Mets Day 524: Dose Dense MVAC Q&A

In the past few days I have exchanged a number of emails with Drs. Apolo and Aragon-Ching, and this morning I had a follow-up phone 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 was going to have my cancer sequenced.  Could that data provide any insight into whether dose dense MVAC (or perhaps a future clinical trial) might be appropriate for me?
 Aragon-Ching Answer 1:   I would defer to Dr. Apolo.

Aragon-Ching Question 2:  You told me that you could not identify any data comparing median overall survival of patients with mets BC who do not have dose dense chemo to those who do.  Where could I find data on those who do not have any treatment?
Aragon-Ching Answer 2:  One phase III trial comparing a salvage chemotherapy drug called vinflunine (not approved in the US, this was mainly a European trial) was compared to what we call best supportive care (no chemo) and the median overall survival was a little over 4 months (link here)

Aragon-Ching Question 3:  The PET scan showed there was questionable focal uptake in the right medial hepatic lobe.  Does the possibility of metastatic activity in the liver support going forward with dose dense chemo, or is it irrelevant because it is indeterminate?   
Aragon-Ching Answer 3:  The presence of known visceral disease is an adverse prognostic factor, compared to just adenopathy alone ... it would support treatment with chemotherapy.

Aragon-Ching Question 4:  The 2001 study that you gave me (http://www.ncbi.nlm.nih.gov/pubmed/11352955) paradoxically showed that patients receiving dose dense MVAC had a somewhat higher response rate (62% to 50%) and two year survival rate (35% vs. 25%) than patients receiving regular MVAC, but that there was no statistical difference in either the overall survival rate, or time to progression of further metastases.  I'm having a hard time understanding these data.  Can you shed some insight on it?  Also, that study was of patients who had not previously received platinum-based therapy, so it seems less applicable to me.  Am I misreading it?
Aragon-Ching Answer 4:  You are absolutely right in reading this...this was a neoadjuvant trial in patients never been treated with chemo (so this is not technically applicable to you) but I wanted to give you an idea of what the regimen contained & its schedule (dose dense) and it was being compared to the standard dose MVAC.  Having said this, patients who undergo dose dense MVAC who have been previously treated may in fact develop more toxicities than what this paper is discussing.

Aragon-Ching Question 5:  The 2012 study (http://www.ncbi.nlm.nih.gov/pubmed/22364733) found there was a 61% response rate, with 10% having a complete response.  Digging deeper into the data, it appears that the positive rates are skewed by the inclusion of patients who did not have distant metastatic disease: three of the four patients who had a complete response did not have metastatic disease.  For those with distant metastases, the median time to progression was 4.4 months, and median overall survival was 5.7 months.  These don't sound very encouraging to me.  Am I missing something? 
Aragon-Ching Answer 5:  This trial included all patients with metastatic sites of disease but made no distinction whether they were distant sites or not.

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


Apolo Question 1:  Dr. Aragon-Ching said that, if I was to proceed with dose dense MVAC, it could disqualify me from later clinical trials.  You and I had discussed several possible trials; would any of those be closed off if I proceeded?
 Apolo Answer 1:  You would still be eligible for my clinical trials if you have proceed with MVAC.

Apolo Question 2:  Even if those trial were foreclosed to me, would you still recommend my proceeding with dose dense MVAC?
 Apolo Answer 2:   Yes, but they are not

Apolo Question 3: You said that you were going to have my cancer sequenced.  Has that happened yet, and if so, does that data provide any insights of what kind of therapy or trial might be the most appropriate for me?
Apolo Answer 3:  I will follow up on the sequencing on Thursday when I meet with our pathologist. This may make a differences what you receive after chemo but the panel is only 50 genes, so the findings are limited.  Foundation medicine has a panel with 200 genes and I think insurance
covers this. I am not sure if I can send this out from the NCI because we don’t deal with insurance but maybe Dr. Aragon-Ching can, I will ask her.

Apolo Question 4:  Can you point me to data showing median overall survival of patients with mets BC who do not have dose dense chemo?
Apolo Answer 4:  I have attached some pivotal papers on first line chemotherapy for metastatic disease. Including the phase 3 of (gemcitabine and cisplatin) GC vs MVAC (link here) and the PCG (paclitaxel/gem/cis) vs GC (link here). I have also including a retrospective report from France on patients that received ddMVAC after GC (link here).

