Chemo regimens as a bridge to clinical trials - 1260229

Jazz
Posts:279

I've searched a bit but can't find quite the right topic, so here goes. I missed the boat on enrolling in one trial; I'm exploring another, the consultation/signing is Nov. 4. Biopsy has to be done and tissue sent off, so that's another 2 weeks, plus a week before dosing, if not two. With 3 - 4 weeks before dosing, and chemo being continuously put off, I'm now out 5 months from the last cycle of carbo-gemzar (stable). I've been on Tarceva since. Things are going south fast, but in case I can't wait to start a trial, my oncologist has ordered Cisplatin (50mg)+ Navelbine. I didn't realize this meant a central line which needs to be flushed twice/day or a port (2 - 3 weeks to be placed), nor did I know it was a 7 hour infusion. This would be something like 6th line, but without expectation of anything more than stabilization

Dr. West described cisplatin-navelbine in adjuvant therapy as being "soul-crushing", that people would discontinue, inspite of the survival benefit. I'm wondering if the combination is overkill in terms of seeking symptom arrest? I wouldn't want to be so debilitated that I couldn't go on to another trial. It sounds very difficult and awful.

Might another combination - like Alimta+Gemcitabine (or even Gemzar+Navelbine) - do well for arresting symptoms? For the record I've had 8 Carbo, 6 Gemzar, and many Alimta infusions (with acceptable response). Or is there another non-platinum doublet I might consider? I thought Gemzar + Tarceva might hold me, but more chemo kept being put off. Does this make trying Gemzar + Tarceva not reasonable?

Thanks for any insights,

Jazz

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Reply # - October 31, 2013, 07:56 AM

JimC
Posts: 2753

Jazz,

It seems to me that your thinking is pretty much on target. If this "bridge chemo" is only intended to keep symptoms in check, it shouldn't be something so difficult that it causes side effects that make you just as miserable.

Once you reach later lines of therapy as you have, there really isn't a guidebook to help choose the next regiment. But some general principles might be helpful. Since you've already had 8 rounds of platinum I would be hesitant to try more, especially since you're stepping up to cisplatin, which can be even tougher to tolerate than carboplatin. The same reasoning might apply to using a doublet rather than a single agent - is the extra toxicity going to be worth the marginal benefit of two agents? Generally, oncologists like to use an agent that hasn't previously been tried, or an agent on which you didn't progress either while on that regimen or soon after stopping it. So I would think you could make a good argument for a new agent, such as Navelbine, or one of the other drugs you've used and to which you've responded well. And of course I'm sure you're aware that you don't want to add any agent that might disqualify you from the trial.

Good luck with your choice.

JimC
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Reply # - October 31, 2013, 10:21 AM

catdander
Posts:

Hi Jazz,
It looks like you may not have progressed on Alimta, if not it would fit into Jim's discussion above. Gemzar and Navelbine could be used as single agents too.
A possible reason for wanting to put you on a central line may be the navelbine, it can wreck havoc on your veins. My husband used it without a port with carbo and it did burn more than others. Gemzar was much easier on the infusion sight.

I hope you find some relief to make it to the trial you want,
Janine

Reply # - October 31, 2013, 07:57 PM

Dr West
Posts: 4735

Jazz,

I think "soul-crushing" was an extreme and overly negative assessment, and I really like to see the context in which I said it, because I really think that "challenging" would be a more accurate portrayal (your description makes me think I was unusually harsh vs. my broader assessment of it). It's the cisplatin that is the issue, and it's really hard to envision giving that in meaningful doses to someone who has already received a lot of prior chemo -- it's just a notoriously tough therapy even first line, let alone fourth line or later.

I'd have to say that it's hard to get enthusiastic about returning to agents that your cancer has been treated with many times before. Returning to a taxane, perhaps back to docetaxel, or maybe Abraxane, or switching to something new and different, such as irinotecan (very rarely used for NSCLC, but that's mostly because it was never followed up and marketed for that, not that it's far less active than other options) might be an option. These ideas get kind of "out there", but there's no option that has any significant amount of evidence after many prior lines of therapy, so it requires a bit of a shot in the dark.

Good luck.

-Dr. West

Reply # - November 2, 2013, 09:02 AM

laya d.
Posts: 714

Hi Jazz. . .

