ABVD
Encyclopedia
ABVD is a chemotherapy regimen used in the first-line treatment of Hodgkin lymphoma, supplanting the older MOPP protocol. It consists of concurrent treatment with the chemotherapy drugs:
regimen.
, with fairly dismal long-term survival and cure rates. With advances in the understanding of chemotherapy resistance and the development of combination chemotherapy, Vincent T. DeVita
and George Canellos
at the National Cancer Institute
(United States) developed the MOPP
regimen. This combination of mechlorethamine, vincristine
(Oncovin), procarbazine
, and prednisone
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
remained significant. Aside from bone marrow suppression, frequent side effects included nerve injury
caused by vincristine and allergic reactions 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 or acute leukemia
was increased up to 14-fold in patients who received MOPP. These treatment-related hematological malignancies peaked at 5 to 9 years after treatment for Hodgkin's lymphoma, and were associated with a dismally poor prognosis.
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 regimen were published at Università degli Studi di Milano,Facoltà di Medicina e Chirurgia, ( anno accademico : 1974/75 ) in : 'Studio comparativo di due schemi di polichemioterapia negli stadi avanzati della Malattia di Hodgkin' , (relatore prof. F. A . ), tesi di laurea di Fossati Vittorio , Matr. 81.606 ,(thesis of a student led by Bonadonna Gianni) and these initial results were also published in 1975 by an Italian
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 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 .
Typical dosages for one 28-day cycle of ABVD are as follows
The total 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
, or other side effects.
A FDG PET scan is commonly advised after two or three cycles of ABVD to assess response to therapy.
, 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
), corticosteroid
s, and benzodiazepine
s before chemotherapy to prevent nausea. These medicines are also effective after nausea develops, as are phenothiazine
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.
to produce more of a certain kind of blood cell
. Commonly used examples include G-CSF and erythropoietin
. These drugs are sometimes used with ABVD to prevent neutropenia
(low white blood cell
count) and anemia
related to the chemotherapy, although their use is not universal.
- Adriamycin (doxorubicinDoxorubicinDoxorubicin INN is a drug used in cancer chemotherapy. It is an anthracycline antibiotic, closely related to the natural product daunomycin, and like all anthracyclines, it works by intercalating DNA....
/Hydroxydaunorubicin, the H in CHOP) - bleomycinBleomycinBleomycin is a glycopeptide antibiotic produced by the bacterium Streptomyces verticillus. Bleomycin refers to a family of structurally related compounds. When used as an anticancer agent, the chemotherapeutical forms are primarily bleomycin A2 and B2. It works by causing breaks in DNA...
- vinblastineVinblastineVinblastine is an antimicrotubule drug used to treat certain kinds of cancer, including Hodgkin's lymphoma, non-small cell lung cancer, breast cancer, head and neck cancer, and testicular cancer. It is also used to treat Langerhan cell histiocytosis....
- dacarbazineDacarbazineDacarbazine is an antineoplastic chemotherapy drug used in the treatment of various cancers, among them malignant melanoma, Hodgkin lymphoma, sarcoma, and islet cell carcinoma of the pancreas.Dacarbazine is a member of the class of alkylating agents, which destroy cancer cells by adding an alkyl...
(similar to ProcarbazineProcarbazineProcarbazine Procarbazine Procarbazine (Matulane (US), Natulan (Canada), Indicarb (India) is an antineoplastic chemotherapy drug for the treatment of Hodgkin's lymphoma and certain brain cancers (such as Glioblastoma multiforme). It is a member of a group of medicines called alkylating agents. It...
, the P in MOPP)
Indications
As of 2007, ABVD is widely used as the initial chemotherapy treatment for newly diagnosed Hodgkin's lymphoma. The other chemotherapy regimen that is widely used in this setting is the Stanford VStanford V
Stanford V is a chemotherapy regimen intended as a first line treatment for Hodgkin's lymphoma...
regimen.
History
Prior to the mid-1960s, advanced-stage Hodgkin disease was treated with single-agent chemotherapyChemotherapy
Chemotherapy is the treatment of cancer with an antineoplastic drug or with a combination of such drugs into a standardized treatment regimen....
, with fairly dismal long-term survival and cure rates. With advances in the understanding of chemotherapy resistance and the development of combination chemotherapy, Vincent T. DeVita
Vincent T. DeVita
Vincent T. DeVita, Jr., MD is an internationally recognized pioneer physician in the field of oncology.DeVita earned his Bachelor of Science degree from the College of William and Mary in 1957. He was awarded his MD degree with distinction from the George Washington University School of Medicine in...
and George Canellos
George Canellos
George P. Canellos is a renowned American oncologist and cancer researcher. His research career spans many decades as well as several areas of therapeutic agents for the treatment of malignant diseases. He is perhaps most known for his work with Vincent T. DeVita in which he developed the...
at the National Cancer Institute
National Cancer Institute
The National Cancer Institute is part of the National Institutes of Health , which is one of 11 agencies that are part of the U.S. Department of Health and Human Services. The NCI coordinates the U.S...
