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How Many Chemotherapy Sessions are Best for Osteosarcoma in Dogs?

If you are researching osteosarcoma chemotherapy choices for cats and dogs, you may find conflicting information about the most effective number of chemotherapy treatments for this cancer. Veterinary oncologists recommend anywhere from four to six rounds of chemotherapy, depending on their own remission success rates and which veterinary oncology studies they follow.

Jackson

Read about Jackson’s osteosarcoma chemotherapy

CSU Studies Carboplatin, Doxorubicin Protocols for Dogs with Osteosarcoma

In an attempt to reach a consensus about the best number of chemo sessions for canine osteosarcoma patients, researchers at Colorado State University’s College of Veterinary Medicine and Biomedical Sciences conducted a study called

Comparison of Carboplatin and Doxorubicin-Based Chemotherapy Protocols in 470 Dogs after Amputation for Treatment of Appendicular Osteosarcoma.”

We don’t have the scientific background to interpret the study but thankfully Tripawds member Katy Richards-Hrdlicka, aka Jackson’s Mom, does! She kindly wrote the following guest blog post to help us makes sense of the study and its accompanying conclusions. Here it is (along with fun photos and video of Tripawd Hero Jackson, 18 months post -diagnosis and doing great!).

“Many pawrents here grapple with the decision to proceed with IV chemotherapy for very good reasons. There are side effects to consider, types of drug(s), route of administration (oral, known as metronomic chemotherapy vs intravenous, the more common and traditional), duration (3, 4, 5, or 6 rounds, 1 year, 1.5 years, etc), and cost. If you have a great relationship with your oncologist and that oncologist is up on the literature, having a discussion about these factors can be a relief, grant sanity, ease restless nights, form bonds, and give life.

But then there’s the assessment that no one can answer: will it work? Is it worth it?

When a new Tripawd joins the club due to osteosarcoma, we see different treatment plans. For the most part, carboplatin is the recommended drug and it’s administered 4-6 times, each 3 weeks apart. Understandably, when one dog gets 6 rounds and another 4, folks may think (especially the owners!) “more is better.”

jackson

Jackson lovin’ life

To address this concern, we turn to a recent study out of Colorado State University’s College of Veterinary Medicine. We respond with: “there’s no difference between 4 and 6, so save the time and money and go with 4 rounds of carboplatin.”

Here’s the rub, for me anyway: I’m a trained scientist, so when I hear there’s no difference between 4 or 6 rounds of IV carboplatin for osteosarcoma, I want to know the details. I got in touch with the study’s lead author and when the final paper came out, Dr Selmic emailed me its PDF.

Here’s the title, author info, and abstract:

Comparison of Carboplatin and Doxorubicin-Based Chemotherapy Protocols in 470 Dogs after Amputation for Treatment of Appendicular Osteosarcoma: L.E. Selmic, J.H. Burton, D.H. Thamm, S.J. Withrow, and S.E. Lana

Many chemotherapy protocols have been reported for treatment of canine appendicular osteosarcoma (OSA), but outcome comparisons in a single population are lacking.

Objective: To evaluate the effects of protocol and dose intensity (DI) on treatment outcomes for carboplatin and doxorubicin-based chemotherapy protocols.

Animals: Four hundred and seventy dogs with appendicular OSA.

Methods: A retrospective cohort study was performed comprising consecutive dogs treated (1997 – 2012) with amputation followed by 1 of 5 chemotherapy protocols: carboplatin 300 mg/m2 IV q21d for 4 or 6 cycles (CARBO6), doxorubicin 30 mg/m2 IV q14d or q21d for 5 cycles, and alternating carboplatin 300 mg/m2 IV and doxorubicin 30 mg/m2 IV q21d for 3 cycles.

Adverse events (AE) and DI were evaluated. Kaplan–Meier survival curves and Cox proportional hazards regression were used to compare disease-free interval (DFI) and survival time (ST) among protocols.

Results: The overall median DFI and ST were 291 days and 284 days, respectively. A lower proportion of dogs prescribed CARBO6 experienced AEs compared to other protocols (48.4% versus 60.8–75.8%; P = .001). DI was not associated with development of metastases or death. After adjustment for baseline characteristics and prognostic factors, none of the protocols provided a significant reduction in risk of development of metastases or death.

