CCNU +/- L'asparaginase
CCNU is an alkylating agent and a good choice for dogs that have failed CHOP-L protocols. In those treated with CCNU alone
as a rescue, the reported complete and partial response rate was 25 percent for a duration of 86 days (Frimberger 1999). This
response is typical for most rescue protocols.
L'asparaginase usually is not used as a maintenance agent in most CHOP-L protocols and is not subject to multi-drug resistance.
The use of L'asparaginase and CCNU combined may be more effective, given the different mechanisms. The toxicities are non-overlapping,
making this a well-tolerated protocol. Both drugs are given once every three weeks.
L'asparaginase can cause allergic reactions when used multiple times, so pre-medication with Benadryl +/- steroids can be
considered. CCNU can cause hepatoxicity, so periodic evaluation of liver enzymes is advised.
MOPP (Mustargen, vincristine, prednisone and procarbazine) is one of the first protocols developed to treat lymphoma in humans.
It no longer is used as a standard treatment option in humans but is used either as a first-line protocol for T-cell lymphoma
or as a first-line rescue protocol in canine patients.
Both Mustargen and procarbazine are alkylating agents, so may be effective in dogs that have failed CHOP-L protocols. In one
study, 31 percent of dogs achieved a complete remission for a median duration of 63 days (Mooney 2002).
D-MAC (dexamethasone, actinomycin-D, cytosine arabinoside and melphalan) is a multi-drug rescue protocol reported to have
a combined response rate (PR +CR) of 72 percent (Cuoto 2006).
The duration of remission was 112 weeks for complete responders and 44 days for partial responders. Actinomycin-D is an anthracycline
similar to doxorubicin but does not carry the risk of cardiomyopathy.
Cross-resistance between actinomycin-D and doxorubicin can be an issue. Cytosine is an anti-metabolite while melphalan is
an alkylating agent so cross-resistance is not an issue with these two drugs.
Doxorubicin remains one of the most effective chemotherapeutics for the treatment of canine lymphoma. However, the development
of resistance ultimately limits its use as a rescue agent.
Dacarbazine is a non-traditional alkylating agent that is not part of first line agents for lymphoma due to limited efficacy
as a single agent.
When these two drugs are given in combination, there appears to be a synergy that can reverse drug resistance to doxorubicin.
In one study, five of 15 dogs who were resistant to doxorubicin were found to achieve a response with a median survival time
of 105 days (Van Vechten 1990). The cumulative dose of doxorubicin should not exceed 180 mg/m2.
Radiation therapy has been an effective modality in the treatment of lymphoma in humans.
Different applications would include localized or regional radiation therapy, half-body radiation therapy or total-body irradiation
If there is only a single node or set of lymph nodes that are resistant, radiation therapy protocols that involve multiple
daily fractions of radiation therapy can be considered.
Half-body radiation therapy has been used for dogs that have failed systemically.
Half-body radiation resulted in complete or partial response in five of 14 dogs with a mean duration of 102 and 54 days, respectively
(Laing et al., 1989).
The cranial and caudal halves of the body are treated separately and need to be separated by three to four weeks to allow
for bone-marrow recovery in the treated half.
Potential toxicities include alopecia, bone-marrow suppression and gastrointestinal toxicity.
Effective protocols for the use TBI as a rescue therapy have not been published because one limiting factor is severe myelosuppression.