Theophylline in Treating Cancer Patients With Shortness of Breath
Theophylline in Treating Cancer Patients With Shortness of Breath
RATIONALE: Theophylline may help to relieve shortness of breath in patients who have cancer.
 It is not yet known whether theophylline is more effective than no further treatment for
 shortness of breath.

 PURPOSE: Randomized phase III trial to determine the effectiveness of theophylline in
 treating shortness of breath in patients who have cancer.
OBJECTIVES: I. Determine whether theophylline will improve the dyspnea rating of patients
 with cancer who are short of breath and have evidence of respiratory muscle weakness. II.
 Determine whether this drug will improve the ability to perform daily activities in this
 group of patients. III. Determine whether this drug will improve objective measures of lung
 function (e.g., FEV-1, FVC) and maximum inspiratory pressure in these patients. IV. Determine
 whether the serum theophylline level is related to the magnitude of the effect that is
 observed in this patient population. V. Determine whether this drug will improve a global
 rating of quality of life in this patient group.

 OUTLINE: This is a randomized, double blind, multicenter study. Patients are stratified
 according to those who can complete a 6 minute walking test versus those who cannot. Patients
 receive either oral theophylline or placebo once daily for 3 days. In the absence of dose
 limiting toxicity (DLT), patients receive an increased dose for an additional 4 days. In the
 presence of DLT, patients receive a decreased dose or treatment is stopped. Following
 completion of the 7 day study period, patients may be given the option to continue on active
 drug or placebo for 1 additional month unless toxic side effects develop. Quality of life is
 assessed on days 1 and 8 and at the end of the additional 1 month period.

 PROJECTED ACCRUAL: A total of 60 patients (30 in each arm) will be accrued for this study.
DISEASE CHARACTERISTICS: Histologically or cytologically proven diagnosis of cancer
 FEV-1/FVC at least 80% of predicted OR FEV-1/FVC less than 80% AND improvement in FEV-1
 less than 15% after using a bronchodilator Maximum inspiratory pressure no greater than -50
 cm of water Oximetry at least 90% Rating of dyspnea "moderate" or "severe" on verbal rating
 scale (VRS) of "none, mild, moderate, or severe" to describe "usual breathlessness" when
 walking over the past 24 hours Score for pain of "none" or "mild" on a VRS of "none, mild,
 moderate, or severe" for "unusual pain" over the past 24 hours

 PATIENT CHARACTERISTICS: Age: 16 and over Performance status: Not specified Life
 expectancy: Greater than 10 days Hematopoietic: Hemoglobin at least 8.5 g/dL Hepatic:
 AST/ALT no greater than 2 times upper limit of normal (ULN) No liver disease Renal:
 Creatinine no greater than 2 times ULN No kidney disease Cardiovascular: No acute
 congestive heart failure Greater than 3 months since prior myocardial infarction No
 coronary artery disease where cardiac stimulation might prove harmful (i.e., no unstable
 angina) No uncontrolled hypertension Pulmonary: See Disease Characteristics Other: Folstein
 Mini-Mental Status Exam score of at least 24 Able (i.e., sufficiently fluent) and willing
 to complete quality of life questionnaire and other assessments in either English or French
 No history of clinically significant allergy or intolerance to theophylline, aminophylline,
 or other methylxanthines No active peptic ulcer disease No uncontrolled hyperthyroidism

 PRIOR CONCURRENT THERAPY: Biologic therapy: Not specified Chemotherapy: At least 14 days
 since prior chemotherapy No concurrent chemotherapy Endocrine therapy: At least 2 months
 since prior initiation of hormonal therapy Hormones as appetite stimulant allowed if
 received for more than 2 weeks No concurrent oral contraceptives Concurrent steroids
 allowed if taken for at least 1 week prior to study Concurrent inhaled or oral
 corticosteroids allowed if taken for at least 1 week prior to study No concurrent
 initiation of a new hormonal manipulation Radiotherapy: At least 28 days since prior
 radiotherapy that includes the lung in the treatment field No concurrent radiotherapy that
 includes the lung in the treatment field Surgery: Not specified Other: No concurrent
 digitalis glycosides, lithium, coumarin anticoagulants, other xanthines, cimetidine,
 quinolone antibiotics (e.g, ciprofloxacin and norfloxacin), macrolide antibiotics (e.g.,
 erythromycin), fluvoxamine, and calcium channel blockers Concurrent nebulized or inhaled
 cromolyn, nedocromil, beta2-agonists, ipratropium, opioids, benzodiazepines, oxygen, and
 diuretics allowed if dose is stable for more than 1 week prior to study No concurrent
 paracentesis (i.e., thoracentesis) No concurrent blood transfusion