Conclusions and Clinical Importance: Although choice of protocol did not result in significant differences in DFI or ST, the CARBO6 protocol resulted in a lower proportion of dogs experiencing AEs, which could be advantageous in maintaining high quality of life during treatment. DI was not a prognostic indicator in this study.

I’m now going to summarize the study, give you my thoughts as a scientist (I have a PhD in genetics from Yale University) and doggie-mom (Jackson is 18 months post-amp for OSA in his right hind limb), and some context:

Which Osteosarcoma Dogs Were Studied?

  • 470 dogs were enrolled in this study. It was retrospective. They basically called clinics and got records of dogs that fit the criteria: OSA, amputation, followed by 1 of 5 different chemo options. The 5 chemo options:
  1. carbo x 4 doses,
  2. carbo x 6,
  3. doxy every 14 days x 5,
  4. doxy every 21 days x 5, or
  5. alternating carbo and doxy for a total of 3 doses each (grand total, 6 doses of chemo).
  • This is perhaps the largest sample size ever! Kudos! But, retrospective is tough. They had no control over what else came with the criteria, such as equal sample sizes per chemo option or exact dosage levels per body weight. They also had no control over how or how often the dogs were monitored, which impacts a major, common statistic: disease free interval (DFI) – more on this later.
  • I learned that nearly 40% of dogs will not complete their prescribed treatment! I didn’t realize it was this high. The protocols that have the highest dropout rate are mostly explained by the time commitment (3 vs 6 rounds) and side effects. Owners and sometimes our wallets take a beating and we cannot proceed with as many treatments as prescribed. Or there are vacations, family events, etc., that postpone (called, “treatment delay”) or cancel chemo plans altogether. Dogs getting carbo6 had the most treatment delays; this was one of the two significant findings from the study.
  • The other significant finding was that all pets, no matter the treatment, experienced fewer side effects as treatments continued, especially in the carbo6 group. This could be that physiologically, chemo was less harmful as the patient proceeded through treatment. However, what is probably happening (and we read it here all the time) is that owners learn how to manage side effects better so there simply is less data on side effects. I also have a pet theory: carbo is expensive and if given 6 doses, the owner had the time and resources for it. I wonder if with carbo, anti-nausea are more commonly administered? It’s an economic issue, then, and maybe not a “side effect” issue. I wonder if dogs that got carbo ALSO got meds and advice to help mitigate side effects altogether?
  • Perhaps another similar economic sidenote: dogs that developed mets and got subsequent metronomic therapy and/or Palladia were more likely to have had carbo, especially 6 rounds of it, than anything else. Carbo is more pricey. If an owner has committed the resources to carbo AND 6 rounds of it, I suspect (another pet theory of mine!) that owner is also more likely to keep fighting with metronomic therapy and/or Palladia.

Here”s the revelatory part. I was stunned. Speechless.

The common, industry-approved metric for processing these stats is to lump all the patients together based on their PRESCRIBED treatment, not by what they actually got. That means that if you agreed to 6 rounds of carbo, but mets were discovered before the 3rd round and you stopped treatment, your dog and all her stats would be included in the “6 rounds of carbo” group.

This is a major problem. I understand that this stat needs to continue as so many foundational studies have used this and that means folks can compare outcomes. Or does it? Thankfully, Dr Selmic did other analyses with the ACTUAL doses in the Supplemental Info, but not in the manuscript’s main text. If you also have access to her work, you”ll now notice I’m going to largely ignore the rest of the tables and data from the main text and focus on the Supplemental Info.

Which Osteosarcoma Dogs Lived Longest?

