Trinka and Osteosarcoma

My name is Diane and we for various reasons went the palliative route for our dog Trinka. Our vet gave our Trinka only 2 months to live when they discovered the OS during xray of a broken leg. Due to the return of the biopsy as NEG, we went ahead and had her leg set with a steel rod. The Vet was convinced that there was cancer in there and took 5 more biopsies. (and didn't seal the bone afterward). This time the results came back POS. :( But we decided since Trinka was a large #120 Rott/Lab Mix that she was not a good candidate for amputation. Plus I had promised her I would not take her leg.

The following is a paraphrase of some of my previous postings and you may find some additional tools in them to help you fight osteosarcoma. We sadly sent Trinka over the Rainbow Bridge on Sept 24th. But we had a full year of beach trips and quality time with our little (120#Rott/Lab ) mischievous angel.

This is a very hard battle we are all fighting with you. I have called this a shape shifter disease in the past and it is indeed a disease that seems to be different for each of our companions and different each day/week/month in our own pup. You will have a gut feel as to what will work and what won't for osteosarcoma. Others have said to focus on your pet, not the Cancer, and they are right, because the amount of research you will try to do can definitely cause a "brain fade" :) But if you are like most of us…. You will nod your head, smile and research until your head is swimming anyway…because we just have to.

You may want to look into Fosamax for osteosarcoma. It worked for Trinka and Fosamax along with various vitamins, flax oil and cottage cheese, minerals and milk thistle and Essiac tea tincture and a supplement called Inflamaway made her quality of life for over 1 yr as if nothing had really happened to her other than a huge lump encompassing her leg.

Trinka got lots of turkey and chicken (we got soup and casseroles :)), fresh veggies and a very little kibble. One thing I do want to tell you about the Fosamax is VERY IMPORTANT.... It must be given on an empty stomach with lots of water. I solved the lots of water trick by putting enough turkey fat(about 1/4 teaspoon) in warm water to make her think it was REALLY GOOD STUFF and she would drink the whole bowl (8-12 oz)of smell good, no food water. heheh.. And you can not give food or other meds for another hour or so. Our routine was Fosamax then outside for a short walk, then back inside to watch me "prepare - stall" her breakfast.

"Alendronate, or Fosamax, is a bisphosphonate. This class of drugs has been used for several years to treat human bone cancers. It inhibits the activity of cells called osteoclasts, which are specialized cells that tear down and remove old bone cells, clearing the way for their replacement by new cells. However, in bone cancer, the osteoclasts proliferate too rapidly. As the bone weakens and becomes more fragile, it causes the great pain. While alendronate may destroy some of the osteosarcoma tumor cells, it is not a cure for bone cancer. However, it may extend high-quality, comfortable life in the dog. There have since been others that have tried or are using Fosamax as an additional treatment. Some have had positive results, some have had no results.

Here is a little more about it. "Alendronate, or Fosamax, is a bisphosphonate. This class of drugs has been used for several years to treat human bone cancers. There are now second and third generation drugs which are being used. It inhibits the activity of cells called osteoclasts, which are specialized cells that tear down and remove old bone cells, clearing the way for their replacement by new cells. However, in bone cancer, the osteoclasts proliferate too rapidly. As the bone weakens and becomes more fragile, it causes the great pain. While alendronate may destroy some of the osteosarcoma tumor cells, it is not a cure for bone cancer. However, it may extend high- quality, comfortable life in the dog. An article in Veterinary Record described an extremely limited canine trial, in which two dogs with bone cancer were given alendronate as palliative therapy. (one of these dogs also had a broken leg as Trinka did). Both dogs had survival times equivalent or greater to those of standard amputation/chemotherapy, with good quality of life, and no side effects. A non-toxic therapy which could prolong comfortable life would touch many dogs and their families. The university of California in Davis is currently doing a study. It can be administered daily or weekly. Orally or by IV. We choose the daily. It took a few days for the drug to really take effect during which time I used codeine as pain management - REMEMBER THIS IS NOT A CURE BUT A WAY TO KEEP QUALITY OF LIFE HIGHER for as long as possible. I can honestly say the fosamax made a difference with trinka. BUT this stupid, horrid disease is a "shape shifter" and not one case is like another. You know your pup the best of all and if you use your instincts you will always do what is best. There are new studies using Fosamax in Humans that you can look at.