Apolo Question 5:  The PET scan showed there was questionable focal uptake in the right medial hepatic lobe.  Does the possibility of metastatic activity in the liver support going forward with dose dense chemo, or is it irrelevant because it is indeterminate?
Apolo Answer 5:  If you do have disease in the liver then ddMVAC would not be the best choice of therapy because my goal is to have you achieve a complete response (CR) with the ddMVAC. The chances that you achieve a CR are highest with lymph node disease and low with liver disease. Chemotherapy in your setting is given for palliation but you don’t have symptoms, this is Dr. Plimack's reservation. My goal is to a achieve a CR which is generally achieved in 5% of patients with GC and 20% with ddMVAC when it is given as the first chemotherapy to patients with metastatic disease. You would be given ddMVAC as your second chemotherapy BUT first in the metastatic setting. The French studied showed a CR rate of 10% with ddMVAC (in your setting). Patients that achieve a complete response have longer survivals. That being said ddMVAC has a lot of side effects and is hard to get through.  I highly respect Dr. Steinberg but he is a urologist not a medical oncologist. I consulted your case with Dr. Cora Sternberg the oncologist who developed ddMVAC (I attached her original publication from 2001) (link here) and she completely agrees with me.

 Apolo Question 6.  Your email notes that ddMVAC would not be the best choice if I have liver disease.  Given the ambiguous results from the PET scan, does it make sense to try to rule that out before embarking on ddMVAC?  How would I go about doing that?
Apolo Answer 6:  The PET scan is inconclusive.  It's very had to tell from a PET scan whether there is metastatic activity in the liver, because the entire liver is hot.  We use CT scans to tell whether there is node enlargement or tumors in the liver.  The PET scan suggests that, if there was metastatic activity in your liver, it is not in the lymph nodes, but within your liver.  If a subsequent CT scan showed a tumor in the liver, then you should not proceed with ddMVAC, or you should stop it if it was started. 

Apolo Question 7:  Thank you for consulting with Dr. Cora Sternberg, who developed the 2001 study.  As I read it, that study has a paradox.  On the one hand, it showed that patients receiving ddMVAC had a somewhat higher response rate (62% to 50%) and two year survival rate (35% vs. 25%) than patients receiving regular MVAC, but on the other hand, it showed that there was no statistically significant difference in either the overall survival rate, or time to progression of further metastases.  I'm having a hard time reconciling these data, especially as they may apply to my situation.  Does this suggest that there is a better chance that ddMVAC may provide a complete response (CR) or partial response (PR) while I have the chemo, but once the distant tumors develop, the disease moves faster, so my OS will be similar?  Also, that study was of patients who had not previously received platinum-based therapy; as we know, I failed GemCis, so I'm wondering how applicable that data is to me.
Apolo Answer 7:  The study does have that paradox, and we struggle with the data.  The studies suggest that the rates of CR are significantly higher with ddMVAC than with regular MVAC or GC chemo, especially perioperatively.  These data support ddMVAC as a second line therapy.  There has never been a phase III clinical trial comparing GC to ddMVAC.  We are starting that now.  The data suggest that median progression-free survival for ddMVAC is 9.1 months, with regular MVAC it is 8.2 months, with GC it is 7.4 months, and with no therapy, about 5.5 months.  Extrapolating from the studies, ddMVAC gives you your best chance of CR or PR.
   
Apolo Question 8:  The 2012 French retrospective study appears to divide patients into two groups:  adjuvant chemo and metastatic disease.  While it found there was a 61% response rate with ddMVAC, with 10% having a complete response, it appears that the best results were obtained by patients who had adjuvant chemo but did not did not have distant metastatic disease. For those with distant metastases, the median time to progression was 4.4 months, and median overall survival was 5.7 months.  Am I correct to put myself into the mets group, and anticipate a lower likelihood of CR or PR?
Apolo Answer 8:  You are between the two groups.  You had positive nodes after your surgery, but it has not spread systemically, and you had no distant tumors.  Looking at your cancer from the lymph node that we biopsied under the microscope, it was poorly differentiated, and very aggressive.  It did not have many of the characteristics of micropappillary bladder cancer.  Instead, it looked like a tumor that will grow quickly.  It does not look like a cancer that will be indolent, meaning that it will grow slowly.  