  • If you’re wondering whether my non-oncologist instinct was correct: when all dogs, no matter if they completed their prescribed treatment, are examined for survival time (regardless of chemo option), the average survival time is 284 days (actually, statistically between 248-316 days). When the dogs that dropped out of chemo are removed from the same calculation, it jumps to 367 days (actually, between 325-401 days)! THAT, my friends, shows there’s a SIGNIFICANT difference between chemo drop-outs and sticking to the plan…most certainly when it comes to stats. I’m assuming the dogs that dropped out had 1 or 2 or 3 doses of chemo.
  • The results show the same trend with DFI (291 days vs 398 days for dogs that completed chemo). A little more about DFI: for this type of cancer, it’s known to progress to the lungs next. It can go elsewhere, too, but primarily to the lungs. There are some owners out there who have chest xrays done every 3 months and there are others who never do (I am one of those pawrents). An owner who prefers regular xrays is bound to find mets earlier than an owner like me. Because this was a retrospective study, there’s no good way for the authors to tell the “true” time of mets – before clinical signs (i.e., mets appeared in chest xrays) or with clinical signs (with or without xrays to confirm). Thus, I think the stat of DFI is skewed and hard to interpret. I prefer to look at survival time, as death is an obvious endpoint. Of course using death as the endpoint is also problematic: what about the dogs that live for 2 weeks with mets vs a year with mets? In this case, the endpoint is still obvious (death), but the quality of life is different!
  • Dogs that had 6 rounds of carbo lived longer and developed mets less often! Hold on, though, it gets complicated. Let me introduce some other important factors about fighting this battle:
  • For years now, oncologists have known there are certain predictors that increase the likelihood your dog will succumb earlier or later to OSA. These include if the tumor was in the proximal humerus (nearest the body, not the paws, which is radial), high grade tumor or high mitotic rate, and elevated serum ALP. Also, pure bred dogs and heavier dogs (note, this isn’t saying overweight, as in obese) fare less well. The age of the dog only predicted a shorter survival time, but that’s not saying much: senior dogs die more often than young dogs just like elderly humans die more often than younger humans.
  • The above info is really important just on its own. If your pup has any of these predictors, studies suggest your battle will be shorter. Some may read that and decide that it’s not worth investing loads of vet visits and money into a cancer that’s really aggressive. Some will read that and decide that it’s even more important to fight like the dickens and throw every resource at it.
  • I suggest is you bring this knowledge to your oncologist and discuss, as there are particulars: is the mitotic index crazy wicked high (grade 3 vs. 20, for example)? Maybe the tumor was in the proximal humerus, but you guys caught it early so that spread was probably more contained than if the tumor were huge. PLEASE discuss these predictors with your oncologist!

Back to the paper. OK, so 6 rounds of carbo show the longest DFI and ST. But, not really. That’s because once the authors controlled for the above predictors in only the dogs that actually completed the prescribed protocol, there was no statistical difference among ANY chemo option in terms of DFI or ST. What does this mean? Dogs that made it through their prescribed protocol and did NOT have any of the known predictors above were used in the statistical calculations.

  • This shows that the predictors are real, as the statistical test had different results between the two pools of dogs (those with predictors and regardless of predictors). Dogs that have all the above predictors had shorter DFIs and STs.
  • It also means that if your dog doesn’t have one of these predictors and completes its prescribed chemo, your pup’s DFI and ST aren’t influenced by the chemo protocol!
  • Or, they didn’t have a large enough sample size to detect a difference.
  • Here are the data for dogs that actually completed their prescribed protocol (in the supplemental info section, table 3). We see that there is a longer DFI (605 days) and longer ST (390 days) when given 6 rounds of carbo vs 4. But what isn’t shown here are the stats (confidence intervals) that go with these, but the authors tell us there’s no statistical significant difference. The results are equal because the power to assess the true ST and DFI is either too low (thus, too few dogs enrolled in each of these treatment groups), or there really is no difference:

062814_ChemoTreatments

Do Your Best to Complete Chemotherapy

In conclusion, the type of chemo given didn’t make a statistical difference about the dog’s DFI or ST, assuming the dog finished its prescribed protocol. What DID make the difference was whether the treatment was finished at all. And by “finished,” at the least, that’s 4 doses of anything. This aspect was not emphasized in the paper. It wasn’t really the paper’s aim, but as a Tripawd-Warrior mom, that IS my aim!

I want to know how many doses should we go for? If there are side effects and we’ve done 3, should we push it and do 1 more or 3 more? From these data, it appears doing anything for 4 rounds is as good as 6 rounds of anything.

Then again, there may not have been enough pups enrolled to differentiate between 4, 5 or 6 rounds, or of what protocol.

