Taxol Dosing – new study

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Paclitaxel was originally isolated from the bark of the Pacific yew tree, where it is synthesized by endophytic fungi.

“The addition of new chemotherapy drugs has not improved outcomes. Thus, we need to give the active drugs in the best way,” says G. Thomas Budd MD of the Cleveland Clinic. Dr. Budd reported a very interesting study comparing two dosing regimens of Taxol (paclitaxel) at ASCO 2013, this year’s annual meeting of the American Society of Clinical Oncology, which took place from May 31st to June 4th.

I was particularly drawn to this abstract because Taxol caused what was probably the most unpleasant experience I have had to date on chemotherapy. Oh, I lost four kilos a treatment on the AC schedule, but vomiting could be controlled. But Taxol… Taxol quite literally took my breath away. My chest hurt and I was coughing and gasping for air. The friend who had accompanied me to that first dose, a nurse herself, started me on oxygen and went for the chemo nurse. They put me on steroids and something else that made me sleep. From then and for the rest of the series of Taxol treatments, I received a bag of IV steroids before the treatment, then something that made me sleep, then finally the Taxol. It was not fun.

So it was interesting to read this abstract. I won’t go into the details of the protocol, but you can read about it at the links I’ve provided below. The part that concerns us was the comparison of two dosing regimens for Taxol: the traditional “dose-dense approach” given every two weeks that was developed at Sloan-Kettering, and a lower dose given weekly.

Discussing the conclusions of the survey, Dr. Budd said: “Either regimen can be selected on the basis of efficacy. So in practice, treatment can be selected based on other considerations, such as toxicity.”

Toxicity of cancer drugs is graded on a scale called the Common Terminology Criteria for Adverse Events (see National Cancer Institute Wiki FAQ on the CTCAE) that ranges from  0 (no adverse effect to 4 (life-threatening adverse effect). (Grade 5, death, does exist on the scale, but was not a factor in this study). The study found that both regimens had grade 3/4 toxicity, but that the “toxicity profile” differed between the two. The dose-dense protocol led to more allergic-type reactions, whereas the lower weekly dose showed more hematological toxicity.

The study concluded that 12 weeks of low-dose Taxol produces less overall toxicity than  six cycles of dose-dense treatment (one cycle every two weeks).

What are the implications for me? If my oncologist should suggest putting me back on Taxol (it has been shown to have some efficacy in stage IV breast cancer), I would definitely ask about the weekly schedule. (It may not be possible in my case due to chronic neutropenia, but it’s worth investigating.)

Notes:

It should be remembered that these findings were presented orally at ASCO and have not yet been published in a peer-reviewed journal.

The study was funded by the (American) National Institute of Health and Amgen.

The abstract, which was presented orally, can be read online here and there is a discussion of it by Medpage Today staff writer Charles Bankhead here.

17 thoughts on “Taxol Dosing – new study

  1. Oh TK what you must have endured to gain some quality and quantity of life – I pray I will never have to go through that!
    Blessings and Prayers
    Maxine

  2. I had a different cancer (uterine), and a different staging (one with complicating factors) and took Taxol as an adjuvant care (because it was hoped that no cancer remained after surgery but no lymph nodes had been removed for testing), but I had six weekly doses of Taxol (so not quite what either group received in this test). On several days, I had the same reaction that you described. I was awake throughout the treatments. The problem was addressed with more Benadryl (there may have been more steroids, too). Then the speed of administration was slowed way down. The nurse started me at very low speeds and raised the speed gradually as I took the Taxol without a renewed allergic reaction. The sessions for Taxol were very long, but the alternative was inability to breathe to the point that I could not speak and the sensation of having been hit in the back by a car (sounds like what you described). Maybe you could suggest a slower administration rate to your doctor whether dosing is weekly or alternate weeks. My thoughts are with you. My own experience was for six weeks, and I feel like I’m still recovering after more than a year. And there is no way to know whether or not I will one day find myself back in treatment. I feel incredible empathy for anyone experiencing repeated treatment as you and so many other Stage IV patients have. Thanks for sharing your knowledge and experience. I’m sending my best wishes for good outcomes.

    • Thank you so much for sharing, Not Down or Out. Taxol is indeed used as adjuvant chemotherapy in cancers besides breast cancer.

      They gave it to me slowly, too. I had a pronounced allergic reaction anyway. Happens. I hope that the new low dose weekly protocol will help avoid that in other patients.

      Thanks for your empathy and good wishes and especially for sharing your experience with us.