The Inflamaway is an anti-inflammatory which is comprised of herbs that are tumor inhibitors also. I even tried the Inflamaway to see what the results were - I found it to work extremely well! Inflamaway is made by Premier Labs in Southern California. It is designed for human digestive tracts so it works best if you crush the tablets and just mix it in the food. Otherwise you get "pills in the poop" The added benefit of crushing the tablets is that is also then becomes a digestive aid and helps in the "cancer wasting" that can occur.

The other treatment we did was several rounds of Artemeter. A Chinese herb being tested at the University of Washington for the treatment of breast cancer. My suspicion is that it is most effective on soft tissue cancers as the "suspicious" areas of Trinka's lungs cleared up and at the time of her death there was no sign of any cancer metastasis to lungs, internal organs or other bones.

I think that had the "Navy Protocol" been known at the time, I would have tried that too.

With nothing other than the Fosamax, Vitamin Supplements, Echinacea, Milk Thistle, Essiac, Hoxley, Mushrooms, and a product called Inflamaway (by Premier Labs)Later adding codein as a pain med - she didn't tolerate NASIDs or Piroxicam.

When Trinka's tumor began growing so fast I put Bag Balm on it and wrapped it lightly to keep her from licking it. Bag Balm is the stuff they have used for donkey's years on cows teats. It has antiseptic and anagelsic(sp) properties and really worked with Trinka. Her tumor eventually reached 21 inches in girth. but the skin never split due to the bag balm. You can get it in most drug stores usually near the baby creams. It is in a green tin. If the skin looked raw I added some neosporin - worked like a charm. I also would sponge the area with lightly salted warm water followed by clean warm water. Trinka would actually go to sleep when I did this. It must have felt really good to her. Then put the bag balm and neosporin on a piece of gause and place it over the tumor area. and wrap lightly.

She lived for the next 11 months with little discomfort even though her tumor increased in size. Her eyes were bright, mind clear, continued her daily walks with "dad",and fully enjoying the home cooked meals with the cottage cheese and flax oil additions. If the bone below the tumor had not broken ( 12 months after DX) she would be here still as at that point I was unable to control the pain and we (my husband and I) decided to end it. But we had her much longer than our vet expected without amputation or chemo… Sending ear scratches and a BIG CYBER HUG and a box of Kleenex to you from us. Diane, John, Tammy and angle Trinka.


Morgy and osteosarcoma-Morgy's story about his treatment of osteosarcoma using alternative methods for fighting cancer such as flaxseed. He survived for two and half years
J Am Vet Med Assoc 2001 Sep 1;219(5):614-7 : Spontaneous regression of osteosarcoma in four dogs.
Mehl ML, Withrow SJ, Seguin B, Powers BE, Dernell WS, Pardo AD, Rosenthal RC, Dolginow SZ, Park RD.
Department of Clinical Sciences,
College of Veterinary Medicine and Biomedical Sciences,
Colorado State University, Fort Collins 80523, USA.

Spontaneous regression of primary malignant bone tumors is rare but has been reported in the human literature. To the authors' knowledge, spontaneous regression of primary bone tumors in dogs or cats has not been reported. Osteosarcoma (OSA) is the most common primary bone tumor in humans, and it has been reported that the incidence of OSA is 40 to 50 times greater in dogs than humans. In this report, high-grade OSA was diagnosed in biopsy specimens obtained from 4 dogs that subsequently underwent spontaneous regression without tumor-specific treatment. Osteosarcoma in dogs has characteristics similar to that of OSA in humans.
Am J Vet Res 2001 Aug;62(8):1234-9 : Metabolic alterations in dogs with osteosarcoma.
Mazzaferro EM, Hackett TB, Stein TP, Ogilvie GK, Wingfield WE, Walton J, Turner AS, Fettman MJ.
Department of Clinical Sciences,
College of Veterinary Medicine and Biomedical Sciences,
Colorado State University, Fort Collins 80523, USA.

