Non-Hodgkin's Lymphoma

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Questions to Ask Your Doctor About Your Cancer
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Chemotherapy

Chemotherapy is a general term that is used to describe cancer-killing drugs. Such drugs can be given: intravenously, through a vein; orally, by mouth; subcutaneously, injected under the skin; intramuscularly, injected into a muscle; or intrathecally, injected into the cerebrospinal fluid (CSF).

Chemotherapy for lymphoma is varied, because there are so many different forms of this disease. Treatment may rely on a single anticancer medication - that is, single agent chemotherapy - or it may involve combination chemotherapy with a number of different anticancer drugs. Such drugs destroy cancer cells by preventing them from growing and dividing rapidly. Unfortunately, a number of the body's normal, noncancerous cells also divide rapidly and therefore are harmed by chemotherapy. Specifically, the hair follicles, red and white blood cells, platelets (blood particles responsible for clotting), and cells that line the gastrointestinal system may be damaged or destroyed, causing side effects. Such side effects depend upon the type and dose of drugs taken, as well as the length of time that they are used.

Because NHL patients often are diagnosed with widespread disease, chemotherapy is the cornerstone of treatment, and drug resistance becomes a primary obstacle to cure. There is a likelihood that some tumor cells already are resistant to any single chemotherapeutic drug when patients first are treated for large tumors. Fortunately, there are a number of new approaches to the chemotherapeutic management of NHLs. In particular, promising results have been obtained from a class of drugs known as nucleosides or antimetabolites. These new compounds include fludarabine phosphate (FDA), cladribine (2-CDA; 2-chloro-2'-deoxyadenosine), and pentostatin (2-DCF; 2'-deoxycoformycin). They are very active as single agents, and lack cross-resistance with most other drugs.

Side Effects
Chemotherapeutic side effects may include temporary hair loss, mouth sores, anemia (decreased numbers of red blood cells, which may cause fatigue, dizziness, and shortness of breath), leukopenia (decreased numbers of white blood cells, which may lower resistance to infection), thrombocytopenia (decreased numbers of platelets, which may lead to easy bleeding or bruising), and gastrointestinal symptoms like nausea, vomiting, and diarrhea.

Tumor lysis syndrome is a specific side effect of therapy for some bulky lymphomas. This condition occurs when there is a rapid breakdown of NHL cells due to chemotherapeutic drugs. The cells split apart and release cell fragments, metabolic byproducts, and minerals into the bloodstream. These substances can damage the kidneys, heart, and nervous system. Therefore, physicians often monitor lymphoma patients for this syndrome. They may prescribe fluids, sodium bicarbonate, and allopurinol, a drug used to reduce uric acid in the blood, to rid the body of unwanted chemicals and cell remains.

Slow-Growing NHLs
If an individual is diagnosed with slow-growing (indolent) NHL at Stages 1 or 2, current treatment options include single nucleosides (fludarabine, cladribine, pentostatin), single alkylating agents (chlorambucil, cyclophosphamide [Neosar®]), or an alkylating agent plus prednisone. It is important to note that these treatments also are used for patients with recurrent slow-growing NHLs.

Option 1: Chemotherapy with a single nucleoside (e.g., fludarabine phosphate [FDA], or cladribine [2-CDA; 2-chloro-2'-deoxyadenosine])

• How are the drug given: Fludarabine or cladribine: intravenously (IV)
• What is the duration: Fludarabine is given every day for 5 days; cladribine is given every day for 7 days.
• What are the side effects: Fludarabine - nervous system effects, stomatitis (mouth inflammation), hepatitis (liver inflammation); cladribine - immune system suppression

Option 2: Chemotherapy with a single alkylating agent (e.g., chlorambucil [Leukeran®], or cyclophosphamide [Neosar®])

• How are the drugs given: Chlorambucil: orally
  Cyclophosphamide (Neosar®): (IV)
  
• What is the duration: Chlorambucil is taken in pill form (orally) every day; cyclophosphamide (Neosar®) is given by injection (IV) every 3 to 4 weeks.
  
• What are the side effects: Chlorambucil - leukemia; cyclophosphamide - cystitis (bladder inflammation), lung fibrosis, water retention.

There are several approaches to the management of individuals with advanced (Stage 3 or 4) low-grade NHL. These include single-agent chemotherapy (e.g., with an alkylating agent or nucleoside) or aggressive combination chemotherapy (e.g., cyclophosphamide [Neosar®], vincristine, and prednisone ["CVP"]), with or without total nodal irradiation.

