Please select the eligibility criteria that correspond to the clinical trial below.
Title: Temozolomid (One Week on/One Week Off) Versus Strahlentherapie in Der Primärtherapie Anaplastischer Astrozytome Und Glioblastome Bei älteren Patienten: Eine Randomisierte Phase III-Studie (Methvsalem)
Brief Summary: The study aims to optimize the treatment of elderly subjects (\> 65) with anaplastic astrocytoma and glioblastoma. Current treatment policies tend to be no more than palliative. There is no consensus as to how radical the surgery should be. Involved-field radiotherapy is the treatment most likely to be accepted apart from supportive and palliative measures. The role of chemotherapy is barely defined. Study data available to date does not suggest that this patient population would benefit from combined radiochemotherapy. The aim of the study is to verify the hypothesis that first-line chemotherapy with one week on/one week off temozolomide is not inferior to extended-field radiotherapy in the first-line treatment of anaplastic astrocytoma and glioblastoma in the elderly (\> 65 age group). The primary endpoint is median survival, as life expectancy is limited to several months. Secondary endpoints are response rates in both arms (CR, PR, MacDonald et al. 1990), median progression-free survival, 1-year and 2-year survival rates, definition of MGMT as molecular genetic prognostic or predictive markers, and quality of life. Theoretically, it should be possible to preserve quality of life in the first-line chemotherapy arm of the study.


Options:
A: Inclusion Criteria:

All the eligibility criteria must be met before registration :

* delay upper or equal to 14 days from stereotaxic biopsy and 28 days from surgical biopsy
* Histopathologically proven diagnosis of glioblastoma (WHO grade IV astrocytoma)
* Patient belonging to the RPA V class or associated
* only supratentorial glioblastoma
* Diagnosis must be obtained by a stereotactic or surgical biopsy
* Age between 18 and 70
* A contrast-enhanced MRI must be performed within 28 days prior to study registration
* Total or partial surgical resection deemed as not possible by a neurosurgeon
* Karnofsky Index (KI) performance status over 50
* Life expectancy of at least 3 months
* A stable dose of corticosteroid for at least 7 days to control intracranial pressure and neurological symptoms
* Adequate blood function : absolute neutrophil count \> 1.5 x 109/L, platelets count \> 100 x 109/L platelets; hemoglobin \> 10 g/dl after blood transfusion if required
* Adequate liver function: bilirubin \< 1.5 ULN (upper limit of normal), ALT and AST \< 2.5 ULN, Prothrombin rate \> 75 %
* Adequate renal function: creatinine \< 1.2 ULN; proteinuria test 0 or trace (or urine protein concentration \< 1g/24h if proteinuria test is + or ++).
* Negative pregnancy test for women of childbearing potential and adequate contraception for men and women.
* systolic arterial blood pressure at rest ≤ 170 mmHg
* Patient must have been informed and must have signed the specific informed consent form.
* holder of a coverage by the health insurance

Exclusion Criteria:

* patient belonging to the RPA III or IV
* prior malignant tumor in the recent 5 years or concomitant malignancy
* prior anti-tumoral chemotherapy or radiotherapy
* prior gross resection of the brain tumor
* patient receiving gliadel
* cardiovascular contra-indications to bevacizumab : prior angina pectoris, prior myocardial infarction, prior brain stroke, even transient, distal severe arteriopathy, uncontrolled high blood pressure
* anticomitial drug p450 cytochrome inductors
* other substances inducing p450 cytochrome
* proteinuria ≥ 1g/L
* concurrent anticoagulant or platelet anti-aggregant treatment
* congenital haemorrhagic pathology (haemophilia, Willebrandt)
* sign of brain haemorrhage on the RMI initial exam
* non resolved infectious disease
* non controlled arterial hypertension (≥170 mmHg)
* intracranial high pressure not controlled by a stable dose of steroids for at least 7 days
* pregnancy or refusal of the contraception for women and men
* psychiatric, behavioural disorders or geographical situation precluding the administration or follow-up of the protocol (including claustrophobia)
* digestive haemorrhage and / or gastro-duodenal ulcer occurring in the last 3 months
* pregnant, nursing woman, or without contraception
* private individuals of freedom or under tutelage (including legal guardianship)
B: Inclusion Criteria:

