Mets Day 524Dose Dense MVAC Q&A

Mets Day 524Dose Dense MVAC Q&A

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In the past few days I have exchanged a pair of emails with Drs. Apolo and Aragon-Ching, and this morning I had a follow-up cell consultation with Dr. Apolo, on whether to proceed with dose dense (dd) MVAC chemotherapy. Following are my questions and their answers:
Q&A with Dr. Aragon-Ching of George Washington University:

Aragon-Ching Question 1: Dr. Apolo said that she changed into going to have my cancer sequenced. Could that proof supply any conception into whether dose dense MVAC (or probably a fate clinical trial) is most likely compatible for me?
Aragon-Ching Answer 1: I would defer to Dr. Apolo.

Aragon-Ching Question 2: You told me that you couldn't determine any proof comparing median overall survival of sufferers with mets BC who should not ever have dose dense chemo to those that do. Where may well I favor proof on those that are meant to not ever have any cure?
Aragon-Ching Answer 2: One part III trial comparing a salvage chemotherapy drug is understood as vinflunine (now not accredited throughout the US, this changed into primarily a European trial) changed into compared to what we call most unparalleled supportive care (no chemo) and the median overall survival changed into a bit over 4 months (hyperlink the following)

Aragon-Ching Question 3: The PET experiment confirmed there changed into questionable focal uptake throughout the right medial hepatic lobe. Does the risk of metastatic pastime throughout the liver support going ahead with dose dense chemo, or is it irrelevant as it is indeterminate?
Aragon-Ching Answer 3: The presence of recognised visceral disease is an antagonistic prognostic limitation, compared to just adenopathy alone … it'd support cure with chemotherapy.

Aragon-Ching Question 4: The 2001 glance at that you gave me (http://www.ncbi.nlm.nih.gov/pubmed/11352955) ironically confirmed that sufferers receiving dose dense MVAC had a somewhat extra ideal response significance (sixty two% to 50%) and two yr survival significance (35% vs. 25%) than sufferers receiving fixed MVAC, nonetheless that there changed into no statistical difference in either the final survival significance, or time to progression of additional metastases. I'm having a troublesome time understanding these proof. Can you shed some conception on it? Also, that glance at changed into of sufferers who had now not formerly got platinum-primarily based therapy, so it appears much less applicable to me. Am I misreading it?
Aragon-Ching Answer 4: You are most achievable right in reading this…this changed into a neoadjuvant trial in sufferers on no account been taken care of with chemo (so this is now not technically applicable to you) nonetheless I wanted to offer you an idea-about what the regimen contained & its schedule (dose dense)and it changed into being compared tothe useful dose MVAC. Having said this, sufferers who cross via dose dense MVAC who have been formerly taken care of also can as a matter of truth present a expand to extra toxicities than what this paper is discussing.

Aragon-Ching Question 5: The 2012 glance at (http://www.ncbi.nlm.nih.gov/pubmed/22364733) noticed throughout the industry changed into a sixty one% response significance, with 10% having a total response. Digging deeper into the proof, it appears that the confident prices are skewed by the inclusion of sufferers who didn't have far-off metastatic disease: three of the four sufferers who had a total response didn't have metastatic disease. For men and women folk with far-off metastases, the median time to progression changed into 4.4 months, and median overall survival changed into 5.7 months. These do now not sound very encouraging to me. Am I lacking it doesn't matter what?
Aragon-Ching Answer 5: This trial covered all sufferers with metastatic websites of diseasebut made no distinctionwhether they were far-off websites or now not.

Q&A with Dr. Apolo of NIH's National Cancer Institute:

Apolo Question 1: Dr. Aragon-Ching said that, if I changed into to proceed with dose dense MVAC, it is going to disqualify me from later clinical trials. You and I had discussed a ramification of feasible trials; would any of those be closed off if I proceeded?
Apolo Answer 1: You would nonetheless be eligible for my clinical trials if in case you have proceed with MVAC.

Apolo Question 2: Even if those trial were foreclosed to me, would you nonetheless put forward my proceeding with dose dense MVAC?
Apolo Answer 2: Yes, nonetheless they are now not

Apolo Question 3: You said that you were going to have my cancer sequenced. Has that passed off but, and in that case, does that proof supply any insights of what reasonably therapy or trial is some of the compatible for me?
Apolo Answer 3: I will follow up on the sequencing on Thursday when I meet with our pathologist. This also may well make a adjustments what you acquire after chemo nonetheless the panel is merely 50 genes, so the findings are constrained. Foundation medicine has a panel with 200 genes and I think policy cowl
covers this. I am not sure if I can send this out from the NCI with out a hassle because we dont handle policy cowl nonetheless most likely Dr. Aragon-Ching can, I will ask her.

