Phase II Trial of Sequential Chemotherapy and Radiotherapy for AIDS-Related Primary Central Nervous System Lymphoma
Phase II Trial of Sequential Chemotherapy and Radiotherapy for AIDS-Related Primary Central Nervous System Lymphoma
To estimate the response rate, overall and disease-free survival, toxicities, factors
 associated with outcome, and effect on quality of life in patients with AIDS-related primary
 CNS lymphoma treated with CHOD (cyclophosphamide, doxorubicin, vincristine, and
 dexamethasone) plus filgrastim (granulocyte-colony stimulating factor; G-CSF) and external
 beam irradiation. To determine other clinical markers present in this patient population.

 Combined modality therapy may prove of benefit for patients with AIDS-related primary CNS
 lymphoma.
Combined modality therapy may prove of benefit for patients with AIDS-related primary CNS
 lymphoma.

 Patients who upon staging workup are found to be without systemic involvement undergo one
 cycle of chemotherapy with cyclophosphamide, doxorubicin, vincristine, dexamethasone, and
 G-CSF. Cyclophosphamide, doxorubicin, and vincristine are administered intravenously on day
 1. Dexamethasone is administered intravenously on day 1 and then orally thereafter with
 gradual discontinuation. G-CSF is administered subcutaneously daily beginning on day 2 and
 continuing for a total of 10 days or until blood counts have recovered to an acceptable
 level. Patients with evidence of cancer cells in their cerebrospinal fluid (CSF) will receive
 chemotherapy with intrathecal cytarabine twice weekly until no further evidence of cancer
 cells is found in the CSF, then once weekly for 6 weeks, and then monthly for 10 months.
 Seven to ten days following completion of one cycle of chemotherapy, patients undergo
 radiotherapy to the brain at a dose of 2.5 Gy daily for 5 days per week for approximately 4
 weeks. Total dose to the whole brain and meninges is 30.0 Gy in 12 fractions, and total dose
 to the primary boost volume is 10.0 Gy in 4 fractions. During therapy, blood is drawn weekly
 and brain scans are performed every 3-12 weeks. An initial CSF sample will be obtained by
 lumbar puncture.
Inclusion Criteria

 Concurrent Medication: Required:

 -  PCP prophylaxis with Bactrim, dapsone, or aerosolized pentamidine.

 -  Oral candidiasis prophylaxis with fluconazole, ketoconazole, or clotrimazole oral
 troches.

 -  Antiretroviral agent available by therapy IND.

 -  MAI prophylaxis with rifabutin (in patients with CD4 counts < 100 cells/mm3).

 Patients must have:

 -  HIV infection.

 -  Primary CNS lymphoma with NO systemic involvement.

 Prior Medication:

 Allowed:

 -  Prior corticosteroids.

 Exclusion Criteria

 Co-existing Condition:

 Patients with the following symptoms or conditions are excluded:

 -  Concomitant malignancy other than Kaposi's sarcoma, curatively treated carcinoma in
 situ of the cervix, or squamous or basal cell carcinoma of the skin.

 -  Active uncontrolled infection.

 -  Renal failure, active nonmalignant duodenal ulcer, uncontrolled diabetes mellitus, or
 other serious medical conditions that would preclude aggressive cytotoxic chemotherapy
 administration.

 -  Active heart disease (congestive heart failure or heart block greater than first
 degree on EKG).

 Concurrent Medication:

 Excluded:

 -  Any investigational agent other than antiretroviral agents available by therapy IND.

 Patients with the following prior conditions are excluded:

 -  No prior malignancy other than Kaposi's sarcoma, curatively treated carcinoma in situ
 of the cervix, or squamous cell or basal cell carcinoma of the skin.

 -  No new infectious complications within the past 2 weeks that require a change in
 antibiotics.

 -  History of myocardial infarction within the past 3 months.

 Prior Medication:

 Excluded:

 -  Prior chemotherapy other than for Kaposi's sarcoma.