Dexamethasone Methods for Preventing Allergic Reactions to Chemotherapy

Overseen By Linda Hong, MD

Age: 18+

Sex: Female

Trial Phase: Phase 3

Sponsor: Loma Linda University

Must be taking: Dexamethasone, H1 antagonists, H2 antagonists

Must not be taking: Steroid therapy

Disqualifiers: Autoimmune diseases, Uncontrolled diabetes, others

No Placebo Group All trial participants will receive the active study treatment (no placebo)

Pivotal Trial (Near Approval) This treatment is in the last trial phase before FDA approval

Prior Safety Data This treatment has passed at least one previous human trial

Approved in 4 Jurisdictions This treatment is already approved in other countries

Compensation: Varies

Number of Visits: Unknown

Duration: 6 weeks

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial seeks to determine the best method to prevent allergic reactions in women with breast or gynecologic cancers receiving paclitaxel, a common chemotherapy drug. It compares three methods of administering dexamethasone, a medication that reduces allergic reactions. Participants will be randomly assigned to one of the three methods, taking the medication orally and intravenously at different times before paclitaxel treatment. Women with breast or gynecologic cancers planning to receive paclitaxel treatment at Loma Linda University Health may be suitable for this trial, especially if they haven't used similar drugs before and aren't currently on steroids. As a Phase 3 trial, this study represents the final step before FDA approval, offering participants a chance to contribute to potentially groundbreaking advancements in cancer treatment.

Will I have to stop taking my current medications?

The trial does not specify if you need to stop taking your current medications, but if you are on steroid therapy, it must be stopped at least a week before starting chemotherapy.

Is there any evidence suggesting that this trial's treatments are likely to be safe?

Research has shown that dexamethasone, used to prevent allergic reactions during chemotherapy, is generally safe for short-term use. Studies have found that taking dexamethasone for a few days rarely leads to serious side effects. Some individuals might experience mild issues such as trouble sleeping, stomach upset, or elevated blood sugar levels.

In rare instances, dexamethasone can cause severe allergic reactions, but this is uncommon. Short-term use, as in the methods under study, is not usually associated with major problems. Thus, dexamethasone is considered safe for preventing allergic reactions to chemotherapy drugs like paclitaxel, especially when used as directed for a limited time.

All three methods tested in this trial involve the careful use of dexamethasone to minimize risks. For any concerns, consulting a healthcare provider is advisable. ^{1 2 3 4 5}

Why are researchers excited about this trial?

Researchers are excited about these dexamethasone methods for preventing allergic reactions to chemotherapy because they explore different administration strategies to improve patient comfort and outcomes. Unlike the conventional method, which involves multiple doses of oral dexamethasone before chemotherapy, the Short-Course arm simplifies the process with an intravenous dose given just 30 minutes prior to treatment. The Combined arm offers a balance between convenience and immediate effectiveness by combining a pre-treatment oral dose with an intravenous dose on the day of chemotherapy. These variations aim to reduce the burden of multiple pre-treatment doses while maintaining or enhancing the effectiveness in preventing allergic reactions, potentially making chemotherapy easier to tolerate for patients.

What evidence suggests that this trial's treatments could be effective for preventing allergic reactions to chemotherapy?

Research shows that dexamethasone helps prevent allergic reactions to paclitaxel, a chemotherapy drug. In this trial, participants will join different treatment arms to evaluate the effectiveness of various dexamethasone administration methods. The "Conventional" arm involves taking oral dexamethasone 12 and 6 hours before treatment, along with medications that reduce allergic reactions, and has proven effective in reducing severe allergic reactions. The "Short-Course" arm involves intravenous administration of dexamethasone shortly before treatment. The "Combined" arm includes both oral dexamethasone at home and intravenous administration at the clinic. Overall, dexamethasone reliably manages these allergic reactions. ^{5 6 7 8 9}

Who Is on the Research Team?

Linda Hong, MD

Principal Investigator

Loma Linda University Cancer Center

Are You a Good Fit for This Trial?

This trial is for adult female patients over 18 with breast or gynecologic cancer who will receive paclitaxel as their first chemo at LLUH Cancer Centers. They must not have had taxanes before, be English or Spanish speakers, and plan to undergo at least 3 cycles of treatment with specific regimens including paclitaxel.

Inclusion Criteria

I have been diagnosed with breast or gynecologic cancer at any stage.

