Calcitriol in Preventing Lung Cancer in Smokers and Former Smokers at High Risk of Lung Cancer

A Pilot Study of Oral Calcitriol in Patients at High Risk for Lung Cancer

RATIONALE: Calcitriol may prevent lung cancer in patients with metaplasia or dysplasia of the lungs.

PURPOSE: This clinical trial is studying the side effects and best dose of calcitriol in preventing lung cancer in current smokers and former smokers at high risk of lung cancer.

OBJECTIVES:

Primary

• To establish the safety of calcitriol in patients at high risk of lung cancer.
• To determine the dose-limiting toxicities of calcitriol in these patients.

OUTLINE: Patients receive oral calcitriol on day 1. Courses repeat every 2 weeks for 3 months in absence of unacceptable toxicity.

Patients undergo blood collection periodically for pharmacokinetic and molecular analysis.

After completion of study therapy, patients are followed periodically.

DISEASE CHARACTERISTICS:

• Pathologically confirmed squamous metaplasia or squamous dysplasia of the lungs by autofluorescence bronchoscopy within the past 5 years

• Must be a current or former smoker

• No evidence of concurrent disease with lung cancer or head and neck cancer

  • History of treated lung cancer or head and neck cancer treated with curative intent allowed, provided that there has been no evidence of disease for > 1 year

PATIENT CHARACTERISTICS:

• ECOG performance status 0-1

• Total granulocyte count > 1,500 x 10^9cells/L

• Platelet count > 100,000 x 10^9cells/L

• Calculated Creatinine clearance > 60 mL/min (using the Cockcroft-Gault formula)

• Calcium concentration 50-300 mg/24 hours

• Total bilirubin 0.2-1.3 mg%

• ALT/AST ≤ 2.5 times upper limit of normal (ULN)

• Alkaline phosphatase ≤ 2.5 times ULN

• Albumin ≥ 2.5 g/dL

• Ionized serum calcium normal (1.19-1.29 mmol/L)

• Corrected serum calcium ≤ 10.2 mg/dL

• Willing to attend all scheduled study visits, complete all study questionnaires, and allow biological specimen collection, including a bronchoscopy

• Not pregnant or nursing

• Negative pregnancy test

• Fertile patients must use effective contraception during and for at least 1 month after completion of study therapy

• No life-threatening medical conditions that would preclude bronchoscopy, including but not limited to, any of the following:

  • Acute cardiac failure
  • Uncontrolled hypertension
  • Uncontrolled diabetes mellitus
  • Unstable coronary artery disease

• No severe metabolic disorders that would preclude calcitriol administration

• No history of any other malignancy within 3 years except for nonmelanoma skin cancer or cervical carcinoma in situ

• No history or evidence of kidney stones

• No patients who are susceptible to calcium-related dysrhythmias

• No known hypersensitivity to calcitriol

• No known allergies to tree nuts (i.e., almonds)

PRIOR CONCURRENT THERAPY:

• At least 2 months since prior and no concurrent calcium supplements
• Concurrent multivitamin supplement allowed provided the amount of vitamin D in the supplement is not in excess of the recommended daily dose
• No concurrent thiazides, phenobarbital, or digitalis
• No concurrent digoxin
• No concurrent bile acid binding drugs (i.e., cholestyramine, colestipol)
• No concurrent danazol or aluminum-based antacids
• No concurrent ketoconazole or other azole antifungals