Please select the eligibility criteria that correspond to the clinical trial below.
Title: Neoadjuvant Chemotherapy and Extrapleural Pneumonectomy of Malignant Pleural Mesothelioma (MPM) With or Without Hemithoracic Radiotherapy. A Randomized Multicenter Phase II Trial
Brief Summary: RATIONALE: Drugs used in chemotherapy, such as pemetrexed disodium and cisplatin, work in different ways to stop the growth of tumor cells, either by killing the cells or by stopping them from dividing. Giving chemotherapy before surgery may make the tumor smaller and reduce the amount of normal tissue that needs to be removed. Radiation therapy uses high-energy x-rays to kill tumor cells. Giving radiation therapy after surgery may kill any tumor cells that remain after surgery.

PURPOSE: This randomized phase II trial is studying how well giving pemetrexed disodium together with cisplatin followed by surgery with or without radiation therapy works in treating patients with malignant pleural mesothelioma.


Options:
A: 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 \[e.g., naproxen, piroxicam, diflunisal, or nabumetone\])
B: Inclusion Criteria:

* Malignant, histologically proved, non resectable pleural Mesothelioma
* In case of pleural effusion, a talc pleurodesis, although not recommended, is allowed in accordance with current local practice, at the time of diagnostic thorascopy, with inclusion CT scan performed after pleurodesis.
* ECOG Performance status 0-2
* Mesothelioma with only pleural effusion without uni- or bidimensionally measurable disease will be eligible (adapted RECIST criteria)
* At least 18 years of age, less than 76 years of age
* Radiation therapy of thoracocentis tract (3 x 7Gy) performed before beginning medical study treatment, and the interval between thoracoscopic procedure and radiation will not exceed 28 days

Exclusion Criteria:

* Prior chemotherapy
* Brain metastasis
* History of cerebral vascular accident (CVA) or transient ischemic attack
C: Inclusion Criteria:

* Histologically or cytologically confirmed malignant mesothelioma (MM)
* Have received only one prior systemic chemotherapy platinum-based regimen for advanced MM
* Disease not amenable to curative surgery
* No known brain metastasis
* Age 18 and over
* Performance status 0-2
* Life expectancy \> 12 weeks
* Adequate hematologic, hepatic and renal function
* Not pregnant or nursing
* Patient must be willing and able to provide written informed consent, and the trial have to be approved by the institutional review board at each institution

Exclusion Criteria:

* Symptomatic chronic inflammatory or autoimmune disease
* Active hepatitis B or C
* Clinically relevant cardiovascular disease, i.e., myocardial infarction or other severe coronary artery diseases within the prior 6 months, cardiac arrythmia requiring medication, uncontrolled hypertension, overt cardiac failure or not compensated chronic heart disease in NYHA class II or more
* History of psychiatric disabilities, potentially interfering with the capability of giving adequate informed consent
* Uncontrolled active infections
* Other concurrent chemotherapy, immunotherapy, radiotherapy or investigational agents
* History of other malignancies except for adequately treated basal cell carcinoma or squamous cell skin cancer or carcinoma of cervix, unless the patient has been disease-free for at least 5 years
D: DISEASE CHARACTERISTICS:

* Histologically or cytologically confirmed malignant pleural mesothelioma

  * T1-3, N0-2, M0 disease according to International Mesothelioma Interest Group staging system
* No obvious invasion of mediastinal structures by CT scan (e.g., heart, aorta, spine, esophagus)
* No obvious widespread chest wall invasion

  * Resectable chest wall lesions allowed

PATIENT CHARACTERISTICS:

* WHO performance score 0-1
* Fit for neoadjuvant therapy, surgery, and postoperative radiotherapy
* Creatinine clearance \> 60 mL/min
* Hemoglobin ≥ 10.0 g/dL
* WBC ≥ 3,500/mm³
* Absolute neutrophil count ≥ 1,500/mm³
* Platelet count ≥ 100,000/mm³
* Bilirubin ≤ 1.5 times upper limit of normal (ULN)
* AST and ALT ≤ 1.5 times ULN
* Alkaline phosphatase ≤ 1.5 times ULN
* Not pregnant or nursing
* Negative pregnancy test
* Fertile patients must use effective contraception during and for up to 12 months after completion of study treatment
* FEV_1 ≥ 40% of predicted based on spirometry and lung perfusion scan, if necessary
* No serious underlying medical condition that would preclude study requirements (e.g., active autoimmune disease or uncontrolled diabetes)
* No known hypersensitivity against pemetrexed disodium, cisplatin, or other platinum-containing substances or any other components used for the preparation of the drugs
* No restricted power of hearing (especially in the upper frequency range)
* No acute infections

PRIOR CONCURRENT THERAPY:

* No prior chemotherapy
* No treatment on another clinical trial within the past 30 days
* No prior pleurectomy or lung resection
* No prior radiotherapy of the lower neck, thorax, or upper abdomen
* No aspirin, cyclooxygenase-2 inhibitors, or nonsteroidal anti-inflammatory agents for 5 days prior to, during, and for 2 days after pemetrexed disodium administration
* No other concurrent experimental drugs or anticancer therapy
* No concurrent drugs that would contraindicate study drugs
* No concurrent vaccination against yellow fever

Answer: D