Many different types of chemotherapy may be used for Hodgkin lymphoma.

The most commonly used combination of

drugs in the United States is called ABVD. Another combination of drugs, known as BEACOPP, is now widely used in
Europe and is being used more often in the United States. There are other combinations that are less commonly used and
not listed here. The drugs that make up these two more common combinations of chemotherapy are listed below.

 ABVD: Doxorubicin (Adriamycin), bleomycin (Blenoxane), vinblastine (Velban, Velsar), and dacarbazine
(DTIC-Dome). ABVD chemotherapy is usually given every two weeks for two to eight months.

 BEACOPP: Bleomycin, etoposide (Toposar, VePesid), doxorubicin, cyclophosphamide (Cytoxan, Neosar),

vincristine (Vincasar PFS, Oncovin), procarbazine (Matulane), and prednisone (multiple brand names). There are
several different treatment schedules, but different drugs are usually given every two weeks.

Doxorubicin (Adriamycin)

- binds and intercalates into DNA, inhibiting nucleic acid and protein synthesis; triggers DNA cleavage by
topoisomerase II
- Doxorubicin is an antineoplastic in the anthracycline class. General properties of drugs in this class include:
interaction with DNA in a variety of different ways including intercalation (squeezing between the base pairs),
DNA strand breakage and inhibition with the enzyme topoisomerase II. Most of these compounds have been
isolated from natural sources and antibiotics. However, they lack the specificity of the antimicrobial antibiotics
and thus produce significant toxicity. The anthracyclines are among the most important antitumor drugs
available. Doxorubicin is widely used for the treatment of several solid tumors while daunorubicin and idarubicin
are used exclusively for the treatment of leukemia. Doxorubicin may also inhibit polymerase activity, affect
regulation of gene expression, and produce free radical damage to DNA. Doxorubicin possesses an antitumor
effect against a wide spectrum of tumors, either grafted or spontaneous. The anthracyclines are cell cycle-
nonspecific. (Chemotherapy drugs that affect cells when they are at rest are called cell-cycle non-specific.)
- Doxorubicin has antimitotic and cytotoxic activity through a number of proposed mechanisms of action:
Doxorubicin forms complexes with DNA by intercalation between base pairs, and it inhibits topoisomerase II
activity by stabilizing the DNA-topoisomerase II complex, preventing the religation portion of the ligation-
religation reaction that topoisomerase II catalyzes.
- The cytotoxic effect of doxorubicin on malignant cells and its toxic effects on various organs are thought to be
related to nucleotide base intercalation and cell membrane lipid binding activities of doxorubicin. Intercalation
inhibits nucleotide replication and action of DNA and RNA polymerases. The interaction of doxorubicin with
topoisomerase II to form DNA-cleavable complexes appears to be an important mechanism of doxorubicin
cytocidal activity.
- Doxorubicin cellular membrane binding may affect a variety of cellular functions. Enzymatic electron reduction
of doxorubicin by a variety of oxidases, reductases and dehydrogenases generates highly reactive species
including the hydroxyl free radical OH•. Free radical formation has been implicated in doxorubicin cardiotoxicity
by means of Cu (II) and Fe (III) reduction at the cellular level.
- Cells treated with doxorubicin have been shown to manifest the characteristic morphologic changes associated
with apoptosis or programmed cell death. Doxorubicin-induced apoptosis may be an integral component of the
cellular mechanism of action relating to therapeutic effects, toxicities, or both.

bleomycin (Blenoxane)

