Cisplatin With or Without Raltitrexed in Treating Patients With Malignant Mesothelioma of the Pleura

OBJECTIVES:

• Compare overall survival in patients with malignant pleural mesothelioma treated with raltitrexed with or without cisplatin.
• Assess toxicity, progression free survival, and quality of life with these treatment regimens in these patients.
• Evaluate objective response and duration of response to these treatment regimens in patients with measurable disease.

OUTLINE: This is a randomized, open, multicenter study. Patients are stratified according to performance status (0 vs 1-2) and WBC count (less than 8,300/mm3 vs 8,300/mm3 or more). Patients are randomized to one of two treatment arms.

• Arm I: Patients receive cisplatin IV over 1-2 hours on day 1.
• Arm II: Patients receive raltitrexed IV over 15 minutes followed by cisplatin IV over 1-2 hours on day 1.

Treatment continues every 3 weeks in the absence of disease progression or unacceptable toxicity.

Quality of life is assessed before study, prior to each course, after the last course, and then every 6 weeks for 1 year.

Patients are followed every 6 weeks until death.

PROJECTED ACCRUAL: A total of 240 patients will be accrued for this study over 24 months.

DISEASE CHARACTERISTICS:

• Histologically confirmed malignant pleural mesothelioma
• No CNS metastases

PATIENT CHARACTERISTICS:

Age:

• Over 18

Performance status:

• ZUBROD, ECOG, WHO 0-2

Life expectancy:

• Not specified

Hematopoietic:

• Hemoglobin at least 10.0 g/dL
• WBC at least 4,000/mm^3
• Absolute neutrophil count at least 2,000/mm^3
• Platelet count at least 100,000/mm^3

Hepatic:

• Bilirubin less than 1.46 mg/dL
• Albumin at least 3.0 g/dL
• ALAT/ASAT less than 2.5 times upper limit of normal (ULN) (less than 5 times ULN if liver involvement)

Renal:

• Creatinine less than 1.69 mg/dL
• Creatinine clearance at least 65 mL/min

Cardiovascular:

• Not specified

Pulmonary:

• Not specified

Other:

• No other prior or concurrent malignancies within past 5 years except adequately treated carcinoma in situ of the cervix or basal or squamous cell carcinoma of the skin
• No prior malignant melanoma, hypernephroma or breast carcinoma
• Not pregnant or nursing
• Negative pregnancy test
• Fertile patients must use effective contraception during and for 6 months after study
• No uncontrolled infections
• No psychological, familial, sociological, or geographical condition that precludes study compliance

PRIOR CONCURRENT THERAPY:

Biologic therapy:

• No concurrent immunotherapy before first disease progression

Chemotherapy:

• No prior systemic or intracavitary cytotoxic chemotherapy
• No other prior or concurrent chemotherapy before first disease progression
• No prior or concurrent pleurodesis with cytotoxic drugs (e.g., bleomycin)

Endocrine therapy:

• No concurrent hormonal therapy except corticosteroids before first disease progression

Radiotherapy:

• At least 4 weeks since prior radiotherapy to target lesion and progression observed
• Concurrent palliative radiotherapy to painful lesions allowed only if target lesion outside of irradiated field

Surgery:

• Prior surgery allowed if followed by disease progression

Other:

• At least 1 month since prior investigational drugs