Prevention of Pemetrexed-Induced Rash Using Low-Dose Corticosteroids: A Phase II Study.

BACKGROUND: Rash eruptions are a common side-effect of pemetrexed, for which the administration of 8 mg/day of dexamethasone for 3 days from the day preceding pemetrexed administration is recommended. This study aimed to prospectively assess the effectiveness of prophylactic administration of low-dose dexamethasone for pemetrexed-induced rashes. METHODS: This single-arm, phase II study recruited patients with non-squamous non-small cell lung cancer and malignant pleural mesothelioma scheduled to receive chemotherapy including pemetrexed. Patients received 2 mg of dexamethasone daily from days 2 to 6 after chemotherapy with pemetrexed. The primary endpoint was the 3-week incidence of rash eruptions. RESULTS: Twenty-five patients were enrolled between September 2017 and May 2019. The incidence of rash after 3 weeks was 16.7%. Rashes erupted mainly on the upper half of the body, such as the chest and neck, and were of grades 1 and 2 in 2 patients each. No rashes of grade 3 or higher were observed, and there were no adverse events associated with additional corticosteroids. CONCLUSION: Prophylactic administration of low-dose dexamethasone for 5 days from the day after pemetrexed administration resulted in a milder incidence and severity of rash. These findings may provide a standard preventative strategy for pemetrexed-induced rashes. (Trial identifier: UMIN000025666).

Preceding bortezomib administration for a certain period reduces the risk of lenalidomide-induced skin rash.

WHAT IS KNOWN AND OBJECTIVE: It was previously reported that the incidence of lenalidomide (LEN)-induced skin rash is reduced by administration of bortezomib (BOR) prior to LEN administration in patients with multiple myeloma (MM). Therefore, we investigated whether LEN-induced skin rash is affected by the duration of BOR administration and the dosing interval between BOR and LEN administration. METHOD: A retrospective investigation was conducted among MM patients who received BOR treatment prior to LEN treatment in Eiju General Hospital from May 2010 to December 2020. We investigated whether the BOR administration duration and interval duration from the completion of BOR administration to the initial LEN administration affect the development of LEN-induced skin rash. RESULT AND DISCUSSION: Twenty-eight of the 81 patients exhibited LEN-induced skin rash (34.6%). The administered duration, but not the interval, was significantly longer in the group without skin rash. Cut-off values were set for the duration of administration and interval, which were 35 days and 30 days, respectively. Multivariate analysis was performed on patients which are administered duration of more than 35 days and intervals of less than 30 days, and those who are not applicable. A significant difference was observed in the incidence of skin rash for each factor. WHAT IS NEW AND CONCLUSION: The risk of reduced LEN-induced skin rash is affected not only by the presence of prior BOR administration, but also by the duration of BOR and the interval from the completion of BOR to the initial LEN administration.

Prophylactic Topical Treatment for EGFR Inhibitor-Induced Papulopustular Rash: A Randomized Clinical Trial.

BACKGROUND: The incidence of epidermal growth factor receptor inhibitor (EGFRI)-induced papulopustular rash is 60-85%. OBJECTIVE: To investigate prophylactic topical treatment for EGFRI-induced rash. METHODS: A single-center, randomized, double-blind, placebo-controlled trial. Adult cancer patients initiating treatment with EGFRIs were randomized to receive facial topical treatment with chloramphenicol 3% + prednisolone 0.5% (CHL-PRED) ointment, chloramphenicol 3% (CHL) ointment, or aqua cream (AQUA). The primary end points were the incidence of ≥grade 3 rash using the Common Terminology Criteria for Adverse Events (CTCAE), on days 14 and 30. A subanalysis was conducted for incidence of a protocol-specified significant rash, defined as ≥10 facial papulopustular lesions. RESULTS: The per-protocol analysis on day 14 included 69 patients, who received CHL-PRED (21), CHL (23), or AQUA (25). The incidence of CTCAE ≥grade 3 rash was not statistically significant between arms; however, the incidence of the protocol-specified significant rash was: CHL-PRED 14%, CHL 39%, and AQUA 48% (p = 0.03, CHL-PRED vs. AQUA). At 30 days, the CTCAE ≥grade 3 incidence was similar, but the incidences of protocol-specified significant rash were 6%, 16%, and 43% (p = 0.03, CHL-PRED vs. AQUA). No significant differences were found between CHL and CHL-PRED and between CHL and AQUA. CONCLUSIONS: Prophylactic topical CHL-PRED was efficacious when compared to AQUA, in the treatment of EGFRI-induced facial papulopustular rash.