(United States) developed the MOPP
MOPP (medicine)
MOPP is a combination chemotherapy regimen used to treat Hodgkin's disease. The acronym is derived from the component drugs of the regimen:*Mustargen...
regimen. This combination of mechlorethamine, vincristine
Vincristine
Vincristine , formally known as leurocristine, sometimes abbreviated "VCR", is a vinca alkaloid from the Catharanthus roseus , formerly Vinca rosea and hence its name. It is a mitotic inhibitor, and is used in cancer chemotherapy.-Mechanism:Tubulin is a structural protein that polymerizes to...
(Oncovin), procarbazine
Procarbazine
Procarbazine Procarbazine Procarbazine (Matulane (US), Natulan (Canada), Indicarb (India) is an antineoplastic chemotherapy drug for the treatment of Hodgkin's lymphoma and certain brain cancers (such as Glioblastoma multiforme). It is a member of a group of medicines called alkylating agents. It...
, and prednisone
Prednisone
Prednisone is a synthetic corticosteroid drug that is particularly effective as an immunosuppressant drug. It is used to treat certain inflammatory diseases and some types of cancer, but has significant adverse effects...
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
Toxicity is the degree to which a substance can damage a living or non-living organisms. Toxicity can refer to the effect on a whole organism, such as an animal, bacterium, or plant, as well as the effect on a substructure of the organism, such as a cell or an organ , such as the liver...
remained significant. Aside from bone marrow suppression, frequent side effects included nerve injury
Neurotoxicity
Neurotoxicity occurs when the exposure to natural or artificial toxic substances, which are called neurotoxins, alters the normal activity of the nervous system in such a way as to cause damage to nervous tissue. This can eventually disrupt or even kill neurons, key cells that transmit and process...
caused by vincristine and allergic reactions to procarbazine. Long-term effects were also a concern, as patients were often cured and could expect long survival after chemotherapy. Infertility
Infertility
Infertility primarily refers to the biological inability of a person to contribute to conception. Infertility may also refer to the state of a woman who is unable to carry a pregnancy to full term...
was a major long-term side effect, and even more seriously, the risk of developing treatment-related myelodysplasia or acute leukemia
Acute leukemia
Acute leukemia or acute leukaemia is a generic term used to describe a family of serious medical conditions relating to an original diagnosis of leukemia...
was increased up to 14-fold in patients who received MOPP. These treatment-related hematological malignancies peaked at 5 to 9 years after treatment for Hodgkin's lymphoma, and were associated with a dismally poor prognosis.
Development of ABVD
Therefore, alternate regimens were tested in an attempt to avoid alkylating agentAlkylating antineoplastic agent
An alkylating antineoplastic agent is an alkylating agent used in cancer treatment that attaches an alkyl group to DNA.The alkyl group is attached to the guanine base of DNA, at the number 7 nitrogen atom of the purine ring....
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 regimen were published at Università degli Studi di Milano,Facoltà di Medicina e Chirurgia, ( anno accademico : 1974/75 ) in : 'Studio comparativo di due schemi di polichemioterapia negli stadi avanzati della Malattia di Hodgkin' , (relatore prof. F. A . ), tesi di laurea di Fossati Vittorio , Matr. 81.606 ,(thesis of a student led by Bonadonna Gianni) and these initial results were also published in 1975 by an Italian
Italy
Italy , officially the Italian Republic languages]] under the European Charter for Regional or Minority Languages. In each of these, Italy's official name is as follows:;;;;;;;;), is a unitary parliamentary republic in South-Central Europe. To the north it borders France, Switzerland, Austria and...
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 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 .
Administration
One cycle of ABVD chemotherapy is typically given over 4 weeks, with two doses in each cycle (on day 1 and day 15). All four of the chemotherapy drugs are given intravenously. ABVD chemotherapy is usually given in the outpatient setting — that is, it does not require hospitalization.Typical dosages for one 28-day cycle of ABVD are as follows
- Adriamycin 25 mg/m2 IV on days 1 and 15
- BleomycinBleomycinBleomycin is a glycopeptide antibiotic produced by the bacterium Streptomyces verticillus. Bleomycin refers to a family of structurally related compounds. When used as an anticancer agent, the chemotherapeutical forms are primarily bleomycin A2 and B2. It works by causing breaks in DNA...
