• Pathological complete response rate [ Designated as safety issue: No ]
  

OBJECTIVES:

Primary

• Determine the pathological complete response rate in patients with stage I, II, or III pleural mesothelioma treated with neoadjuvant pemetrexed disodium and cisplatin followed by extrapleural pneumonectomy and radiotherapy.

Secondary

• Determine the 1- and 2-year disease-free and median survival of patients treated with this regimen.
• Determine the clinical response rate by radiological assessment in patients treated with this regimen.
• Determine the quantitative and qualitative toxic effects of this regimen in these patients.
• Determine the pattern of relapse (local vs metastatic) in patients treated with this regimen.
• Determine the time to event efficacy variables (i.e., time to objective tumor response, time to treatment failure, time to progressive disease, and overall survival) in patients treated with this regimen.
• Correlate response to treatment with this regimen with levels of TS, DHFR, GARFT, FPGS, DPD, RFCI, alpha-FR, and ERCC1 in the mesothelioma tissue of these patients.

OUTLINE: This is an open-label, multicenter study.

• Preoperative chemotherapy: Patients receive pemetrexed disodium IV over 10 minutes and cisplatin IV over 1 hour on day 1. Treatment repeats every 21 days for 4 courses in the absence of disease progression or unacceptable toxicity.
• Extrapleural pneumonectomy: Patients undergo extrapleural pneumonectomy within 3-8 weeks after the last course of chemotherapy.
• Hemi-thoracic radiotherapy: Beginning 4-8 weeks after surgery, patients undergo radiotherapy to the chest once daily 5 days a week for 6 weeks.

Patients are followed every 3 months for 2 years.

PROJECTED ACCRUAL: A total of 77 patients will be accrued for this study.

DISEASE CHARACTERISTICS:

• Histologically confirmed pleural mesothelioma

  • Stage I, II, or III (T1-3, N0-2, M0)
• No cardiac involvement

PATIENT CHARACTERISTICS:

Age

• 18 and over

Performance status

• ECOG 0-1

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 9 g/dL

Hepatic

• Bilirubin no greater than 1.5 times upper limit of normal (ULN)
• Alkaline phosphatase no greater than 3.0 times ULN
• AST and ALT no greater than 3.0 times ULN

Renal

• Creatinine clearance at least 45 mL/min

Cardiovascular

• See Disease Characteristics
• Cardiac function adequate by radionuclide stress test, exercise stress test to maximal exercise level, or stress echocardiogram

Pulmonary

• FEV_1 at least 2 L OR at least 35% of predicted postoperative (ppoFEV_1)
• DLCO greater than 35% of ppoFEV_1
• PCO_2 less than 50 on ABG

Other

• Not pregnant or nursing
• Negative pregnancy test
• Fertile patients must use effective contraception during and for 3 months after study participation
• Able and willing to take folic acid, cyanocobalamin, or dexamethasone
• Willing to have cytoreduction by extrapleural pneumonectomy
• No active infection
• Suitable candidate for this study therapy
• No concurrent serious systemic disorder (e.g., active infection) that would compromise the patient's safety or ability to complete the study
• No other primary malignancy except carcinoma in situ of the cervix, adequately treated nonmelanoma skin cancer, low-grade (Gleason score no greater than 6) localized adenocarcinoma of the prostate, or other malignancy curatively treated within the past 2 years with no evidence of recurrence

PRIOR CONCURRENT THERAPY:

Biologic therapy

• No prior immunotherapy or biologic therapy
• No prior intracavity immunomodulators (chemical pleurodesis allowed)
• No concurrent immunotherapy or biologic therapy
• No concurrent routine filgrastim (G-CSF)
• No concurrent stimulator of thrombopoiesis

Chemotherapy

• No prior systemic chemotherapy
• No other concurrent chemotherapy

Endocrine therapy

• No concurrent anticancer hormonal therapy

Radiotherapy

• No prior radiotherapy
• No concurrent radiotherapy

Surgery

• No prior surgical resection of mesothelioma

  • Prior chemical pleurodesis allowed
• No concurrent anticancer surgery

Other

• More than 30 days since prior drug not approved for any indication
• No prior intracavity cytotoxic drugs (chemical pleurodesis allowed)
• No prior participation in this study or any other study investigating pemetrexed disodium
• No other concurrent experimental medication (thymidine allowed)
• No other concurrent anticancer therapy

• No nonsteroidal anti-inflammatory drugs (NSAIDs) or salicylates 2 days before, the day of, or 2 days after study therapy

  • No NSAIDs or salicylates with a long half-life (e.g., piroxicam or nabumetone) 5 days before, the day of, or 2 days after study therapy