Page 1334 - Small Animal Internal Medicine, 6th Edition

1306 PART XII Oncology

MSTs reported for dogs with multicentric lymphoma are 10 Numerous “rescue” protocols have been described in the
to 12 months. Cats treated with CHOP-based protocols for literature, and as a general rule, the practitioner may have
VetBooks.ir high-grade lymphoma experience overall lower MSTs than difficulty deciding what protocol to choose since the final
decision is frequently based on personal experience. Typi-
dogs; however, approximately 30% of cats have long-term
cally, if a patient has completed the induction phase of COP
survivals of over 1 to 2 years.
or the entirety of the CHOP protocol before relapse, reinduc-
Should You Use COP-Based or tion with one of these protocols is considered the most likely
CHOP-Based Protocols? to induce another remission. There are also alternative rescue
Clinicians have been debating the relative merits of COP- chemotherapy options consisting of multi- or single-agent
and CHOP-based protocols for several years. However, due protocols that can be considered for use if the COP or CHOP
to the fact that most institutions or clinicians prefer one protocol is unsuccessful at reinducing remission, or the
protocol over the other (illustrated by the differing protocols owner opts to proceed with an alternative protocol.
used in this chapter by both authors), most reports on COP- One author (GC) currently uses the D-MAC protocol (see
based protocols are 10 to 20 years old, and most reports of Box 79.1) as the first alternative to COP, which consists of
COP- or CHOP-based chemotherapy studies have remission dexamethasone, melphalan, cytosine arabinoside, and acti-
times as endpoints rather than survival times, a definitive nomycin D (Alvarez et al., 2006). This protocol results in a
answer is not readily available. There is no clear advantage greater than 70% remission rate in dogs with relapsing lym-
of one protocol over the other, so it is recommended that the phoma; it has a relatively low toxicity compared with that of
clinician make decisions based on various factors (e.g., the doxorubicin-containing protocols, and it is necessary for the
owner’s perception, the patient’s clinical signs, other concur- owner to go to the veterinarian only once every 2 weeks
rent illnesses, the veterinarian’s “comfort” with a given pro- (instead of every week). The median duration of remission
tocol or drug, etc.). See Figures 79.12 and 79.13. using the D-MAC protocol was 61 days (range 2-467+ days)
Intensification in a previous study (Alvarez et al., 2006). Previous use of
If a dog with large-cell lymphoma is undergoing induc- doxorubicin and failure to induce remission with the induc-
tion therapy (with either COP- or CHOP-based protocols), tion protocol were negative prognostic factors for response
but only partial remission (PR) is obtained, intensification to this protocol. Thrombocytopenia occurred in 56% of the
with one or two doses of L-asparaginase (10,000-20,000 IU/ dogs, neutropenia in 17%, and gastrointestinal toxicity in
m intramuscular [IM] or SC, repeated once at a 2- to 3-week 22%; 3 of the 56 dogs required hospitalization because of
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interval) may be indicated. This drug can rapidly induce toxicity. Because the long-term use of melphalan is associ-
CR in most dogs with lymphoma that have shown only PR ated with severe chronic thrombocytopenia, chlorambucil,
while receiving COP or CHOP. Additionally, in patients 20 mg/m , is substituted for melphalan after four cycles. If
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that are unwell or have cytopenias, we frequently induce the complete or partial remissions are achieved after the admin-
initial remission, before initiation of either COP or CHOP, istration of four to six cycles of D-MAC, the patient can be
with L-asparaginase, given the lack of adverse effects and started on a maintenance protocol again. If the response to
the high probability of response. This can be quite benefi- D-MAC is poor (i.e., the disease progresses), GC then
cial for dogs that are sick from their lymphoma and cannot pursues the CHOP protocol (see Box 79.1). This protocol
tolerate traditional chemotherapy. Caution is recommended calls for two or three cycles of CHOP; if CR is obtained, the
in dogs with a history of pancreatitis or in those that are patient is started on maintenance chemotherapy at the end
at high risk for acute pancreatitis (i.e., obese, middle- of the second or third CHOP cycle. The maintenance proto-
aged female dogs), as asparaginase can cause pancreatitis; col in these animals also includes LMP, with the possible
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however, in our experience, this is an uncommon adverse addition of vincristine (0.5-0.75 mg/m IV once weekly to
effect. L-asparaginase appears to be less effective in cats than every other week, alternating weeks with the chlorambucil)
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in dogs, only inducing remission in approximately 30% or cytosine arabinoside (200-400 mg/m SC every other
of cats. week, alternating weeks with the chlorambucil). After a
Reinduction of remission or rescue second relapse occurs, GC generally proceeds with an addi-
Virtually every dog and cat with lymphoma treated with tional D-MAC or CHOP protocol for two additional cycles,
either COP- or CHOP-based chemotherapy protocols will as described in the preceding paragraph.
eventually relapse; this generally occurs 3 to 6 months after If a CHOP-based protocol is unsuccessful at reinducing a
the start of induction therapy with COP (median: ≈4 remission, or owners opt to not proceed with another CHOP-
months), and 8 to 9 months after initiation of the CHOP. At based protocol, KC generally discusses different rescue
this time, reinduction of remission is indicated. In our expe- options with owners to decide which protocol is most suit-
rience, remission can be reinduced one to four additional able. The main considerations include whether the owners
times in most dogs with relapsing lymphoma. Reinduction are able to commit to weekly or every other week office visits,
of remission is usually not as successful in cats (i.e., remis- finances, and the health of the patient at relapse. The proto-
sion is difficult to reinduce in most cats with relapsing lym- cols commonly considered are listed in Box 79.1, with the
phoma). Therefore the following discussion on “rescue” single-agent protocols (e.g., dacarbazine, CCNU) having
pertains mostly to dogs with lymphoma. response rates of approximately 30% to 40% and the