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ABVD is a
chemotherapy regimen A chemotherapy regimen is a regimen for chemotherapy, defining the drugs to be used, their dosage, the frequency and duration of treatments, and other considerations. In modern oncology, many regimens combine several chemotherapy drugs in combina ...
used in the first-line treatment of
Hodgkin lymphoma Hodgkin lymphoma (HL) is a type of lymphoma, in which cancer originates from a specific type of white blood cell called lymphocytes, where multinucleated Reed–Sternberg cells (RS cells) are present in the patient's lymph nodes. The condition w ...
, replacing the older MOPP protocol. It consists of concurrent treatment with the chemotherapy drugs: *
Adriamycin Doxorubicin, sold under the brand name Adriamycin among others, is a chemotherapy medication used to treat cancer. This includes breast cancer, bladder cancer, Kaposi's sarcoma, lymphoma, and acute lymphocytic leukemia. It is often used toget ...
(also known as
doxorubicin Doxorubicin, sold under the brand name Adriamycin among others, is a chemotherapy medication used to treat cancer. This includes breast cancer, bladder cancer, Kaposi's sarcoma, lymphoma, and acute lymphocytic leukemia. It is often used toge ...
/ hydroxydaunorubicin, designated as H in CHOP) *
Bleomycin -13- (1''H''-imidazol-5-yl)methyl9-hydroxy-5- 1''R'')-1-hydroxyethyl8,10-dimethyl-4,7,12,15-tetraoxo-3,6,11,14-tetraazapentadec-1-yl}-2,4'-bi-1,3-thiazol-4-yl)carbonyl]amino}propyl)(dimethyl)sulfonium , chemical_formula = , C=55 , H=84 , N=1 ...
*
Vinblastine Vinblastine (VBL), sold under the brand name Velban among others, is a chemotherapy medication, typically used with other medications, to treat a number of types of cancer. This includes Hodgkin's lymphoma, non-small cell lung cancer, bladder ca ...
*
Dacarbazine Dacarbazine (DTIC), also known as imidazole carboxamide, is a chemotherapy medication used in the treatment of melanoma and Hodgkin's lymphoma. For Hodgkin's it is often used together with vinblastine, bleomycin, and doxorubicin. It is given ...
(similar to
procarbazine Procarbazine is a chemotherapy medication used for the treatment of Hodgkin's lymphoma and brain cancers. For Hodgkin's it is often used together with chlormethine, vincristine, and prednisone while for brain cancers such as glioblastoma multif ...
, designated as P in MOPP and in COPP)


Medical uses

As of 2007, ABVD is widely used as the initial chemotherapy treatment for newly diagnosed Hodgkin lymphoma. It has been the most effective and least toxic chemotherapy regimen available for treating early-stage Hodgkin Lymphoma. The other chemotherapy regimens that are widely used in this setting is the Stanford V and
BEACOPP BEACOPP is a chemotherapy regimen for treatment of Hodgkin lymphoma developed by the German Hodgkin Study Group used for patients in Stages > II or early (IA or IB) with unfavorable risk factors. Patients typically receive treatment in cycles of 21 ...
regimens.


Administration

One cycle of ABVD chemotherapy is typically given over 4 weeks in two doses, with the first on day 1 and the second dose on day 15. All four of the chemotherapy drugs are given intravenously. ABVD chemotherapy is usually given in the
outpatient A patient is any recipient of health care services that are performed by healthcare professionals. The patient is most often ill or injured and in need of treatment by a physician, nurse, optometrist, dentist, veterinarian, or other health care ...
setting — that is, it does not require
hospitalization A hospital is a health care institution providing patient treatment with specialized health science and auxiliary healthcare staff and medical equipment. The best-known type of hospital is the general hospital, which typically has an emergency ...
. Typical dosages for one 28-day cycle of ABVD are: The number of cycles given depends upon the stage of the disease and how well the patient tolerates chemotherapy. Doses may be delayed because of neutropenia,
thrombocytopenia Thrombocytopenia is a condition characterized by abnormally low levels of platelets, also known as thrombocytes, in the blood. It is the most common coagulation disorder among intensive care patients and is seen in a fifth of medical patients a ...
, or other side effects. A FDG
PET scan Positron emission tomography (PET) is a functional imaging technique that uses radioactive substances known as radiotracers to visualize and measure changes in metabolic processes, and in other physiological activities including blood flow, ...
is commonly advised following the completion of ABVD to assess response to the therapy. Interim PET (following 2 cycles) may be useful in aiding prognostication, but does not yet guide changes in therapy except within clinical trial protocols.