OBJECTIVE: To evaluate changes in resting energy expenditure (REE) as well as protein and carbohydrate metabolism in dogs with osteosarcoma (OSA). ANIMALS: 15 weight-stable dogs with OSA that did not have other concurrent metabolic or endocrine illness and twelve 1-year-old sexually intact female Beagles (control dogs). PROCEDURES: Indirect calorimetry was performed on all dogs to determine REE and respiratory quotient (RQ). Stable isotope tracers (15N-glycine, 4.5 mg/kg of body weight, IV; 6,6-deuterium-glucose, 4.5 mg/kg, IV as a bolus, followed by continuous-rate infusion at 1.5 mg/kg/h for 3 hours) were used to determine rate of protein synthesis and glucose flux in all dogs. Dual-energy x-ray absorptiometry (DEXA) scans were performed to determine total body composition. RESULTS: Accounting for metabolic body size, REE in dogs with OSA was significantly higher before and after surgery, compared with REE of healthy control dogs. The RQ values did not differ significantly between groups. Dogs with OSA also had decreased rates of protein synthesis, increased urinary nitrogen loss, and increased glucose flux during the postoperative period. CONCLUSIONS AND CLINICAL RELEVANCE: Alterations in energy expenditure, protein synthesis, urinary nitrogen loss, and carbohydrate flux were evident in dogs with OSA, similar to results documented in humans with neoplasia. Changes were documented in REE as well as protein and carbohydrate metabolism in dogs with OSA. These changes were evident even in dogs that did not have clinical signs of cachexia.
Vet Rec 2000 Jul 29;147(5):129-32 : Use of the bisphosphonate drug alendronate for palliative management of osteosarcoma in two dogs.
Tomlin JL, Sturgeon C, Pead MJ, Muir P.
The Royal Veterinary College,
Department of Small Animal Medicine and Surgery,
Hawkshead Lane, North Mymms.

The bisphosphonate drug alendronate was used to suppress bone remodelling and tumour osteolysis as a palliative treatment for two dogs with osteosarcoma, one of the tibia and one of the maxilla. A spiral fracture associated with the tibial tumour healed after it was stabilised with an external skeletal fixator. Both dogs remained comfortable and survived for 12 and 10 months respectively after diagnosis, despite the fact that neither primary tumour was resected.
: Vet Surg 2002 Nov-Dec;31(6):525-32 : Pasteurized tumoral autograft as a novel procedure for limb sparing in the dog: A clinical report.
Buracco P, Morello E, Martano M, Vasconi ME.
Department of Animal Pathology, School of Veterinary Medicine, Turin, Italy.

Objective-To evaluate use of a pasteurized tumoral autograft prepared from the resected primary bone neoplasm for limb sparing in a dog with distal radial osteosarcoma (OSA). Study Design-Clinical case report. Animals-A 9-year-old male Maremma shepherd dog. Methods-After right distal radial OSA removal, the tumoral autograft was pasteurized. The excised bone segment was placed in a sterile watertight box containing sterile saline solution preheated to 65 degrees C in a water bath. The box was kept immersed in the water bath at 65 degrees C for 40 minutes to kill the tumor cells. The autograft was then fixed in the host with a plate and screws based on standard AO/ASIF technique for carpal arthrodesis. Three doses of cisplatin (70 mg/m(2) intravenously) were administered, 3 weeks apart; the initial dose was administered the day after surgery. Results-The autograft was incorporated in a manner comparable to an allograft, and after 708 days, the metallic implants were removed. A 1-month activity restriction as well as spoon splint to protect the leg from a full loading were used thereafter. Limb function was fair to good, and the dog remains disease free after 56 months. Conclusions-A pasteurized autograft consisting of the resected primary bone neoplasm is a valid alternative to a cortical bone allograft for limb sparing in dogs with appendicular OSA in terms of feasibility and pattern of healing. Clinical Relevance-This procedure can be an alternative method of limb sparing when difficulties are encountered in establishing and maintaining a canine bone allograft bank.
J Am Anim Hosp Assoc 2002 Sep-Oct;38(5):445-51 : Four fraction palliative radiotherapy for osteosarcoma in 24 dogs.
Green EM, Adams WM, Forrest LJ.
Department of Surgical Sciences, School of Veterinary Medicine,
University of Wisconsin-Madison, 53706, USA.

