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

270 Participants Needed

Trial Summary

What is the purpose of this trial?

This trial tests three different ways to prevent allergic reactions in women with gynecologic cancers who are treated with paclitaxel. The methods involve using steroids and antihistamines before the treatment. The goal is to find out which method works best to keep patients safe from allergic reactions. Paclitaxel is a plant product highly active in numerous cancers, but it has a significant incidence of hypersensitivity reactions, which are typically managed with steroids and antihistamines.

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.

What data supports the effectiveness of the drug Dexamethasone in preventing allergic reactions to chemotherapy?

Research shows that Dexamethasone is effective in preventing allergic reactions to the chemotherapy drug paclitaxel, as it is used to reduce hypersensitivity reactions (allergic reactions) when given before treatment. ^{1 2 3 4 5}

Is dexamethasone safe for preventing allergic reactions to chemotherapy?

Dexamethasone is commonly used to prevent allergic reactions to chemotherapy drugs like paclitaxel, and it is generally considered safe for this purpose. It can be given either as a pill or through an IV (intravenous, meaning directly into a vein), and both methods have been studied for their safety and effectiveness. ^{1 2 5 6 7}

How does dexamethasone prevent allergic reactions to chemotherapy?

Dexamethasone is used to prevent allergic reactions to chemotherapy drugs like paclitaxel by reducing inflammation and immune responses. It can be given either as a pill or through an IV, with the timing and method of administration potentially affecting its effectiveness. ^{1 2 4 6 7}

Research Team

Linda Hong, MD

Principal Investigator

Loma Linda University Cancer Center

Eligibility Criteria

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

I am under care for gynecologic or breast cancer but not receiving paclitaxel.

Timeline

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

Treatment Details

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.

Participant Groups

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+

Findings from Research

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]

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]

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]

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]

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]

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]

References

1. United States pubmed.ncbi.nlm.nih.gov

Prophylaxis for paclitaxel hypersensitivity reactions. [2017]

2. Australia 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. [2018]

3. England pubmed.ncbi.nlm.nih.gov

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

4. Singapore pubmed.ncbi.nlm.nih.gov

The effect of aprepitant and dexamethasone combination on paclitaxel-induced hypersensitivity reaction. [2020]

5. United States pubmed.ncbi.nlm.nih.gov

Dexamethasone protects against Cisplatin-induced activation of the mitochondrial apoptotic pathway in human osteosarcoma cells. [2020]

6. England pubmed.ncbi.nlm.nih.gov

Intravenous versus oral dexamethasone premedication in preventing Paclitaxel infusion hypersensitivity reactions in gynecological malignancies. [2018]

7. United States pubmed.ncbi.nlm.nih.gov

Meta-analysis of the effects of oral and intravenous dexamethasone premedication in the prevention of paclitaxel-induced allergic reactions. [2018]