Page 727 - Withrow and MacEwen's Small Animal Clinical Oncology, 6th Edition

CHAPTER 33 Hematopoietic Tumors 705

(the patient relapses) after achievement of a remission (termed • BOX 33.3 Current Canine Lymphoma Protocol

reinduction), and, finally, to induce remissions when the cancer (UW-Madison-19)
fails to respond to induction or reinduction using drugs not pres-
VetBooks.ir ent in the initial protocols (termed rescue). Week 1: Vincristine, 0.7 mg/m IV
2
An unanswered question in the treatment of lymphoma has
Prednisone, 2 mg/kg, PO, daily
been whether long-term maintenance chemotherapy is useful after Week 2: Cyclophosphamide, 250 mg/m IV or PO
a
2
an initial course of aggressive induction chemotherapy lasting 6 Prednisone, 1.5 mg/kg, PO, daily
2
months or less. Long-term maintenance chemotherapy has not Week 3: Vincristine, 0.7 mg/m IV
been shown to be of significant value in humans with most aggres- Prednisone, 1.0 mg/kg, PO, daily
2
b
sive forms of NHL; however, in humans, the initial induction Week 4: Doxorubicin, 30 mg/m IV
course of chemotherapy is much more aggressive than that used in Prednisone, 0.5 mg/kg, PO, daily
Week 6: Vincristine, 0.7 mg/m IV
2
veterinary patients. Although no randomized prospective studies Week 7: Cyclophosphamide, 250 mg/m IV or PO
a
2
have been performed to address the therapeutic benefit of long- Week 8: Vincristine, 0.7 mg/m IV
2
term maintenance chemotherapy in dogs, most comparisons of Week 9: Doxorubicin, 30 mg/m IV
2
b
dogs treated with CHOP-based protocols do not show any clear Week 11: Vincristine, 0.7 mg/m IV
2
advantage for a maintenance or consolidation phase after induc- Week 12: Cyclophosphamide, 250 mg/m IV or PO
2
a
2
tion therapy. 229,231,232,234,240,242–245,247,258–262 Indeed, in most Week 13: Vincristine, 0.7 mg/m IV
2
b
reports, dogs receiving shorter, less costly protocols that do not Week 14: Doxorubicin, 30 mg/m IV
2
include a prolonged maintenance phase have comparable remis- Week 16: Vincristine, 0.7 mg/m IV
2
a
sion and progression-free survival (PFS) durations and appear to Week 17: Cyclophosphamide, 250 mg/m IV or PO
2
more readily achieve second remissions when they relapse after Week 18: Vincristine, 0.7 mg/m IV
2
Week 19: Doxorubicin, 30 mg/m IV
b
completion of chemotherapy than their counterparts receiving 1. All treatments are discontinued after week 19 if in complete remission.
long-term maintenance. These data, taken together, suggest that 2. A complete blood count (CBC) should be performed before each
maintenance therapy is not beneficial for most dogs with lym- chemotherapy. If neutrophil count is <1500 wait 5 to 7 days and
phoma. Until well-designed randomized prospective trials indi- repeat CBC.
cate otherwise, the author (DMV) prefers protocols that utilize an 3. If sterile hemorrhagic cystitis occurs on cyclophosphamide, discontinue
aggressive induction without maintenance. and substitute chlorambucil (1.4 mg/kg PO) for subsequently scheduled
cyclophosphamide treatments.
Single-Agent Chemotherapy with Known Activity 4. For acute lymphocytic leukemia (ALL)–administer l-asparaginase 400
for Dogs with Lymphoma IU/kg SQ with each vincristine injection, until a complete response is
The most effective currently available chemotherapeutic agents for achieved.
canine lymphoma include doxorubicin (DOX), l-asparaginase, a Furosemide (1–2 mg/kg) is given IV or PO, concurrent with cyclophosphamide to lessen the
vincristine, cyclophosphamide, and prednisone, most of which incidence of sterile hemorrhagic cystitis. 2
b
are represented to one degree or another in most first-line multia- In dogs less than 15 kg in body weight, a doxorubicin dose of 1 mg/kg is substituted for 30 mg/m
gent chemotherapy protocols. Other drugs that have documented
activity are often considered second-line agents and include rabac-
fosadine (Tanovea-CA1), lomustine, vinblastine, actinomycin-D,
mitoxantrone, mustargen, chlorambucil, methotrexate, dacarba- Overall Chemotherapy Recommendations
zine (DTIC), 9-aminocamptothecin, ifosfamide, cytosine ara- for Multicentric Lymphoma (Author [DMV] Preference)
binoside, procarbazine, bleomycin, and gemcitabine. Of these, Several factors should be considered and discussed with caregiv-
cytosine arabinoside, 263 ifosfamide, 264 bleomycin, 265 and gem- ers on a case-by-case basis when choosing the treatment protocol.
citabine 266 appear to have minimal activity. With the exception These factors include cost, time commitment involved, efficacy,
of DOX, single-agent induction therapy does not typically result adverse event profiles, and experience of the clinician with the
in durable remission durations compared with standard combina- protocols under consideration.
tion protocols. Incorporation of other standard cytotoxic drugs
with single-agent activity into standard CHOP-based protocols Induction in Treatment-Naïve Patients
has not resulted in significant gains or has not been adequately It is now clearly established that “standard-of-care” combination
evaluated, and most are reserved for subsequent rescue settings. protocols used in dogs with intermediate- and high-grade lym-
The use of rabacfosadine (Tanovea-CA1) warrants a brief dis- phoma are essentially variations of CHOP protocols (see Table
cussion as it is the only chemotherapy agent currently approved, 33.4). Specific details regarding dose and timing of the CHOP
albeit conditionally, by the US Food and Drug Administration protocol currently preferred by the author (DMV) are outlined in
(FDA) for the treatment of dogs with lymphoma (see Chapter 12 Box 33.3. This protocol does not have a maintenance component
for a specific discussion of rabacfosadine). Rabacfosadine has been and all treatments cease at 19 weeks, provided the animal is in
evaluated in hundreds of dogs with lymphoma and activity has complete clinical remission. Although several other CHOP-based
been documented as a single-agent for treatment of cutaneous protocols include l-asparaginase either at initiation or at varying
lymphoma, multiple myeloma, and naïve and relapsed multicen- times throughout the protocol, several studies suggest this does
tric lymphoma, as well as in combination with DOX for lym- not result in clinically relevant increases in remission rate, speed of
phoma. 226,230,267–270 Currently, rabacfosadine is most commonly attaining remission, or first-remission duration, and therefore the
used as a rescue agent at relapse or as a first-line treatment in com- author reserves its use for rescue situations. 246,260,271,272
bination with DOX owing to a less intense treatment protocol If client or other considerations preclude a CHOP-based pro-
2
while maintaining similar remission durations compared with tocol, single-agent DOX (30 mg/m , intravenous [IV], every 3
CHOP in a nonrandomized fashion. 230 weeks for five total treatments) is offered along with a 4-week