I have nothing substantive to add here, but just wanted to send you my love (and my best). . .And, have my fingers-crossed for the least life-crimping "bridge" available to you out there. . .

xoxo,
Laya

Reply # - November 6, 2013, 07:36 PM

ssflxl
Posts: 204

Jazz

Which trial are you waiting for? I am waiting for the Clovis trial at Stanford, but I talked to the trial coordinator today and she said Phase II won't open until Jan. I am thinking of perhaps getting a bridging dose of chemo - maybe Alimta in the meantime if possible. I didn't know you can do such a thing as get chemo to bridge before trial starts. My tumor has progressed since July and I am now getting some neuropathy - with arm pain and tingling. I am not sure I can wait until Jan for trial. I haven't done a repeat biopsy yet but will see if I can get one in Dec. If I am neg for T790M, then I will not be eligible and will then have to go with chemo

:-|

Reply # - November 6, 2013, 08:31 PM

Jazz
Posts: 279

Here's the post, re: cisplatin-vinorelbine:

I’ve certainly seen this in many of my own patients, on or off of a clinical trial — even if they know that there is a potential survival benefit to be gained, some express that they’d rather be dead than to continue on cisplatin-based chemo. The trial actually confirmed that the cisplatin/Navelbine regimen as best studied is quite difficult to administer on any kind of regular schedule, at least without it being a soul-crushing experience; cisplatin/Alimta was more feasible, though not a cake walk itself either.

It's here: http://cancergrace.org/lung/2011/08/12/sacrilegious-thoughts-on-adjuvan…

SSFLXL, I enrolled in the Merck anti-pd1 trial, as a slot in the Phase 1 Clovis trial won't be available until early December, & it seems like a moving target at this point. Not sure if I can wait that long so I'm moving forward, having already missed the boat on the Genentech PDL-1 trial. I am reasonably sure I still have the T790 mutation so if I have to wait for Phase II, so be it. If tissue is PDL-1 neg, gotta wait for Clovis anyway.

IMHO, If you're uncertain of T790m status, get biopsied soon or get on in Phase 1. Chemo can be a bridge, but it complicates things in terms of 30-day washout periods prior to starting, ensuring your blood counts are adequate, and side effects have diminished to Grade 1. If you need the Clovis trial @ Phase 1, assert yourself with your oncologist. I believe California doesn't allow providers to deny coverage of Phase 1 trials. You may have to fight for it but there are Kaiser pts. on Phase 1 trials.

Laya, Thanks for your continued support. You are an extraordinary nurturer with amazing reserves of strength & compassion...<3

Dr. West, Jim, Janine - Thanks for your responses. No one thinks cisplatin is a good idea - I'm baffled why my oncologist ordered it. UCLA onc thinks Tarceva continues to benefit; keep it simple, I'll last a month...

Jaz

Reply # - November 6, 2013, 09:06 PM

ssflxl
Posts: 204

Jazz,

The Clovis Phase I trial is closed, and they are hoping to start Phase II in Jan, but I don't think I can wait that long!! I don't have biopsy yet because I thought tissue has to be sent to special lab (Central Processing) but it doesn't appear to be the case. If my biopsy is neg for T790M, then I will wind up with chemo. The other Phase I anti-PD trial in UCSF (MK3475) requires you to fail chemo also, so I can't get in anyway. Stanford will be doing a Phase 1 trial for MPD for solid tumors, not for NSCLC as their Phase II trial for this is already filled.
You should try Taxane to bridge yourself in the meantime, if you need something.

ssflxl

Reply # - November 6, 2013, 09:38 PM

Jazz
Posts: 279

SSFLXL,

I didn't realize Clovis Phase 1 closed at Stanford. There was a new amendment, but their waiting list was quite long. Still, phase 2 in January is good news and chances are you have the T790m.

I'm allergic to Taxanes, unless I do a desensitization protocol (I started a topic for that but have to look for it). The only chemo I haven't used is Navelbine, which is tough on the veins so a central line is always prescribed. Both docs at UC Denver and UCLA say they give vinorelbine through the vein, though a central line is practical if given weekly. The academic docs do not seem to favor getting a port or central line, and I don't know if it's risk of infection or what. Maybe faculty can clarify this? It's become a bit of an issue with me.

