- HyperCVAD
HyperCVAD is a chemotherapy regimen used to treat some forms of
leukemia ,non-Hodgkin lymphoma (high grade) andlymphoblastic lymphoma .ummary
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 some of the drugs used in courses A and B. 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 regime, 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 catheter (PICC), ahickman line or aport-a-cath . It should be noted that the exact combination of drugs used, doses and protocols used for administration are generally determined on a facility-by-facility basis - the following is a general guide. Dosage is individualized, based on factors such as body-weight, body surface area and the overall health of the patient.Course A:
*
Cyclophosphamide (Cytoxan) is analkylating agent given at 300mg/m2 by IV for 3 hours (6 doses) Days 1, 2, and 3
*Vincristine (Oncovin) is amitotic inhibitor , 2mg IV Days 4 and 11
*Doxorubicin (Adriamycin or Rubex) is an antibiotic with anti-tumour effects, 50mg/m2 IV Day 4
*Dexamethasone is an Immunosuppressant 40mg/day IV or PO Days 1 to 4 Days 11-14
*Cytarabine or Ara-C (Cytosar) is an antimetabolite 70mg IT Day 7
*Mesna (Uromitexan) is a compound used to reduce the incidence ofhaemorrhagic 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.
*Methotrexate , an antimetabolite, may be given via theintrathecal route when it is necessary to give chemotherapy which will pass through theblood-brain barrier . 12mg IT Day 2Course B:
*
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 bicarbonate 600mg PO (starting day before methotrexate) TID X 4 Days. Sodium bicarbonate is used to produce a mildmetabolic alkalosis , desirable when administering large quantities of methotrexate. Urine pH values will be checked to ensure alkalosis prior to the commencement of methotrexate.
*Cytarabine 3000mg/m2 IV over 2 hours Q12H X 4 doses Days 2 and 3ide-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 , includinganaemia ,thrombocytopenia , andleukopenia , due to themyelosuppressive effect of chemotherapy. Anaemia and thrombocytopenia can cause clinical problems, and transfusion of red blood cells and platelets may be necessary supportive therapies. Leukopenia, particularlyneutropenia 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 anyfevers 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 asmethicillin-resistant staphylococcus aureus (MRSA) and Vancomycin-Resistant Enterococcus (VRE). It is not uncommon for patients to require hospitalisation to treat infections.Other side-effects
Hair-loss is a common side-effect.
Nausea and vomiting are commonly experienced both during and following administration. A variety ofantiemetic drugs may be used, includinggranisetron ,ondansetron ,metoclopramide andcyclizine .Fertility is often compromised following the administration of hyper-CVAD chemotherapy. Patients who wish to may elect to store
gametes as a contingency.Peripheral neuropathy may be problematic following the administration of vincristine.
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