Side effects

Side effects of ABVD can be divided into acute (those occurring while receiving chemotherapy) and delayed (those occurring months to years after completion of chemotherapy). Delayed side effects have assumed particular importance because many patients treated for Hodgkin lymphoma are cured and can expect long lives after completion of chemotherapy.


Acute side effects

* Hair loss, or
alopecia Hair loss, also known as alopecia or baldness, refers to a loss of hair from part of the head or body. Typically at least the head is involved. The severity of hair loss can vary from a small area to the entire body. Inflammation or scar ...
, is a fairly common but not universal side effect of ABVD. Hair that is lost returns in the months after completion of chemotherapy. * Nausea and vomiting can occur with ABVD, although treatments for chemotherapy-induced nausea and vomiting have improved substantially (see ''Supportive care'' below). * Low blood counts, or
myelosuppression Bone marrow suppression also known as myelotoxicity or myelosuppression, is the decrease in production of cells responsible for providing immunity (leukocytes), carrying oxygen (erythrocytes), and/or those responsible for normal blood clotting (t ...
, occur about 50% of the time with ABVD. Blood cell
growth factors A growth factor is a naturally occurring substance capable of stimulating cell proliferation, wound healing, and occasionally cellular differentiation. Usually it is a secreted protein or a steroid hormone. Growth factors are important for reg ...
are sometimes used to prevent this (see ''Supportive care'' below). Blood counts are checked frequently while receiving chemotherapy. Any fever or sign of infection that develops needs to be promptly evaluated; severe infections can develop rapidly in a person with a low white blood cell count due to chemotherapy. * Allergic reactions to bleomycin can occur. A small test dose of bleomycin is often given prior to the first round of ABVD to screen for patients who may be allergic. * Neuropathy:
Chemotherapy-induced peripheral neuropathy Chemotherapy-induced peripheral neuropathy (CIPN) is a nerve-damaging side effect of antineoplastic agents in the common cancer treatment, chemotherapy. CIPN afflicts between 30% and 40% of patients undergoing chemotherapy. Antineoplastic agents ...
, a progressive and enduring tingling numbness, intense pain, and hypersensitivity to cold, beginning in the hands and feet and sometimes involving the arms and legs.


