HyperCVAD
Encyclopedia
HyperCVAD is a chemotherapy regimen used to treat some forms of leukemia
, non-Hodgkin lymphoma
(high grade) and lymphoblastic lymphoma
.
(PICC), a hickman line
or a port-a-cath. The following is only a general guide (The exact combination of drugs used, doses and protocols used for administration are generally determined on a facility-by-facility basis). Dosage is individualized, based on factors such as body-weight, body surface area and the overall health of the patient.
Hematologic and immune system
The majority of patients will experience a degree of pancytopenia
, including anaemia, thrombocytopenia
, and leukopenia
, due to the myelosuppressive effect of chemotherapy. Anaemia and thrombocytopenia can cause clinical problems, and transfusion of red blood cells and platelets may be necessary supportive therapies. Leukopenia, particularly neutropenia
may lead to profound compromise of the immune system until the number of neutrophils recovers. Patients must therefore be vigilant to ensure that they report any fevers
to their clinician. Anti-infective drugs are commonly given as a prophylaxis during and in-between cycles, to prevent against community acquired infections. Patients are also at risk of hospital acquired infections, such as methicillin-resistant staphylococcus aureus
(MRSA) and Vancomycin-Resistant Enterococcus
(VRE). It is not uncommon for patients to require hospitalisation to treat infections.
Other side effects
Temporary hair loss is a common side effect. Nausea
and vomiting are commonly experienced both during and following administration. A variety of antiemetic
drugs may be used, including granisetron
, ondansetron
, metoclopramide
and cyclizine
.
Fertility is often compromised following the administration of hyper-CVAD chemotherapy. Patients who wish may elect to store gametes as a contingency.
Peripheral neuropathy
may be problematic following the administration of vincristine.
Leukemia
Leukemia 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...
, non-Hodgkin lymphoma
Non-Hodgkin lymphoma
The non-Hodgkin lymphomas are a diverse group of blood cancers that include any kind of lymphoma except Hodgkin's lymphomas. Types of NHL vary significantly in their severity, from indolent to very aggressive....
(high grade) and lymphoblastic lymphoma
Lymphoblastic lymphoma
Lymphoblastic lymphoma is a rare type of non-Hodgkin lymphoma, a result of abnormal adaptive immune cells, typically T-cells. It usually occurs in children....
.
Summary
The term 'hyper' refers to the hyperfractionated nature of the chemotherapy, which is given in smaller doses, more frequently, to minimize side effects. 'CVAD' is the acronym of the drugs used in courses A and B. CVAD (Cyclophosphamide, Vincristine, Doxorubicin (also known as Adriamycin [brand name]),and Dexamethasone (the D in hyper CVAD- this last one being a steroid)). The other part of Hyper CVAD is Methotrexate and Cytarabine. The protocol was originally developed to treat leukemia in young, fit and ambulant patients, but has since begun to be used more widely.Indications
Hyper-CVAD chemotherapy is generally reserved for use in the treatment of serious and aggressive forms of hematological malignancy. There are serious side effects and complications arising from the administration of the various agents, which require careful management in an appropriate health-care setting. Patients who receive hyper-CVAD receive a careful work-up to assess their overall wellness prior to the commencement of the regimen, in order to minimise undesirable outcomes. Patients considered for the protocol will generally be under 65.Administration
Each course is given up to 4 times, with up to 8 cycles in total. Each cycle is approximately two to three weeks apart. The aim is to administer as many cycles as possible or necessary in as short a time as possible. Timing of cycles will be somewhat dependent on the patient's recovery from the last cycle. The regimen is usually administered on an in-patient basis, using a continuous venous access device such as a peripherally inserted central catheterPeripherally inserted central catheter
A peripherally inserted central catheter is a form of intravenous access that can be used for a prolonged period of time...
(PICC), a hickman line
Hickman line
A Hickman line is an intravenous catheter most often used for the administration of chemotherapy or other medications, as well as for the withdrawal of blood for analysis. Some types of Hickman lines are used mainly for the purpose of apheresis or dialysis...
or a port-a-cath. The following is only a general guide (The exact combination of drugs used, doses and protocols used for administration are generally determined on a facility-by-facility basis). Dosage is individualized, based on factors such as body-weight, body surface area and the overall health of the patient.
