IAC (chemotherapy)
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"7+3" in the context of
chemotherapy Chemotherapy (often abbreviated chemo, sometimes CTX and CTx) is the type of cancer treatment that uses one or more anti-cancer drugs (list of chemotherapeutic agents, chemotherapeutic agents or alkylating agents) in a standard chemotherapy re ...
is an
acronym An acronym is a type of abbreviation consisting of a phrase whose only pronounced elements are the initial letters or initial sounds of words inside that phrase. Acronyms are often spelled with the initial Letter (alphabet), letter of each wor ...
for 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 combi ...
that is most often used today (as of 2014) as first-line induction therapy (to induce remission) in
acute myelogenous leukemia Acute myeloid leukemia (AML) is a cancer of the myeloid line of blood cells, characterized by the rapid growth of abnormal cells that build up in the bone marrow and blood and interfere with normal blood cell production. Symptoms may includ ...
,Comparison of three remission induction regimens and two postinduction strategies for the treatment of acute nonlymphocytic leukemia: a cancer and leukemia group B study
/ref> excluding the
acute promyelocytic leukemia Acute promyelocytic leukemia (APML, APL) is a subtype of acute myeloid leukemia (AML), a cancer of the white blood cells. In APL, there is an abnormal accumulation of immature granulocytes called promyelocytes. The disease is characterized by ...
form, which is better treated with ATRA and/or
arsenic trioxide Arsenic trioxide is an inorganic compound with the formula . As an industrial chemical, its major uses include the manufacture of wood preservatives, pesticides, and glass. It is sold under the brand name Trisenox among others when used as a m ...
and requires less chemotherapy (if requires it at all, which is not always the case). The name "7+3" comes from the duration of chemotherapy course, which consists of 7 days of standard-dose
cytarabine Cytarabine, also known as cytosine arabinoside (ara-C), is a chemotherapy medication used to treat acute myeloid leukemia (AML), acute lymphocytic leukemia (ALL), chronic myelogenous leukemia (CML), and non-Hodgkin's lymphoma. It is given b ...
, and 3 days of an
anthracycline Anthracyclines are a class of drugs used in cancer chemotherapy that are extracted from '' Streptomyces peucetius'' bacterium. These compounds are used to treat many cancers, including leukemias, lymphomas, breast, stomach, uterine, ovarian, b ...
antibiotic An antibiotic is a type of antimicrobial substance active against bacteria. It is the most important type of antibacterial agent for fighting pathogenic bacteria, bacterial infections, and antibiotic medications are widely used in the therapy ...
or an anthracenedione, most often
daunorubicin Daunorubicin, also known as daunomycin, is a chemotherapy medication used to treat cancer. Specifically it is used for acute myeloid leukemia (AML), acute lymphoblastic leukemia (ALL), chronic myelogenous leukemia (CML), and Kaposi's sarcoma. I ...
(can be substituted for
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 ...
or
idarubicin Idarubicin or 4-demethoxydaunorubicin is an anthracycline antileukemic drug. It inserts itself into DNA and prevents DNA unwinding by interfering with the enzyme topoisomerase II. It is an analog of daunorubicin, but the absence of a methoxy gro ...
or
mitoxantrone Mitoxantrone (INN, BAN, USAN; also known as Mitozantrone in Australia; trade name Novantrone) is an anthracenedione antineoplastic agent. Uses Mitoxantrone is used to treat certain types of cancer, mostly acute myeloid leukemia. It improves th ...
).


Dosing regimen


Standard-dose cytarabine plus daunorubicin (DA or DAC chemotherapy)


Standard-dose cytarabine plus idarubicin (IA or IAC chemotherapy)


Standard-dose cytarabine plus mitoxantrone (MA or MAC chemotherapy)


