Page 726 - Withrow and MacEwen's Small Animal Clinical Oncology, 6th Edition

704 PART IV Specific Malignancies in the Small Animal Patient

100 100
90 90
80
VetBooks.ir 70 80
Percent surviving 50 P 0.001 Percent surviving 50 P 0.001
70
60
60
40
40
30
20 30
20
10 10
0 0
0 250 500 750 1000 0 250 500 750 1000
Days Days
CD3 negative (n 37) Substage ‘a’
Median 389 days Median 345 days
CD3 positive (n 10) Substage ‘b’
A Median 159 days B Median 44 days
• Fig. 33.11 (A) Kaplan–Meier survival duration estimates for a group of 55 dogs with lymphoma treated
with an identical CHOP-based combination chemotherapy protocol. Dogs with CD3 immunoreactive
(T-cell) lymphoma had significantly shorter survival durations. (B) Kaplan–Meier survival duration estimates
for a group of 55 dogs with lymphoma treated with an identical CHOP based combination chemotherapy
protocol at the University of Wisconsin. Dogs with substage b disease (i.e., clinically ill) had significantly
shorter survival durations. (From Vail DM. Hematopoietic tumors. In Ettinger SJ, Feldman EC, eds. Text-
book of Veterinary Internal Medicine. 6th ed. St. Louis: Elsevier; 2005.)

these studies include sufficient numbers of dogs for adequate sta- frequency of administration, and the laboratory tests required to
tistical power and even fewer compare treatment protocols in a monitor adverse events and response.
randomized prospective fashion. In addition, staging, inclusion, In an attempt to better standardize response criteria and
and response criteria vary considerably among reports. Therefore outcome reporting of future trials, the Veterinary Cooperative
evaluations of efficacy among various protocols are subject to Oncology Group (VCOG) published response evaluation crite-
substantial bias, making direct comparisons difficult and indeed ria (v1.0) 253 that can be applied in the routine practice setting.
precarious. A recurring theme in the concluding statement in The greatest obstacle to performance of prospective randomized
most of these published protocols is some variation of “prospec- comparative lymphoma trials in veterinary oncology is financial;
tive randomized trials will be required to confirm these suggestive that is, clinical trials are inherently costly, and because most of the
findings.” Despite the plethora of available combination proto- known effective drugs are unregistered off-label human generic
cols, most are modifications of CHOP protocols initially designed (i.e., off-patent) drugs, the incentive for pharmaceutical-funded,
for human oncologic use, and currently randomized prospective sufficiently powered, randomized field trials is low, resulting in a
evidence does not exist in dogs to clearly recommend one over general lack of comparative data.
the other as long as the basic CHOP components are present. Dogs responding to chemotherapy and undergoing complete
CHOP represents combinations of cyclophosphamide (C), doxo- “clinical” remission are usually free of clinical signs associated with
rubicin (H, hydroxydaunorubicin), vincristine (O, Oncovin), and lymphoma and subsequently return to a very good quality of life,
prednisone (P). In the 1980s and early 1990s, physicians treat- making the treatment of dogs with lymphoma initially gratifying.
ing human patients with advanced, intermediate- or high-grade Most dogs tolerate chemotherapy well, and although dose reduc-
lymphoma faced a similar dilemma in that many different varia- tions and treatment breaks (“treatment holidays”) are sometimes
tions of CHOP existed and no randomized data were available to required in individual cases, only a minority of dogs develop sig-
determine which protocols were superior. Eventually, a national nificant adverse events requiring hospitalization. 254,255 Studies
randomized trial involving more than 1000 people with interme- assessing client perceptions of medical treatment for cancer in
diate/high grade NHL was conducted comparing the plethora of general and lymphoma in particular report a positive experience;
protocols available, and the results indicated that CHOP was as most owners feel treatment was worthwhile, that it resulted in
effective as any of the more complicated protocols and had the improvement in the well-being of their pet, and that quality of life
safest adverse event profile. 252 CHOP subsequently became (and during treatment was good. 256,257 Very few clients express regret
remains, with the addition of monoclonal antibody therapy) the about treating lymphoma using a multidrug protocol.
standard of care for people with intermediate-/high-grade NHL. Importantly, it must be realized that cures are rare, and though
Conventional CHOP-based chemotherapy induces remission complete clinical remissions are the norm, complete molecular
in approximately 80% to 95% of dogs, with overall MSTs of 10 remissions (iCR), which can be documented only with molecular
to 12 months. Approximately 20% to 25% of treated dogs will techniques, are rarely achieved in dogs; thus the utility of docu-
be alive 2 years after initiation of these protocols (Fig. 33.11). menting iCR, in the absence of meaningful therapeutic options, is
Response rates and durations of response vary according to the limited to investigative trials striving to achieve them.
presence or absence of prognostic factors discussed in the text With lymphoma, the fundamental goals of chemotherapy are
that follows. The relative cost of the various protocols to the cli- to induce a complete durable (>6 months) first remission (termed
ent depends on the drug(s) selected, the size of the animal, the induction), to reinduce a remission when the tumor recrudesces