Patient case: 45-year-old female with colon cancer; genetic feature: ERBB2 amplification

Clinical trial: Gefitinib With or Without Carboplatin and Paclitaxel in Treating Older Patients With Unresectable or Metastatic Non-Small Cell Lung Cancer

Summary: RATIONALE: Biological therapies such as gefitinib may interfere with the growth of cancer cells and slow the growth of the tumor. Drugs used in chemotherapy such as carboplatin and paclitaxel use different ways to stop tumor cells from dividing so they stop growing or die. Combining gefitinib with carboplatin and paclitaxel may kill more tumor cells.
  PURPOSE: This phase II trial is studying how well giving gefitinib alone or together with carboplatin and paclitaxel works in treating older patients with unresectable or metastatic non-small cell lung cancer.

Detailed description: OBJECTIVES:
  Primary
  -  Determine the 6-month progression status of older patients with unresectable or metastatic non-small cell lung cancer treated with gefitinib alone or with carboplatin and paclitaxel.
  Secondary
  -  Determine the response rate in patients treated with these regimens.
  -  Determine the quality of life of patients treated with these regimens.
  -  Determine whether serum-secreted or soluble epidermal growth factor receptor (EGFR) concentrations predict response in patients treated with these regimens.
  -  Correlate the presence of social support for these patients with toxicity and efficacy of these regimens.
  -  Determine whether social support for these patients differs according to gender.
  -  Determine the reasons an oncologist would choose a chemotherapy vs a nonchemotherapy regimen for these patients.
  Tertiary
  -  Correlate EGFR signaling pathway markers, RNA expression profile, gene polymorphisms of prespecified germline and tumor genes, and plasma and urine proteomic patterns with response rate and time to progression of patients receiving treatment in group I.
  OUTLINE: This is a nonrandomized, multicenter study. Patients are assigned to 1 of 2 treatment groups as determined by their treating physician.
  -  Group I: Patients receive oral gefitinib on days 1-28. Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity.
  -  Group II: Patients receive paclitaxel IV over 1 hour and carboplatin IV over 30 minutes on days 1, 8, and 15. Treatment repeats every 28 days for up to 4 courses in the absence of disease progression or unacceptable toxicity. After completion of chemotherapy and in the absence of disease progression, patients receive oral gefitinib as in group I.
  Quality of life is assessed at baseline and after the completion of course 2.
  Patients are followed every 3 months for 5 years.
  PROJECTED ACCRUAL: A total of 107 patients (51 for group I and 56 for group II) will be accrued for this study within 1.7 years.

Eligibility: DISEASE CHARACTERISTICS:
  -  Histologically or cytologically confirmed non-small cell lung cancer (NSCLC)
  -  Metastatic or unresectable disease
  -  Measurable disease
  -  At least 1 lesion at least 2.0 cm
  -  Disease must be completely outside prior radiotherapy port OR documented disease progression since the completion of radiotherapy
  -  No meningeal carcinomatosis
  -  No untreated brain metastases
  -  Current metastatic CNS disease must have been treated and clinically stable for at least 2 weeks prior to study chemotherapy
  -  No potentially curative treatment options available (e.g., chemotherapy with surgery or radiotherapy)
  PATIENT CHARACTERISTICS:
  Age
  -  65 and over
  Performance status
  -  ECOG 0-2
  Life expectancy
  -  At least 12 weeks
  Hematopoietic
  -  Absolute neutrophil count at least 1,500/mm^3
  -  Platelet count at least 100,000/mm^3
  -  Hemoglobin at least 10.0 g/dL
  Hepatic
  -  Bilirubin no greater than 2.0 mg/dL
  -  No uncontrolled hepatic disease
  Renal
  -  Creatinine no greater than 2 times upper limit of normal
  -  No uncontrolled renal disease
  Cardiovascular
  -  No uncontrolled cardiac disease
  Pulmonary
  -  No clinically active interstitial lung disease
  -  Asymptomatic, chronic stable radiographic changes allowed
  -  No uncontrolled respiratory disease
  Other
  -  Fertile patients must use effective contraception
  -  Able and willing to complete questionnaires alone or with assistance
  -  No known hypersensitivity to gefitinib or any of its excipients
  -  No active infection within the past 2 weeks
  -  No other prior malignancy within the past 5 years except basal cell skin cancer
  -  No grade 2 or greater peripheral neuropathy (CTC v2.0)
  -  No uncontrolled diabetes mellitus (for patients receiving study chemotherapy)
  -  No dysphagia or inability to swallow intact capsules
  -  No significant medical condition that would preclude study treatment or follow-up
  -  No severe or uncontrolled systemic disease
  PRIOR CONCURRENT THERAPY:
  Biologic therapy
  -  Not specified
  Chemotherapy
  -  See Disease Characteristics
  -  No prior chemotherapy for metastatic NSCLC
  Endocrine therapy
  -  Concurrent steroids allowed provided the dose is not changed
  Radiotherapy
  -  See Disease Characteristics
  -  At least 3 weeks since prior radiotherapy and recovered
  -  No prior radiotherapy to more than 25% of marrow-containing skeleton
  -  No concurrent radiotherapy (including palliative)
  Surgery
  -  See Disease Characteristics
  -  At least 3 weeks since prior major surgery
  -  No surgery within 7 days after study participation
  Other
  -  More than 30 days since prior non-FDA approved investigational drugs
  -  No concurrent oral retinoids
  -  No concurrent CYP3A4-inducing agents, including the following:
  -  Carbamazepine
  -  Oxcarbazepine
  -  Modafinil
  -  Ethosuximide
  -  Griseofulvin
  -  Nafcillin
  -  Phenobarbital
  -  Phenylbutazone
  -  Phenytoin
  -  Primidone
  -  Rifampin
  -  Hypericum perforatum (St. John's wort)
  -  Barbiturates
  -  Sulfinpyrazone
  -  No concurrent drugs that cause sustained elevation of gastric pH (≥ 5)
  -  No concurrent antacids within 4 hours before, during, and within 4 hours after gefitinib administration
  -  No concurrent itraconazole, fluconazole, ketoconazole, or erythromycin

Relevance to patient case: not relevant