Alisertib with Fulvestrant

Anne45, good to know that this is working for you and that your hair is growing back. Sometimes I struggle to keep my eye on the prize and your post helps with that.

My neutrophils were also low, so my onc delayed the start of my second cycle and lowered the dose. My first scans are in July.

Heartburn, intermittent diarrhea, chemo brain, fatigued, and declining vision are my SEs. It reminds me a lot of the first round of chemo.

Cure-ious, I asked my onc about mutations but I don’t have any of note. If I didn’t have chemo brain I might have remembered to ask about the aspirin/NSAIDS.

anne45- fantastic news!

Great news Anne, thanks for checking back in! Also glad to hear your hair is growing back in! It may be weird to focus on vanity in our situation but I'm always happy to hear about drugs that dont take our hair. I hope its easy on the eyebrows and lashes, that always made me look like I was sick.

Scan results from first scan since I started this trial are in. My onc is pleased. There is one spot that increased in size, but the big one is smaller, liver is less enlarged and liver function is good.

My neutrophils are still taking a hit. I hope I can develop a tolerance.

The hair that I didn't lose is starting to grow. I still look like an old man, but it's promising. My eyebrows thinned. I've been using eyebrow growth serum and it seems to help.

Turns out I'm a whisper away from triple negative: 10% ER, 0% PR, 10% HER-2. Or at least what feels like a whisper to me.I need to double check the HER-2 number

Anne45, I use something called neubrow. It's about $75, but you can find it cheaper on Amazon.

My neutrophils are all over the place. Not sure if I will be able to stay in the trial.

Good tip on the ginger. I also have random waves of nausea. Will try it.

An interesting paper came out last month in Cancer Research:

"Aurora A inhibition eliminates myeloid cell-mediated Immunosuppression and enhances the efficacy of anti-PDL1 therapy in Breast Cancer"

Abstract: Here, we demonstrated that inhibition of Aurora A directly reshaped the immune microenvironment through removal of tumor-promoting myeloid cells and enrichment of anticancer T lymphocytes, which established a tumor-suppressive microenvironment and significantly contributed to the regression of murine mammary tumors. Mechanistically, alisertib treatment triggered apoptosis in myeloid-derived suppressor cells (MDSC) and macrophages, resulting in their elimination from tumors. Furthermore, alisertib treatment disrupted the immunosuppressive functions of MDSC by inhibiting Stat3-mediated ROS production. These alterations led to significant increases of active CD8⁺ and CD4⁺ T lymphocytes, which efficiently inhibited the proliferation of tumor cells. Intriguingly, alisertib combined with PD-L1 blockade showed synergistic efficacy in the treatment of mammary tumors. These results detail the effects of Aurora A inhibition on the immune microenvironment and provide a novel chemo-immunotherapy strategy for advanced breast cancers.

Significance: These findings show that inhibition of Aurora A facilitates an anticancer immune microenvironment, which can suppress tumor progression and enhance anti–PD-L1 therapy in breast cancer.

In short, this paper shows that Alisertib is enhancing the ability of the immune system to infiltrate and destroy the cancer, and it enhances the response of solid tumors to immunotherapy (I-O). This might explain why some people are getting really long (2-3 years) responses on this drug, and would predict that some scans may improve the longer someone is on the drug.

Previous work from UCSF showed that Alisertib also strongly synergizes with Alpelisib (PI3K inhibitor). Hopefully Alisertib is a tolerable drug and can be used in combination with I-O or Alpelisib for future clinical trials.

Anne45, congrats on the scan results! I had scans this week and the cancer is stable. My ANC is getting crushed so I’m on Zarxio twice a week now.

Zarxio has not been bad: very slight chest and joint pain. I take a Claritin the day of the shot. I’m getting it twice a week. My oncologist lowered the alisertib dose to 30 mg, but told me it would still be effective.

I get fatigued if I over do it, but other than that I feel pretty good.

Hair is slowly, but surely growing back.

Funny how 93 sounds like a spring chicken to me now.

Anne45. Sorry to hear about your Monday nights. I’m in the meds Wednesday through Friday. Sunday is usually my nausea day. I don’t have diarrhea on the regular anymore, but I have to think about what I eat. Veggie burgers and shiitake mushrooms are not my friends.

Are you still on the full dose? They’ve reduced my dose to only 6 pills a day and I had to skip the first week of this cycle because my ANC was too low. I worry that I’m progressing because I’m not getting enough medicine.

I just started reading Anti-Cancer. The author is dead and the research is old, but it is still giving me a good perspective - my goal is to be on the long tail of the bellcurve, if that makes sense.

Hope you are too.

P.S.

Sounds like your father-in-law is doing old age right!

Hi, If i have the PIK3ca mutation I will join this trial as well. Will provably have some answers by mid january

Thank you M3llon, I hate to lose my hair again and worried about the other side effects. Hearing your experience helps.

Hi Ann, how long have you been in this treatment? What are the results so far?