Bottom line: do your best to complete the chemo protocol, on time, with the proper dosage.

Jackson Osteosarcoma Survivor

Tripawd Jackson kicks cancer’s butt!

Many thanks to Katy for contributing this important information to the Tripawds nation. If you have experience in an applicable topic that you’d like to share with the community, contact us today, we especially love guest blog volunteers!

19 Responses to “How Many Chemotherapy Sessions are Best for Osteosarcoma in Dogs?”

  1. Thank you Katy for taking time to do this. Rufus gets amputated 10/9 at the vet and first oncologist appointment at WSU vet school 10/24. Now that I have a little schema, I’ll be able to understand a little bit more while my mind has an out of body experience or spins out of control. I know I want little AE, and increased DFI! Here’s to a long ST.

    Thank you for clearly pointing out the limitations of this study. Just because 6 doses were prescribed doesn’t mean it happened so the data gets skewed.

  2. Thanks for this info, it is true that it is all very confusing for ‘normal people’ and all statistics give averages and medians, but every individual dog and case is different. Our dog Rasco (mixed amstaff-Belgian sheppard (Malinois) had a tumor in his left front paw. After we saw the video’s on this site we decided to go for amputation and chemo. So far we’re glad we went throgh with it. He has had his 3rd chemo last week. The plan was 6 times carboplatin, with 3 weeks intervals. However the 2nd and 3rd chemo had to be postponed because his white bloodcells don’t seem to recover fast enough. Apparently he needs at least 4 week intervals. After his 3rd chemo we were considering to stop it, because an x-ray shows his lungs are still cllean (as with te x-ray taken before the treatment) because he seems to feel bad for about 3 days after each treatment, and we thought maybe we are making him suffer unnecessarily. With this new info we will reconsider, and talk it over with the vet. About the interval between treatments however, we have no choice, he need his time to recover.

    • I’m so glad you found this article and found it useful. This is exactly the type of info I hope you bring to your oncologist and have a discussion. Delaying chemo b/c of low WBC is fairly common and having to extend the interval is also a common solution. I’m glad it’s worked so far! It can be tough to see our pals go through side effects, but maybe Rasco’s chemo journey is over or perhaps, after long discussions with him and his vet, there’s only 1 last dose in his future. Best wishes!
      ~ Katy & Jackson

  3. My boy Rowdy, 11-year-old German shepherd, recently completed six sessions of chemo, carbo alternating with doxy. Just as I was feeling good about his prospects for some quality time as a dog rather than a patient, he got sick and has been diagnosed with leukemia. This of course was devastating news. The doctors say they know of no association between the two cancers. It’s just bad luck. I am not inclined to put him through the aggressive chemo therapy for leukemia, given what he’s already been through and the poor prognosis.

    Has anyone else had this experience? Any advice for maintaining quality of life under these circumstances?

  4. Katy,
    Great job breaking this down. I love the fact that you did this. I am almost tempted to take it to our vet and I may still. Dr Boyer is always really receptive about stuff. I am going to book mark this article and re-read it again. Then take it to her.

    Thank you once again. I guess Sassy fell into the completed we got through 4 and were scheduled for 5 or maybe she didn’t get the completed stage but either way we did the best we could.

    Hugs
    Michelle & Angel Sassy

    • I’m glad you found this helpful, Michelle. I’ll be curious what Dr Boyer thinks – not only of the original work (did she read it?!) and my distillation.

      You DID the best you could for SassyBear! The BEST!
      ~ Katy & Jackson

  5. Katy….the time and energy, and blood, sweat and probably a few tears, you put into this astounds me! .Colorado State needs to put you on their payroll!

    And this is just an aside for anyone reading this. This post is about a chemo study and not an indicator of whether one should pursue cheno or not. As Katy has pointed out, chemo is a personal choice and not the right route for everyone. As everyone knows researching this site, there are many dogs who have incredible extended quality time with just goiing a holistic and lr supplements/nutritional route. Every dog is different! And, as everyone knows, some dogs pass before even getting to complete two or three rounds, or even shortly after co,pleting five or six. I know all that’s “factored” in the study, but no o e should second guess themselves on the choices they made. I know it’s hard to read a study like this when your dog’s time has come and gone and start second guessing!! Don’t do it! Katy has provided a wonderful breakdown of slme very confusing innformation as a great sourceto discuss with your vet. Also, things change sooooooo rapidly, this study could very well be out of date! So much headway has been made with nutrition, holistic, etc. To me, those types of things need to be factored jn also for a study to be really valid these days!, But I’m getting off base.

