: new horizons for an old problem

Carboplatin, a second-generation platinum compound, is a chemotherapeutic drug effective in many types of cancers. Its use is limited by the development of systemic allergic reactions in up to 30% of the cancer patients. Therefore, it is very important to make a correct diagnosis of true carboplatin allergy, for the crucial clinical implications. In this regard, no biological test is actually available to detect specific immunoglobulin E in the sera of patients allergic to carboplatin. We evaluated a new experimental biological test in patients with suspected immunoglobulin E-mediated reactions to carboplatin. Three patients with suspected hypersensitivity reactions to carboplatin underwent skin tests with an undiluted aliquot (10 mg/ml) of carboplatin preparation planned for infusion. Total serum immunoglobulin E and specific immunoglobulin E to the two platinum salts carboplatin and cisplatin were determined with the ImmunoCAP system (Phadia AB, Uppsala, Sweden). We detected specific immunoglobulin E to carboplatin in all three patients, whereas specific immunoglobulin E to cisplatin was observed in one patient. The positivity of specific immunoglobulin E against carboplatin in these three patients is a new and encouraging observation for the development of a new important instrument that can help clinicians in their therapeutic decisions, after a hypersensitivity reaction to a platinum salt.     

Carboplatin Hypersensitivity Reactions: A Single Institution Experience

Abstract

Carboplatin-related hypersensitivity reactions, frequently encountered in the heavily pretreated subpopulation of patients with gynecologic malignancies, can be severe and even potentially lethal—precluding these patients from an effective salvage treatment. We describe our experience in the management of such reactions and the application of a pretreatment protocol with corticosteroids, antihistamines and a slow infusion rate in order to safely re-administer carboplatin to the above patients.

From 1998 to 2004, twenty patients developed an allergic reaction to carboplatin. Sixteen of them (80%) suffered from ovarian cancer. Upon resolution of the acute reaction, thirteen patients were pretreated according to our protocol and were re-exposed to carboplatin.

Fifteen patients experienced the reaction during second-line carboplatin-based treatment and 5 patients after 3 or more regimens. Fifteen of the reactions (75%) were severe. Thirteen patients were re-treated with carboplatin after the application of our protocol, all of them successfully, even though 10 patients (77%) experienced minor symptoms during subsequent courses. On the contrary, only one of the 6 patients who were re-treated without the application of the protocol was able to receive further platinum-based treatment.

In conclusion, pretreatment with corticosteroids, antihistamines and a slower infusion rate may make re-treatment possible in patients having experienced hypersensitivity to carboplatin.     

DLST as a method for detecting TS-1-induced allergy

Drug-induced allergic adverse events including rash, interstitial pneumonia and hepatic injury are often observed in a few patients treated with anticancer drugs that are 5-FU derivatives, including TS-1. In patients suspected to be liable to develop allergic reactions, the drug-induced lymphocyte stimulation test (DLST), based on the (3)H-thymidine incorporation ratio into the DNA of lymphocytes derived from the patients, is generally employed to identify drugs that could induce allergy. In this case report, we conducted the DLST on 20 healthy volunteers without TS-1 treatment in order to obtain reference data on the evaluation of TS-1-induced allergy. Even though all 20 volunteers were healthy, there were 6 positive responses to the DLST. In view of the positive response to TS-1 in healthy volunteers undergoing the DLST, it is suggested that the DLST could show a false positive response through an intracellular function that accelerates incorporation of thymidine in the lymphocytes by the salvage pathway after inhibition of DNA de novo synthesis caused by 5-FU derivative anticancer, including TS-1. Therefore, such a positive response to the drugs is considered, in fact, to be false-positive in the DLST. In view of the occurrence of false-positive results, the possibility of drug-induced allergy in patients receiving TS-1 should be carefully evaluated using a combination of other clinical examinations.     