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

Apolo Question 10:  Boiling everything down, I'm trying to decide whether 3 months of
feeling lousy while having ddMVAC is going to be worth it.  If it adds 3 months of life to the back end, but I lose three months while going through the chemo, then it seems to be a wash, and probably not worth it.  If there is a reasonable prospect of getting a complete response and substantially adding more time, then it becomes more attractive. But if it's going to permanently weaken my immune system and compromise my remaining time with little likelihood of success, then I'd rather not do it.  Do you agree with how I've boiled it down?
Apolo Answer 10:  It's a fair way of looking at it.  You may get 3 months or more on the back end, or you may not.  Don't pay too much attention to the French retrospective study on toxicities, because we have learned so much on how to minimize the toxicities.  I give 3 liters of hydration with the MVAC, so it can take up to 9 hours to receive the full chemo dose -- 6 hours for hydration, 3 hours for the drugs.  I usually keep patients overnight unless they live very close by.  Many of my patients tolerate ddMVAC very well.  Most recently, I gave 5 rounds of ddMVAC to a nurse who works at the NCI hospital.  She kept working while having each round, except for round 5, when she developed mouth sores and could not eat.  Another recent patient lived on a farm and continued to work as a farmer while having the chemo.  Each patient is different.  The most common side effects are mouth sores, fatigue, and fever.  You are relatively young and otherwise healthy, so you should be able to tolerate the ddMVAC well. 

Apolo Question 11:  I understand that, on balance, you believe that the pros substantially outweigh the cons, that I'll get through ddMVAC, and have a fair chance at either CR or PR for some period of time.  I'm unclear from the literature how long the CR or PR typically lasts.  It appears that, for some, it's just while the chemo is being administered, and once it stops, the disease comes back like gangbusters.  For a minority of other patients, it appears that the response extends beyond the period of treatment.  Is it fair to say that, in my case, there is no way of knowing whether I'll have any favorable response, but that you believe that having ddMVAC is the best way to extend my life while still maintaining a decent quality of life?
Apolo Answer 11:  I would suggest proceeding with ddMVAC with Dr. Aragon-Ching. You do
not need to get restaged with Dr. Plimack, I can do it or Dr. Aragon-Ching can do it. Treating you with ddMVAC is the most aggressive option.  If it were me in you shoes, I'd do ddMVAC.  If you decide not proceed with the chemotherapy that's OK too, it really it is a personal choice.

Mets Day 522: My GW Oncologist says do ddMVAC chemo

This morning Jennifer and I met with Dr. Aragon-Ching, my clinical oncologist who supervised my GemCis chemotherapy between January and April 2012.  She had received all of the information regarding last month's CT scan from Fox Chase, and my PET scan and biopsy from NIH.  She also had exchanged a series of emails regarding my treatment with Dr. Apolo (NIH), Dr. Plimack (Fox Chase), and Dr. Steinberg (U. Chicago).  She also had a telephone conference with Dr. Apolo, and had collected the input from the other three doctors.

Dr. Aragon-Ching reviewed what we already knew:  my neoadjuvant GemCis chemo had failed; I had pathologically confirmed metastatic activity as of May 2, 2012; it had taken 15 months for a scan to detect distant metastatic activity, which had been proven by my biopsy.  However, because the node was not larger than 1.5 cm on its short axis, I did not currently have "clinically significant" distant metastatic activity that would qualify me for most clinical trials.  She noted that, the early detection and confirmation of my distant metastatic activity was because I had been so proactive in my treatment.

At this stage, the question is whether to have any clinical therapy.  Dr. Aragon-Ching reiterated what I already knew:  there is no known way to cure metastatic bladder cancer.  Unlike some other cancers, such as breast cancer or lymphoma, there is no evidence that any therapy can put mets BC into remission.  Thus, any treatment for mets BC cannot be considered curative, but palliative (e.g., relieving or soothing the symptoms of the cancer without effecting a cure).  The issue is whether the benefits of the proposed therapy are worth the risks.

