Randomized, Blinded Trial of Mesna to Prevent Doxorubicin-induced Plasma Protein Oxidation and TNF-α Release
Participants must have histologically or cytologically confirmed breast cancer or
non-hodgkin lymphoma and independent of protocol eligibility be determined to require one
of the chemotherapy regimens listed below
Participants must require as standard-of-care treatment a chemotherapy regimen that
includes one of the following combinations:
- doxorubicin 60 mg/m2 and cyclophosphamide 600 mg/m2;
- doxorubicin 50 mg/m2, cyclophosphamide 500 mg/m2, and docetaxel 75 mg/m2;
- doxorubicin 50 mg/m2, cyclophosphamide 750 mg/m2, vincristine 1.4 mg/m2 (capped at 2
mg dose), and prednisone 100 mg +/- rituximab 375 mg/m2
Age >18 years.Because these treatment regimens are rarely used in pediatric oncology,
children are excluded from this study but will be eligible for future pediatric phase 2
Life expectancy of greater than 6 months.
Zubrod performance status 2 or better.
Patients must have normal organ and marrow function as defined below:
- leukocytes >3,000/mcL (unless due to cancer in marrow)
- absoluteneutrophil count >1,500/mcL (unless due to cancer in marrow)
- platelets >100,000/mcL (unless due to cancer in marrow)
- total bilirubin <1.5 X normal institutional limits
- AST(SGOT)/ALT(SGPT) <2.5 X institutional upper limit of normal
- creatinine within normal institutional limits OR
- creatinine clearance >60 mL/min/1.73 m2 for patients with creatinine levels above
- left ventricular function ≥ 50 % ejection fraction
Because the standard of care chemotherapy agents are known to be teratogenic, women of
child-bearing potential and men must agree to use adequate contraception (hormonal or
barrier method of birth control; abstinence) prior to study entry and for the duration of
study participation. Should a woman become pregnant or suspect she is pregnant while
participating in this study, she should inform her treating physician immediately.
Ability to understand and the willingness to sign a written informed consent document.
Patients who have had chemotherapy or radiotherapy within 4 weeks (6 weeks for
nitrosoureas or mitomycin C) prior to entering the study or those who have not recovered
from adverse events due to agents administered more than 4 weeks earlier.
Patients may not be receiving any other investigational agents
Patients with known brain metastases should be excluded from this clinical trial because
progressive neurologic dysfunction would confound the evaluation of neuro-cognitive
History of allergic reactions attributed to compounds of similar chemical or biologic
composition to mesna or other agents used in the study (ie. sulfur containing drugs
including "sulfa antibiotics" and celecoxib).
Patients requiring ongoing pharmacologic treatment of dementia are excluded.
Uncontrolled intercurrent illness including, but not limited to, ongoing or active
infection, symptomatic congestive heart failure, unstable angina pectoris, cardiac
arrhythmia, or psychiatric illness/social situations that would limit compliance with
Pregnant women are excluded from this study because the chemotherapy agents have known
teratogenic or abortifacient effects. Because there is a potential risk for adverse events
in nursing infants secondary to treatment of the mother with chemotherapy, breastfeeding
should be discontinued if the mother is treated with chemotherapy.
HIV-positivity is NOT a specific exclusion criteria.