Twenty-four dogs underwent palliative radiotherapy consisting of four 8 gray (Gy) fractions of 60Co radiation on days 0, 7, 14, and 21 at 26 sites for axial (n=11) or appendicular (n=15) osteosarcoma. Response was noted in 92% of sites treated. Seventeen dogs were euthanized due to local or metastatic disease, one dog died of metastatic disease, five dogs died of unrelated causes, and one dog is alive. The four fraction protocol is effective for palliation of clinical signs associated with axial or appendicular osteosarcoma and may result in a higher response rate and longer survival time than three fraction palliative protocols.
Cancer Chemother Pharmacol 2002 Aug;50(2):131-6 : STEALTH liposome-encapsulated cisplatin (SPI-77) versus carboplatin as adjuvant therapy for spontaneously arising osteosarcoma (OSA) in the dog: a randomized multicenter clinical trial.
Vail DM, Kurzman ID, Glawe PC, O'Brien MG, Chun R, Garrett LD, Obradovich JE, Fred RM 3rd, Khanna C, Colbern GT, Working PK.
The Comprehensive Cancer Center,
University of Wisconsin-Madison, Madison, WI 53706, USA.
vaild@svm.vetmed.wisc.edu

PURPOSE: This trial was designed to compare the efficacy of adjuvant STEALH liposome-encapsulated cisplatin (SPI-77) to "standard-of-care" carboplatin therapy in dogs with osteosarcoma (OSA) in the context of a randomized study design. METHODS: The study included 40 pet dogs with spontaneously arising OSA which were randomized to receive SPI-77 (350 mg/m(2) i.v. every 3 weeks for four treatments) or carboplatin (300 mg/m(2) i.v. every 3 weeks for four treatments) along with amputation of the affected limb. Median disease-free (DFS) and overall survival (OS) were compared using standard life-table analysis. RESULTS: The median follow-up was 693 days (range 321-730 days). Of 38 dogs eligible for follow-up, 25 were dead of their disease, 9 were alive and disease-free (8 receiving SPI-77, 1 receiving carboplatin; P=0.02), 2 were free of disease when they were lost to follow-up at 321 and 395 days, and 2 had died of an unrelated disease. The median DFS times for dogs treated with SPI-77 and carboplatin were 156 and 123 days, respectively ( P=0.19). The median OS times for dogs treated with SPI-77 and carboplatin were 333 and 207 days, respectively ( P=0.18). CONCLUSIONS: While STEALTH liposome encapsulation of cisplatin allowed the safe administration of five times the maximally tolerated dose of free cisplatin to dogs without concurrent hydration protocols, this did not translate into significantly prolonged DFS or OS. However, a larger proportion of dogs receiving SPI-77 enjoyed long-term DFS when compared with dogs receiving carboplatin.
: J Am Vet Med Assoc 2002 Apr 15;220(8):1171-6 : Comparison of radiography, computed tomography, and magnetic resonance imaging for evaluation of appendicular osteosarcoma in dogs.
Davis GJ, Kapatkin AS, Craig LE, Heins GS, Wortman JA.
Department of Clinical Studies, College of Veterinary Medicine,
University of Pennsylvania, Philadelphia 19104, USA.

OBJECTIVE: To determine which imaging modality best determines the microscopic extent of primary appendicular osteosarcoma in amputated limbs in dogs. DESIGN: Case series. ANIMALS: 10 dogs with appendicular osteosarcoma. PROCEDURE: 10 dogs with appendicular osteosarcoma that did not receive neoadjuvent chemotherapy were treated by use of limb amputation. Amputated limbs were imaged by use of radiography, computed tomography (CT), and magnetic resonance imaging (MRI) and examined microscopically to determine longitudinal extent of neoplastic cell involvement and length of associated intramedullary fibrosis. Changes detected by use of the various imaging studies were compared with the actual tumor length determined microscopically. Data were analyzed to determine which imaging technique most closely predicted tumor length. RESULTS: Measurements obtained by use of craniocaudal radiographic views were most accurate at predicting tumor length but underestimated tumor length substantially in 1 limb and slightly in another limb. Measurements made by use of CT were most accurate at predicting tumor length when intramedullary fibrosis was taken into account but underestimated tumor length in 1 limb. Measurements made by use of MRI were least accurate but did not underestimate tumor length in any of the limbs. CONCLUSIONS AND CLINICAL RELEVANCE: Although radiography is used in diagnosis of osteosarcoma in dogs, additional imaging studies to confirm the extent of neoplasia prior to limb-sparing ostectomy may be beneficial. Underestimation of tumor length would be associated with higher incidence of incomplete excision and local tumor recurrence.
Biochem Biophys Res Commun 2002 Apr 12;292(4):886-91 : The role of angiostatin in the spontaneous bone and prostate cancers of pet dogs.
Pirie-Shepherd SR, Coffman KT, Resnick D, Chan R, Kisker O, Folkman J, Waters DJ.
Surgical Research Laboratory,
Children's Hospital, 300 Longwood Avenue, Boston, Massachusetts 02115, USA.
shepherd@attenuon.com