Amphotericin B deoxycholate (d-AMB) use in cases with febrile neutropenia and fungal infections: lower toxicity with suitable premedication

In spite of the development of new antifungal drugs, amphotericin B deoxycholate (d-AMB) remains the gold standard in the treatment of severe fungal infections in immunosuppressed hosts. However, d-AMB is a toxic drug, the most important dose-limiting toxicities being nephrotoxicity and infusion-related allergic reactions. Lipid and liposomal formulations of d-AMB have relatively lower toxicity and are considered alternative choices. However, the routine use of these formulations is limited by their higher cost. Using retrospective analysis, we explored the incidence of nephrotoxicity and allergic reactions requiring the cessation of conventional d-AMB in 113 cases treated with the drug. In contrast to knowledge in the relevant literature, we did not detect significant toxicity, which would have required discontinuation of the d-AMB treatment. Mean serum creatinine levels were 0.72 +/- 0.25 and 0.84 +/- 0.31 mg dl(-1) before and after therapy, respectively. Although the difference between creatinine levels before and after d-AMB is statistically significant, the creatinine level increased twofold in only eight cases. Mean serum potassium levels were 3.8 +/- 0.54 and 3.6 +/- 0.7 mmol l(-1) before and after d-AMB respectively. Potassium levels below 3 mmol l(-1) were found in 7 and 17 cases before and after d-AMB respectively. Potassium levels were statistically lower in cases with fungal mucositis. Severe infusion-related allergic reactions were observed in three cases. Antihistamine and corticosteroid were added to the treatment in these cases. With these findings, we can conclude that d-AMB is a tolerable, low cost drug which can be safely used provided there is suitable premedication and monitoring of blood urea nitrogen, serum potassium and magnesium levels.     

Hypersensitivity or development of antibodies to asparaginase does not impact treatment outcome of childhood acute lymphoblastic leukemia.

PURPOSE: Development of antibodies and hypersensitivity to asparaginase are common and may attenuate asparaginase effect. Our aim was to determine the relationship between antiasparaginase antibodies or hypersensitivity reactions and event-free survival (EFS). PATIENTS AND METHODS: One hundred fifty-four children with acute lymphoblastic leukemia received Escherichia coli asparaginase 10,000 IU/m(2) intramuscularly three times weekly for nine doses during multiagent induction and reinduction phases and for seven monthly doses during continuation treatment. Erwinia asparaginase was used in case of clinical hypersensitivity to E coli but not for subclinical development of antibodies. Plasma antiasparaginase antibody concentrations were measured on day 29 of induction in 152 patients. RESULTS: Antibodies were detectable in 54 patients (35.5%), of whom 30 (55.6%) exhibited hypersensitivity to asparaginase. Of the 98 patients who had no detectable antibodies, 18 (18.4%) had allergic reactions. Patients with antibodies were more likely to have a reaction than those without antibodies (P <.001). Among the 50 patients who experienced allergic reactions (including two for whom antibodies were not measured), 36 (72.0%) were subsequently given Erwinia asparaginase; seven (19.4%) reacted to this preparation. EFS did not differ among patients who did and did not have antibodies (P =.54), with 4-year EFS (+/- 1 SE) of 83% +/- 6% and 76% +/- 5%, respectively. Similarly, EFS did not differ among patients who did and did not develop allergic reactions (P =.68), with 4-year estimates of 82% +/- 6% and 78% +/- 5%, respectively. CONCLUSION: In this setting, in which most patients with allergy were switched to another preparation, there was no adverse prognostic impact of clinical or subclinical allergy to asparaginase.     

Oral premedication for the prevention of hypersensitivity reactions to paclitaxel

Premedication with dexamethasone, H1 and H2 receptor antagonists given intravenously prior to paclitaxel are highly successful in preventing life-threatening hypersensitivity reactions. We conducted a prospective study to assess the availability and safety of the administration of promethazine and dexamethasone per os in the premedication of paclitaxel hypersensitivity reactions. Of 180 eligible cancer patients, 100 patients received paclitaxel weekly and 80 patients, every 3 weeks. Patients received premedication with promethazine 25 mg per os, dexamethasone 2–20 mg per os and cimetidine 300 mg intravenously. One hundred patients in the weekly group received 940 cycles of paclitaxel. Hypersensitivity reactions occurred in one (1%) patient. There were no hypersensitivity reactions in 99% of patients. Eighty patients in the 3 weekly group received 464 cycles of paclitaxel. Hypersensitivity reactions occurred in (3) 4% of patients while 96% of patients had no hypersensitivity reactions. Two of these three patients had no further hypersensitivity reactions after receiving premedication intravenously. In the two groups 40 min/cycle reduction in treatment duration was observed. In conclusion, this study shows that drugs used for premedication prior to paclitaxel can be given orally. This strategy is feasible, gives excellent results in reducing hypersensitivity reactions and shortens the time of treatment for patients and treating staff.