I am scheduled for treatment with a paclitaxel-based regimen.

I am receiving paclitaxel alone or with other drugs.

Exclusion Criteria

I do not have autoimmune diseases or other conditions that need steroids during chemotherapy.

Patients who are not with the gynecologic or breast oncology service

Patients who are allergic to diphenhydramine and/or dexamethasone

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive one of three pre-medication regimens to prevent paclitaxel-related hypersensitivity reactions

6 weeks

Weekly visits for paclitaxel infusion

Follow-up

Participants are monitored for safety and effectiveness after treatment

4 weeks

What Are the Treatments Tested in This Trial?

Interventions

• Dexamethasone

Trial Overview The study compares three methods to prevent hypersensitivity reactions from paclitaxel: conventional oral dexamethasone taken twice before infusion; short-course IV dexamethasone given just before infusion; and a combined method using both oral and IV dexamethasone.

How Is the Trial Designed?

Group I: Short-Course Active Control 1 Intervention

Intravenous administration of dexamethasone 20 mg, along with an intravenous administration of diphenhydramine 50 mg and famotidine 20 mg, administered 30 minutes prior to paclitaxel infusion.

Group II: Combined Active Control 1 Intervention

Oral dexamethasone (20 mg) at home, 12 hours prior to paclitaxel infusion. On the day of treatment at the clinic, an additional intravenous administration of dexamethasone 20 mg, along with an intravenous administration of diphenhydramine 50 mg and famotidine 20 mg, administered 30 minutes prior to paclitaxel infusion.

Group III: Conventional Active Control 1 Intervention

Oral dexamethasone (20 mg) at home, 12 hours and 6 hours prior to paclitaxel infusion. On the day of treatment at the clinic, an intravenous administration of diphenhydramine 50 mg and famotidine 20 mg, administered 30 minutes prior to paclitaxel infusion.

Who Is Running the Clinical Trial?

Loma Linda University

Lead Sponsor

Trials

322

Recruited

267,000+

Published Research Related to This Trial

Oral dexamethasone (PO-D) is more effective than intravenous dexamethasone (IV-D) in reducing the incidence of severe hypersensitivity reactions (HSRs) related to paclitaxel, based on a meta-analysis of six studies involving 1347 patients.

While PO-D significantly decreased severe HSRs (OR 0.53), there was no overall difference in the rates of all paclitaxel-related HSRs between the two regimens, indicating that while PO-D is better for severe cases, both methods may have similar overall effectiveness.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Meta-analysis of the effects of oral and intravenous dexamethasone premedication in the prevention of paclitaxel-induced allergic reactions. Chen, FC., Wang, LH., Zheng, XY., et al.[2018]

In a study involving 288 patients with ovarian and related cancers, both intravenous (IV) and oral dexamethasone were found to be equally effective in preventing paclitaxel-associated hypersensitivity reactions (P-HSR), with rates of 17.9% for IV and 19.1% for oral dexamethasone.

However, patients receiving oral dexamethasone experienced more side effects, particularly acne (10.6% vs. 2.1% for IV), suggesting that intravenous dexamethasone may be a safer option with fewer adverse effects.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Intravenous versus oral dexamethasone for prophylaxis of paclitaxel-associated hypersensitivity reaction in patients with primary ovarian, fallopian tube and peritoneal cancer: A double-blind randomized controlled trial. Yanaranop, M., Chaithongwongwatthana, S.[2018]

Oral dexamethasone (PO-D) is more effective than intravenous dexamethasone (IV-D) in preventing hypersensitivity reactions (HSRs) during paclitaxel treatment, with HSR rates of 5.4% for PO-D compared to 14.5% for IV-D in a study of 148 patients.

For patients who experience HSRs, continuing paclitaxel treatment through a desensitization protocol is a cost-effective strategy, rather than discontinuing the medication altogether.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Intravenous versus oral dexamethasone premedication in preventing Paclitaxel infusion hypersensitivity reactions in gynecological malignancies. O'Cathail, SM., Shaboodien, R., Mahmoud, S., et al.[2018]

Reduced doses of dexamethasone for preventing hypersensitivity reactions and skin toxicities in patients receiving weekly taxane treatments appear to be safe and feasible, based on a review of clinical trials from 1990 to 2010.