She noted that, at this point, because I do not have sufficiently large metastatic nodes, or distant solid tumors, the choices boiled down to either having "second line" chemotherapy, or doing nothing for now.  Second line chemo refers to a second attempt at a different chemo regimen after the preferred chemo was tried and failed.  It also is called salvage chemotherapy.  In her opinion, if I was going to have any therapy at this point, the most logical choice was dose dense MVAC.  This is a four drug chemo that is given every two weeks, with fewer dose delays and less toxicity.  The "M" drug (methotrexate) is given on Monday, the "VAC" drugs (vinblastine, doxorubicin, and cisplatin) on Tuesday, on Wednesday I'd get a Neulastia shot (a growth hormone), then I'd have 10 days to recover before I do it again.  If I was to do this, she'd recommend starting with 6 cycles over 12 weeks, and see how I'd tolerate it.

She said that the arguments for proceeding with dose dense MVAC chemo at this point were as follows: 1) there was some evidence that dose dense MVAC had a positive effect on patients who previously had failed GemCis chemo; 2) my distant mets cancer was small, and my cancer burden low, making it more likely that it might respond to chemo than later, when my cancer burden was greater; 3) I was relatively strong, had no other co-morbidities, and should be able to tolerate the chemo. She readily acknowledged that there was no established evidence that dose dense MVAC would work in my circumstances, and said that she was making her recommendation based upon her personal philosophy and experience.  She also said that Dr. Apolo had come down on the side of proceeding with dose dense MVAC, although her recommendation was a soft "yes", not an emphatic one.  Dr. Aragon-Ching likewise said that her own recommendation was as a result of weighing the totality of the circumstances. I was reminded of my legal practice and burdens of proof, and got the impression that, for her, having me proceed with chemo passed the preponderance of the evidence standard, but probably didn't meet the clear and convincing evidence, and certainly didn't meet the beyond a reasonable doubt standard. 

Knowing that I liked to dig into the literature, Dr. Aragon-Ching gave me two articles to review about dose dense MVAC.  The first article, titled Randomized phase III trial of high-dose-intensity methotrexate, vinblastine, doxorubicin, and cisplatin (MVAC) chemotherapy and recombinant human granulocyte colony-stimulating factor versus classic MVAC in advanced urothelial tract tumors: European Organization for Research and Treatment of Cancer Protocol no. 30924, is the first major study that compared regular MVAC to dose dense MVAC.  It's a European study published in 2001 in the Journal of Clinical Oncology.  The study paradoxically showed that patients receiving dose dense MVAC had a somewhat higher response rate (62% to 50%) and two year survival rate (35% vs. 25%) than patients receiving regular MVAC, but curiously, there was no statistical difference in either the overall survival rate, or time to progression of further metastases.  The study extrapolated that patients receiving does dense MVAC were 25% less likely to relapse or die than MVAC patients.

The second study a 2012 retrospective study published in the European Journal of Cancer titled Accelerated MVAC chemotherapy in patients with advanced bladder cancer previously treated with a platinum-gemcitabine regimen.  It looked at records of 45 patients who had received dose dense MVAC.  It found there was a 61% response rate, with 10% having a complete response, but also showing that 69% of patients had severe toxicities, and 10% died because of the chemotherapy.  Digging deeper into the data, it appears that the positive rates are skewed by the inclusion of patients who did not have distant metastatic disease: three of the four patients who had a complete response did not have metastatic disease.  For those with distant median time to progression was 4.4 months, and median overall survival was 5.7 months.  Ugh.

To her immense credit, Dr. Aragon-Ching explained that proceeding with dose dense MVAC at this point was an aggressive treatment, and that waiting was the most conservative option.  The arguments for waiting, she said, were that 1) my disease had progressed relatively slowly (15 months from local mets to distant mets), and that it might continue to progress slowly; 2) there was no established proof that any second-line chemo would either cure, or delay, the progression of the cancer; 3) the side effects and risks of the chemo were high; and 4) proceeding with a second chemo regimen might later disqualify me from clinical trials.  She said that Dr. Plimack and Dr. Steinberg both had recommended holding off on chemo.  

