Conventional Prophylactic Oral Dexamethasone vs Short-course IV Dexamethasone in Paclitaxel Hypersensitivity

One of the potentially serious and dose-limiting toxicities of paclitaxel is the development
of hypersensitivity reactions (HSRs). Up to 42% of patients receiving paclitaxel experience
an HSR, with serious (> grade 3) reactions observed in about 2% of patients. Paclitaxel
prescribing information and many other references therefore strongly recommend pre-medicating
patients who are to be treated with paclitaxel-containing regimen with a corticosteroid, a
histamine-1 (H1), and a histamine-2 (H2) antagonist prior to paclitaxel infusion. This is
done to help prevent or minimize the occurrence of HSRs that could be caused by treating
patients with paclitaxel. However, the method and timing of administering these
pre-medications (particularly in the case of dexamethasone) have not been standardized. The
current and most commonly used methods of preventing paclitaxel HSR includes one of the
following: 1. Administering oral dexamethasone (20 mg), 12 hours and 6 hours prior to
paclitaxel infusion and intravenous administration of H1 and H2 receptor antagonists 30
minutes prior to paclitaxel infusion (Conventional method); 2. Administering intravenous
dexamethasone (20 mg), concurrently with H1 and H2 antagonists, 30 minutes prior to
paclitaxel infusion (Short-course method); 3. Administering oral dexamethasone (20 mg), 12
hours prior to treatment in addition to intravenous dexamethasone (20 mg), H1 and H2 receptor
antagonists administered 30 minutes prior to paclitaxel infusion. The goal of this study is
to do a single center, prospective, randomized, open-label study to determine the most
effective method in preventing paclitaxel HSR among these three commonly used methods.

Inclusion Criteria:

1. Adult female patients > 18 years of age

2. Patients of the Loma Linda University Health (LLUH) gynecologic oncology service

3. Confirmed gynecologic cancer diagnosis of any stage and any gynecologic malignancy

4. Planned treatment with paclitaxel containing regimen either in the adjuvant setting or
for palliation

5. Planned treatment with paclitaxel should be for 3 or more cycles given as a weekly or
every 3 weeks cycle

6. Paclitaxel should be given as a monotherapy or as part of a combination regimen. If
paclitaxel is part of a regimen containing other drugs, the following conditions must
be met:

1. Paclitaxel will be the first chemotherapy regimen to be infused when patient
comes in for treatment

2. Chemotherapy regimen that would be approved for the study are the following:

i. Paclitaxel/ Carboplatin ii. Paclitaxel/Carboplatin/Bevacizumab iii.
Paclitaxel/Cisplatin/Bevacizumab iv. Paclitaxel/Bevacizumab v. Paclitaxel/ Ifosfamide
vi. Paclitaxel/ Pazopanib

7. Patients should have no prior exposure to taxanes (this includes: paclitaxel,
docetaxel, and protein-bound paclitaxel)

8. The chemotherapy treatment should be at one of the LLUH Adult Cancer Centers

9. The patient should be an English or Spanish speaking patient

Exclusion Criteria:

1. Patients who are not with the gynecologic oncology service

2. Patients who are with the gynecologic oncology service but are not receiving
paclitaxel either as a monotherapy or in combination with other regimen

3. Patients who have had prior exposure to taxanes (this includes: paclitaxel, docetaxel,
and protein-bound paclitaxel)

4. Patients who are currently on steroid therapy and it is anticipated that therapy will
not be discontinued at least a week prior to start of chemotherapy

5. Patients with autoimmune diseases, malignancies, and any other co-morbid condition
that might require steroid therapy during chemotherapy. This includes, but not limited
to:

1. Crohn's disease

2. Immune thrombocytopenia

3. Lupus nephritis

4. Multiple sclerosis

5. Primary brain tumors

6. Multiple Myeloma

7. Hodgkin's Lymphoma

6. Patients with uncontrolled diabetes or diabetic or pre-diabetic patients with baseline
A1C levels > 8.5

7. Patients who are allergic to diphenhydramine and/or dexamethasone

8. Non-English and Non-Spanish speaking patients