  3. Very interesting. I was on Taxol every three weeks for a year. I had an allergic reaction the first time and subsequently received Benedryl and steroids plus a slower infusion rate of Taxol. It shrank my liver mets dramatically! And with reasonable quality of life. I’ve found Tamoxifen as hard to take as Taxol, but I get to keep my hair.

    I don’t know if the Canadian protocols are different from other countries, but I think every 3 weeks is standard here. Though I should say that for the first six months I got the Taxol in split doses on days 1 and 8 of 21.

    For me, after a year I was given a chemo break. When we next checked, the tumours had stabilized and I was started on Tamoxifen. The doctor indicated that the cancer cells can forget their resistance to a chemo drug after a year. So, if next winter I have progression, I’m very willing to try Taxol again, in hopes of more shrinkage. But then, will the infusions come every one week, two or three? I must be sure to discuss this study with my doctor when the time comes.

    • Hi, Kate.

      I’m so glad you had good results with Taxol! I didn’t have any trouble at all with Tamoxifen; I wonder if this is because I was already menopausal when I started it.

      I’m hoping with you for great results on your next scans.

  4. Hmm. I wonder what the consensus was at last night’s online discussion about this study. Given your previous experience, I would think that severe respiratory distress and the possibility of the side effect of death would make my decision for me. But, that’s just me. I’m a maverick.

    G

    • Hi Greg. I’m wondering, too. The #bcsm tweet chat transcript will be online later today, and I’m looking forward to reading it.

      According the Results section of the abstract (see link above): “Grade 5 toxicity [death KT] occurred in 4 patients on ddP [dose dense regimen KT] and 2 on weekly P.” So the “side effect of death” is at a very low risk. I think that the lower occurrence of allergic reactions on the weekly dose would be enough to decide me in favor of receiving it again.

      But, as you say, that’s just me.

      Thanks for reading and commenting.

  5. I remember being very concerned about many of the side effects for taxol…thankfully my onc was willing to work with me a little and I chose to do taxotere administered weekly. For some women taxotere seems to be better tolerated yet theoretically without sacrificing efficacy. I also received decadon (a steroid) but that was already an automatic part of the regimen.

    The A/C part sucked for me big time…they were able to stop the vomiting but the nausea never went away. I honestly don’t know how I did it, now looking back. But the taxotere part wasn’t nearly as bad. But that’s for me…I’ve heard an entire spectrum of experiences.

  6. Just catching up on your blog, so this is a little late. Anyway, this time 2 years ago i was finishing up my taxol. My oncologist split my chemo in two, 4 AC three weeks apart and then 12 weekly taxols. The AC was definitely hellish. Fungal infections, neutropenia, steroid wackiness and 5 days in bed after my tx.

    I’d read a lot about taxol, especially the bits about adverse reactions and i was scared. So my oncologist assured me that the reactions are rare, i would have antihistamines in addition to steroids and the nurse would be right there, and especially watchful the first 20 minutes or so. Yeah, ok, but it did work. I wonder though if steroids and antihistamines are standards in taxol administration these days. The worst part of taxol for me was reflux during administration, and now I’m trying to remember if i had emend too – i know I was on 40 mg omeprazole the whole time i had chemo and rads.

    My understanding of the dose dense protocol is that you can give lower doses over a shorter interval and therefore increase exposure to chemo. So the more frequent dose is the dense one. But I’m dyslexic and forever confusing this stuff. At any rate, the weekly taxol was so much easier to take – i had no issues with neutropenia, a much lower steroid dose and thus much less craziness.

    • The side effects of AC and Taxol can be very different. When I had AC the first time I lost 4 kilos after after dose from vomiting. Taxol was hellish in a different way. Sigh.

      On the bright side, I was diagnosed with metastasis eight years ago, so something is working!

  7. Just ran into this, so I know this comment is late.
    My oncologist is also a med school professor and actively involved in research. He had me on the weekly taxol schedule, followed by AC every other week for 8 weeks. From the very beginning, I got a predose “cocktail” of steroids, benedryl, antinausea meds, and probably some other stuff. I know it used to knock me out. Halfway through my 12 weeks of taxol, I broke out in an allergic all-over rash, so they switched me to a form of it in a less allergenic carrier.
    Taxol was bad, and they kept telling me I was doing great. AC was worse. I finally asked what their definition of doing great was. It was if they didn’t have to take a break in your treatment or hospitalize you!

    • Yes, AC was horrendous, but Taxol was really bad in other ways. Nothing fun about getting poisoned, no matter how good the cause!

      Thanks so much for reading and commenting, Elizabeth.

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