Delayed side effects

* Infertility is probably infrequent with ABVD. Several studies have suggested that, while
sperm count A semen analysis (plural: semen analyses), also called seminogram or spermiogram, evaluates certain characteristics of a male's semen and the sperm contained therein. It is done to help evaluate male fertility, whether for those seeking pregna ...
s in men decrease during chemotherapy, they return to normal after completion of ABVD. In women, follicle-stimulating hormone levels remained normal while receiving ABVD, suggesting preserved ovarian function. Regardless of these data, fertility options (e.g.
semen cryopreservation Semen cryopreservation (commonly called sperm banking or sperm freezing) is a procedure to preserve sperm cells. Semen can be used successfully indefinitely after cryopreservation. It can be used for sperm donation where the recipient wants the tr ...
,
oocyte cryopreservation Human oocyte cryopreservation (egg freezing) is a procedure to preserve a woman's eggs (oocytes). This technique has been used to enable women to postpone pregnancy to a later date – whether for medical reasons (such as cancer treatment), or fo ...
,
embryo cryopreservation Cryopreservation of embryos is the process of Cryopreservation, preserving an embryo at sub-zero temperatures, generally at an embryogenesis stage corresponding to pre-implantation, that is, from fertilisation to the blastocyst stage. Indications ...
) should be discussed with an
oncologist Oncology is a branch of medicine that deals with the study, treatment, diagnosis and prevention of cancer. A medical professional who practices oncology is an ''oncologist''. The name's etymological origin is the Greek word ὄγκος (''ó ...
before beginning ABVD therapy. * Pulmonary toxicity, or lung damage, can occur with the use of
bleomycin -13- (1''H''-imidazol-5-yl)methyl9-hydroxy-5- 1''R'')-1-hydroxyethyl8,10-dimethyl-4,7,12,15-tetraoxo-3,6,11,14-tetraazapentadec-1-yl}-2,4'-bi-1,3-thiazol-4-yl)carbonyl]amino}propyl)(dimethyl)sulfonium , chemical_formula = , C=55 , H=84 , N=1 ...
in ABVD, especially when
radiation therapy Radiation therapy or radiotherapy, often abbreviated RT, RTx, or XRT, is a therapy using ionizing radiation, generally provided as part of cancer treatment to control or kill malignant cells and normally delivered by a linear accelerator. Radi ...
to the chest is also given as part of the treatment for Hodgkin lymphoma. This toxicity develops months to years after completing chemotherapy, and usually manifests as
cough A cough is a sudden expulsion of air through the large breathing passages that can help clear them of fluids, irritants, foreign particles and microbes. As a protective reflex, coughing can be repetitive with the cough reflex following three ph ...
and
shortness of breath Shortness of breath (SOB), also medically known as dyspnea (in AmE) or dyspnoea (in BrE), is an uncomfortable feeling of not being able to breathe well enough. The American Thoracic Society defines it as "a subjective experience of breathing di ...
. High concentrations of oxygen, such as those often used in surgery, can trigger lung damage in patients who have received bleomycin, even years later.
Pulmonary function test Pulmonary function testing (PFT) is a complete evaluation of the respiratory system including patient history, physical examinations, and tests of pulmonary function. The primary purpose of pulmonary function testing is to identify the severity ...
s are often used to assess for bleomycin-related damage to the lungs. One study found bleomycin lung damage in 18% of patients receiving ABVD for Hodgkin disease. Retrospective analyses have questioned whether bleomycin is necessary at all; however, at this point it remains a standard part of ABVD. * Cardiac toxicity, or cardiomyopathy, can be a late side effect of
adriamycin Doxorubicin, sold under the brand name Adriamycin among others, is a chemotherapy medication used to treat cancer. This includes breast cancer, bladder cancer, Kaposi's sarcoma, lymphoma, and acute lymphocytic leukemia. It is often used toget ...
. The occurrence of adriamycin-related cardiac toxicity is related to the total lifetime dose of adriamycin, and increases sharply in people who receive a cumulative dose of more than 400 mg/m2. Almost all patients treated with ABVD receive less than this dose (for 6 cycles of ABVD, the cumulative adriamycin dose is 300 mg/m2); therefore, adriamycin-related cardiac toxicity is very uncommon with ABVD. * Secondary malignancies. Patients cured of Hodgkin lymphoma remain at increased risk of developing other (secondary) cancers. Treatment-related
leukemia Leukemia ( also spelled leukaemia and pronounced ) is a group of blood cancers that usually begin in the bone marrow and result in high numbers of abnormal blood cells. These blood cells are not fully developed and are called ''blasts'' or ...
s are uncommon with ABVD, especially as compared with MOPP. However, one study found a risk of second cancers as high as 28% at 25 years after treatment for Hodgkin lymphoma, although most of the patients in this study were treated with MOPP chemotherapy rather than ABVD. Many of these second cancers were lung cancers or, in women, breast cancers, emphasizing the importance of
smoking cessation Smoking cessation, usually called quitting smoking or stopping smoking, is the process of discontinuing tobacco smoking. Tobacco smoke contains nicotine, which is addictive and can cause dependence. As a result, nicotine withdrawal often m ...
and regular
preventive care Preventive healthcare, or prophylaxis, consists of measures taken for the purposes of disease prevention.Hugh R. Leavell and E. Gurney Clark as "the science and art of preventing disease, prolonging life, and promoting physical and mental hea ...
after completion of treatment. Radiation and chemotherapy probably both play a role in the development of these secondary malignancies; the exact contribution of chemotherapy such as ABVD can be difficult to tease out.


Supportive care

''Supportive care'' refers to efforts to prevent or treat side effects of ABVD chemotherapy, and to help people get through the chemotherapy with the least possible discomfort.


Antiemetics

Significant advances in
antiemetic An antiemetic is a drug that is effective against vomiting and nausea. Antiemetics are typically used to treat motion sickness and the side effects of opioid analgesics, general anaesthetics, and chemotherapy directed against cancer. They m ...
, or anti-nausea, medications have been made in the beginning of the 21st century. Patients will often receive a combination of 5-HT3 receptor antagonists (e.g.
ondansetron Ondansetron, sold under the brand name Zofran among others, is a medication used to prevent nausea and vomiting caused by cancer chemotherapy, radiation therapy, or surgery. It is also effective for treating gastroenteritis. It can be given by ...
), corticosteroids, and benzodiazepines before chemotherapy to prevent nausea. These medicines are also effective after nausea develops, as are
phenothiazine Phenothiazine, abbreviated PTZ, is an organic compound that has the formula S(C6H4)2NH and is related to the thiazine-class of heterocyclic compounds. Derivatives of phenothiazine are highly bioactive and have widespread use and rich history. T ...
s. Each person's sensitivity to nausea and vomiting varies. Overall, while patients often experience some mild to moderate nausea, severe nausea or vomiting are uncommon with ABVD. Emetogenicity is high. has recommendations for preventing nausea and vomiting. Ensure that patients have sufficient antiemetics for breakthrough emesis with
Metoclopramide Metoclopramide is a medication used for stomach and esophageal problems. It is commonly used to treat and prevent nausea and vomiting, to help with emptying of the stomach in people with delayed stomach emptying, and to help with gastroesoph ...
10 mg to 20 mg every 4 to 6 hours when necessary OR
Prochlorperazine Prochlorperazine, formerly sold under the brand name Compazine among others, is a medication used to treat nausea, migraines, schizophrenia, psychosis and anxiety. It is a less preferred medication for anxiety. It may be taken by mouth, rectally ...
10 mg PO or 12.5 mg IV every 4 to 6 hours when necessary.