10 units/m2 IV on days 1 and 15 - VinblastineVinblastineVinblastine is an antimicrotubule drug used to treat certain kinds of cancer, including Hodgkin's lymphoma, non-small cell lung cancer, breast cancer, head and neck cancer, and testicular cancer. It is also used to treat Langerhan cell histiocytosis....
6 mg/m2 IV on days 1 and 15 - DacarbazineDacarbazineDacarbazine is an antineoplastic chemotherapy drug used in the treatment of various cancers, among them malignant melanoma, Hodgkin lymphoma, sarcoma, and islet cell carcinoma of the pancreas.Dacarbazine is a member of the class of alkylating agents, which destroy cancer cells by adding an alkyl...
375 mg/m2 IV on days 1 and 15
The total 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
Neutropenia
Neutropenia, from Latin prefix neutro- and Greek suffix -πενία , is a granulocyte disorder characterized by an abnormally low number of neutrophils, the most important type of white blood cell...
, thrombocytopenia
Thrombocytopenia
Thrombocytopenia is a relative decrease of platelets in blood.A normal human platelet count ranges from 150,000 to 450,000 platelets per microliter of blood. These limits are determined by the 2.5th lower and upper percentile, so values outside this range do not necessarily indicate disease...
, or other side effects.
A FDG PET scan is commonly advised after two or three cycles of ABVD to assess response to therapy.
Side effects
In the relative spectrum of cancer chemotherapy, ABVD is not a particularly toxic regimen. 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 alopeciaAlopeciaAlopecia means loss of hair from the head or body. Alopecia can mean baldness, a term generally reserved for pattern alopecia or androgenic alopecia. Compulsive pulling of hair can also produce hair loss. Hairstyling routines such as tight ponytails or braids may induce Traction alopecia. Both...
, 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 vomitingChemotherapy-induced nausea and vomitingChemotherapy-induced nausea and vomiting is a common side-effect of many cancer treatments. Nausea and vomiting are two of the most feared cancer treatment-related side effects for cancer patients and their families. In 1983, Coates et al. found that patients receiving chemotherapy ranked nausea...
have improved substantially (see Supportive care below). - Low blood counts, or myelosuppression, occur about 50% of the time with ABVD. Blood cell growth factors 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 cellWhite blood cellWhite blood cells, or leukocytes , are cells of the immune system involved in defending the body against both infectious disease and foreign materials. Five different and diverse types of leukocytes exist, but they are all produced and derived from a multipotent cell in the bone marrow known as a...
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 Numbness in tips of fingers and toes, this can be temporary or permanent.
Delayed side effects
- Infertility is probably infrequent with ABVD. Several studies have suggested that, while sperm counts in men decrease during chemotherapy, they return to normal after completion of ABVD. In women, follicle-stimulating hormoneFollicle-stimulating hormoneFollicle-stimulating hormone is a hormone found in humans and other animals. It is synthesized and secreted by gonadotrophs of the anterior pituitary gland. FSH regulates the development, growth, pubertal maturation, and reproductive processes of the body. FSH and Luteinizing hormone act...
levels remained normal while receiving ABVD, suggesting preserved ovarian function. Regardless of these data, fertility options (e.g. sperm bankSperm bankA sperm bank, semen bank or cryobank is a facility that collects and stores human sperm mainly from sperm donors, primarily for the purpose of achieving pregnancies through third party reproduction, notably by artificial insemination...
ing) should be discussed with an oncologist before beginning ABVD therapy. - Pulmonary toxicity, or lungLungThe lung is the essential respiration organ in many air-breathing animals, including most tetrapods, a few fish and a few snails. In mammals and the more complex life forms, the two lungs are located near the backbone on either side of the heart...
damage, can occur with the use of bleomycinBleomycinBleomycin is a glycopeptide antibiotic produced by the bacterium Streptomyces verticillus. Bleomycin refers to a family of structurally related compounds. When used as an anticancer agent, the chemotherapeutical forms are primarily bleomycin A2 and B2. It works by causing breaks in DNA...
in ABVD, especially when radiation therapyRadiation therapyRadiation therapy , radiation oncology, or radiotherapy , sometimes abbreviated to XRT or DXT, is the medical use of ionizing radiation, generally as part of cancer treatment to control malignant cells.Radiation therapy is commonly applied to the cancerous tumor because of its ability to control...
to the chest is also given as part of the treatment for Hodgkin's lymphoma. This toxicity develops months to years after completing chemotherapy, and usually manifests as coughCoughA cough is a sudden and often repetitively occurring reflex which helps to clear the large breathing passages from secretions, irritants, foreign particles and microbes...
and shortness of breathDyspneaDyspnea , shortness of breath , or air hunger, is the subjective symptom of breathlessness.It is a normal symptom of heavy exertion but becomes pathological if it occurs in unexpected situations...