- Although the exact mechanism of action of BLENOXANE (bleomycin sulfate injection) is unknown, available
evidence indicates that the main mode of action is the inhibition of DNA synthesis with some evidence of lesser
inhibition of RNA and protein synthesis.
- Bleomycin is known to cause single, and to a lesser extent, double-stranded breaks in DNA. In in vitro and in vivo
experiments, bleomycin has been shown to cause cell cycle arrest in G2 and in mitosis.
- When administered into the pleural cavity in the treatment of malignant pleural effusion, BLENOXANE
(bleomycin sulfate injection) acts as a sclerosing agent.
- Although the exact mechanism of action of bleomycin is unknown, available evidence would seem to indicate
that the main mode of action is the inhibition of DNA synthesis with some evidence of lesser inhibition of RNA
and protein synthesis. DNA cleavage by bleomycin depends on oxygen and metal ions, at least in vitro. It is
 believed that bleomycin chelates metal ions (primarily iron) producing a pseudoenzyme that reacts with oxygen
to produce superoxide and hydroxide free radicals that cleave DNA.
- Bleomycin is an antibiotic which has been shown to have antitumor activity. Bleomycin selectively inhibits the
synthesis of deoxyribonucleic acid (DNA). The guanine and cytosine content correlates with the degree of
mitomycin-induced cross-linking. At high concentrations of the drug, cellular RNA and protein synthesis are also
suppressed. Bleomycin has been shown in vitro to inhibit B cell, T cell, and macrophage proliferation and impair
antigen presentation, as well as the secretion of interferon gamma, TNFa, and IL-2. The antibiotic antitumor
drugs are cell cycle-nonspecific except for Bleomycin (which has major effects in G2 and M phases).

vinblastine (Velban, Velsar)

- inhibits microtubule formation, arresting mitosis in metaphase

- Vinblastine treatment causes M phase specific cell cycle arrest by disrupting microtubule assembly and proper
formation of the mitotic spindle and the kinetochore, each of which are necessary for the separation of
chromosomes during anaphase of mitosis.
- The antitumor activity of vinblastine is thought to be due primarily to inhibition of mitosis at metaphase through
its interaction with tubulin. Vinblastine binds to the microtubular proteins of the mitotic spindle, leading to
crystallization of the microtubule and mitotic arrest or cell death.
- Other studies indicate that vinblastine sulfate (vinblastine sulfate injection) has an effect on cell-energy
production required for mitosis and interferes with nucleic acidsynthesis.
- The mechanism of action of vinblastine sulfate (vinblastine sulfate injection) has been related to the inhibition of
microtubule formation in the mitotic spindle, resulting in an arrest of dividing cells at the metaphasestage.

dacarbazine (DTIC-Dome)

- exact mechanism of action unknown; alkylates and crosslinks DNA, inhibiting nucleic acid synthesis
- The mechanism of action is not known, but appears to exert cytotoxic effects via its action as an alkylating
agent. Other theories include DNA synthesis inhibition by its action as a purine analog, and interaction with SH
groups. Dacarbazine is not cell cycle-phase specific. (any phase, including G0, although final toxicity may be
manifested during a specific phase)

If Hodgkin lymphoma comes back after initial (first-line) treatment with ABVD or BEACOPP, known as a recurrence,
there are several second-line treatments. Many of these treatments are given in preparation for an autologous stem cell
transplant (see below), but they can also be given to control the disease and its symptoms.

 ICE: Ifosfamide (Ifex), carboplatin (Paraplatin), etoposide. ICE is usually given every two or three weeks for two
to three months.

 ESHAP or DHAP: Etoposide, methylprenisolone sodium succinate (Solu-Medrol), high dose cytarabine (Cytosar-
U), cisplatin (Platinol); OR dexamethasone (multiple brand names), high dose cytarabine, cisplatin. ESHAP or
DHAP regimens are given every three weeks for two to three months.

 GVD, Gem-Ox, or GDP: Gemcitabine (Gemzar), vinorelbine (Navelbine), doxorubicin; OR gemcitabine,

oxaliplatin (Eloxatin); OR gemcitabine, dexamethasone, cisplatin. Gemcitabine-based regimens are either given
two weeks in a row followed by an off-week or every other week.

 Brentuximabvedotin (Adcetris): Brentuximabvedotin is an antibody-drug conjugate, which means it delivers

chemotherapy only to cells that have a special protein on the surface called CD30. Brentuximabvedotin is usually
given every three weeks for up to sixteen cycles, although sometimes it is given every four weeks.

It is unclear which of these chemotherapy treatments is best for patients with Hodgkin lymphoma, and the best treatment
may differ depending on the type and stage of the lymphoma. For this reason, many clinical trials are underway to
compare these different chemotherapy treatments. These clinical trials are designed to find out which combination works
best with the fewest short-term and long-term side effects.