Growth suppression of human oral cancer cells by candidate agents for cetuximab-side effects.

Cetuximab, an inhibitor of the epidermal growth factor receptor that is used widely to treat human cancers including oral squamous cell carcinoma (OSCC), has characteristic side effects of skin rash and hypomagnesemia. However, the mechanisms of and therapeutic agents for skin rashes and hypomagnesemia are still poorly understood. Our gene expression profiling analyses showed that cetuximab activates the p38 MAPK pathways in human skin cells (human keratinocyte cell line [HaCaT]) and inhibits c-Fos-related signals in human embryonic kidney cells (HEK293). We found that while the p38 inhibitor SB203580 inhibited the expression of p38 MAPK targets in HaCaT cells, flavagline reactivated c-Fos-related factors in HEK293 cells. It is noteworthy that, in addition to not interfering with the effect of cetuximab by both compounds, flavagline has additive effect for OSCC growth inhibition in vivo. Collectively, our results indicate that combination of cetuximab and these potential therapeutic agents for cetuximab-related toxicities could be a promising therapeutic strategy for patients with OSCC.

Meconium-stained amniotic fluid as a protective factor against childhood dermatitis and skin rash-related hospitalization in the offspring - a population-based cohort analysis.

BACKGROUND: Gut microbiome influences cutaneous diseases including atopic dermatitis. Possible impact of intrauterine exposure to meconium on the occurrence of dermatitis and skin rash was proposed. OBJECTIVE: We investigated the possible influence of intrauterine exposure to meconium-stained amniotic fluid (MSAF) on the occurrence of dermatitis and skin rash-related hospitalizations throughout childhood. METHODS: Singleton deliveries occurring between 1991 and 2014 at a single medical centre were divided into two study groups based on presence or lack of MSAF during delivery. Population-based cohort analysis, Kaplan-Meier survival analysis and Cox proportional hazards model were used to study the association between MSAF and cutaneous morbidity-related hospitalizations. RESULTS: A lower rate of the total dermatitis or skin eruption-related hospitalization was documented in the MSAF-exposed group; 0.78 per 1000-person years (0.9%, n = 312), as compared to 0.98 per 1000-person years in the unexposed group (1.0%, n = 1992) with a hazard ratio of 0.86 (95% CI 0.76-0.96, P = 0.011). The survival curve showed lower cumulative hospitalization rate in the MSAF-exposed group as compared to the unexposed group (log rank P = 0.01). The Cox analysis, controlled for confounders, demonstrated MSAF exposure to be an independent protective factor for dermatitis and skin rash-related hospitalizations during childhood (adjusted HR 0.878 (95% CI 0.779-0.990, P = 0.034). CONCLUSION: Fetal exposure to MSAF appears to be an independent protective factor for dermatitis and skin rash-related hospitalizations in the offspring throughout childhood and adolescence.

Travelers' tropical skin diseases: Challenges and interventions.

Tropical regions receive a significant part of the traveling population. It is very important that health professionals are familiar with the main tropical skin diseases and able to advice patients appropriately. This article reviews the main tropical diseases of travelers, with an emphasis on diagnosis, management, and prevention. Among others, cutaneous larva migrans, myiasis, tungiasis, Chagas disease, Dengue fever, African trypanosomiasis, filariasis, and leishmaniasis are discussed. Increasing awareness among travelers and health care professionals can help reduce morbidity and mortality. Continued research on new drugs and vaccines is needed to reduce the risks of tropical diseases.

