Hodgkin's Disease

Description

Other Treatments

Chemotherapy uses cytotoxic (cell-killing) drugs to kill cancer cells throughout the body, and it is therefore referred to as systemic therapy.

Cytotoxic agents may be given orally or as injections. Treatment may be administered at a medical center, physician's office, or even a patient's home. Some patients receiving chemotherapy may need to remain in the hospital for several days so the effects of the drug can be monitored.

Patients may receive up to 8 cycles of chemotherapy, depending on the stage. A cycle is usually 28 days and consists of several doses of drug administration followed by a period of rest.

Specific Agents and Drug Combinations Used in Hodgkin's Disease

A number of chemotherapy regimens have proven to be effective. Different drugs in each regimen may need to be taken orally or by injection. Toxicity varies depending on the combination. Researchers are investigating the use of chemotherapy regimens used alone, taken in alternate cycles with another regimen, or as hybrids (combining one or two drugs from one regimen with drugs from another).

The following are regimens that are very effective in the treatment of Hodgkin's disease.

• ABVD [doxorubicin (Adriamycin), bleomycin, vinblastine, dacarbazine] is now the first choice for most patients who need chemotherapy. It is the most effective and least toxic regimen available to date. Unlike MOPP, for example, it does not pose a significant risk for leukemia or infertility.
• MOPP and MOPP-ABV. The introduction of MOPP [mechlorethamine (Mustargen), vincristine (Oncovin), procarbazine, prednisone] in the 1960s resulted in dramatic reductions in mortality rates from HD. A hybrid of MOPP and ABV [doxorubicin (Adriamycin), bleomycin, vinblastine] has often been used for advanced HD. MOPP can cause infertility and carries a 3% risk for leukemia, however.
• BEACOPP (bleomycin, etoposide, Adriamycin, cyclophosphamide, vincristine, procarbazine, and prednisone). This regimen is proving to be very effective, particularly in advanced stages, with studies reporting remission rates of over 90% in patients with advanced Hodgkin's. The risk of long-term side effects, such as leukemia, requires longer follow-up.
• Stanford V (Seven drugs administered over a shorter time but more frequently than MOPP or ABVD). Mechlorethamine (Mustargen), doxorubicin (Adriamycin), vinblastine (Velban), vincristine (Oncovin), bleomycin (Blenoxane), etoposide (VP-16), prednisone by mouth every other day. This regimen is proving to be effective for extensive and advanced HD, although it is not known whether it is superior to more standard regimens, such as ABVD.

Other regimens continue to be tested for effectiveness and safety in both early and late stage HD. They include the following:

• ChlVPP (chlorambucil, vinblastine, procarbazine, and prednisone). Studies are showing that it is effective in specific patients. For example, it is proving to be to beneficial and less toxic for children. In one 2002 study, a hybrid regimen using ChlVPP and another regimen containing doxorubicin improved response compared to ChlVPP alone for elderly patients.
• VAPEC-B (vincristine, doxorubicin, prednisolone, etoposide, cyclophosphamide, and bleomycin). This is a short-course regimen that might be useful in some patients, although it is not as effective as others.

Regimens with fewer toxic effects, such as ChlVPP and others, are being tested in children and adolescents in early stages, with some showing promise. Certain agents, such as etoposide, cause less injury to male reproductive organs and can be substituted for more toxic agents, notably procarbazine.

Specific regimens are also being studied for elderly patients.

Agents Used with Relapsed or Previously Untreatable HD. For patients who relapse or have only partial remissions other agents, called salvage chemotherapy, may be needed or high-dose chemotherapy may be used in combinations with stem cell transplantation.

Common regimens include the following:

• BEAM [carmustine (BCNU), VP-16, cytosine arabinoside, and melphalan]. Used with stem cell transplantation. (An alternative regimen known as mini-BEAM uses lower doses and is used without stem cell transplantation.)
• CBV [cyclophosphamide, carmustine (BCNU), etoposide (VP-16)]. Used with stem cell transplantation.

Other agents or combinations are showing promise for relapsing or previously untreatable Hodgkin's and including the following:

• ASHAP [doxorubicin (Adriamycin), methylprednisolone (Solumedrol), high-dose cytosine arabinoside, and cisplatin (platinum)].
• DHAP (dexamethasone, cytarabine, cisplatin).
• GEM-P (gemcitabine, cisplatin and methylprednisolone).
• Agents that have shown some effectiveness in combinations for relapsed or progressive HD in children and adolescents include cisplatin plus regimens with high-dose cytarabine, ifosfamide, carboplatin, and etoposide and ifosfamide plus vinorelbine. Gemcitabine has shown promise as a single agent in patients with relapsed Hodgkin's disease.

Sequential High-Dose Chemotherapy. A promising approach called sequential high-dose chemotherapy employs few drugs given at the highest possible doses and administered at intervals of one to three weeks.

