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Clinical Trials

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

localized malignant mesothelioma advanced malignant mesothelioma recurrent malignant mesothelioma

Folic Acid Cisplatin Mesothelioma Raltitrexed

Adenoma Recurrence Neoplasms, Glandular and Epithelial

Mesothelioma Antimetabolites Neoplasms by Histologic Type Antimetabolites, Antineoplastic Molecular Mechanisms of Pharmacological Action Neoplasms, Mesothelial Antineoplastic Agents

Physiological Effects of Drugs Enzyme Inhibitors Folic Acid Antagonists Pharmacologic Actions Neoplasms Radiation-Sensitizing Agents Therapeutic Uses