Dr. Aragon-Ching addressed each of those arguments during our discussion.  She said that the slow progression of the disease cut both ways, noting her comments re relative cancer burden.  On the no established proof, she said that the best data she had was from the two studies that she gave me, and her own personal bias and experience.  On the side effects, she was confident that they could be managed and tolerated.  On the possible disqualification of clinical trials, she said that should not be a deciding factor, since clinical trials wee more for the research than actually helping the patient.

I asked her of the overall survival for patients receiving dose dense MVAC vs. no treatment.  She said that there never had been a Phase III clinical trial comparing the two, and could not give that data.  I also noted that we had a new baby in he house, and whether either her or I would be at increased risk because of the chemo.  She said that there was no risk for the baby, but since they could be little germ magnets, when I was doing chemo, I should want to stay clear of the baby if she was sick.

So the bidding stands at two doctors for dose dense MVAC, and two doctors against.  I told Dr. Aragon-Ching that I wanted to review the literature, and go forward with my appointment at Fox Chase on October 1.  She understood my caution and supported my decision to have the next scan.  She said she would confirm that my insurance would pay for the dose dense MVAC, but would not schedule me for treatment until I gave the go ahead.

When I came home, I discussed these conflicting recommendations with my daughter, a fourth-year medical school student.  She came up with the following questions:  1) Are there any data comparing the median overall survival rates of those receiving dose dense MVAC vs. no treatment?  2)  Could NIH's DNA sequencing of my cancer give any insights regarding potential treatment options?  For example, if the sequencing suggests that certain treatments of clinical trials might be beneficial, does it make sense to go ahead with dose dense MVAC if that might later preclude participation in those trials?  Good questions; I'll follow up.  I'm also going to do some more reading and see what else I can find.

I'm not going to make a decision until after I meet with Dr. Plimack on October 1.  For now, I'm not persuaded that dose dense chemo will provide a greater benefit.  If it buys me three more months at the back end, but causes me to be sick for three more months now, is that worth it?  Probably not. 

Mets Day 520 - Officially a Grandpa

Yesterday afternoon my 25 year old daughter, Chelsea, gave birth to her first child, and my first grandchild.  My granddaughter is has a big head (of course), a strong cry, and a piercing stare.  All is well with everyone involved. 

Chelsea and I had agreed that during the actual delivery, only the doctor, her husband, and Jennifer should be present.  I sat in the room but on on the other side of curtain, and listened, as the doctor was giving instructions, Jennifer was counting, Josh was reassuring his wife, and Chelsea was alternating between pushing and catching her breath.  I had a quiet conversation with God as this went on for about an hour.  I realized that, in many ways, the curtain was like a veil separating me from my family.  I could sense their presence, send my prayers and light and love to my daughter, and experience the event, but I was not physically present.

Death will be like this, I believe.  My soul, and all that I am, will continue on.  I will not be physically present, but still will be in their presence, will be able to send my prayers and light and love to my family, and experience their joy and sorrows.  As Sullivan Ballou wrote to his wife the week before he died in the first battle of Bull Run, "I shall always be near you; in the gladdest days and in the darkest nights . . . always, always, and if there be a soft breeze upon your cheek, it shall be my breath, as the cool air fans your throbbing temple, it shall be my spirit passing by. [D]o not mourn me dead; think I am gone and wait for thee, for we shall meet again."

Holding my granddaughter, I felt great joy and rejoicing in my posterity.  The next generation of my family has started.  Life continues on. 

Mets Day 517: My Fox Chase oncologist says don't do ddMVAC chemo

Dr. Plimack, the oncologist from Fox Chase who has been running my post-RC scans, called me this morning.  I'd emailed her on Monday night, after I spoke with Dr. Apolo, updating her on the PET and biopsy results, and asked for her opinion on whether I should get chemo or some other treatment, or do nothing.

