Lapatinib in Treating Patients With Prostate Cancer That Did Not Respond to Hormone Therapy

DISEASE CHARACTERISTICS:

• Histologically confirmed adenocarcinoma of the prostate

• Hormone-refractory disease

  • Prior androgen-deprivation therapy (either bilateral orchiectomy or medical castration resulting in a testosterone level < 50 ng/dL) for prostate cancer required

    • Biochemical progression on androgen-deprivation therapy with rising PSA, defined as elevated PSA (≥ 5 ng/mL) that has risen serially from baseline on 2 occasions ≥ 1 week apart
• No known brain metastases

PATIENT CHARACTERISTICS:

• ECOG performance status 0-2
• Life expectancy > 12 weeks
• WBC ≥ 3,000/mm³
• ANC ≥ 1,500/mm³
• Platelet count ≥ 100,000/mm³
• Bilirubin normal
• AST and ALT ≤ 2.5 times upper limit of normal
• Creatinine normal OR creatinine clearance ≥ 60 mL/min
• Cardiac ejection fraction normal by ECHO or MUGA
• Fertile patients must use effective contraception
• Able to swallow and retain oral medication
• No history of allergic reaction to compounds of similar chemical or biological composition to lapatinib ditosylate
• No other concurrent illness including, but not limited to, ongoing or active infection, symptomatic congestive heart failure, unstable angina pectoris, or cardiac arrhythmia
• No psychiatric illness or social situation that would limit study compliance
• No HIV positivity
• No gastrointestinal (GI) tract disease resulting in an inability to take oral medication
• No malabsorption syndrome
• No requirement for IV alimentation
• No uncontrolled inflammatory GI disease (e.g., Crohn's, ulcerative colitis)
• No current active hepatic or biliary disease (with the exception of patients with Gilbert syndrome, asymptomatic gallstones, liver metastases, or stable chronic liver disease per investigator assessment)

PRIOR CONCURRENT THERAPY:

• Recovered from all prior therapies
• No prior chemotherapy for prostate cancer
• No prior or concurrent cytotoxic chemotherapy
• At least 4 weeks since prior anti-androgen therapy, including flutamide (6 weeks for bicalutamide and nilutamide)
• At least 4 weeks since prior radiotherapy
• At least 4 weeks since prior surgery
• At least 4 weeks since other prior hormonal therapy, including ketoconazole, megestrol acetate, and aminoglutethimide
• At least 4 weeks since other prior chemotherapy
• At least 4 weeks since prior investigational agents

• At least 7 days since prior and no concurrent inhibitors of CYP3A4, including any of the following:

  • Antibiotics (clarithromycin, erythromycin, troleandomycin)
  • Antifungals (itraconazole, ketoconazole, fluconazole [> 150 mg daily], voriconazole)
  • Antiretrovirals or protease inhibitors (delavirdine, nelfinavir, amprenavir, ritonavir, indinavir, saquinavir, lopinavir)
  • Calcium channel blockers (verapamil, diltiazem)
  • Antidepressants (nefazodone, fluvoxamine)
  • Gastrointestinal agents (cimetidine, aprepitant)
  • Grapefruit or grapefruit juice
• At least 6 months since prior and no concurrent amiodarone
• At least 14 days since prior and no concurrent herbal or dietary supplements

• At least 14 days since prior and no concurrent inducers of CYP3A4, including any of the following:

  • Antibiotics (all rifamycin class agents [e.g., rifampicin, rifabutin, rifapentine])
  • Anticonvulsants (phenytoin, carbamazepine, barbiturates [e.g., phenobarbital])
  • Antiretrovirals (efavirenz, nevirapine)

  • Glucocorticoids (cortisone [> 50 mg], hydrocortisone [> 40 mg], prednisone [> 10 mg], methylprednisolone [> 8 mg], dexamethasone [> 1.5 mg])

    • Daily oral glucocorticoid doses ≤ 1.5 mg of dexamethasone (or equivalent) allowed
  • Hypericum perforatum (St. John's wort)
  • Modafinil
• No prior ErbB family-targeting therapies
• No prior surgical procedures affecting absorption
• No concurrent local radiotherapy for pain control or life-threatening situations (i.e., spinal cord compression, superior vena cava syndrome)