ABVD

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:

Contents

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 V regimen.

History

Prior to the mid-1960s, 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 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.[1][2]

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.[3] 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; 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.[4] A number of trials then compared MOPP vs. MOPP plus ABVD[5] 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.[6] 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.[7] 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

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.

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

Delayed side effects

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 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.

See also

References

  1. ^ DeVita V, Simon R, Hubbard S, Young R, Berard C, Moxley J, Frei E, Carbone P, Canellos G (1980). "Curability of advanced Hodgkin's disease with chemotherapy. Long-term follow-up of MOPP-treated patients at the National Cancer Institute". Ann Intern Med 92 (5): 587–95. PMID 6892984. 
  2. ^ Longo D, Young R, Wesley M, Hubbard S, Duffey P, Jaffe E, DeVita V (1986). "Twenty years of MOPP therapy for Hodgkin's disease". J Clin Oncol 4 (9): 1295–306. PMID 3528400. 
  3. ^ Kaldor J, Day N, Clarke E, Van Leeuwen F, Henry-Amar M, Fiorentino M, Bell J, Pedersen D, Band P, Assouline D (1990). "Leukemia following Hodgkin's disease". N Engl J Med 322 (1): 7–13. doi:10.1056/NEJM199001043220102. PMID 2403650. 
  4. ^ Bonadonna G, Zucali R, Monfardini S, De Lena M, Uslenghi C (1975). "Combination chemotherapy of Hodgkin's disease with adriamycin, bleomycin, vinblastine, and imidazole carboxamide versus MOPP". Cancer 36 (1): 252–9. doi:10.1002/1097-0142(197507)36:1<252::AID-CNCR2820360128>3.0.CO;2-7. PMID 54209. 
  5. ^ Bonadonna, G., Fossati, V., De Lena, M. (1978). ": MOPP versus MOPP plus ABVD in Stage IV Hodgkin's disease". Proc. Am. Assoc. Cancer Res.-ASCO 19: 363. 
  6. ^ Canellos G, Anderson J, Propert K, Nissen N, Cooper M, Henderson E, Green M, Gottlieb A, Peterson B (1992). "Chemotherapy of advanced Hodgkin's disease with MOPP, ABVD, or MOPP alternating with ABVD". N Engl J Med 327 (21): 1478–84. doi:10.1056/NEJM199211193272102. PMID 1383821. 
  7. ^ a b c Santoro A, Bonadonna G, Valagussa P, Zucali R, Viviani S, Villani F, Pagnoni A, Bonfante V, Musumeci R, Crippa F (1987). "Long-term results of combined chemotherapy-radiotherapy approach in Hodgkin's disease: superiority of ABVD plus radiotherapy versus MOPP plus radiotherapy". J Clin Oncol 5 (1): 27–37. PMID 2433409. 
  8. ^ Viviani S, Santoro A, Ragni G, Bonfante V, Bestetti O, Bonadonna G (1985). "Gonadal toxicity after combination chemotherapy for Hodgkin's disease. Comparative results of MOPP vs ABVD". Eur J Cancer Clin Oncol 21 (5): 601–5. doi:10.1016/0277-5379(85)90088-4. PMID 2408897. 
  9. ^ Anselmo A, Cartoni C, Bellantuono P, Maurizi-Enrici R, Aboulkair N, Ermini M (1990). "Risk of infertility in patients with Hodgkin's disease treated with ABVD vs MOPP vs ABVD/MOPP". Haematologica 75 (2): 155–8. PMID 1694156. 
  10. ^ Martin W, Ristow K, Habermann T, Colgan J, Witzig T, Ansell S (2005). "Bleomycin pulmonary toxicity has a negative impact on the outcome of patients with Hodgkin's lymphoma". J Clin Oncol 23 (30): 7614–20. doi:10.1200/JCO.2005.02.7243. PMID 16186594. 
  11. ^ Canellos G, Duggan D, Johnson J, Niedzwiecki D (2004). "How important is bleomycin in the adriamycin + bleomycin + vinblastine + dacarbazine regimen?". J Clin Oncol 22 (8): 1532–3. doi:10.1200/JCO.2004.99.010. PMID 15084636. 
  12. ^ van Leeuwen F, Klokman W, Veer M, Hagenbeek A, Krol A, Vetter U, Schaapveld M, van Heerde P, Burgers J, Somers R, Aleman B (2000). "Long-term risk of second malignancy in survivors of Hodgkin's disease treated during adolescence or young adulthood". J Clin Oncol 18 (3): 487–97. PMID 10653864. 

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