HyperCVAD

Indication

Lymphoblastic Lymphoma, Mantle Cell Lymphoma

Regimen

Course A

Cycle 1,3,5,7 (3-4 wks/cycle)

CYCLOPHOSPHAMIDE 300mg/m2 IV over 3 hours Q12H x 6 doses Days 1, 2, and 3
MESNA may be given as an uroprotectant at the same total dose as cyclophosphamide but given by continuous infusion starting with cyclophosphamide 
and ending 6 hours after the last dose. (Although Mesna is recommended in the cited reference (Kantarjian et al.), 
most RCC’s usually do not administer Mesna with this dose of Cyclophosphamide.)
METHOTREXATE 12mg IT Day 2
DOXORUBICIN 50mg/ m2 IV Day 4
VINCRISTINE 2mg IV Days 4 and 11
DEXAMETHASONE 40mg/day IV or PO Days 1 to 4, Days 11-14
CYTARABINE 70mg IT Day 7

Course B:

Cycle 2,4,6,8 (3-4 wks/cycle)

METHOTREXATE 1000mg/ m2 IV over 24 hours Day 1
LEUCOVORIN 25mg/ m2 IV 24 hours after starting Methotrexate infusion Q6H X 6 doses
Sodium Bicarbonate 600mg PO (starting day before Methotrexate) TID X 4 Days
CYTARABINE 3000mg/ m2 IV over 2 hours (1 g/m2 for patients over 60 years old)  Q12H X 4 doses Days 2 and 3

CYCLE FREQUENCY

A total of 8 cycles is administered (4 X A, 4 X B) with the goal to give treatment as rapidly as possible.

PREMEDICATION AND SUPPORTIVE MEASURES

ANTIEMETIC REGIMENS:

HESKETH LEVEL 5

· With high dose Methotrexate, give hydration with Sodium Bicarbonate for 48 hours.
· Prophylactic use of Dexamethasone 0.1% or Pred Forte Ophthalmic solution 1-2 drops q4h while awake for 7 days (during high dose Cytarabine) to prevent conjunctivitis
· Antibiotic prophylaxis may be given

DOSE MODIFICATION

Doses should be modified according to the protocol by which the patient is being treated. The following recommendations are in use at some centres.

Hematologic Toxicities
G-CSF support should be considered after first episode of febrile neutropenia or delay of dose > or = 1 week.

Renal Dysfunction
Creatinine Clearance
0.2-0.8mL/sec REDUCE Methotrexate to 50% dose
<0.2mL/sec OMIT dose of Methotrexate
There is no consistent evidence indicating a need for Cyclophosphamide dosage modification in patient with renal impairment.
Dosage may be halved or interval increased by 50-100% if Creat Clearance <0.3 mL/second. If there is evidence of renal insufficiency (inc Serum Creatinine / dec Creatinine Clearance), consider alternate therapy (Cerebellar toxicity with high-dose Cytarabine associated with reduced renal clearance).

Schema

References

• Thomas, DA et al. Outcome with the hyper-CVAD regimens in lymphoblastic lymphoma. Blood 2004; 104:1624
• IF Khouri et al. Hyper-CVAD and high-dose methotrexate/cytarabine followed by stem-cell transplantation: an active regimen for aggressive mantle-cell lymphoma. Journal of Clinical Oncology, 1998 Vol 16, 3803-3809