. 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 tests 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 cardiomyopathyCardiomyopathyCardiomyopathy, which literally means "heart muscle disease," is the deterioration of the function of the myocardium for any reason. People with cardiomyopathy are often at risk of arrhythmia or sudden cardiac death or both. Cardiomyopathy can often go undetected, making it especially dangerous to...
, can be a late side effect of adriamycin. 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 leukemiaLeukemiaLeukemia or leukaemia is a type of cancer of the blood or bone marrow characterized by an abnormal increase of immature white blood cells called "blasts". Leukemia is a broad term covering a spectrum of diseases...
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 MOPPMOPP (medicine)MOPP is a combination chemotherapy regimen used to treat Hodgkin's disease. The acronym is derived from the component drugs of the regimen:*Mustargen...
chemotherapy rather than ABVD. Many of these second cancers were lung cancers or, in women, breast cancers, emphasizing the importance of smoking cessationSmoking cessationSmoking cessation is the process of discontinuing the practice of inhaling a smoked substance. This article focuses exclusively on cessation of tobacco smoking; however, the methods described may apply to cessation of smoking other substances that can be difficult to stop using due to the...
and regular preventive care 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 patients get through the chemotherapy with the least possible discomfort.Antiemetics
Significant advances in antiemeticAntiemetic
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....
, 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
Ondansetron is a serotonin 5-HT3 receptor antagonist used mainly as an antiemetic , often following chemotherapy. Its effects are thought to be on both peripheral and central nerves...
), corticosteroid
Corticosteroid
Corticosteroids are a class of steroid hormones that are produced in the adrenal cortex. Corticosteroids are involved in a wide range of physiologic systems such as stress response, immune response and regulation of inflammation, carbohydrate metabolism, protein catabolism, blood electrolyte...
s, and benzodiazepine
Benzodiazepine
A benzodiazepine is a psychoactive drug whose core chemical structure is the fusion of a benzene ring and a diazepine ring...
s before chemotherapy to prevent nausea. These medicines are also effective after nausea develops, as are phenothiazine
Phenothiazine
Phenothiazine is an organic compound that occurs in various antipsychotic and antihistaminic drugs. It has the formula S2NH. This yellow tricyclic compound is soluble in acetic acid, benzene, and ether. The compound is related to the thiazine-class of heterocyclic compounds...
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.
Growth factors
Blood growth factors are medicines that stimulate the bone marrowBone marrow
Bone marrow is the flexible tissue found in the interior of bones. In humans, bone marrow in large bones produces new blood cells. On average, bone marrow constitutes 4% of the total body mass of humans; in adults weighing 65 kg , bone marrow accounts for approximately 2.6 kg...
to produce more of a certain kind of blood cell
Blood cell
A blood cell, also called a hematocyte, is a cell normally found in blood. In mammals, these fall into three general categories:* red blood cells — Erythrocytes* white blood cells — Leukocytes* platelets — Thrombocytes...
. Commonly used examples include G-CSF and erythropoietin
Erythropoietin
Erythropoietin, or its alternatives erythropoetin or erthropoyetin or EPO, is a glycoprotein hormone that controls erythropoiesis, or red blood cell production...
. These drugs are sometimes used with ABVD to prevent neutropenia
Neutropenia
Neutropenia, from Latin prefix neutro- and Greek suffix -πενία , is a granulocyte disorder characterized by an abnormally low number of neutrophils, the most important type of white blood cell...
(low white blood cell
White blood cell
White blood cells, or leukocytes , are cells of the immune system involved in defending the body against both infectious disease and foreign materials. Five different and diverse types of leukocytes exist, but they are all produced and derived from a multipotent cell in the bone marrow known as a...
count) and anemia
Anemia
Anemia is a decrease in number of red blood cells or less than the normal quantity of hemoglobin in the blood. However, it can include decreased oxygen-binding ability of each hemoglobin molecule due to deformity or lack in numerical development as in some other types of hemoglobin...
related to the chemotherapy, although their use is not universal.
External links
- Chemotherapy information from the American Cancer Society
- Treatment of Hodgkin's Lymphoma at the U.S. National Cancer InstituteNational Cancer InstituteThe National Cancer Institute is part of the National Institutes of Health , which is one of 11 agencies that are part of the U.S. Department of Health and Human Services. The NCI coordinates the U.S...