Genetic testing for prevention of severe drug-induced skin rash.

BACKGROUND: Drug-induced skin reactions present with a range of clinical symptoms, from mild maculopapular skin rashes to potentially fatal blistering skin rashes - such as Stevens-Johnson syndrome (SJS) or toxic epidermal necrolysis (TEN) - which may result in death. Milder reactions may be troublesome and lead to low drug compliance. The pathogenesis of these drug reactions is not yet fully understood; however, there is evidence that pretreatment genetic testing may help to predict and prevent these reactions in some cases. OBJECTIVES: To assess the effects of prospective pharmacogenetic screening to reduce drug-associated skin reactions in a patient population. SEARCH METHODS: We searched the following databases up to July 2018: the Cochrane Skin Specialised Register, CENTRAL, MEDLINE, Embase and LILACS. We also searched five trials registers, and checked the reference lists of included studies and relevant reviews for further references to relevant randomised controlled trials (RCTs). SELECTION CRITERIA: We included RCTs of participants who had prospective pharmacogenetic screening to determine genetic variants associated with hypersensitivity reactions, compared with those who did not have prospective pharmacogenetic screening. We included participants in any setting, who were of any age, gender, and ethnicity, who had been prescribed drugs known to cause delayed type hypersensitivity reactions. DATA COLLECTION AND ANALYSIS: We used standard methodological procedures expected by Cochrane. To assess studies for inclusion, two review authors independently screened all of the titles and abstracts of publications identified by the searches. Because there was only one included study, many of the planned data analyses were not applicable to the review. We used GRADE to assess the quality of the included study.The review's primary outcomes were the incidence of severe skin rashes with systemic symptoms (such as fever and multiple organ involvement), and long-term effects (such as scarring of eyelids or lung tissue). Secondary outcomes were hospitalisation for drug-induced skin reactions, blistering skin reactions (such as SJS, hypersensitivity (HSS) syndrome), and death. MAIN RESULTS: One study, which was a randomised, double-blind, controlled, multicentre trial, fulfilled our inclusion criteria. The trial included 1956 adult participants (74% men, with a mean age of 42 years) across 265 centres (medical centres, hospitals, outpatient clinics) in 19 countries around the world who were infected with HIV-type 1 and who had not received abacavir previously. The participants, who had a clinical need for treatment with an antiretroviral-drug regimen containing abacavir, were randomly assigned to undergo prospective human leukocyte antigen (HLA) Class I, locus B, allele 57:01 (HLA-B*57:01) screening (prospective-screening group) before this treatment, or to undergo a standard-care approach of abacavir use without prospective HLA-B*57:01 screening (control group). Participants who tested positive for HLA-B*57:01 were not given abacavir; instead, they received antiretroviral therapy that did not include abacavir. The control group did have retrospective HLA-B*57:01 pharmacogenetic testing. The trial duration was six months. Each participant was observed for six weeks. Assessments were performed at the time of study entry, at baseline (day one of abacavir treatment), and at weeks one, two and six. This study was funded by the manufacturer of abacavir, GlaxoSmithKline.The study did not assess any of our primary outcomes, and it measured none of our secondary outcomes in isolation. However, it did assess an outcome of (characteristically severe) hypersensitivity reaction which included (but was not limited to) our secondary outcomes of HSS and SJS/TEN.The study demonstrated that prospective HLA-B*57:01 screening probably reduces the incidence of hypersensitivity reaction to abacavir. The incidence of clinically diagnosed HSS reaction to abacavir was lower in the screening arm (risk ratio (RR) 0.43, 95% confidence interval (CI) 0.28 to 0.67; 1650 participants; moderate-quality evidence), as was immunologically confirmed HSS reaction (RR 0.02, 95% 0.00 to 0.37; 1644 participants; moderate-quality evidence). A positive result from an epicutaneous patch test performed six to ten weeks after clinical diagnosis provided immunological confirmation.Overall, the study demonstrates a low risk of bias across five out of seven domains. There was a high risk of detection bias because hypersensitivity reactions were diagnosed by the principal investigator at the recruitment site without the use of predefined clinical criteria. Although there was also high risk of attrition bias due to excluding participants with incomplete follow-up from analyses, the authors did undertake a series of sensitivity analyses based on the intention-to-treat population, which demonstrated consistent results with the primary analysis. We rated the study quality as moderate-quality using GRADE criteria. AUTHORS' CONCLUSIONS: Prospective screening for HLA-B*57:01 probably reduces severe hypersensitivity skin reactions to abacavir in patients positive for HIV-type 1. However, these results are only based on one study, which was at high risk of attrition and detection bias.Our primary outcomes (incidence of severe skin rashes with systemic symptoms, and long-term effects) were not assessed by the trial, and only one of the review's secondary outcomes was measured (hypersensitivity reaction); thus, we found no evidence relating to hospitalisation, death, or long-term conditions resulting from drug injury.We found no eligible evidence on genetic testing for severe drug-induced skin rash in relation to different drugs and classes of drugs. Further clinical trials based on other drugs, and in different patient populations, would be useful for advising policy changes for improving the prevention of adverse skin reactions to drug treatments.