Intensified versions

There were attempts to intensify the "7+3" regimen in order to try to improve its efficacy. Attempts were made to prolong the course (cytarabine for 10 days instead of 7, or daunorubicin/idarubicin for 4–5 days instead of 3). On the other hand, there were attempts to minimize the toxicity of the regimen by reducing the dose or the duration of the course, but these attempts compromised the efficacy of the regimen. The addition of vinca alkaloids (
vincristine Vincristine, also known as leurocristine and sold 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 lym ...
or
vinblastine Vinblastine, 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 canc ...
) to the "7+3" regimen, which was quite popular in AML(ALL?) in old times (when the biology of AML and the differences between AML and ALL was poorly understood) proved to be harmful in AML, lowering the chance of the patient achieving remission. This is because vinca alkaloids are rapidly deactivated in myeloid cells by their
enzyme An enzyme () is a protein that acts as a biological catalyst by accelerating chemical reactions. The molecules upon which enzymes may act are called substrate (chemistry), substrates, and the enzyme converts the substrates into different mol ...
myeloperoxidase Myeloperoxidase (MPO) is a peroxidase enzyme that in humans is encoded by the ''MPO'' gene on chromosome 17. MPO is most abundantly expressed in neutrophils (a subtype of white blood cells), and produces hypohalous acids to carry out their anti ...
. So the vinca alkaloids do much more damage to the lymphoid cell lines (including the T-cell lines responsible for antileukemic immunity) than to the myeloid cell lines. Moreover, vinca alkaloids in the context of AML cause AML cells to undergo a cell cycle arrest in the phase that renders those cells less sensitive to cytarabine and anthracyclines. Addition of
glucocorticoid Glucocorticoids (or, less commonly, glucocorticosteroids) are a class of corticosteroids, which are a class of steroid hormones. Glucocorticoids are corticosteroids that bind to the glucocorticoid receptor that is present in almost every vertebra ...
s (like
prednisolone Prednisolone is a corticosteroid, a steroid hormone used to treat certain types of allergies, inflammation, inflammatory conditions, autoimmune disorders, and cancers, Electrolyte imbalance, electrolyte imbalances and skin conditions. Some of ...
) or
methotrexate Methotrexate, formerly known as amethopterin, is a chemotherapy agent and immunosuppressive drug, immune-system suppressant. It is used to treat cancer, autoimmune diseases, and ectopic pregnancy, ectopic pregnancies. Types of cancers it is u ...
or alkylating drugs (like
cyclophosphamide Cyclophosphamide (CP), also known as cytophosphane among other names, is a medication used as chemotherapy and to suppress the immune system. As chemotherapy it is used to treat lymphoma, multiple myeloma, leukemia, ovarian cancer, breast cancer ...
or
melphalan Melphalan, sold under the brand name Alkeran among others, is a chemotherapy medication used to treat multiple myeloma; malignant lymphoma; lymphoblastic and myeloblastic leukemia; childhood neuroblastoma; ovarian cancer; mammary adenocar ...
) to the "7+3" regimen is also of no benefit in AML. The addition of
etoposide Etoposide, sold under the brand name Vepesid among others, is a chemotherapy medication used for the treatments of a number of types of cancer including testicular cancer, lung cancer, lymphoma, leukemia, neuroblastoma, and ovarian cancer. It is ...
to the standard "7+3" regimen is ''sometimes'' of benefit in poor-risk patients (many of whom are primary refractory to standard "7+3" induction regimens). It gave rise to the so-called ADE (or DAE = DA + etoposide) induction regimen in AML. The ADE induction (unlike, say, combinations of 7+3 with vinca alkaloids or prednisolone) is still sometimes used, especially in poor-risk AML patients. The addition of
6-thioguanine Tioguanine, also known as thioguanine or 6-thioguanine (6-TG) or tabloid is a medication used to treat acute myeloid leukemia (AML), acute lymphocytic leukemia (ALL), and chronic myeloid leukemia (CML). Long-term use is not recommended. It is gi ...
gave rise to the DAT regimen, and the addition of
6-mercaptopurine Mercaptopurine (6-MP), sold under the brand name Purinethol among others, is a medication used for cancer and autoimmune diseases. Specifically it is used to treat acute lymphocytic leukemia (ALL), acute promyelocytic leukemia (APL), Crohn's d ...
gave rise to the
DAM A dam is a barrier that stops or restricts the flow of surface water or underground streams. Reservoirs created by dams not only suppress floods but also provide water for activities such as irrigation, human consumption, industrial use, aqua ...
regimen.


References

{{reflist Chemotherapy regimens used in acute myeloid leukemia