HyperCVAD

HyperCVAD is a chemotherapy regimen used to treat some forms of leukemia, non-Hodgkin lymphoma (high grade) and lymphoblastic lymphoma.

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Summary

The term 'hyper' refers to the hyperfractionated nature of the chemotherapy, which is given in smaller doses, more frequently, to minimise 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 dependant 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), a hickman line or a port-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 individualised, based on factors such as body-weight, body surface area and the overall health of the patient.

Course A:

• Cyclophosphamide (Cytoxan®) is an alkylating agent given at 300mg/m2 by IV for 3 hours (6 doses) Days 1, 2, and 3
• Vincristine (Oncovin®) is a mitotic 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 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.
• Methotrexate, an antimetabolite, may be given via the intrathecal route when it is necessary to give chemotherapy which will pass through the blood-brain barrier. 12mg IT Day 2

Course 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 mild metabolic alkalosis, desirable when administering large quantities of methotrexate. Urine pH values will be checked to ensure alkalosis prior to the commencement of methotrexate.
• Cytarabine3000mg/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, 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

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 to may elect to store gametes as a contingency.

Peripheral neuropathy may be problematic following the administration of vincristine.