Long-term omalizumab outcomes in chronic idiopathic urticaria: a real-world study.

Background: Although clinical trials documented omalizumab's efficacy in U.S. patients with chronic idiopathic urticaria (CIU), the real-world evidence on its long-term effectiveness is lacking. Objective: To assess omalizumab use and the long-term response in a large sample of U.S. real-world patients. Methods: Patients with CIU and ≥ 12 years old who were initiated on omalizumab (index date) and with ≥ 6 months of postindex data were identified in an electronic medical record system (2007-2018). Omalizumab use was described. Provider assessments of disease control and course, and patient-reported symptoms were compared at 6-month intervals postindex versus baseline in the patients with values available at both time points. Results: A total of 1096 patients (mean age, 44.1 years; 74.7% women) were followed up for a mean of 19 months postindex. Patients, predominantly initiated on a 300-mg dose, received a mean of 15 omalizumab administrations and were treated continuously for a mean of 14.2 months. At 6 months postindex versus baseline, the patients (n = 708) were more likely to be well controlled (odds ratio [OR] 31.68 [95% confidence interval {CI}, 17.20-58.36]) with an improved disease course (OR 15.73 [95% CI, 11.33-21.85]). Moreover, the patients (n = 373) were less likely to report itching (OR 0.39 [95% CI, 0.21-0.76]), rash (OR 0.59 [95% CI, 0.45-0.78]), and swelling (OR 0.46 [95% CI, 0.36-0.59]). Benefits associated with omalizumab treatment were sustained through month 24 and beyond. Conclusion: This real-world study showed that the patients who received a mean of 15 omalizumab administrations over a mean of 14.2 months experienced, starting at 6 and through 24 months after omalizumab initiation and beyond, improved CIU control, course, and symptoms.

EVITA-a double-blind, vehicle-controlled, randomized phase II trial of vitamin K1 cream as prophylaxis for cetuximab-induced skin toxicity.

Background: Acne-like skin rash is a frequently occurring adverse event associated with drugs against the epidermal growth factor receptor. This randomized vehicle-controlled study investigated the addition of vitamin K1 cream to doxycycline in patients with metastatic colorectal cancer treated with cetuximab. Patients and methods: Patients receiving first-line cetuximab + FOLFIRI were randomly assigned to prophylactic treatment with doxycylin and vitamin K1 cream or doxycycline and the vehicle. The primary end point of the study was the incidence of grade ≥ 2 skin rash (NCI CTCAE version 4.02) during 8 weeks of skin treatment. Secondary end points comprised skin rash according to a more thorough tripartite skin toxicity score (WoMo), quality of life, efficacy, and compliance. The study had 80% power to show a 20% reduction of the incidence of grade ≥ 2 skin rash. Results: A total of 126 patients were analyzed. The incidence of skin rash grade ≥ 2 was comparable between the arms. Likewise, no difference was seen in the WoMo score with respect to the percentage of skin affected. However, starting in week 5 and increasing over time patients treated with vitamin K1 cream had less severe rash and fewer fissures. Quality of life as well as efficacy and compliance with study medication and anticancer treatment was comparable in both arms. Conclusion: The primary end point of decreasing grade ≥ 2 skin rash was not met. However, using vitamin K1 cream as part of prophylactic treatment decreased the severity of acne-like skin rash according to WoMo, an alternative and more thorough skin toxicity scoring tool.