Angiostatin is a potent inhibitor of angiogenesis generated in cancer-bearing hosts by tumor-derived proteases. Because the naturally occurring bone and prostate cancers of pet dogs provide unique model systems to study factors that regulate cancer progression and tumor dormancy, we investigated the capacity of these tumors to generate angiostatin. We determined that angiostatin fragments are present in urine of dogs with bone cancer. The identity of these fragments was confirmed by comparison of the experimentally determined protein sequence to that of a clone of canine angiostatin. Importantly, these fragments were absent in urine collected from the same dogs after complete surgical removal of the primary tumor. We also demonstrate that canine prostate cancer cells are capable of processing plasminogen to angiostatin in vitro. These findings provide rationale for using spontaneous canine tumor models to isolate endogenous angiogenesis inhibitors and to investigate their therapeutic use against cancer.
Vet Pathol 2002 Mar;39(2):240-6 : Prognostic significance of a new histologic grading system for canine osteosarcoma.
Kirpensteijn J, Kik M, Rutteman GR, Teske E.
Department of Clinical Sciences of Companion Animals,
Faculty of Veterinary Medicine,
Utrecht University, The Netherlands.

Histologic grade is an important determinant in clinical outcome of human osteosarcoma (OS). In this study, the histologic characteristics of primary and metastatic canine OS were evaluated using a new classification system. Histologic characteristics were classified in 166 primary and 34 metastatic canine OS. Prognostic variables for clinical outcome were determined using multivariate analysis. Most OS were histologically characterized by severe to extreme cellular pleomorphism, a variable number of mitoses, small to moderate amounts of matrix, a high percentage of tumor cells, and minimal to moderate amounts of necrosis. Tumor invasion into vessels was present in 117/152 (71%) tumors, and 12/50 (24%) of the regional lymph nodes had evidence of metastasis. Classification of the 166 tumors resulted in seven (4%) grade 1, 34 (21%) grade II, and 125 (75%) grade III OS. In the multivariate analysis, histologic grade III OS and elevated pretreatment plasma alkaline phosphatase (AP) levels were independent predictors of clinical outcome. Dogs with high-grade tumors and elevated AP should be carefully evaluated for the presence of metastatic disease before starting adjunctive therapy protocols.
J Vet Intern Med 2000 Nov-Dec;14(6):587-92 : Prognostic significance of serum alkaline phosphatase activity in canine appendicular osteosarcoma.
Garzotto CK, Berg J, Hoffmann WE, Rand WM.
Department of Clinical Sciences,
Tufts University, School of Veterinary Medicine, North Grafton, MA 01536, USA.

Sixty-one dogs with appendicular osteosarcoma were treated with amputation and chemotherapy of cisplatin and doxorubicin. Serum samples were obtained before and after treatment for determination of total alkaline phosphatase (TALP) activity as well as the activities of the constituent bone (BALP), liver (LALP), and corticosteroid-induced (CALP) isoenzymes. The relationship between alkaline phosphatase activities and survival was examined by Cox proportional hazards regression analysis and Kaplan-Meier log rank analysis. Mean activity of TALP, BALP, and LALP decreased significantly after treatment (P < .001). TALP and LALP activities before treatment were significantly correlated with survival (P = .006 and .001, respectively). The correlation between BALP activity before treatment and survival approached significance (P = .054). CALP activity and TALP, BALP, and LALP activities after treatment were not significantly correlated with survival. Dogs with normal pretreatment TALP and BALP activities survived significantly longer than dogs with increased pretreatment activities (P = .001 and .003, respectively). Median survival times for dogs with normal or increased TALP activities before treatment were 12.5 and 5.5 months, respectively; and median survival times for dogs with normal or increased BALP activities before treatment were 16.6 and 9.5 months, respectively. In the design of future clinical trials involving dogs with osteosarcoma, consideration should be given to stratifying the randomization according to alkaline phosphatase activity. In addition, alkaline phosphatase activity should be a factor considered by clinicians attempting to tailor the aggressiveness of adjuvant chemotherapy to the needs of individual patients or owners.