Vitamin E in Preventing Peripheral Neuropathy Caused by Chemotherapy in Patients Receiving Chemotherapy for Cancer

OUTLINE: This is a randomized, double-blind, placebo-controlled, multicenter study. Patients
are stratified according to type of chemotherapy (taxane vs cisplatin vs carboplatin vs
oxaliplatin vs combination), age (≤ 50 years vs > 50 years), and gender. Patients are
randomized to 1 of 2 treatment arms.

OBJECTIVES:

Primary

- Compare the incidence of chemotherapy-induced sensory peripheral neuropathy ≥ grade 2
in patients undergoing curative neurotoxic chemotherapy for cancer treated with vitamin
E vs placebo.

Secondary

- Compare the proportion of patients requiring dose reductions of chemotherapy secondary
to sensory peripheral neuropathy.

- Compare the proportion of patients stopping chemotherapy before treatment is complete
secondary to sensory peripheral neuropathy.

- Assess the toxicity of vitamin E in these patients.

After completion of study treatment, patients are followed at 6 months.

Required Characteristics:

1. Scheduled to undergo curative-intent adjuvant treatment with neurotoxic chemotherapy.
Patients must have had his/her tumor removed, but may have microscopic residual
disease, or residual margin involvement and still be eligible.

The patient's chemotherapy regimen must include one or more of the following
neurotoxic chemotherapeutic agents: taxanes (paclitaxel, docetaxel); platinum
compounds (cisplatin, carboplatin, oxaliplatin)-(oxaliplatin patients should
preferentially be enrolled in protocol N04C7 while it is available).

2. ≥ 18 years of age

3. Ability to sign informed consent and understand the nature of a placebo-controlled
trial

4. ECOG Performance Status (PS) of 0, 1, or 2 e.g.

5. Ability to complete questionnaire(s) by themselves or with assistance

6. Life expectancy ≥ 6 months

Contraindications:

1. Undergoing chemotherapy for palliative care

2. Pre-existing history of peripheral neuropathy due to any cause (diabetes, alcohol,
toxin, hereditary, etc).

3. Prior treatment with neurotoxic chemotherapy (exception: Patient started neurotoxic
chemotherapy ≤ 4 days of starting vitamin E on this study and has not been treated
previously with other neurotoxic chemotherapy agents).

4. Taking regular opioid-containing medications. (Exception: opioids, given for the
short term treatment of chemotherapy-induced myalgias or arthralgias caused by
taxanes are permitted.)

5. Concurrent treatment with anticonvulsants, tricyclic antidepressants, or other
neuropathic pain medications agents such as carbamazepine, phenytoin, valproic acid,
gabapentin, lamotrigine, topical lidocaine patch, capsaicin cream, etc.

6. History of coronary artery disease (i.e. MI, PTCA, or CABG ≤ 5 years or diagnosis of
congestive heart failure of any NY heart class I-IV) Valve replacements are permitted
as long as patient has fully recovered from the surgery.

7. Other medical conditions, which in the opinion of the treating physician/allied
health professional would make this protocol unreasonably hazardous for the patient.

8. Vitamin E supplementation for any reason ≤ 7 days prior to randomization. (Exception:

one multivitamin per day that contains ≤ 100 IU [mg] of Vitamin E, will be
permitted.)

9. Any of the following: pregnant women, nursing women and men or women of childbearing
potential who are unwilling to employ adequate contraception

10. Taking anticoagulant medication (i.e. coumadin, low molecular weight heparin (LMWH),
or platelet aggregation inhibitors such as clopidgrel or aspirin) with the exception
that 1 mg/day of coumadin for central line maintenance is allowed.

11. Diagnosed diabetes requiring insulin or oral hypoglycemic medications

12. Head or neck cancers

13. Scheduled to undergo radiation therapy while on study

14. History of hemorrhagic stroke

15. Patients receiving neo-adjuvant therapy