Canine Lymphoma In Vivo Chemotherapy Assay
Purpose of the Study
The goal of this study is determine the ability of a novel microneedle
tumor injection device to correctly identify drug response in either
chemotherapy naïve or Madison-Wisconsin (CHOP) based chemotherapy
resistant canine lymphoma patients. If successful, these findings will
be used to develop future prospective trials for customized chemotherapy
regimens for lymphoma patients in both dogs and in humans with newly
diagnosed and resistant lymphoma.
Lymphoma is the most common canine
hematopoietic malignancy, with the most common form characterized by
generalized lymphadenopathy (multicentric form). Multi-agent
combination chemotherapy such as those in Madison-Wisconsin or "CHOP"-based protocols (cyclophosphamide, doxorubicin, vincristine, and
prednisone) is currently considered the standard of care with response
rates of 60-90%; median survival of just over 1 year, and 20% surviving
2 years of longer. Long term control of this cancer is rarely achieved
due to multi-drug resistance either at the beginning or eventual
development during course of therapy. New approaches to treatment of
this uniformly fatal tumor are needed.
A better understanding of
tumor-specific chemotherapy resistance profiles prior to therapy has the
potential to improve patient treatment outcomes while minimizing
exposure to chemotherapeutics that have no benefit. A micro needle drug
array device has been developed as a potential in vivo (in patient)
chemotherapy assay. The device delivers a panel of chemotherapeutics in
a specific spacial and geometric pattern directly into solid tumors 1-3
days prior to surgical biopsy. Histopathologic markers for cell
proliferation and apoptosis then allow qualitative assessment of tumor
sensitivity or resistance to selected chemotherapeutics. A prototype
device has been used in clinical canine patients here at WSU Oncology
service since early 2012. In this trial, we will be using a novel tumor
injection device to predict resistance to standard chemotherapy drugs of
the Madison-Wisconsin / CHOP-based protocol in two groups of clinical
canine patients: a group with naïve lymphoma that have never been
treated with chemotherapy, and a group with naturally occurring lymphoma
that have clearly documented clinically relapsed or failed initial
chemotherapy with all drugs in the protocol. By proving that this micro
needle device array is a viable in vivo technique for identification of
specific chemotherapy resistance in dogs, this would provide a reason to
explore further studies such as prospective tailored chemotherapy
regimens for canine patients and provide further framework for pilot
studies in humans to help improve patient survival and reduce
unnecessary side effects from ineffective chemotherapy drugs.
Patient Entry Criteria
Dogs with lymphoma will be divided into two treatment groups:
chemotherapy naïve or resistant.
Group 1 (Naïve lymphoma): Dogs with newly diagnosed
multicentric lymphoma (confirmed via cytology or histopathology. These
patients will not have received any previous cytotoxic chemotherapy
drugs (including prednisone) or any other supplements that are purported
to treat cancer.
Group 2 (Refractory-resistant lymphoma): Dogs with
multicentric lymphoma (B or T cell phenotype) previously confirmed on
cytology or histopathology. These patients will have been previously
treated at least once with each of the drugs in the Madison-Wisconsin (cyclophosphamide,
doxorubicin, vincristine and prednisone) based chemotherapy protocol and
have either failed initial induction by week 4 of treatment or relapsed
and become refractory to the same drugs documented by records of
progressive disease. The last dose of chemotherapy must be at least 1
week prior to the study to allow clearance of previously administered
cytotoxic drugs. Patients must have a popliteal lymph node of at least
2cm in diameter (minimum size for needle array administration). No
other herbal supplements or anti-tumor chemotherapeutics can be given
while in this 24-72 hour test period.
Financial Incentives
All costs associated with the microneedle array trial will be covered
(anesthesia, tumor injection, 24 hour boarding, popliteal lymph node biopsy,
tissue analysis for chemotherapy sensitivity/resistance; $500-700), cytology
and histopathology of the lymph node including immunohistochemistry to
identify specific lymphoma phenotype (B or T cell; $150), oncology
consultation ($102) and complete blood tests (complete blood count,
biochemistry, urinalysis, blood smear; $120). Total value $870-1200. For
naïve patients the clinical benefits are: portion of staging procedures at
no cost (histopathology, cytology, immunophenotyping of lymphoma, blood
tests) and potential to identify ineffective drugs prior to administration
of the CHOP-based chemotherapy protocols.
Owner Responsibilities
In resistant lymphoma cases dogs must be brought for examination and
will undergo the initial injections. If the patient is taken home they
must return for the scheduled lymph node removal 24-72 hours later.
After removal of the node there is no further obligation but we will be
happy to help guide further therapy.
In Naïve lymphoma cases, the same is true for the injection
procedure. If it is desired to go forward with chemotherapy, clients
are responsible for remaining lymphoma staging procedures (thoracic
radiographs, abdominal ultrasound and aspirates, bone marrow aspiration
and additional imaging if required) that would usually cost an
additional $500-600 at WSU, and to pay for the multi-agent chemotherapy,
but recheck exams are free as is the data obtained from the chemotherapy
assay. These chemotherapy appointments can be performed either at WSU
Oncology (typically $2500-3500 spread over 6 months of chemotherapy for
a 70-80Lb dog) or coordinated with your local veterinarian if possible.
It is highly desirable that once beginning therapy, owners of naïve
patients go forward with chemotherapy administration to correlate
clinical response to that predicted by the tumor injection assay. A
physical examination, complete blood count, and precise lymph node
measurements should be performed weekly for the first 4 weeks of the
chemotherapy protocol and if a positive response is seen, these rechecks
may be then followed up with your local veterinarian if possible.
Contact Information
If interested please contact Betsy Wheeler or Pam Thompson at the WSU VTH
509-335-0711.