    My Happy Hannah had four rounds of carbo (my Oonco was a recent graduate of Cornell at the time and was a proponet of four. She did NOT fall into the category that “more was better”, that’s for sure. But she did want all four rounds completed!

    Anyway, I’d like my Happy Hannah to be a “footnote” in their study!, She’s a pure bred Bull Mastiff…..a senior….and “heavy”….possibly a touch “fat” (sorry to put that on your footnote Hannah!) My Happy Hannah graced me with her joyful and loving presence for 425 days!!!

    Katy, “awesome” is such an over used word…..but you did an AWESOME job! The contributions you and Jackson continue to make here are incredible!!

    AND, we got to see some more great pics of that astonishing boy!

    Gratefully,

    Sally and Happy Hannan

    • Thanks, Sally! Yes, this has been a major piece in prep for a long time. I wanted to break it down for this community and unveil how oncologists get their info. As to your point about Hannah being pure bred and large being against the stats, well, some reasons for her marvelous life post-amp could be because her cancer was slower, you caught it early, and that she did get 4 rounds of chemo! I’d add LOVE, but we all love our pups and kitties around here.

      About predictors: as scientists we can make guesses as to what to look for, but sometimes we miss things. Such as, maybe cranium size is important! Or, maybe whether she was spayed or he neutered? Or, the number of meals fed in a day? Who knows! There’s no reason to think oncologists have it all figured out, which again supports our take here: fight like hell and make it worth it! For some, that’s vet visits and others, it’s a staunch aversion to the oncologist. At the very least, this study shows that at least 4 rounds of anything seems to help. May science and medicine move quickly AND with wisdom here.
      ~ Katy & Jackson

    • You bring up so many great points Sally. Yep, there are no right or wrong decisions about chemo, just gotta do the best you can to ensure the happiness of the pack. It’s about quality of life, always.

  6. Nice job. It looks great! I hope this is helpful for many out there.
    ~ Katy & Jackson

  7. What amazing timing on this post. Thank you so much for sharing your scientific knowledge in a way that laypersons can understand.

    I have just decided to stop Bart’s treatment and had understood that there are many protocols that only go for 4 rounds, which he completed last week. His protocol was different than those in the study you discussed – he was on an alternating Cysplastin / Doxo plan which he had every 3 weeks. He never rebounded after the 3rd, he became worse after the 4th and it is naive of me to think (hope) he would suddenly do well after a 5th.

    Bart is very atypical, however, because this is his 2nd bout with OSA. He had been cancer free for almost 6 years when a lump on his side was removed and confirmed to be OSA.

    In any event, I really do appreciate you spending time to discuss this with all of us.

    Darcy & Bart

    • Bart is a Tripawd Hero! You’re right – Bart’s story is very unique and he’s probably the only case out there so you’re in murky water as what is best. Going with your gut at this point and celebrating Quality of Life is always a superb strategy. Let’s hope these last 4 round of chemo for Bart are his last, kicking OSA and all other cancers to the curb. We love Bart!
      ~ Katy & Jackson

    • Darcy, as hard and emotional as they’ve been, every decision you’ve made on this journey has worked together to help Bart continue being the amazing, inspawrational hero that he is. This latest decision had to be so difficult but is sure to help him continue thriving and sharing his successes with the world. May he hop on for a long, long time!

    • As someone just entering this scary journey, I would give anything to make six years with my Eva. She’s only three. I read Bart’s journey and just have so much hope and faith in the potential that my princess might have more than just a day count. I want so badly to be at the point where I can’t remember how many days since all of this began. You’re all such helpful and inspirational people and you’re helping me so much on what is proving to be such a difficult night.

      • Eva and family, thank you for the beautiful feedback. We are here for you so please join us and let us know how we can help OK?

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