Course A
- CyclophosphamideCyclophosphamideCyclophosphamide , also known as cytophosphane, is a nitrogen mustard alkylating agent, from the oxazophorines group....
(Cytoxan) is an alkylating agent given at 300mg/m2 by IV Q12hours over 3 hours (6 doses) Days 1, 2, and 3 - VincristineVincristineVincristine , 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) is a mitotic inhibitorMitotic inhibitorA mitotic inhibitor is a drug that inhibits mitosis, or cell division. These drugs disrupt microtubules, which are structures that pull the cell apart when it divides...
, 2mg IV Days 4 and 11 - 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....
(Adriamycin or Rubex) is an antibiotic with anti-tumour effects, 50mg/m2 IV Day 4 - DexamethasoneDexamethasoneDexamethasone is a potent synthetic member of the glucocorticoid class of steroid drugs. It acts as an anti-inflammatory and immunosuppressant...
is an Immunosuppressant 40mg/day IV or PO Days 1 to 4 Days 11-14 - CytarabineCytarabineCytarabine, or cytosine arabinoside, is a chemotherapy agent used mainly in the treatment of cancers of white blood cells such as acute myeloid leukemia and non-Hodgkin lymphoma. It is also known as Ara-C...
or Ara-C (Cytosar) is an antimetabolite 70mg IT Day 7 - MesnaMesnaMesna is an organosulfur compound. It is used in cancer chemotherapy involving cyclophosphamide and ifosfamide as an adjuvant. It is marketed by Baxter as Uromitexan and Mesnex...
(Uromitexan) is a compound used to reduce the incidence of haemorrhagic cystitis, a common side effect of the administration of cyclophosphamide. It is generally given via intravenous infusion or orally at the same time as cyclophosphamide. - MethotrexateMethotrexateMethotrexate , abbreviated MTX and formerly known as amethopterin, is an antimetabolite and antifolate drug. It is used in treatment of cancer, autoimmune diseases, ectopic pregnancy, and for the induction of medical abortions. It acts by inhibiting the metabolism of folic acid. Methotrexate...
, an antimetabolite, may be given via the intrathecalIntrathecalIntrathecal is an adjective that refers to something introduced into or occurring in the space under the arachnoid membrane of the brain or spinal cord...
route when it is necessary to give chemotherapy which will pass through the blood-brain barrierBlood-brain barrierThe blood–brain barrier is a separation of circulating blood and the brain extracellular fluid in the central nervous system . It occurs along all capillaries and consists of tight junctions around the capillaries that do not exist in normal circulation. Endothelial cells restrict the diffusion...
. 12mg IT Day 2
Course B
- MethotrexateMethotrexateMethotrexate , abbreviated MTX and formerly known as amethopterin, is an antimetabolite and antifolate drug. It is used in treatment of cancer, autoimmune diseases, ectopic pregnancy, and for the induction of medical abortions. It acts by inhibiting the metabolism of folic acid. Methotrexate...
1000mg/m2 IV over 24 hours Day 1 - Leucovorin 25mg/ m2 IV 24 hours after starting methotrexate infusion Q6H X 6 doses. Leucovorin is used as a 'rescue' agent to prevent excessive cellular damage by methotrexate.
- Sodium bicarbonateSodium bicarbonateSodium bicarbonate or sodium hydrogen carbonate is the chemical compound with the formula Na HCO3. Sodium bicarbonate is a white solid that is crystalline but often appears as a fine powder. It has a slightly salty, alkaline taste resembling that of washing soda . The natural mineral form is...
600mg PO (starting day before methotrexate) TID X 4 Days. Sodium bicarbonate is used to produce a mild metabolic alkalosisMetabolic alkalosisMetabolic alkalosis is a metabolic condition in which the pH of tissue is elevated beyond the normal range . This is the result of decreased hydrogen ion concentration, leading to increased bicarbonate, or alternatively a direct result of increased bicarbonate concentrations.-Terminology:*Alkalosis...