She told me that it was unusual to have a single positive node that was so high in my chest, and so small.  She said that having whole-body chemo was probably not a good idea, for three reasons:  1) Platinium based chemo did not work for me before, so there is little reason to think it would work again.  2) There is very little evidence that adjuvant chemo helps extend life for those with mets BC, and in the meantime, it can make the days that remain more miserable.  In other words, she doesn't think that chemo will cure me of mets BC, and probably won't slow the progression either.  3) My progression to distant mets has been relatively slow -- 16 months since the nodes outside my bladder were detected by CT scan, and 15 months since my RC.  That suggests that maybe my additional mets progression may not be that fast.  She also said that the micropapillary bladder cancer that I have does not necessarily progress faster once it's mets -- it's just the most aggressive to gt out of the bladder, since it thrives on bladder muscle tissue.  Once it's out, micropap mets patients don't die any faster than normal mets BC patients.  This was news to me. 

Dr. Plimack said that the decision of whether to have adjuvant chemo is very much an art, and not a science.  It varies with each patient, and often with each doctor.  Dr. Plimack's philosophy is to not do chemotherapy prophylactically, and in the absence of good evidence to do something, don't do it.

She said that dose dense MVAC is very hard on the system.  She's never had patients tolerate more than 12 does.  I don't want to be sick as a dog with a hard type of chemo if there is little evidence that it works.  She said that triple chemo with a taxene can be tolerated longer, perhaps as much as a year, but the evidence for that is limited.

We also talked about clinical trials.  She said that clinical trials require a measurable disease (e.g., a node with a short axis of 1.5 cm or larger), so they can measure whether the experiment worked.  Makes sense:  with no cheese, no one knows why the mouse wandered through the maze.  She suggested that we continue with the scans and see if more nodes are enlarged.  We wouldn't need another biopsy, because we already know I've got systemic cancer in my lymphatic system.

She suggested that I read up about MK-3475, an experimental anti-PD1 antibody that Merck is researching.  It's also called lambrolizumab. According to this article on Cancer Commons, the drug blocks activity of the programmed death 1 (PD-1) molecule, an immune checkpoint receptor found on a type of white blood cell called a ‘T cell.’ T cells fight infections in our bodies and also facilitate the body’s attack on tumors.  The PD-1 molecule on T cells interacts with another molecule, the programmed death 1 ligand (PD-L1) that fits with PD-1 like a lock and key. This interaction helps to modulate the immune response of T cells to various stimuli, including infections. PD-L1 is found on cells throughout the body, but tumor cells can also express PD-L1, resulting in a dampened response of the immune system to the tumor. Anti-PD1 antibodies block the interaction between PD1 and PD-L1 to boost T-cell activity in response to tumors.

MK-3475 has shown promising activity in other types of cancers, especially melanoma.  Here is a link to a clinical trial that is testing MK-3475 in patients with progressive locally advanced or metastatic carcinoma of any type. Dr. Plimack said that the drug is given by IV every two weeks.  Preliminary studies have shown that some patients have tumor shrinkage that may be sustained even after the trial treatment ends.

As I type this, I am mentally rolling my eyes at all of the clinical trial choices.  Bladder cancer has been studied for so many years, with so little success.  There hasn't been a new drug approved for bladder cancer in over 20 years.  It's such a complex beast, and so unlike the more straightforward cancers like breast or prostate cancer.  Maybe one of these clinical trials might be the magic bullet for bladder cancer, but it's highly unlikely.  I'll probably participate in one or more trials, but I'm not holding my breath.  I doubt if I'll find cheese at the end of my maze. 

Mets Day 515: biopsy positive for distant mets

Dr. Apolo just called a few minutes ago to tell me that the pathology from last Thursday's biopsy was positive for metastatic bladder cancer.  Not unexpected, but the news still sucks.  

We talked for while about my treatment options.  She said that the mets was unresectable, meaning that it can't be removed, and likely will show up in additional lymph nodes as time goes on.  Humans have 500-600 lymph nodes, and they can't all be removed.  

She is going to have my cancer sequenced in their DNA machine, and that might give her some additional insights into how many genetic abnormalities there are in my cancer.  (BC usually has a lot.)  

We talked about clinical trials.  She said that, until the short axis of a lymph node could be measured to be over 1.5 cm in size, I would not be eligible for the clinical trials that she would most inclined to recommend.  One of these trials is a study of Cabozanitinib (XL184), and consists of me taking a pill with an experimental compound so see if it inhibits the cancer blood supply.  The trial is not currently recruiting patients, but she'd be able to slip me into it.  Another trial uses AdHER2/neu dendritic cell vaccine, which is a custom-made experimental vaccine using the patient's own immune cells. 