Growth factors

Blood growth factors are medicines that stimulate the bone marrow to produce more of a certain kind of
blood cell A blood cell, also called a hematopoietic cell, hemocyte, or hematocyte, is a cell produced through hematopoiesis and found mainly in the blood. Major types of blood cells include red blood cells (erythrocytes), white blood cells (leukocytes) ...
. Commonly used examples include
G-CSF Granulocyte colony-stimulating factor (G-CSF or GCSF), also known as colony-stimulating factor 3 (CSF 3), is a glycoprotein that stimulates the bone marrow to produce granulocytes and stem cells and release them into the bloodstream. Functiona ...
and erythropoietin. These drugs are sometimes used with ABVD to prevent neutropenia (low white blood cell count) and
anemia Anemia or anaemia (British English) is a blood disorder in which the blood has a reduced ability to carry oxygen due to a lower than normal number of red blood cells, or a reduction in the amount of hemoglobin. When anemia comes on slowly, t ...
related to the chemotherapy, although their use is not universal.


History

Prior to the mid-1960s, advanced-stage Hodgkin disease was treated with single-agent
chemotherapy Chemotherapy (often abbreviated to chemo and sometimes CTX or CTx) is a type of cancer treatment that uses one or more anti-cancer drugs ( chemotherapeutic agents or alkylating agents) as part of a standardized chemotherapy regimen. Chemothe ...
, with fairly dismal long-term survival and cure rates. With advances in the understanding of chemotherapy resistance and the development of
combination chemotherapy The era of cancer chemotherapy began in the 1940s with the first use of nitrogen mustards and folic acid antagonist drugs. The targeted therapy revolution has arrived, but many of the principles and limitations of chemotherapy discovered by t ...
, Vincent T. DeVita and George Canellos at the
National Cancer Institute The National Cancer Institute (NCI) coordinates the United States National Cancer Program and is part of the National Institutes of Health (NIH), which is one of eleven agencies that are part of the U.S. Department of Health and Human Services. ...
(United States) developed the MOPP regimen. This combination of
mechlorethamine Chlormethine ( INN, BAN), also known as mechlorethamine (USAN, USP), mustine, HN2, and (in post-Soviet states) embikhin (эмбихин), is a nitrogen mustard sold under the brand name Mustargen among others. It is the prototype of alkylating ag ...
,
vincristine Vincristine, also known as leurocristine and marketed under the brand name Oncovin among others, is a chemotherapy medication used to treat a number of types of cancer. This includes acute lymphocytic leukemia, acute myeloid leukemia, Hodgkin's ...
(Oncovin),
procarbazine Procarbazine is a chemotherapy medication used for the treatment of Hodgkin's lymphoma and brain cancers. For Hodgkin's it is often used together with chlormethine, vincristine, and prednisone while for brain cancers such as glioblastoma multif ...
, and
prednisone Prednisone is a glucocorticoid medication mostly used to suppress the immune system and decrease inflammation in conditions such as asthma, COPD, and rheumatologic diseases. It is also used to treat high blood calcium due to cancer and ad ...
proved capable of curing almost 70% of patients with advanced-stage Hodgkin lymphoma. While MOPP was remarkably successful in curing advanced Hodgkin lymphoma, its
toxicity Toxicity is the degree to which a chemical substance or a particular mixture of substances can damage an organism. Toxicity can refer to the effect on a whole organism, such as an animal, bacterium, or plant, as well as the effect on a subs ...
remained significant. Aside from
bone marrow suppression Bone marrow suppression also known as myelotoxicity or myelosuppression, is the decrease in production of cells responsible for providing immunity ( leukocytes), carrying oxygen ( erythrocytes), and/or those responsible for normal blood clotting ...
, frequent side effects included
nerve injury Nerve injury is an injury to nervous tissue. There is no single classification system that can describe all the many variations of nerve injuries. In 1941, Seddon introduced a classification of nerve injuries based on three main types of nerve f ...
caused by vincristine and
allergic reaction Allergies, also known as allergic diseases, refer a number of conditions caused by the hypersensitivity of the immune system to typically harmless substances in the environment. These diseases include hay fever, food allergies, atopic derma ...
s to procarbazine. Long-term effects were also a concern, as patients were often cured and could expect long survival after chemotherapy. Infertility was a major long-term side effect, and even more seriously, the risk of developing treatment-related
myelodysplasia A myelodysplastic syndrome (MDS) is one of a group of cancers in which immature blood cells in the bone marrow do not mature, and as a result, do not develop into healthy blood cells. Early on, no symptoms typically are seen. Later, symptoms may ...
or
acute leukemia Acute leukemia or acute leukaemia is a family of serious medical conditions relating to an original diagnosis of leukemia. In most cases, these can be classified according to the lineage, myeloid or lymphoid, of the malignant cells that grow unco ...
was increased up to 14-fold in patients who received MOPP. These treatment-related
hematological malignancies Tumors of the hematopoietic and lymphoid tissues (American English) or tumours of the haematopoietic and lymphoid tissues (British English) are tumors that affect the blood, bone marrow, lymph, and lymphatic system. Because these tissues are al ...
peaked at 5 to 9 years after treatment for Hodgkin's lymphoma, and were associated with a dismally poor prognosis.