Apolo Question 4: Can you aspect me to proof appearing median overall survival of sufferers with mets BC who should not ever have dose dense chemo?
Apolo Answer 4: I have connected some pivotal papers on first line chemotherapy for metastatic disease. Including the part 3 of (gemcitabine and cisplatin) GC vs MVAC (hyperlink the following) and the PCG (paclitaxel/gem/cis) vs GC (hyperlink the following). I have additionally including a retrospective report from France on sufferers that got ddMVAC after GC (hyperlink the following).

Apolo Question 5: The PET experiment confirmed there changed into questionable focal uptake throughout the right medial hepatic lobe. Does the risk of metastatic pastime throughout the liver support going ahead with dose dense chemo, or is it irrelevant as it is indeterminate?
Apolo Answer 5: If you do have disease throughout the liver then ddMVAC would now not be essentially the most unparalleled option of therapy with out a hassle because my objective is to have you in achieving a total response (CR) with the ddMVAC. The possibilities that you in achieving a CR are best with lymph node disease and occasional with liver disease. Chemotherapy for your environment is given for palliation nonetheless you dont have signs, this is Dr. Plimack's reservation. My objective is to a in achieving a CR which is basically full in 5% of sufferers with GC and 20% with ddMVAC when it is given as the primary chemotherapy to sufferers with metastatic disease. You will be given ddMVAC as your 2d chemotherapy BUT first throughout the metastatic environment. The French studied confirmed a CR significance of 10% with ddMVAC (for your environment). Patients that during achieving a total response have longer survivals. That being said ddMVAC has a main quantity of facet results and is troublesome to get via. I ultra acknowledge Dr. Steinberg nonetheless he is a urologist now not a medical oncologist. I consulted your case with Dr. Cora Sternberg the oncologist who constructed ddMVAC (I connected her customary handbook from 2001) (hyperlink the following) and she wholly is of the identical opinion with me.

Apolo Question 6. Your email notes that ddMVAC would now not be essentially the most unparalleled option if I have liver disease. Given the ambiguous results from the PET experiment, does it make sense to are making an effort to rule that out earlier than embarking on ddMVAC? How would I go about doing that?
Apolo Answer 6: The PET experiment is inconclusive. It's very had to tell from a PET experiment whether there is metastatic pastime throughout the liver, with out a hassle since the complete liver is scorching. We use CT scans to tell whether there is node enlargement or tumors throughout the liver. The PET experiment suggests that, if there changed into metastatic pastime for your liver, it is now not throughout the lymph nodes, nonetheless inside your liver. If a next CT experiment confirmed a tumor throughout the liver, then make express you now not proceed with ddMVAC, or make express you cease it if it changed into begun.

Apolo Question 7: Thank you for consulting with Dr. Cora Sternberg, who constructed the 2001 glance at. As I examine it, that glance at has a paradox. On the one hand, it confirmed that sufferers receiving ddMVAC had a somewhat extra ideal response significance (sixty two% to 50%) and two yr survival significance (35% vs. 25%) than sufferers receiving fixed MVAC, nonetheless nevertheless, it confirmed that there changed into no statistically essential difference in either the final survival significance, or time to progression of additional metastases. I'm having a troublesome time reconciling these proof, specially as additionally they can follow to my situation. Does this imply that there is a extra robust risk that ddMVAC also can supply a total response (CR) or partial response (PR) similtaneously I have the chemo, nonetheless once the far-off tumors present a expand to, the disease moves quicker, so my OS will be identical? Also, that glance at changed into of sufferers who had now not formerly got platinum-primarily based therapy; as we know, I failed GemCis, so I'm occupied with how applicable that proof is to me.
Apolo Answer 7: The glance at does have that paradox, and we wrestle with the proof. The studies imply that the costs of CR are enormously extra ideal with ddMVAC than with fixed MVAC or GC chemo, specially perioperatively. These proof support ddMVAC as a 2d line therapy. There hasn't ever been a part III clinical trial comparing GC to ddMVAC. We are commencing that now. The proof imply that median progression-unfastened survival for ddMVAC is 9.1 months, with fixed MVAC it is 8.2 months, with GC it is 7.4 months, and with out a therapy, about 5.5 months. Extrapolating from the studies, ddMVAC presents you your most unparalleled risk of CR or PR.