She also recommended that I consult with my clinical oncologist re chemo options.  I asked Dr. Apolo for her thoughts of whether to proceed which adjuvant chemo at this point, and she said that, while it's a difficult decision, she'd lean towards doing it.  She said that she would not recommend re-doing GemCis, but would consider other regimens.  I didn't catch all of the details, but one was dose-dense MVAC, which is MVAC but given the non-traditional way (every 2 weeks with growth factor support) which is better tolerated and has a higher complete response rate over MVAC.  Another chemo option is triplet chemo, perhaps with a taxene. I've emailed Dr. Aragon-Ching to request an appointment, and she promptly responded with my seeing her on Monday, Sept. 16.  

Dr. Apolo also said that I should continue going to Fox Chase Cancer Center for the CT scans, and should ask Dr. Plimack of her recommendations.  My next scan is October 1.  The three of them will put their heads together and see what vile concoction they can brew.  Double, double, toil and trouble . . . .

I asked Dr. Apolo about the median data for formation of solid secondary tumors and morbidity.  While cautioning me that statistics are not a predictor of what will happen to me, and that her information was only the mid-point for patients with advanced bladder cancer, she said that, of patients who received treatment, the average time for the formation of solid secondary tumors was 7 months, and the average time until death was 14 months.  Patients who do not get treatment have shorter median times.  

I also asked about the actual causes of death.  I had assumed that it was organ failure.  Dr. Apolo said that was not the case.  Instead, the spreading cancer releases various types of toxins that cause fatigue, loss of appetite, lack of motion, which in turn leads to further complications, increasingly poor performance, and eventually death.  Various types of blockages can also occur.  

Looks like 2014 is not going to be easy. 

Mets Day 512: Advice to fellow BC warriors

From time to time other people with bladder cancer will stumble across my blog and reach out to me, and we will engage in an email correspondence sharing thoughts about our common disease, and treatment options.  One example is a firefighter from North Carolina who was diagnosed with micropapillary bladder cancer.  A CT scan showed positive nodes outside of his bladder.  He went forward with a radical cystectomy

Yesterday he emailed me the following:

I have been following your blog. I read today's post and sounds like they are treating you well up there in Maryland.  Help me out here. I am 30 days post RC. Remember my DX was Micro 9 positive nodes, a lot like you. Met with Onco today, he says DDMVAC, he want to start after a CT In 3 weeks.  I am still over 20 lbs light, weighing in at a whopping 132. Can you imagine what I will look like after the treatments? My wife and I cannot see things worse than they are right now.  Maybe the CT will be useful but I am undecided as of yet on the chemo. The doc danced around every one of my percentage question, unable to get any real stat's.from him at all.  Speaks loudly to me that not much chance of a benefit. 

I responded with the following, which I am posting here because it may be of interest to other BC warriors:

The best thing that I could recommend is that you get a second opinion from a major cancer center.  See this link: http://cancerguide.org/second_opinion.html.  Cleveland Clinic has an on-line consultation option; Hopkins also has a second opinion offering that may not require travel.  MD Anderson wants you to travel to Houston.  I'm not sure about Sloan-Kettering in NY.  Oncologists at a major cancer center should be able to answer all of your questions.

Here is a list of great questions to ask your doctor, especially under section III.  http://blcwebcafe.org/content/view/101/111/lang,english/. Print them out and insist on answers.  Note than no doctor can say exactly what will happen to you, and most hate giving odds, but they should be able to tell you what the studies have shown.

Here is a good article about chemo options: http://blcwebcafe.org/content/view/116/126/lang,english/.  MVAC was the standard of care until around 2005.  Since then, many doctors have switched to platinum-based chemo, such as cisplatin.   A 2011 review article (available at http://www.ncbi.nlm.nih.gov/pubmed/22117153) says that "The first-line therapy is cisplatin-based chemotherapy with the response rate approximately 50%. Approximately 30-50% of the patients are unsuitable for cisplatin, and there is no standard of care for this patient population. There is no standard second-line treatment."  Are you a patient who is "unsuitable for cisplatin"?  If so, why?  MVAC is an older chemo regimen with more side effects than cisplatin.  Cisplatin is generally considered a better substitute than MVAC.

