ABVD

ABVD is a chemotherapy regimen used in the first-line treatment of Hodgkin lymphoma. It consists of concurrent treatment with the chemotherapy drugs adriamycin (doxorubicin), bleomycin, vinblastine and dacarbazine.

Indications

As of 2006, ABVD is widely used as the initial chemotherapy treatment for newly diagnosed Hodgkin lymphoma. The other chemotherapy regimen that is widely used in this setting is the Stanford V regimen.

History

Prior to the mid-1960's, advanced-stage Hodgkin disease was treated with single-agent chemotherapy, with fairly dismal long-term survival and cure rates. With advances in the understanding of chemotherapy resistance and the development of combination chemotherapy, Vincent 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. [cite journal | author = DeVita V, Simon R, Hubbard S, Young R, Berard C, Moxley J, Frei E, Carbone P, Canellos G | title = Curability of advanced Hodgkin's disease with chemotherapy. Long-term follow-up of MOPP-treated patients at the National Cancer Institute. | journal = Ann Intern Med | volume = 92 | issue = 5 | pages = 587–95 | year = 1980 | pmid = 6892984] [cite journal | author = Longo D, Young R, Wesley M, Hubbard S, Duffey P, Jaffe E, DeVita V | title = Twenty years of MOPP therapy for Hodgkin's disease. | journal = J Clin Oncol | volume = 4 | issue = 9 | pages = 1295–306 | year = 1986 | pmid = 3528400]

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. [cite journal | author = Kaldor J, Day N, Clarke E, Van Leeuwen F, Henry-Amar M, Fiorentino M, Bell J, Pedersen D, Band P, Assouline D | title = Leukemia following Hodgkin's disease. | journal = N Engl J Med | volume = 322 | issue = 1 | pages = 7–13 | year = 1990 | pmid = 2403650] 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 agents (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; initial results with ABVD were published in 1975 by an Italian group led by Bonadonna. [cite journal | author = Bonadonna G, Zucali R, Monfardini S, De Lena M, Uslenghi C | title = Combination chemotherapy of Hodgkin's disease with adriamycin, bleomycin, vinblastine, and imidazole carboxamide versus MOPP. | journal = Cancer | volume = 36 | issue = 1 | pages = 252–9 | year = 1975 | pmid = 54209 | doi = 10.1002/1097-0142(197507)36:1<252::AID-CNCR2820360128>3.0.CO;2-7 | doilabel = 10.1002/1097-0142(197507)36:1252::AID-CNCR28203601283.0.CO;2-7]

A number of trials then compared ABVD to previous 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. [cite journal | author = Canellos G, Anderson J, Propert K, Nissen N, Cooper M, Henderson E, Green M, Gottlieb A, Peterson B | title = Chemotherapy of advanced Hodgkin's disease with MOPP, ABVD, or MOPP alternating with ABVD. | journal = N Engl J Med | volume = 327 | issue = 21 | pages = 1478–84 | year = 1992 | pmid = 1383821] 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.cite journal | author = Santoro A, Bonadonna G, Valagussa P, Zucali R, Viviani S, Villani F, Pagnoni A, Bonfante V, Musumeci R, Crippa F | title = Long-term results of combined chemotherapy-radiotherapy approach in Hodgkin's disease: superiority of ABVD plus radiotherapy versus MOPP plus radiotherapy. | journal = J Clin Oncol | volume = 5 | issue = 1 | pages = 27–37 | year = 1987 | pmid = 2433409] Taken together, these results led ABVD to the replacement of MOPP with ABVD in the first-line treatment of Hodgkin lymphoma.

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 &mdash; 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
*Bleomycin 10 units/m² IV on days 1 and 15
*Vinblastine 6 mg/m² IV on days 1 and 15
*Dacarbazine 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, thrombocytopenia, or other side effects.

ide 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 alopecia, 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, 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 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 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. [cite journal | author = Viviani S, Santoro A, Ragni G, Bonfante V, Bestetti O, Bonadonna G | title = Gonadal toxicity after combination chemotherapy for Hodgkin's disease. Comparative results of MOPP vs ABVD. | journal = Eur J Cancer Clin Oncol | volume = 21 | issue = 5 | pages = 601–5 | year = 1985 | pmid = 2408897 | doi = 10.1016/0277-5379(85)90088-4] [cite journal | author = Anselmo A, Cartoni C, Bellantuono P, Maurizi-Enrici R, Aboulkair N, Ermini M | title = Risk of infertility in patients with Hodgkin's disease treated with ABVD vs MOPP vs ABVD/MOPP. | journal = Haematologica | volume = 75 | issue = 2 | pages = 155–8 | year = | pmid = 1694156] In women, follicle-stimulating hormone levels remained normal while receiving ABVD, suggesting preserved ovarian function. Regardless of these data, fertility options (eg sperm banking) should be discussed with an oncologist before beginning ABVD therapy.
*Pulmonary toxicity, or lung damage, can occur with the use of bleomycin in ABVD, especially when radiation therapy 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 cough and shortness of breath. 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. [cite journal | author = Martin W, Ristow K, Habermann T, Colgan J, Witzig T, Ansell S | title = Bleomycin pulmonary toxicity has a negative impact on the outcome of patients with Hodgkin's lymphoma. | journal = J Clin Oncol | volume = 23 | issue = 30 | pages = 7614–20 | year = 2005 | pmid = 16186594 | doi = 10.1200/JCO.2005.02.7243] Retrospective analyses have questioned whether bleomycin is necessary at all; [cite journal | author = Canellos G, Duggan D, Johnson J, Niedzwiecki D | title = How important is bleomycin in the adriamycin + bleomycin + vinblastine + dacarbazine regimen? | journal = J Clin Oncol | volume = 22 | issue = 8 | pages = 1532–3 | year = 2004 | pmid = 15084636 | doi = 10.1200/JCO.2004.99.010] however, at this point it remains a standard part of ABVD.
*Cardiac toxicity, or cardiomyopathy, 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 leukemias 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. [cite journal | author = van Leeuwen F, Klokman W, Veer M, Hagenbeek A, Krol A, Vetter U, Schaapveld M, van Heerde P, Burgers J, Somers R, Aleman B | title = Long-term risk of second malignancy in survivors of Hodgkin's disease treated during adolescence or young adulthood. | journal = J Clin Oncol | volume = 18 | issue = 3 | pages = 487–97 | year = 2000 | pmid = 10653864] Many of these second cancers were lung cancers or, in women, breast cancers, emphasizing the importance of smoking cessation 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.

upportive 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 antiemetic, 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), corticosteroids, and benzodiazepines before chemotherapy to prevent nausea. These medicines are also effective after nausea develops, as are phenothiazines. 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 marrow 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.

References

ee also

* Stanford V
* BEACOPP

External links

* [http://www.cancer.org/docroot/CRI/CRI_2_3x.asp?dt=84 American Cancer Society Guide to Hodgkin's Disease]
* [http://www.cancer.gov/cancertopics/types/hodgkinslymphoma Hodgkin's Lymphoma Home Page] at the American National Cancer Institute
* [http://www.lymphomainfo.net/hodgkins/timeline.html Timeline of discovery and treatment of Hodgkin Lymphoma]
* [http://www.lymphomainfo.net/hodgkins/description.html Hodgkin's Lymphoma]