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.