* Confirmation of recurrent glioblastoma
* Life expectancy ≥ 12 weeks
* Received only one prior systemic chemotherapy regimen and this regimen must contain temozolomide

Exclusion Criteria:

* Patients on enzyme-inducing anti-epileptic drugs within 3 weeks prior to randomisation
* Poorly controlled hypertension
* Previous anti-angiogenesis (eg bevacizumab, sorafenib, sunitinib) therapy
C: DISEASE CHARACTERISTICS:

* Histologically confirmed glioblastoma multiforme or gliosarcoma

  * Biopsy or surgical resection within the past 28 days

    * MRI\* with gadolinium performed before registration
    * Patients who undergo a simple biopsy only require preoperative MRI\* with gadolinium
* No more than 2 noncontiguous tumor sites based on T2-weighted MRI (in 3 dimensions)\*
* No prior radiotherapy-delivered cephalad to the interspace between the seventh cervical and the first thoracic vertebral body NOTE: \*If an MRI is not medically feasible, patients may have a CT scan with contrast

PATIENT CHARACTERISTICS:

Age:

* 18 and over

Performance status:

* Zubrod 0-2

Life expectancy:

* Not specified

Hematopoietic:

* Absolute neutrophil count at least 3,000/mm\^3
* Platelet count at least 100,000/mm\^3
* Hemoglobin at least 8 g/dL

Hepatic:

* Bilirubin no greater than 2 times upper limit of normal (ULN)
* SGOT/SGPT no greater than 2 times ULN
* Alkaline phosphatase no greater than 2 times ULN
* PT/PTT no greater than 1.2 times ULN

Renal:

* Not specified

Cardiac:

* No severe cardiac disease, including any of the following:

  * Uncontrolled arrhythmias or conduction defects
  * Major problems with edema (e.g., residual swelling in the legs from deep vein thrombosis)
  * Recent coronary artery disease
  * Poorly controlled hypertension (i.e., diastolic blood pressure greater than 110 mm Hg and/or systolic blood pressure greater than 180 mm Hg)

Pulmonary:

* DLCO at least 70% of predicted
* No severe pulmonary disease

Other:

* HIV negative
* No severe Cushing's syndrome
* No known allergies to any of the study drugs
* No major psychiatric illness
* No poorly controlled diabetes complicated by steroid treatment
* No other medical illness that cannot be adequately controlled or that would preclude study participation
* No other malignancy within the past 5 years except adequately treated basal cell or squamous cell skin cancer, carcinoma in situ of the cervix, or adequately treated stage I or II cancer currently in complete remission
* Not pregnant or nursing
* Fertile patients must use effective contraception

PRIOR CONCURRENT THERAPY:

Biologic therapy:

* Not specified

Chemotherapy:

* No prior chemotherapy
* No other concurrent antitumor chemotherapy

Endocrine therapy:

* No concurrent hormonal therapy except postmenopausal estrogen replacement therapy
* Corticosteroids at stable or decreasing dose for tumor edema allowed

Radiotherapy:

* See Disease Characteristics
* No prior radiotherapy
* No other concurrent radiotherapy (including intensity-modulated radiotherapy) to the index lesion(s)

Surgery:

* See Disease Characteristics
* No concurrent antitumor surgery

Other:

* No other concurrent investigational drugs
* No other concurrent antineoplastic drugs or therapy
D: Inclusion Criteria:

* Histologically confirmed supratentorial anaplastic astrocytoma or glioblastoma
* Age \> 65
* Karnofsky performance score \> 60%
* Neutrophilic granulocyte count \> 1500/µl
* Platelet count \> 100 000/µl
* Hemoglobin \> 10 g/dl
* Serum creatinine \< 1.5 times the lab's upper normal limit
* AST or ALT \< 3 times the lab's upper normal limit
* Alkaline phosphatase \< 3 times the lab's upper normal limit
* No previous systemic chemotherapy
* No previous radiotherapy to the brain
* Written consent

Exclusion Criteria:

* Serious medical or neurological condition with a poor prognosis
* HIV infection
* Second cancer requiring radiotherapy or chemotherapy (contact the study coordinat if necessary)
* Hypersensitivity to temozolomide
* Conditions associated with regular vomiting that might affect oral administration of the drugs
* Psychological, familial, social or geographical circumstances with major implications for compliance with the study visit schedule
* Patient was taking part in other intervention studies within a month of starting this study

Answer: D