AZD2171 and Standard Combination Chemotherapy in Advanced Non-Small Cell Lung Cancer or Colorectal Cancer

DISEASE CHARACTERISTICS:

• Histologically or cytologically confirmed diagnosis of 1 of the following:

  • Non-small cell lung cancer (NSCLC), meeting 1 of the following criteria:

    • Stage IIIB disease

      • No pleural effusion and not a candidate for a combined modality treatment
    • Stage IV disease
    • Local or metastatic failure after surgery and/or radiotherapy

  • Colorectal cancer (CRC)

    • Advanced and/or metastatic disease
    • Suitable for first-line therapy with oxaliplatin, leucovorin calcium, and fluorouracil (FOLFOX-6)

• Clinically or radiologically documented disease

  • No tumor marker elevation as sole evidence of disease
• No necrotic/hemorrhagic metastases or tumor

• No untreated brain or meningeal metastases

  • Previously treated, radiologic or clinical evidence of stable brain metastases allowed provided disease is asymptomatic and corticosteroids are not required

PATIENT CHARACTERISTICS:

• ECOG performance status 0-2
• Hemoglobin normal
• Absolute granulocyte count ≥ 1,500/mm³
• Platelet count ≥ 100,000/mm³
• Creatinine ≤ 1.5 times upper limit of normal (ULN) OR creatinine clearance ≥ 50 mL/min
• Bilirubin ≤ 1.5 times ULN
• AST or ALT ≤ 2 times ULN (5 times ULN if liver involvement)
• Proteinuria ≤ grade 1
• Not pregnant or nursing
• Negative pregnancy test
• Fertile patients must use effective contraception
• No history of other malignancies except adequately treated nonmelanoma skin cancer or other solid tumors curatively treated with no evidence of disease for ≥ 5 years
• No untreated and/or uncontrolled cardiovascular conditions or symptomatic cardiac dysfunction
• No resting blood pressure (BP) consistently higher than systolic BP > 150 mm Hg and diastolic BP > 100 mm Hg (in the presence or absence of a stable dose of antihypertensive medication)
• No poorly controlled hypertension, history of labile hypertension, or poor compliance with antihypertensive medication
• No overt bleeding (≥ 30 mL bleeding/episode) within the past 3 months

• No clinically relevant hemoptysis (≥ 5 mL fresh blood) within the past 4 weeks

  • Flecks of blood in sputum allowed
• No active or uncontrolled infections
• No serious illnesses or medical conditions that would preclude compliance with study requirements
• No mean QTc with Bazett's correction > 470 msec
• No history of familial long QT syndrome
• No peripheral neuropathy > grade 1
• No dihydropyrimidine dehydrogenase deficiency or history of severe hand-foot syndrome after fluoropyrimidines (for patients with CRC)

PRIOR CONCURRENT THERAPY:

• See Disease Characteristics
• Recovered from prior therapy
• At least 6 months since prior adjuvant or neoadjuvant therapy
• At least 6 months since prior adjuvant radiotherapy
• At least 4 weeks since prior chemotherapy (6 weeks for nitrosoureas and mitomycin C) (for patients with NSCLC)
• At least 4 weeks since prior and no concurrent corticosteroids

• At least 3 weeks since prior palliative radiotherapy and recovered

  • Concurrent palliative radiotherapy allowed
• At least 2 weeks since prior epidermal growth factor receptor inhibitor therapy
• At least 2 weeks since prior major surgery
• No more than 1 prior single-agent, nonplatinum-containing chemotherapy regimen for metastatic disease (for patients with NSCLC)
• No prior gemcitabine hydrochloride (for patients with NSCLC)
• No prior oxaliplatin (for patients with CRC)
• No prior angiogenesis inhibitor
• No prior chemotherapy for advanced/metastatic disease (for patients with CRC)
• No other concurrent experimental drugs or anticancer therapy