Using PARP Inhibitors in Advanced Ovarian Cancer.

Poly(ADP-ribose) polymerase (PARP) proteins are used by cells in several DNA repair processes. PARP inhibition can result in preferential death of cancer cells when another mechanism for repairing DNA is defective. Two PARP inhibitors, olaparib and rucaparib, have been approved by the US Food and Drug Administration (FDA) for the treatment of recurrent, BRCA-associated ovarian cancer. More recently, these two and a third PARP inhibitor, niraparib, were approved by the FDA as maintenance therapy following platinum-based chemotherapy for recurrent ovarian cancer. This has caused a paradigm shift in disease management and a challenge for clinicians, who must decide how best to use these agents in individualized treatment. The oral formulation is attractive to patients, but adverse effects such as nausea and fatigue can impact quality of life. As clinicians become comfortable selecting PARP inhibitors and managing associated toxicities, future steps will be to investigate how to safely administer them in combination with other therapies.

Topical Vehicle Formulations in the Treatment of Acne.

Topical treatment is the mainstay of acne therapy. The most commonly prescribed topical medications for acne include benzoyl peroxide, clindamycin, and retinoids. Despite their effectiveness in treating mild to moderate acne vulgaris, these topical medications are found to be irritating, and are historically associated with poor tolerability and diminished patient adherence. Thus, choosing the right formulation that will be effective and well tolerated is essential. Novel formulations that optimize drug concentration and utilize improved delivery vehicles have helped to enhance the tolerability and efficacy, and allow for less frequent application or co-application of drugs that were previously considered incompatible. This article will review the goals of topical therapy for the treatment of acne, in addition to common therapies and their challenges. Advanced formulations and combination formulations of benzoyl peroxide, clindamycin, and tretinoin will also be discussed. J Drugs Dermatol. 2018;17(6 Suppl):s6-10.

Herpes zoster vaccine: a protection for the elderly.

The Herpes Zoster vaccine is strongly recommended by the World Health Organization to promote healthy aging by preventing the corresponding age- related disease, also named shingles. The disease is due to the endogenous reactivation of Varicella Zoster Virus, the causal agent of chickenpox, that becomes latent at the peripheral nervous system level. Here, owing to the host's cell-mediated immunity, it may be confined for several decades. However, the immune senescence allows the possibility of virus reactivation, causing the onset of neuropathic pain and skin rash that characterize the acute disease. Sometimes, the neuralgia becomes chronic causing postherpetic neuralgia that has a significant impact on the quality of patient life, analogously to the ophthalmic HZ, a particularly feared form of disease. Due to the causal relationship between decreasing immune defenses and virus reactivation with disease onset, the incidence of Herpes Zoster, in Italy now equal to 6.42 (95%CI: 5.93-6.95) cases per 1,000 people per year will increase steadily in the future due to the longevity rise of the population. Considering epidemiological impact, complications and sequelae in the short- and long-term, costs of clinical-therapeutical management of patients, and, above all, the poor effectiveness of available therapy the only effective intervention is vaccination of the elderly. Currently in the European Union, there is only one vaccine for Herpes Zoster prevention, formed by live attenuated OKA-Merck virus strain that is also used for paediatric vaccine. According to the Health Technology Assessment surveys, the intervention cost (based on "Quality Adjusted Life Years") is clearly below the discriminating threshold value to judge the feasibility and, as predicted by the Italian National Plan of Vaccinal Prevention 2017-2019, the vaccine is offered free to all subjects >65 years.