UCLA onc (Dr. Goldman) thinks I might be able to try Alimta again, it's been since 2009. Navelbine doesn't seem to rate very highly with him or Dr. C, in not so many words. If neither Merck nor Clovis works out, then I definitely have to do chemo, and it'll probably be Navelbine unless I can convince my doc to try Alimta again... Or, hope AZD9291 is open in Denver or somewhere else accessible (Houston?). Desensitization is the last resort after Navelbine, I suppose.

I hope you get this sorted out. Carbo-Alimta can be very tolerable (see Gail/gn21's thread) and give a durable response if it works for you. Just remember the three rules of getting in clinical trials:

1. Stay strong and active. Don't act sick.
2. DON'T LOSE WEIGHT.
3. Don't be a tough guy. Don't let yourself suffer.
(from a Lung Cancer Living Room session with Dr. Geoff Oxnard)

Good luck ss,
Jazz

Reply # - November 6, 2013, 09:48 PM

Jazz
Posts: 279

ss,
I forgot to mention that Clovis requires a fresh biopsy - within 28 days of dosing. This might change your timing decision as to when to get the biopsy, and whether you want to have Kaiser or Clovis do it. Whatever decision you make, don't allow yourself to get too debilitated. You have to have good performance status to be accepted to a trial.

While I'm in alot of pain, I'm not coughing and can walk 4 miles at a moderate pace. Don't ask me how that can be, but you have to appear to have a life expectancy of 3 months. It's exasperating though, because I get the feeling I get pushed down the waiting list in favor of others who "need" the trial faster than I do.

Be well,
Jazz

Reply # - November 7, 2013, 09:22 AM

catdander
Posts:

Jazz and ssflxl you are both a wealth of information and I'm delighted you're discussions are on Grace. You know how helpful it will be to others. Jazz, I've pasted a link to your thread on desensitization. You can always find the threads you start on your forum profile page. Just click on your avatar. http://cancergrace.org/topic/taxane-desensitization-protocol-any-experi…

My husband's onc didn't want to use a port at the beginning of chemo because it can cause infection and there wasn't really a need at the time. When he moved to carbo/navelbine the onc suggested using a port but my husband refused it. It's difficult to say where his issues with his arms come from, probably the host of assaults to it but he went on to have another 2 years worth on IV chemo, gemzar afterward. D didn't want reminders of chemo, i.e., the port.

Dr. Spigel, a highly regarded research lung cancer specialist suggested retrying alimta as being a good alternitive. In response to a situation very similar to yours he wrote, "The thought on returning to Alimta is a good one – considering there was a prolonged benefit and it’s been over 3 years since then.
"Ideally a clinical trial is the next best step – antiPD1/PDL1, an antibody-drug conjugate, or HSP90 inhibitor-bsed combination are all reasonable next steps. If available, I’d sequence beyond EGFR and HER2 – looking for another potential target – assuming that there are phase I trial opportunities he could pursue. If not, then Alimta is a very reasonable next step." http://cancergrace.org/topic/best-next-step-for-her2-mut-met-nsclc-afte…
Perhaps his thoughts would have some pull with your onc?

Always hopes for a better best for you 2 fab trial women,
Janine

Reply # - November 7, 2013, 10:30 AM

ssflxl
Posts: 204

Jazz,

thanks for the info about biopsy timing. I am trying to see if I can get 1 biopsy tested for both T790M and PD receptor. the problem is that Kaiser will do the T790M, but of course, only Genentech will do PD testing. it is tricky to try both at the same time - there has to be a lot of coordination.
I spoke with the coordinator for The Stanford Phase 1 trial for MPD (Study of the Safety and Pharmacokinetics of MPDL3280A Administered Intravenously As a Single Agent to Patients With Locally Advanced or Metastatic Solid Tumors or Hematologic Malignancies). she said they are looking for small cell lung ca patients or someone with mets outside the lung that can be biopsied. she also revealed that they will be starting a anti-PD 1 trial soon. MPDL 3280A is anti-PDL 1 so the coming one will be anti-PD 1.
Anyway, if I have to wait until Jan, then I will prob need bridging with chemo - perhaps alimta. I don't have much cough or sob, but just arm pain and tingling from nerve impingement from the growing tumor. it feels like a bad toothache
Let's hope everything works out for us.

ssflxl

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