, desirable when administering large quantities of methotrexate. Urine pH values will be checked to ensure alkalosis prior to the commencement of methotrexate. - CytarabineCytarabineCytarabine, or cytosine arabinoside, is a chemotherapy agent used mainly in the treatment of cancers of white blood cells such as acute myeloid leukemia and non-Hodgkin lymphoma. It is also known as Ara-C...
3000mg/m2 IV over 2 hours Q12H X 4 doses Days 2 and 3
Side effects
The side effects of the administration of the chemotherapeutic agents used in hyper-CVAD are complex, and are often dependent on the overall health of the patient.Hematologic and immune system
The majority of patients will experience a degree of pancytopenia
Pancytopenia
Pancytopenia is a medical condition in which there is a reduction in the number of red and white blood cells, as well as platelets.If only two parameters from the full blood count are low, the term bicytopenia can be used...
, including anaemia, 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...
, and leukopenia
Leukopenia
Leukopenia is a decrease in the number of white blood cells found in the blood, which places individuals at increased risk of infection....
, due to the myelosuppressive effect of chemotherapy. Anaemia and thrombocytopenia can cause clinical problems, and transfusion of red blood cells and platelets may be necessary supportive therapies. Leukopenia, particularly 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...
may lead to profound compromise of the immune system until the number of neutrophils recovers. Patients must therefore be vigilant to ensure that they report any fevers
Fevers
Fevers are a five-piece band formed in 2010 in Ottawa, Ontario. The band consists of Colin MacDougall , Jim Hopkins , Martin Charbonneau , Sarah Bradley and Mike Stauffer . Theirs is a fresh take on a classic genre, combining indie rock and electronic music...
to their clinician. Anti-infective drugs are commonly given as a prophylaxis during and in-between cycles, to prevent against community acquired infections. Patients are also at risk of hospital acquired infections, such as methicillin-resistant staphylococcus aureus
Methicillin-resistant Staphylococcus aureus
Methicillin-resistant Staphylococcus aureus is a bacterium responsible for several difficult-to-treat infections in humans. It is also called multidrug-resistant Staphylococcus aureus and oxacillin-resistant Staphylococcus aureus...
(MRSA) and Vancomycin-Resistant Enterococcus
Vancomycin-Resistant Enterococcus
Vancomycin-resistant Enterococcus, or vancomycin-resistant enterococci , are bacterial strains of the genus Enterococcus that are resistant to the antibiotic vancomycin. To become VRE, vancomycin-sensitive enterococci typically obtain new DNA in the form of plasmids or transposons which encode...
(VRE). It is not uncommon for patients to require hospitalisation to treat infections.
Other side effects
Temporary hair loss is a common side effect. Nausea
Nausea
Nausea , is a sensation of unease and discomfort in the upper stomach with an involuntary urge to vomit. It often, but not always, precedes vomiting...
and vomiting are commonly experienced both during and following administration. A variety of antiemetic
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....
drugs may be used, including granisetron
Granisetron
Granisetron is a serotonin 5-HT3 receptor antagonist used as an antiemetic to treat nausea and vomiting following chemotherapy. Its main effect is to reduce the activity of the vagus nerve, which is a nerve that activates the vomiting center in the medulla oblongata. It does not have much effect...
, 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...
, metoclopramide
Metoclopramide
Metoclopramide is an antiemetic and gastroprokinetic agent. It is commonly used to treat nausea and vomiting, to facilitate gastric emptying in people with gastroparesis, and as a treatment for the gastric stasis often associated with migraine headaches.-Medical uses:Metoclopramide is commonly...
and cyclizine
Cyclizine
Cyclizine is an antihistamine drug used to treat nausea, vomiting and dizziness associated with motion sickness, vertigo and post-operatively following administration of general anaesthesia and opioids.-Indications:...
.
Fertility is often compromised following the administration of hyper-CVAD chemotherapy. Patients who wish may elect to store gametes as a contingency.
Peripheral neuropathy
Peripheral neuropathy
Peripheral neuropathy is the term for damage to nerves of the peripheral nervous system, which may be caused either by diseases of or trauma to the nerve or the side-effects of systemic illness....
may be problematic following the administration of vincristine.