Apolo Question 8: The 2012 French retrospective glance at appears to divide sufferers into two organizations: adjuvant chemo and metastatic disease. While it noticed throughout the industry changed into a sixty one% response significance with ddMVAC, with 10% having a total response, it appears that essentially the most unparalleled results were obtained by sufferers who had adjuvant chemo nonetheless didn't didn't have far-off metastatic disease. For men and women folk with far-off metastases, the median time to progression changed into 4.4 months, and median overall survival changed into 5.7 months. Am I physical to positioned myself into the mets network, and expect a diminish likelihood of CR or PR?
Apolo Answer 8: You are one of many two organizations. You had confident nodes after your surgical therapy, nonetheless has now not spread systemically, and you had no far-off tumors. Looking at your cancer from the lymph node that we biopsied lower than the microscope, it changed into poorly differentiated, and as a matter of truth aggressive. It didn't have much of the tendencies of micropappillary bladder cancer. Instead, it looked like a tumor that we could in you to present a expand to right this moment. It doesn't appearance like a cancer that we could in you to be indolent, which implies that that it is going to present a expand to slowly.

Apolo Question 9: The 2012 taxanes glance at is provocative. Is adding a taxane into ddMVAC an option? Is there any downside to trying it?
Apolo Answer 9: Taxanes with ddMVAC is merely too poisonous and is now not an option.

Apolo Question 10: Boiling the entirety down, I'm attempting to favor whether 3 months of
feeling lousy similtaneously having ddMVAC goes to be worth it. If it presents 3 months of life to the returned finish, nonetheless I lose three months similtaneously handling the chemo, then it appears to be a wash, and without doubt now not worth it. If there is a economical prospect of having a total response and radically adding time beyond regulation, then it becomes extra pleasing. But if it is going to permanently weaken my immune machine and compromise my remaining time with little likelihood of fulfillment, then I'd fairly now not do it. Do you handle how I've boiled it down?
Apolo Answer 10: It's an only manner of in need of at it. You also can get 3 months or extra on the returned finish, or you also cannot. Don't pay too much realization to the French retrospective glance at on toxicities, with out a hassle because we have now discovered so much on the right manner to decrease the toxicities. I present 3 liters of hydration with the MVAC, so it may well take as much as 9 hours to procure the full chemo dose — 6 hours for hydration, 3 hours for the tablets. I the complete time stay away from sufferers overnight unless they live very vicinity. Many of my sufferers tolerate ddMVAC o.k.. Most nowadays, I gave 5 rounds of ddMVAC to a nurse who works on the NCI hospital. She saved working similtaneously having each circular, along side for circular 5, when she constructed mouth sores and couldn't consume. Another refreshing affected consumer lived on a farm and endured to paintings as a farmer similtaneously having the chemo. Each affected consumer is the varied. The simplest facet results are mouth sores, fatigue, and fever. You are relatively younger and in a the varied manner suit, so make express you have the aptitude to tolerate the ddMVAC well.

Apolo Question eleven: I remember that, on steadiness, you handle that the professionals radically outweigh the cons, that I'll get via ddMVAC, and have an only risk at either CR or PR for some amount of time. I'm unclear from the literature how long the CR or PR oftentimes lasts. It appears that, for some, it is only similtaneously the chemo is being administered, and once it stops, the disease comes returned like gangbusters. For a minority of other sufferers, it appears that the response extends beyond the period of cure. Is it sincere to claim that, in my case, there is now not any manner of understanding whether I'll have any favorable response, nonetheless that you handle that having ddMVAC is essentially the most unparalleled manner to expand my life similtaneously nonetheless preserving a favorable high quality of life?
Apolo Answer eleven: I would imply proceeding with ddMVAC with Dr. Aragon-Ching. You do
now not want to get restaged with Dr. Plimack, I can do it or Dr. Aragon-Ching can do it. Treating you with ddMVAC is essentially the most aggressive option. If it were me in you footwear, I'd do ddMVAC. If you favor now not proceed with the chemotherapy that's OK too, it as a matter of truth it's a non-public range.

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