[Triggers of exanthematous drug eruptions: Stop intake, treat through or desensitization?] / Auslöser von Arzneiexanthemen: Absetzen, durchbehandeln oder desensibilisieren?

Drug hypersensitivity reactions affect over 7% of the population and are problematic both for patients and doctors. They frequently occur in the form of exanthematous drug eruptions. The clinical manifestation of delayed hypersensitivity reactions is very variable ranging from localized fixed drug eruptions to life-threatening, severe bullous mucocutaneous eruptions or systemic drug hypersensitivity syndromes. In the case of suspicion of an exanthematous drug eruption, the causality should initially be assessed according to the proposed algorithm. If both the chronology and the clinical symptoms are indicative of a delayed drug hypersensitivity reaction, the suspected drug should be avoided. Only in cases of urgent therapeutic indications and if alternative drugs are not available, the options of "treating through" and temporary tolerance induction by "desensitization" should be considered after an individual risk-benefit analysis.

Doxycycline for prevention of erlotinib-induced rash in patients with non-small-cell lung cancer (NSCLC) after failure of first-line chemotherapy: A randomized, open-label trial.

BACKGROUND: Rash is a common epidermal growth factor receptor inhibitor-induced toxicity that can impair quality of life and treatment compliance. OBJECTIVE: We sought to evaluate the efficacy of doxycycline in preventing erlotinib-induced rash (folliculitis) in patients with non-small-cell lung cancer. METHODS: This open-label, randomized, prospective, phase II trial was conducted in 147 patients with locally advanced or metastatic non-small-cell lung cancer progressing after first-line chemotherapy, randomized for 4 months with erlotinib alone 150 mg/d per os (control arm) or combined with doxycycline 100 mg/d (doxycycline arm). Incidence and severity of rash, compliance, survival, and safety were assessed. RESULTS: Baseline characteristics of the 147 patients were well balanced in the intent-to-treat population. Folliculitis occurred in 71% of patients in the doxycycline arm and 81% in the control arm (P = .175). The severity of folliculitis and other skin lesions was lower in the doxycycline arm compared with the control arm. Other adverse events were reported at a similar frequency across arms. There was no significant difference in survival between treatment arms. LIMITATIONS: The open-label design of the study and the duration of the treatment with doxycycline are limitations. CONCLUSION: Doxycycline did not reduce the incidence of erlotinib-induced folliculitis, but significantly reduced its severity.

Skin problems and EGFR-tyrosine kinase inhibitor.

Epidermal growth factor receptor inhibition is a good target for the treatment of lung, colon, pancreatic and head and neck cancers. Epidermal growth factor receptor-tyrosine kinase inhibitor was first approved for the treatment of advanced lung cancer in 2002. Epidermal growth factor receptor-tyrosine kinase inhibitor plays an essential role in the treatment of cancer, especially for patients harbouring epidermal growth factor receptor activating mutation. Hence, skin toxicity is the most concerning issue for the epidermal growth factor receptor-tyrosine kinase inhibitor treatment. Skin toxicity is bothersome and sometimes affects the quality of life and treatment compliance. Thus, it is important for physicians to understand the background and how to manage epidermal growth factor receptor-tyrosine kinase inhibitor-associated skin toxicity. Here, the author reviewed the mechanism and upfront preventive and reactive treatments for epidermal growth factor receptor inhibitor-associated skin toxicities.

Prophylactic versus reactive treatment of acneiform skin rashes from epidermal growth factor receptor inhibitors in metastatic colorectal cancer.