Side Effects and Complications

Side effects and complications of any chemotherapeutic regimen are common, are more severe with higher doses, and increase over the course of treatment, though some trials suggest that toxicities can be reduced by administering the drugs for shorter duration without loss of cancer-killing effects.

Common Side Effects. Common side effects include the following:

• Nausea and vomiting. Drugs known as serotonin antagonists, such as ondansetron (Zofran) or granisteron (Kyril), can relieve these side effects in nearly all patients given moderate drugs and most patients who take more powerful drugs. In one study, nearly all patients who took a combination of dexamethasone (a steroid) in combination with ondansetron within 24 hours of chemotherapy experienced either a significant or complete reduction in nausea and vomiting.
• Diarrhea.
• Hair loss.
• Weight loss.
• Anemia. Studies are investigating the use of epoetin (Procrit), which increases production of red blood cells, to reduce this effect and improve quality of life.
• Depression.

These side effects are nearly always temporary. Most patients are able to continue with normal activities for all but perhaps one or two days a month.

Serious Side Effects. Serious side effects can also occur and may vary depending on the specific agents used. They include the following:

• Increased chance for infection from suppression of the immune system and severe drops in white blood cells (neutropenia). White blood cell count may be improved with the addition of a drug called granulocyte colony-stimulating factor (filgrastim, pegfilgrastim, and lenograstim). (There is no evidence that these agents have any effect on survival or cancer recurrence, however.)
• Liver and kidney damage.
• Abnormal blood clotting (thrombocytopenia).
• Allergic reaction.
• The drug BCNU (carmustine) carries a significant risk for life-threatening pneumonia, particularly in women.

Long-Term Complications.

• Fatigue and Somatic Symptoms. Chemotherapy has been associated with long-term somatic symptoms, which are general conditions, such as fatigue and aches and pains that have no apparent physical basis. Fatigue is especially common after chemotherapy and can even last for years.
• Leukemia. Risk is highest with MOPP, particularly combined with radiation therapy.
• Infertility. Risk is highest with MOPP and less so with ABVD. Investigators are testing an agent called a gonadotropin-releasing hormone analogue that puts women in a temporary pre-pubescent state during chemotherapy and which may preserve fertility in many women.
• Bone injury. This may be related to steroid treatments.
• Heart failure. Certain agents, including anthracyclines (such as doxorubicin) and similar drugs called anthracenediones (e.g., mitoxantrone) pose specific risks to the heart.
• Lung toxicity. Bleomycin (Blenoxane), an antibiotic used in some regimens, is particularly toxic to the lungs. Vinblastine and methotrexate may also pose a risk when used in combination with radiation therapy.

In general, these serious late side effects are dependent on the cumulative drug dose and rate of administration.

Combinations of Chemotherapy and Radiation (Combined Modality)

Regimens. Chemotherapy (usually ABVD) plus radiation, referred to as combined modality, is a common treatment approach for patients with more advanced-stage disease and for those who have early-stage bulky (large mass) disease. In a 2000 study, the Stanford V regimen combined with radiation produced excellent survival and remission rates among patients with early-stage bulky and with stage III/IV disease. A comparison study with ABVD is under way. A 2003 study indicated, however, that radiation added no additional advantages for patients with advanced HD who showed no signs of disease after initial chemotherapy. It also significantly increases the risk for secondary cancers compared to chemotherapy alone. More research is needed to confirm this.

Chemotherapy with low-dose radiation is being used in children with excellent results, even for late stage cancer. In one study, 82% of the children were still disease free at five years. Some chemotherapy drugs or high doses of radiation may be more deleterious to a boy's future fertility than to a girl's. A gender-specific combined regimen for pediatric Hodgkin's reduces the amount of radiation given to boys and also substitutes etoposide for procarbazine in the chemotherapy mixture (procarbazine, vincristine, prednisone, and doxorubicin).

Side Effects and Long-Term Complications. Side effects of combination treatments can be very serious. They not include the adverse effects of the individual treatments but some may be compounded. Examples include the following:

• Combined modality poses a higher risk for secondary cancers than the use or radiation or chemotherapy alone. They, include breast, lung, thyroid, melanoma, and gastrointestinal cancers, which usually develop in near or in the areas treated with radiation. Of note, the risk for breast cancer is lower when chemotherapies using alkylated agents or radiation treatments damage the ovaries, suggesting that hormone stimulation plays a role in this higher risk. Newer agents used in combined modalities may reduce the risk, at least for breast cancer.
• ABVD and other regimens containing bleomycin increase the risk for severe effects on the lungs when used before or after mantle-field radiation. EVA [etoposide, vinblastine, and doxorubicin] is considered to be an effective substitute in patients with lung disease for whom bleomycin and radiation present an unacceptable risk.