Option 1: Chemotherapy with a single alkylating agent (e.g., chlorambucil [Leukeran®], or cyclophosphamide [Neosar®])

Option 2: Chemotherapy with a single nucleoside (e.g., fludarabine phosphate [FDA], or cladribine [2-CDA; 2-chloro-2'-deoxyadenosine])

Option 3: Combination chemotherapy, e.g., cyclophosphamide (Neosar®), vincristine sulfate (Oncovin®), and prednisone; also called "CVP", with/without total nodal irradiation (TDI)

Fast-Growing NHLs
Fast-growing, early stage (Stages 1 or 2) NHL is treated with aggressive, combination chemotherapy plans such as:

• CHOP, cyclophosphamide (Neosar®), hydroxydaunomycin, vincristine (Oncovin®), prednisone;
• BACOD, bleomycin, doxorubicin (Adriamycin®), cyclophosphamide (Neosar®), vincristine (Oncovin®), dexamethasone;
• MACOP-B, methotrexate, doxorubicin (Adriamycin®), cyclophosphamide, vincristine (Oncovin®), prednisone, bleomycin;
• Pro-MACE-CytaBOM, prednisone, methotrexate (with leucovorin rescue), doxorubicin (Adriamycin®), cyclophosphamide (Neosar®), etoposide, cytarabine, bleomycin, vincristine (Oncovin®); or
• EPOCH, etoposide, prednisone, vincristine (Oncovin®), cyclophosphamide (Neosar®), fluoxymesterone (Halotestin®).

Central Nervous System NHLs
There has been a growing interest in the use of systemic (whole-body) chemotherapy for the treatment of NHLs of the central nervous system. These primary central nervous system lymphomas (PCNSL) can be difficult to treat, because many drugs do not pass through the blood-brain barrier of the CNS. In spite of this, some fat-penetrating drugs and those with very small molecules are active against PCNSL, because they are able to cross the barrier and reach the tumor cells. These drugs include ethotrexate, cytarabine, the nitrosoureas, procarbazine, and 5-fluorouracil. In addition, some chemotherapeutic medications like cyclophosphamide (Neosar®) and vincristine show some activity against PCNSL, perhaps because they can cross the barrier at places where it has broken down.

Option 1: Chemotherapy with methotrexate (3.5 g/m2x 3, with leucovorin rescue) after radiation therapy.

Option 2: Chemotherapy with methotrexate (1.5 g/m2) and cyclophosphamide (15-30 mg/kg), plus Procarbazine (100-150 mg/day) and dexamethasone (24 mg/day), plus whole-brain radiation therapy, if needed.

Option 3: Chemotherapy with methotrexate (1.0 g/m2) IV and intrathecally (12 mg x 6), plus Cytarabine (high dose), plus whole-brain radiation therapy and tumor boost.

Gastric NHLs
Gastric, or stomach, NHLs that are not removed by antibiotic therapy may, in some cases, require treatment by surgical removal of the tumor), chemotherapy, or chemotherapy plus radiotherapy. If surgery is not possible, many experts rely on combination chemotherapy using doxorubicin-based therapy (e.g., CHOP) followed by radiation.

Option 1: Combination chemotherapy with cyclophosphamide (Neosar®), hydroxydaunomycin, vincristine sulfate (Oncovin®), and prednisone; also called "CHOP"

Cutaneous (skin) NHLs
The cutaneous, or skin, NHL mycosis fungoides is best treated by methods other than systemic chemotherapy, which affects the whole body and is not confined to the skin. But if systemic chemotherapy is required, the physician may recommend treatment with a combination of drugs. The most widely tested drug combinations have included cyclophosphamide, vincristine sulfate (Oncovin®), and prednisone, with or without doxorubicin (Adriamycin®). Yet complete response rates and disease-free periods have not been outstanding for many patients with mycosis fungoides. By contrast, individuals with Sézary syndrome are relieved of symptoms by systemic chemotherapy. One common plan combines oral chlorambucil and prednisone.

The nucleoside drugs fludarabine and pentostatin have showed some promise in early clinical trials of cutaneous NHL, including mycosis fungoides.

Option 1: Combination chemotherapy with cyclophosphamide (Neosar®), vincristine sulfate (Oncovin®), and prednisone, with/without doxorubicin (Adriamycin®)

Option 2: Combination chemotherapy with chlorambucil (Leukeran®) and prednisone

Option 3: Chemotherapy with a single nucleoside (e.g., fludarabine phosphate [FDA], or pentostatin [2'-deoxycoformycin])

For more information on therapies for the Non-Hodgkin's Lymphomas, please speak with your physician. Open communication leads to improved care. Ask questions and become more informed about your condition. Participation in your health care is essential; become an informed consumer.

Clinical Trials
Many advances are being made in the treatment of NHL. However, continued advances in the field depend upon the participation of patients in clinical trials. Through the use of clinical trials improved treatment outcomes and the development of more risk appropriate strategies can be secured. It is possible participation in a clinical trial may help you and the next unfortunate individual who will be diagnosed in the future. Please consider any clinical trial, which your physician may discuss with you. If clinical trial participation is not discussed, please ask your physician if there any trials for which you may be eligible for participation.

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