Pemetrexed Disodium and Carboplatin in Treating Patients With Extensive-Stage Small Cell Lung Cancer

OBJECTIVES:

Primary

- Determine the complete and partial response rates in patients with previously
untreated, extensive-stage small cell lung cancer treated with pemetrexed disodium and
carboplatin.

Secondary

- Determine the toxicity of this regimen in these patients.

- Determine, preliminarily, the survival of patients treated with this regimen.

- Determine, preliminarily, the response rate in patients 70 years and older treated with
this regimen.

- Determine, preliminarily, the toxicity of this regimen in patients 70 years and older.

OUTLINE: This is a multicenter study. Patients are stratified according to age (< 70 years
vs ≥ 70 years).

Patients receive pemetrexed disodium IV over 10 minutes and carboplatin IV over 30 minutes
on day 1. Treatment repeats every 21 days for up to 6 courses in the absence of disease
progression or unacceptable toxicity. Patients who develop progressive disease in the CNS
only may receive whole-brain radiotherapy and then continue chemotherapy after completion of
whole-brain radiotherapy for up to 6 courses.

After completion of study treatment, patients are followed every 3 months for 1 year and
then every 6 months for 4 years.

PROJECTED ACCRUAL: Approximately 77 patients at least 46 who are < 70 years of age and at
least 24 who are ≥ 70 years of age) will be accrued for this study within 20-26 months.

DISEASE CHARACTERISTICS:

- Histologically or cytologically confirmed small cell lung cancer

- Previously untreated disease

- No mixed histology

- Extensive-stage disease

- Clinically significant effusions (e.g., symptomatic pleural effusion) must be
drained prior to treatment

- Measurable disease, defined as ≥ 1 unidimensionally measurable lesion ≥ 20 mm by
conventional techniques OR ≥ 10 mm by spiral CT scan

- No symptomatic, untreated, or uncontrolled CNS metastases

- CNS metastases previously treated with whole-brain radiotherapy allowed

PATIENT CHARACTERISTICS:

Age

- 18 and over

Performance status

- ECOG 0-2

Life expectancy

- At least 12 weeks

Hematopoietic

- Absolute neutrophil count ≥ 1,500/mm^3

- Platelet count ≥ 100,000/mm^3

- Hemoglobin ≥ 9.0 g/dL

Hepatic

- Total bilirubin ≤ 1.5 times upper limit of normal (ULN) OR

- Direct bilirubin normal

- ALT and AST ≤ 3 times ULN (5 times ULN if there is liver involvement)

Renal

- Creatinine clearance ≥ 45 mL/min

Cardiovascular

- No angina pectoris

- No congestive heart failure within the past 3 months, unless ejection fraction > 40%

- No cardiac arrhythmia

- No myocardial infarction within the past 3 months

- No hypertension, including labile hypertension

Pulmonary

- No interstitial pneumonia

- No extensive and symptomatic interstitial fibrosis of the lung

Other

- Not pregnant or nursing

- Negative pregnancy test

- Fertile patients must use effective contraception

- No history of poor compliance with antihypertensive medication

- Able to take folic acid, cyanocobalamin (vitamin B_12) supplementation, or
dexamethasone

- No uncontrolled diabetes

- No serious condition that would preclude study participation

- No clinically significant infection

- No significant traumatic injury

- No other malignancy within the past 5 years except carcinoma in situ of the cervix or
nonmelanoma skin cancer

- Low-grade (Gleason score ≤ 6), localized prostate cancer allowed even if
diagnosed < 5 years prior to study entry

- No seizure disorder

- No other severe and/or uncontrolled medical condition

PRIOR CONCURRENT THERAPY:

Biologic therapy

- No concurrent immunotherapy

- No concurrent immunomodulating agents

Chemotherapy

- No other concurrent chemotherapy

Endocrine therapy

- No concurrent hormonal therapy

Radiotherapy

- See Disease Characteristics

- Prior palliative radiotherapy allowed

- No prior palliative radiotherapy to the chest except for ≤ 3 fractions for
superior vena cava syndrome

- No concurrent radiotherapy

Surgery

- More than 4 weeks since prior major surgery* (i.e., laparotomy) or open biopsy

- More than 2 weeks since prior minor surgery* NOTE: *Insertion of a vascular access
device is not considered major or minor surgery

Other

- More than 4 weeks since prior investigational therapy

- No concurrent Hypericum perforatum (St. John's wort)

- No concurrent inducers or inhibitors of CYP3A4

- No concurrent medications that are metabolized by CYP3A4

- No aspirin dose ≥ 1.3 grams per day for ≥ 10 days prior to and after study treatment

- No other concurrent cytostatic or cytotoxic agents