Current dexamethasone regimens designed for every 3-week taxane administration may lead to increased steroid-related side effects when used weekly, highlighting the need for further research to determine the optimal dosing schedule.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Dexamethasone premedication for prophylaxis of taxane toxicities: can the doses be reduced when paclitaxel or docetaxel are given weekly? Schwartz, JR.[2018]

In a study of 51 patients receiving paclitaxel (PTX) with aprepitant (APR) and varying doses of dexamethasone (DEX), the incidence of hypersensitivity reactions (HSR) was similar regardless of whether the DEX dose was reduced (51.5% in the higher dose group vs. 53.8% in the lower dose group).

The results indicate that while it is safe to reduce the DEX dose when using APR, this reduction does not decrease the risk of PTX-induced HSR, suggesting that monitoring for adverse effects remains crucial.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

The effect of aprepitant and dexamethasone combination on paclitaxel-induced hypersensitivity reaction. Yamamoto, T., Natio, M., Hara, S., et al.[2020]

Single-dose intravenous dexamethasone, when given with other medications, is effective in preventing hypersensitivity reactions (HSRs) during paclitaxel infusions, based on a review of clinical literature.

This approach offers a simplified prophylactic strategy compared to the traditional method of administering multiple doses of dexamethasone before treatment.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Prophylaxis for paclitaxel hypersensitivity reactions. Kintzel, PE.[2017]

Dexamethasone (Dx) can reduce the effectiveness of cisplatin (cDDP) in inducing apoptosis in osteosarcoma cells, decreasing apoptosis by 10-25% when used as a pre or cotreatment.

The protective effect of Dx is linked to the upregulation of the survival factor Akt and a potential direct action on the mitochondrial apoptotic pathway, suggesting that the timing of glucocorticoid administration in cancer treatment should be carefully considered.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Dexamethasone protects against Cisplatin-induced activation of the mitochondrial apoptotic pathway in human osteosarcoma cells. Meyer, S., Eden, T., Kalirai, H.[2020]

Citations

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Meta-analysis of the effects of oral and intravenous ... In this report, we analysed the effects of two common administration routes of dexamethasone premedication on the prevention of paclitaxel-induced HSRs. We also ...

2. journals.sagepub.com journals.sagepub.com/doi/10.1177/1078155220984369?int.sj-full-text.similar-articles.5=

Comparative study of oral and IV dexamethasone ... Intravenous dexamethasone minimize the risk of hypersensitivity reactions as compared to oral dexamethasone. This can improve patient compliance ...

3. withpower.com withpower.com/trial/phase-3-hypersensitivity-7-2018-81fd3

Dexamethasone Methods for Preventing Allergic Reactions ... Oral dexamethasone (PO-D) is more effective than intravenous dexamethasone (IV-D) in reducing the incidence of severe hypersensitivity reactions (HSRs) related ...

4. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC12357464/

The efficacy of premedication with 10 mg versus 20 ... We discovered the success rate of the drugs to indicate the risk of HSRs in Dexamethasone 10 mg and 20 mg were 5% [4] and 4% [5], respectively.

5. oncotarget.com oncotarget.com/article/13705/

Meta-analysis of the effects of oral and intravenous ... Meta-analysis of the effects of oral and intravenous dexamethasone premedication in the prevention of paclitaxel-induced allergic reactions.

6. ncbi.nlm.nih.gov ncbi.nlm.nih.gov/books/NBK482130/

Dexamethasone - StatPearls - NCBI Bookshelf - NIH Treatment with high-dose dexamethasone is not recommended beyond 2 to 3 days. Research has shown that allergic reactions improve with a 6-day regimen ...

7. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC4839331/

Dexamethasone co-medication in cancer patients undergoing ... Dexamethasone co-medication in cancer patients undergoing chemotherapy causes substantial immunomodulatory effects with implications for chemo-immunotherapy ...

8. rxlist.com rxlist.com/dexamethasone-drug.htm

Dexamethasone (Dexamethasone): Side Effects, Uses, ... Rare instances of severe allergic reactions (anaphylaxis) have occurred in patients receiving corticosteroid therapy such as dexamethasone. Dosage for ...

9. accessdata.fda.gov accessdata.fda.gov/drugsatfda_docs/label/2014/202356s000lbl.pdf

--ADVERSE REACTIONS Combination therapy with Docetaxel Injection in head and neck cancer. Table 11 summarizes the safety data obtained from patients that received induction.