I think that this article at the Bladder Cancer WebCafe on metastatic cancer is very helpful:  http://blcwebcafe.org/metatcc.asp.  Note that this article is discussing secondary tumors, which you don't have (it's what I'm dealing with right now).

There is no established chemo regimen for patients like you (or me) who had positive nodes and are post-RC.  In other words, studies measuring whether or not adjuvant chemo helps have not shown a clear benefit. Maybe it works, maybe it doesn't.  Since I had failed my ne-adjuvant chemo, my docs didn't see a point to trying adjuvant chemo before I had any secondary metastases.  I don't remember if you already had neoadjuvant chemo - if you did, I would not be inclined to do adjuvant chemo.  If you didn't, then maybe it might be right.  That's got to be a decision between you and your docs.  Get a second opinion, ask lots of questions, then trust your gut.

You should start gaining weight in about 2 weeks (6 weeks post-RC). Your appetite should be coming back around now.  Take things one day at a time.  Remember that, until (and unless) your BC travels though your lymphatic system, latches onto another place, and starts growing, it's not going to hurt you.  That might happen in 6 months, it might happen in 15 months (like me), or it might never happen (about 12% of the time).  Enjoy each day that you have.

Metastatic bladder cancer is a strange and ferocious disease.  There is no proven treatment, and no cure.  Because there is little chance of a physical cure, the primary battle becomes psychological:  How will a BC warrior with mets choose to live?  What are your motivations?  What do you hope to accomplish?  Will you turn inward, withdraw, and give up?  Will you turn outward and seek to help others?  Will you make any changes? 

Mets Day 511: Biopsy at NIH

Jennifer and I arrived at NIH at 6:45 am.  NIH security procedures require each guest to exit the car while it is hand searched and screened for explosives.  Each person must pass through a metal detector, then your license is scanned and an NIH guest ID created.  Only then can you proceed to the parking area.  It usually takes about 15 minutes.  We got up to phlebotomy a bit after 7 am, where I gave 8 vials of blood.  We then went on to Interventional Radiology, where we waited.  At 8:05 am, Chelsea telephoned to say that she thought that her water had broken and was going to the hospital to be checked out.  I wished her good luck and asked that she let us know what was going on.

As soon as I got off the phone with Chelsea, we were called back.  We met Dr. Chang, the senior IR at NIH, who told us that he had consulted with Dr. Apolo and Dr. Wood, and that he would be doing the biopsy.  We were surprised, since we thought Dr. Wood was going to do the procedure.  Dr. Chang assured us that he ready to do it.  He called up the images from the CT and PET scans, and started muttering about how small the node was.  Jennifer and I kept looking at each other with worried expressions.  After a few minutes of muttering, Dr. Chang stood up and said “let’s go” and walked down the hall.  The nurse had me take off my shirt and put on a gown, and I blew a kiss to Jennifer and I walked into the OR.

 The nurse accessed my port, started a saline drip, then put on a nasal O2 line.  Meanwhile, Dr. Change was pressing an ultrasound unit against the left side of my neck and top of my chest, searching for the best way to access the enlarged node.  After a few moments, he was satisfied, and nodded to the nurse to add some sedative to my IV.  I remained conscious throughout the procedure, but felt no pain.  I listened as Dr. Chang first took a fine needle aspiration biopsy, then took three core needle samples.  There was a loud snap each time he cut a section of the node.  I was on the table for less than an hour.  

I was wheeled to the day hospital to be monitored for a couple of hours to make sure everything was ok, including eating and drinking.  I ordered breakfast, and the omelet was a great example of bad hospital food.  Jennifer shivered under an A/C vent until a nurse brought her a heated blanket, and we took turns dozing and texting Chelsea.  While her ultrasound showed a marked decrease in amniotic fluid, she was not leaking on an ongoing basis, and was showing no signs of being in labor. 

I was sent home after a couple of hours, as was Chelsea.  I won’t get the results of the biopsy until sometime next week.  I might become a grandpa first, which is fine with me.  The links of my family chain continue to be forged, and I can have joy in my posterity.