Pemetrexed Disodium and Cisplatin Followed By Surgery and Radiation Therapy in Treating Patients With Malignant Pleural Mesothelioma

OBJECTIVES:

Primary

• Determine the feasibility of neoadjuvant chemotherapy comprising pemetrexed disodium and cisplatin followed by extrapleural pneumonectomy and high-dose postoperative 3D-conformal radiotherapy, in terms of 90-day progression-free survival, in patients with malignant pleural mesothelioma.

Secondary

• Determine the toxicity of this regimen in these patients.
• Determine progression-free survival and overall survival of patients treated with this regimen.

OUTLINE: This is a non-randomized, multicenter study.

• Neoadjuvant chemotherapy: Patients receive pemetrexed disodium IV over 10 minutes and cisplatin IV over 2 hours on day 1. Treatment repeats every 3 weeks for up to 3 courses in the absence of disease progression or unacceptable toxicity. Patients are evaluated 3 weeks after completion of neoadjuvant chemotherapy. Patients without disease progression proceed to surgery.
• Extrapleural pneumonectomy: Within 21-56 days after completion of neoadjuvant chemotherapy, patients undergo extrapleural pneumonectomy. Patients are evaluated 30 days after surgery. Patients without disease progression undergo high-dose 3D-conformal radiotherapy.
• High-dose 3D-conformal radiotherapy: Beginning 30-84 days after surgery, patients undergo high-dose 3D-conformal radiotherapy daily for 30 days.

After completion of study treatment, patients are followed on days 42 and 90, every 3 months for 1 year, and then every 6 months thereafter.

PROJECTED ACCRUAL: A total of 52 patients will be accrued for this study.

DISEASE CHARACTERISTICS:

• Histologically confirmed malignant pleural mesothelioma

• All subtypes allowed
• T1-3, N0-1, M0 disease

• No N2 or N3 involvement confirmed by mediastinoscopy within 21 days before study entry
• No clinical invasion of mediastinal structures (e.g., heart, aorta, spine, esophagus)
• No wide-spread chest wall invasion except focal chest wall lesions
• No clinical or radiological evidence of shrinking hemithorax
• No clinically significant third-space fluid (e.g., pleural effusions or ascites) that cannot be managed with thoracentesis or pleurodesis

PATIENT CHARACTERISTICS:

Age

• Under 70

Performance status

• WHO 0-1

Life expectancy

• Not specified

Hematopoietic

• WBC > 3,500/mm^3
• Absolute neutrophil count > 1,500/mm^3
• Platelet count > 100,000/mm^3
• Hemoglobin ≥ 11 g/dL

Hepatic

• AST and ALT < 1.5 times upper limit of normal (ULN)
• Bilirubin < 1.5 times ULN
• Alkaline phosphatase < 1.5 times ULN

Renal

• Creatinine clearance ≥ 60 mL/min
• Acceptable (predicted) post-radiotherapy renal function by semiquantitative isotope renography, with a relative contribution of the contralateral kidney of ≥ 40%

Pulmonary

• See Disease Characteristics

Other

• Not pregnant or nursing
• Negative pregnancy test
• Fertile patients must use effective contraception during and for 3 months after completion of study treatment
• Deemed to be fit enough to undergo study treatment
• No preexisting sensory neurotoxicity > grade 1
• No uncontrolled infection
• No prior or concurrent melanoma, breast cancer, or hypernephroma
• No other malignancy within the past 5 years except carcinoma in situ of the cervix or adequately treated basal cell skin cancer
• No psychological, familial, sociological, or geographical condition that would preclude study compliance

PRIOR CONCURRENT THERAPY:

Biologic therapy

• No concurrent immunotherapy
• No concurrent routine use of colony-stimulating factors during neoadjuvant chemotherapy

• Concurrent secondary prophylactic use allowed during neoadjuvant chemotherapy
• No concurrent secondary prophylactic use of colony-stimulating factors during post-operative radiotherapy

Chemotherapy

• No prior chemotherapy for mesothelioma

Endocrine therapy

• No concurrent hormonal cancer therapy

Radiotherapy

• No prior radiotherapy to the lower neck, thorax, or upper abdomen

Surgery

• See Disease Characteristics

Other

• No other concurrent anticancer therapy
• No other concurrent experimental medications
• No nonsteroidal anti-inflammatory drugs or salicylates for 2 days before, during, and 2 days after administration of neoadjuvant chemotherapy (5 days before and 2 days after for drugs with a long half-life [e.g., naproxen, piroxicam, diflunisal, or nabumetone])