Development

Therefore, alternative regimens were tested in an attempt to avoid
alkylating agent Alkylation is the transfer of an alkyl group from one molecule to another. The alkyl group may be transferred as an alkyl carbocation, a free radical, a carbanion, or a carbene (or their equivalents). Alkylating agents are reagents for effectin ...
s (such as mechlorethamine), which were thought to be responsible for many of the long-term side effects of MOPP. ABVD was developed as a potentially less toxic and more effective alternative to MOPP; the initial results of ABVD were published in an Italian thesis. The results were published in English in 1975 by an
Italian Italian(s) may refer to: * Anything of, from, or related to the people of Italy over the centuries ** Italians, an ethnic group or simply a citizen of the Italian Republic or Italian Kingdom ** Italian language, a Romance language *** Regional Ita ...
group led by Bonadonna. A number of trials then compared MOPP vs. MOPP plus ABVD and compared ABVD to previous and other regimens for Hodgkin lymphoma. A large trial by
CALGB Cancer and Leukemia Group B (CALGB; former name: Acute Leukemia Group B, ALGB) is a cancer research cooperative group in the United States. CALGB research is focused on seven major disease areas: leukemia, lymphoma, breast cancer, lung cancer, ...
suggested that ABVD was superior to MOPP, with a higher rate of overall response, less hematologic toxicity, better relapse-free survival, and better outcomes after relapse in the patients treated with ABVD. Later studies confirmed the superiority of ABVD in terms of effectiveness, and also demonstrated that late side effects, such as treatment-related acute leukemia, were less common with ABVD as compared to MOPP. Taken together, these results led ABVD to the replacement of MOPP with ABVD in the first-line treatment of Hodgkin lymphoma. A number of trials then compared ABVD or ABVD-like or hybrid MOPP/ABVD to BEACOPP and escalated BEACOPP regimens.


Research


Fertility

Scientists analyzed samples of ovarian tissue donated by eight women who had undergone ABVD chemotherapy, alongside tissue from fifteen healthy women. They found that the tissue from the cancer patients treated with ABVD had between four and 10 times more eggs compared with tissue from women who had received a different chemotherapy, or healthy women of a similar age. The ovarian tissue was in healthy condition, appearing similar to tissue from young women's ovaries. Although the eggs are in an immature state, the scientists are trying to discover how they were created, then work out a way to bring them to maturity. It is unclear if the eggs in their current form would be functional.


See also

*
BEACOPP BEACOPP is a chemotherapy regimen for treatment of Hodgkin lymphoma developed by the German Hodgkin Study Group used for patients in Stages > II or early (IA or IB) with unfavorable risk factors. Patients typically receive treatment in cycles of 21 ...
* CHOP * Stanford V *
Hodgkin lymphoma Hodgkin lymphoma (HL) is a type of lymphoma, in which cancer originates from a specific type of white blood cell called lymphocytes, where multinucleated Reed–Sternberg cells (RS cells) are present in the patient's lymph nodes. The condition w ...


References


External links


Chemotherapy information
from the American Cancer Society
Treatment of Hodgkin's Lymphoma
at the U.S.
National Cancer Institute The National Cancer Institute (NCI) coordinates the United States National Cancer Program and is part of the National Institutes of Health (NIH), which is one of eleven agencies that are part of the U.S. Department of Health and Human Services. ...
{{DEFAULTSORT:Abvd Chemotherapy regimens used in lymphoma Hodgkin lymphoma