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