This study will evaluate the safety and effectiveness of micellar paclitaxel for treating
severe psoriasis. Paclitaxel in another formulation (Taxol) is approved by the Food and
Drug Administration for use in patients with cancer. This drug can decrease growth of
cancer cells and of new blood vessels. Because patients with psoriasis have an increase in
skin cell and blood vessel growth, paclitaxel may also improve their condition. The dose of
drug used in this study is much lower than those used to treat cancer patients and is
expected to cause relatively few side effects.
Patients 18 to 70 years of age with psoriasis lesions affecting at least 20% of their skin
may be eligible for this study. Candidates will be screened with a history and physical
examination, blood and urine tests, electrocardiogram, and possibly an exercise stress test.
Participants will receive six intravenous (through a vein) infusions of paclitaxel over a
6-month period. Each infusion will take about 2 hours. Patients will stay in the clinic
for observation for at least 1 hour before going home and will return to the clinic for
follow-up examination and tests one week after each infusion. However, on weeks 0 and 8
visit will last for approximately 8 hours and will require a return to the clinic the
following morning. Blood collection will be performed during the week 0 and 8 visits to
determine how fast Micellar Paclitaxel is eliminated from your body. Approximately 2
teaspoons of blood will be taken prior to the infusion, twice during the infusion, and eight
times during the 22 hours following the infusion for a total of eleven samples. These
return visits will last approximately 1-2 hours. Patients will have the following
1. A skin biopsy (removal of a small tissue sample for microscopic examination) will be
done at the first visit (week 0) and again at weeks 6, 14 and 22. The area of the
biopsy will be numbed with an anesthetic, and a small circle of skin about the width of
a pencil eraser and half as deep will be cut and lifted away. Stitches will be placed
and removed 1 to 2 weeks later.
2. A history and physical examination will be done at every visit. Patients will be
interviewed about changes in their skin condition and about treatment side effects and
will be examined by a nurse or physician.
3. Blood and urine samples will be collected at frequent intervals (nearly every visit) to
test for side effects.
4. Photographs of the skin will be taken at the first visit and at several later visits to
document changes in psoriasis.
5. A blood sample will be drawn for genetic testing to look for gene changes in people
6. An electrocardiogram will be taken at the last visit. This will be done at week 24 and
compared to the screening EKG.
7. Gonadal toxicity monitoring will be started with all patients entered into the protocol
as of May 2001. Blood will be drawn to measure Inhibit A for females and Inhibit B for
males at weeks 0, 6, 14, and 22.
Paclitaxel is an antiangiogenic chemotherapeutic drug approved by the FDA for use in cancer.
There is anecdotal evidence that some patients with cancer and concomitant psoriasis have
shown improvement in their skin while receiving paclitaxel for cancer. Angiotech
Pharmaceutical, Inc., the company with commercial rights over non-cancer uses of paclitaxel,
has data that suggests paclitaxel demonstrates anti-inflammatory and immunomodulatory
properties, in addition to the better known antiangiogenic and antiproliferative effects
attributed to this compound. In this pilot open-label single-dose study, we initially
treated patients with severe refractory psoriasis using intravenous Micellar Paclitaxel (75
mg/m(2) every 4 weeks) for six months. Because this dosing regimen was well tolerated and
because the dosing interval seemed too long, we now propose to treat patients with
intravenous Micellar Paclitaxel at the adjusted dose of 37.5 mg/m(2) every 2 weeks.
Ability to provide informed consent to all aspects of the study after full information is
Age equal or greater than 18 years, but not greater than 70 years old.
Severe psoriasis of at least 6 months duration as defined by the following criteria:
Classic psoriatic skin lesions with or without nail involvement; PASI score greater than
or equal to 20.
Therapeutic failure or inability to tolerate at least two alternative therapies for severe
psoriasis (e.g., methotrexate, acitretin, cyclosporine A, PUVA, UVB, interleukin-10).
Ability to obtain intravenous access.
Negative urine pregnancy test (if female), and if pre-menopausal and sexually active,
using two effective forms of contraception (one form being a barrier method).
WBC count greater than 5,000/mm(3).
Neutrophils greater than 2,500/mm(3).
Platelets greater than or equal to 125,000/mm(3).
Hemoglobin greater than or equal to 10 mg/dL.
Creatinine less than or equal to 1.4 mg/dL.
AST and ALT less than 2 times upper limits of normal.
Normal EKG (if any abnormalities suggestive of coronary artery disease then a normal
stress thallium test will be required for entry).
Use of topical or systemic medications for psoriasis (except for bland emollients) during
2 weeks prior to study entry.
Pregnant or nursing women.
Current drug or alcohol abuse.
Evidence of HIV exposure or of chronic/active hepatitis.
Persons who are allergic to bee stings.
History of anaphylactic reactions.
Prior or concurrent malignancies, except non-melanoma skin cancer or carcinoma in situ of
the cervix that have been adequately treated.
Any clinically significant past or current history of coronary artery disease.
Any confounding past or present medical illness that in the judgement of the investigators
would pose added risk for study participants.