PURPOSE: There are concerns regarding potential negative effects of prophylactic treatment of epidermal growth factor receptor (EGFR)-inhibitor-related rashes on metastatic colorectal cancer (mCRC) outcomes. We aimed to characterize treatment patterns of EGFR-inhibitor-induced rashes and evaluate prophylactic versus reactive approaches to rash management in relation to overall survival (OS). METHODS: Patients diagnosed with KRAS wild-type mCRC from July 2010 to June 2012 in British Columbia and prescribed cetuximab or panitumumab were reviewed to describe patterns of use of oral antibiotics and steroid creams. Using Cox regression, the relationship between prophylactic versus reactive rash management and OS was characterized. RESULTS: A total 119 patients were analyzed: median age was 63 years, 61 % were male, 34 % received cetuximab, 66 % received panitumumab, and median number of EGFR inhibitor treatment was nine cycles. Rash occurred in >90 % of patients, and reactive was favored over prophylactic treatment (66 vs. 34 %). Older patients and those with Eastern Cooperative Oncology Group (ECOG) performance status 0/1 were more likely to receive prophylactic creams (44 vs. 20 % for age <60, p = 0.01) and oral antibiotics (62 vs. 12 % for ECOG ≥2, p = 0.01), respectively. Median OS was 7.0 months. The number of treatment cycles and OS were similar in both prophylactic and reactive groups (both p > 0.05). In Cox regression, ECOG >2 correlated with worse survival (hazard ratio (HR) 22.01, 95 % confidence interval (CI) 5.25-92.30, p < 0.01). However, survival outcomes were similar between patients prescribed antibiotics prophylactically versus reactively (HR = 1.10, 95 % CI 0.43-2.80, p = 0.85), and steroid creams prophylactically versus reactively (HR = 2.00, 95 % CI 0.58-6.92, p = 0.27). CONCLUSION: Prophylactic treatment of EGFR-inhibitor-related rashes is associated with similar outcomes compared to reactive rash treatment in mCRC.

Erlotinib-associated rash in patients with EGFR mutation-positive non-small-cell lung cancer treated in the EURTAC trial.

AIM: This analysis investigates incidence and time course of rash in the EURTAC study. MATERIALS & METHODS: Patients with EGFR mutation-positive non-small-cell lung cancer were randomized 1:1 to receive once daily erlotinib or 3-weekly cycles of chemotherapy. RESULTS: Of the 86 erlotinib-treated patients, 71 reported rash. Median time to first rash appearance was 0.7 months. Most patients (n = 65) had the same or lower grade rash at final assessment compared with initial assessment. Of the 21 patients with decreased rash grade between initial and final assessments, 61.9% received no erlotinib dose modification, 42.8% had no concomitant rash treatment. CONCLUSION: Most rash cases were mild, occurred within 1 month of erlotinib treatment, and rapidly improved without the need for erlotinib dose alterations.

Pemetrexed-Induced Rash May Be Prevented by Supplementary Corticosteroids.

Pemetrexed, a chemotherapeutic drug, is highly active in non-small cell lung cancer and malignant pleural mesothelioma. Unfortunately, rashes are more commonly associated with pemetrexed than other chemotherapies, and it is recommended that patients receive corticosteroids (8 mg/d of dexamethasone) for 3 d, including the day of pemetrexed administration (day 1). However, the efficacy of corticosteroids in this context has not been fully verified. In this retrospective study, we evaluated the medical records of 78 patients who received pemetrexed between April 2009 and March 2014, to confirm whether supplementary corticosteroids prevented rash development. The incidence of rash was lower in the 47 patients who received supplementary corticosteroids (after day 1) compared with the incidence among the 31 patients who did not receive supplementary corticosteroids (19.1% vs. 38.7%). The average cutoff dosage of supplementary corticosteroids on day 2 and day 3 was 1.5 mg/d of dexamethasone, as calculated using the receiver operating characteristic curve, and the odds ratio was 0.33 (95% confidence interval: 0.12-0.94). Administration of ≥1.5 mg of corticosteroids on day 2 and day 3 significantly reduced the severity of the rash compared to no supplementary treatment (grades 2/3, 13.3% vs. 33.3%, p<0.05). However, increasing the dose of corticosteroids had no additional effect on rash development. These results suggest that ≥1.5 mg of supplementary dexamethasone on day 2 and day 3 (in addition to day 1) may be necessary for preventing pemetrexed-induced rash, but high doses of dexamethasone (e.g., 8 mg/d) are unnecessary.