Page 770 - Withrow and MacEwen's Small Animal Clinical Oncology, 6th Edition

748 PART IV Specific Malignancies in the Small Animal Patient

improve within 2 to 3 days after initiation of melphalan/predni- arsenic trioxide, bisphosphonates, and several molecular tar-
sone chemotherapy without the addition of therapies directed at geting therapies are under investigation; however, their use in
veterinary species is limited or completely absent at present.
hypercalcemia specifically.
VetBooks.ir sis. HVS is best treated in the short term by plasmaphere- Bortezomib has been shown to have activity against canine
melanoma in cell culture and mouse xenograft models.
764,808,813,838,844–846
A
Whole blood is collected from the patient
848
and centrifuged to separate plasma from packed cells. Packed red bortezomib protocol that is well-tolerated in dogs has been
cells are resuspended in normal saline or another crystalloid and used successfully in the treatment of golden retriever muscu-
reinfused into the patient. More advanced plasmapheresis meth- lar dystrophy but has not been, as yet, reported in dogs with
ods have also been used in dogs with HVS. 842 Bleeding diathesis MM. 849 One case report exists of a dog with MM that was
will usually resolve along with HVS; however, platelet-rich plasma resistant to melphalan, prednisone, and doxorubicin that sub-
transfusions may be necessary in the face of thrombocytopenia. sequently achieved a partial response to tyrosine kinase inhibi-
Renal impairment may necessitate aggressive fluid therapy in tor therapy (toceranib) that was maintained for 6 months. 776
the short term and maintenance of adequate hydration in the long Rabacfosadine (Tanovea-CA1) has been used investigationally
term. Careful attention to secondary urinary tract infections and in dogs with MM, either as induction therapy or for rescue in
appropriate antimicrobial therapy is indicated. Ensuring adequate melphalan-resistant disease and significant efficacy, including
water intake at home is important, and occasionally, educating durable molecular complete responses, was noted. 762 However,
owners in subcutaneous fluid administration is indicated. Con- rabacfosadine is currently conditionally approved for use only
tinued monitoring of renal function is recommended along with in dogs with lymphoma.
follow-up directed at tumor response.
Patients with MM can be thought of as immunologically Prognosis
impaired. Some have recommended prophylactic antibiotic
therapy in dogs with MM 764 ; however, in humans, no benefit The prognosis for dogs with MM is good for initial control of
for this approach over diligent monitoring and aggressive anti- tumor and a return to good quality of life. 757,761,762 In a group of
microbial management when indicated has been observed. 806 Cidal 60 dogs with MM, approximately 43% achieved complete remis-
antimicrobials are preferred over static drugs, and avoidance of sion (i.e., serum immunoglobulins normalized), 49% achieved
nephrotoxic antimicrobials is recommended. a partial remission (i.e., immunoglobulins <50% pretreatment
Pathologic fractures of weight-bearing long bones and verte- values), and only 8% did not respond to melphalan and pred-
brae resulting in spinal cord compression may require immediate nisone chemotherapy. 757 Long-term survival is the norm, with
surgical intervention in conjunction with systemic chemotherapy. a median survival time of 540 days reported (Fig. 33.30). More
Orthopedic stabilization of fractures should be undertaken and recently, in 38 dogs treated with melphalan/prednisone, 86%
may be followed with RT (see Fig. 33.25). Inhibition of osteo- had objective responses (94% for pulse-dose protocol and 79%
clast activity by bisphosphonate drugs (in particular zoledronate), for continuous daily protocol) with a median progression-free
has been shown in several meta-analyses to reduce the incidence and overall survival time (MST) of 601 and 930 days, respec-
and severity of skeletal complications (e.g., bone pain, pathologic tively. 761 The 1-, 2-, and 3-year survival rates were 81%, 55%,
fracture) of MM in humans and to result in some prolongation of and 30%, respectively. The presence of hypercalcemia, Bence
overall survival. 835,845,846 This class of drugs may hold promise for Jones proteinuria, and extensive bony lysis were found to be
use in dogs and cats with various skeletal tumors; however, they negative prognostic factors in the dog in one large cohort, 757
have not been adequately evaluated for time-to-event efficacy in but not in another. 761 Only the presence of renal disease and a
MRD in companion species. high peripheral neutrophil:lymphocyte ratio at diagnosis were
negative indices in the latter report. 761 Despite long-term dura-
Rescue Therapy ble responses in treated dogs, MM is generally a uniformly fatal
When MM eventually relapses in dogs and cats undergoing ini- disorder as drug-resistant recurrence of tumor mass and associ-
tial melphalan or alternative alkylator therapy or in the uncom- ated clinical signs is expected. Eventually, the tumor is no lon-
mon case that is initially resistant to alkylating agents, rescue ger responsive to available chemotherapeutics and death follows
therapy may be attempted. Switching to an alternate alkylating from infection, renal failure, or euthanasia for intractable bone
agent (e.g., cyclophosphamide, lomustine, chlorambucil) may be or spinal pain. 757,764
effective. 761,769 The author has also had limited success with VAD, The prognosis for MM in the cat is not as favorable as it is in
which is a combination of doxorubicin (30 mg/m IV, every 21 the dog. 764,767,769–771,788 That being said, approximately 50% to
2
2
days), vincristine (0.7 mg/m IV, days 8 and 15), and dexametha- 83% of cats with MM will respond to chemotherapy and although
sone sodium phosphate (1.0 mg/kg IV, once a week on days 1, older compilations report MSTs of approximately 4 months, sev-
8, and 15), given in 21-day cycles. Whereas most dogs initially eral long-term responses (i.e., >1 year) have been reported and a
respond to rescue protocols, the duration of response tends to be recent compilation documented MSTs of 8 to 13 months with
short, lasting only a few months. Liposomal doxorubicin has pro- treatment. 764,767,769–771,788,790,821 One investigator grouped MM
duced a long-term remission in a dog with MM previously resis- in cats into two prognostic categories (Table 33.17) based on cri-
tant to native doxorubicin. 847 teria known to predict behavior in dogs. 770 Although no rigorous
statistical analysis was performed on this small group of nine cats,
Investigational Therapies the MST for cats in “aggressive” and “nonaggressive” categories
MM is ultimately a uniformly fatal disease in most species and was 5 days and 387 days, respectively.
thus significant effort is being placed on investigational thera- Experience in dogs with IgM macroglobulinemia is lim-
pies for this disease. Currently, bone marrow ablative therapy ited. 764,804–805 Response to chlorambucil is to be expected, and
and marrow or stem cell rescue, thalidomide (and other anti- in nine treated dogs, 77% achieved remission with an MST of 11
angiogenic therapies), bortezomib (a proteasome inhibitor), months. 764