Patient case: 49-year-old male with melanoma; genetic feature: extensive tumor infiltrating lymphocytes

Clinical trial: Combination Chemotherapy With or Without Filgrastim in Treating Patients With Previously Untreated Extensive-Stage Small Cell Lung Cancer

Summary: RATIONALE: Drugs used in chemotherapy use different ways to stop tumor cells from dividing so they stop growing or die. Colony-stimulating factors such as filgrastim may increase the number of immune cells found in bone marrow or peripheral blood and may help a person's immune system recover from the side effects of chemotherapy.
  PURPOSE: Phase II trial to compare the effectiveness of combination chemotherapy with or without filgrastim in treating patients who have extensive-stage small cell lung cancer that has not been previously treated.

Detailed description: OBJECTIVES:
  -  Determine the tolerability of topotecan and carboplatin with or without filgrastim (G-CSF) in patients with extensive stage small cell lung cancer.
  -  Determine response and survival rates in patients treated with these regimens.
  OUTLINE: This is a multicenter study. The first 12 patients are assigned to 1 of 2 treatment regimens (6 per regimen). The next 33 patients receive treatment based on the toxicity experienced by the first 12.
  Regimen A:
  -  Patients receive oral topotecan once daily on days 1-5, carboplatin IV over 30 minutes on day 5, and filgrastim (G-CSF) subcutaneously once daily beginning on day 6 or 7 and continuing for up to 10 days or until blood counts recover.
  -  Patients are evaluated after the first 3-week course of chemotherapy. If no patient experiences unacceptable toxicity or febrile neutropenia, or no more than 1 patient experiences an absolute neutrophil count of less than 500/mm3 for more than 5 days, the next 6 patients begin treatment on regimen B. Otherwise, all patients receive treatment as in regimen A.
  Regimen B:
  -  Patients receive topotecan and carboplatin as in regimen A.
  -  Patients are evaluated after the first 3-week course of chemotherapy. If no patient experiences unacceptable toxicity or febrile neutropenia, the next 33 patients receive treatment as in regimen B; otherwise, patients receive treatment as in regimen A.
  Treatment for all patients repeats every 3 weeks for up to 6 courses in the absence of disease progression or unacceptable toxicity. Patients with disease progression limited to CNS only interrupt chemotherapy to have whole-brain radiotherapy (WBRT). Once WBRT is complete, chemotherapy resumes.
  Quality of life is assessed at baseline and at the beginning of each course of chemotherapy.
  Patients are followed every 3 months for 2 years and then every 6 months for 3 years.
  PROJECTED ACCRUAL: A total of 49 patients will be accrued for this study within 13.5 months.

Eligibility: DISEASE CHARACTERISTICS:
  -  Histologically or cytologically confirmed extensive stage small cell lung cancer
  -  Previously untreated with chemotherapy
  -  No mixed histology
  -  Metastatic disease outside the chest
  -  Contralateral supraclavicular or hilar nodes that cannot be included in a single radiation port OR
  -  Cytologically proven malignant pleural effusion
  -  Measurable disease
  -  No untreated CNS metastases
  -  CNS metastases treated with whole-brain radiotherapy (WBRT) allowed after completion of WBRT
  PATIENT CHARACTERISTICS:
  Age:
  -  18 and over
  Performance status:
  -  ECOG 0-2
  Life expectancy:
  -  Not specified
  Hematopoietic:
  -  Absolute neutrophil count at least 1,500/mm^3
  -  Platelet count at least 100,000/mm^3
  Hepatic:
  -  AST no greater than 5 times upper limit of normal (ULN)
  -  Alkaline phosphatase no greater than 5 times ULN
  -  Bilirubin no greater than 1.5 times ULN OR
  -  Direct bilirubin no greater than ULN
  Renal:
  -  Creatinine no greater than 1.5 times ULN OR
  -  Creatinine clearance at least 50 mL/min
  Cardiovascular:
  -  No uncontrolled angina pectoris
  -  No congestive heart failure within the past 3 months unless ejection fraction is greater than 40%
  -  No uncontrolled cardiac arrhythmias
  -  No myocardial infarction within the past 3 months
  Other:
  -  Not pregnant or nursing
  -  Negative pregnancy test
  -  Fertile patients must use effective contraception
  -  No clinically significant infection
  -  No hypersensitivity to E. coli-derived proteins
  -  No other malignancy within the past 3 years except non-melanoma skin cancer, carcinoma in situ of the cervix, or localized prostate cancer
  PRIOR CONCURRENT THERAPY:
  Biologic therapy:
  -  Not specified
  Chemotherapy:
  -  See Disease Characteristics
  -  At least 5 years since prior chemotherapy for another malignancy
  -  No prior nitrosoureas
  Endocrine therapy:
  -  Not specified
  Radiotherapy:
  -  See Disease Characteristics
  -  No prior thoracic radiotherapy
  -  At least 1 day since prior palliative radiotherapy (except to chest)
  -  No more than 3 fractions to chest for superior vena cava syndrome allowed
  -  No concurrent radiotherapy (including thoracic radiotherapy)
  Surgery:
  -  More than 3 weeks since prior major surgery

Relevance to patient case: not relevant