Today I had a follow-up appointment with Dr. Apolo and a half-dozen others. Apparently my reputation precedes me: as I was giving my history to the fellow who was doing the workup, he mentioned that he was aware of my blog. Maybe it was in my chart, or maybe they've been told to be careful what they say, because it might be published online. The fellow carefully questioned me about my emotional state, trying to find out if I was depressed or sad or angry. He said that 80% of mets cancer patients displayed symptoms of depression. He didn't believe me when I said I wasn't depressed, which made me sad.
Eventually he left and came back with Dr. Apolo and her supporting cast, which included two other NIH doctors, the fellow, a medical student, and a doctor from the FDA who was reviewing proposed clinical trials for mets bladder cancer. Dr. Apolo said that my labs looked fine, and the Lovenox levels were good. She strongly encouraged me to stay on Lovenox for 3-6 months, noting that I had quite a few clots and a rather large and long clot in my hepatic portal vein. We agreed that I'd continue with the twice daily injections until at least Nov. 18, when I am scheduled to have another CT scan, and we'd see how things look then. She had the fellow order me another 21 days worth of Lovenox, which would give me a total of 7 weeks. After admiring my massively bruised love handles, she said that I could also inject the front of my belly (something the NIH nurse said last week that I shouldn't do), and could also give injections into my thighs and arms if I wanted. She also said to avoid contact sports, so I guess that rules out the annual Turkey Bowl football game.
Dr. Apolo said that she had carefully measured my nodes, compared them with the prior scans, and had concluded that me nodes were neither growing nor shrinking, but were stable in size. She also said that the two largest nodes were adjacent to each other, but were sufficiently distinct so that she could not combine them for purposes of clinical trial eligibility. She drew a picture of the two nodes, and explained that they were arranged like a comma, one above and slightly offset from the other. She also said that the scan had picked up a number of other lymph nodes around my left clavicle and upper torso, but none were enlarged enough to be of any clinical significance.
Thus puts me back into the same situation I've been in since I ended my chemotherapy: watchful waiting. We all agreed that the best case scenario would be that my nodes never increased in size enough to pass the threshold for entry into a clinical trial, but if and when that happened, we'd deal with it at that time.
Speaking of clinical trials, I told the FDA doctor that I'd really like to see a new drug approved for use on metastatic bladder cancer, since it had been more than 20 years since the last drug had been approved. He was well aware of that fact, and said that the FDA was fast-tracking investigations into the PD1 and PD-L1 drugs. Dr. Apolo seemed to appreciate my blatant lobbying, but then again, I have a vested interest.
Tuesday, October 14, 2014
Monday, October 13, 2014
Mets Day 915: Consultation with my clinical oncologist
Today I met with my clinical oncologist, Dr. Aragon-Ching of GW's Medical Faculty Associates. She and I had traded emails and spoken by phone last week. The purpose of today's meeting was to further discuss whether I should stay on Lovenox long-term, or eventually switch over to an oral anticoagulant. I also wanted to get her thoughts on my clinical trial options.
Prior to my meeting with her, I did some research on whether Lovenox can help suppress growth of my cancer. Along the way, I got an education on the use of low molecular weight heparins (LMWHs) to combat venous thromboembolism (VTE). VTE includes deep vein thrombosis (DVT) and pulmonary embolism (PE). Patients with cancer -- especially metastatic cancer, and who have had chemotherapy -- are at increased risk for VTE. A good overview of VTE, and the emerging use of oral anticoagulants, is available here.
The question I was looking into is whether LMWHs such as Lovenox can help inhibit the growth of my metastatic bladder cancer. Lovenox is an injected form of LMWH, with the generic name of enoxaparin sodium. I'm currently injecting myself with 120 mg of Lovenox twice a day. If there is evidence that enoxaparin can help slow the spread of my cancer, then I'm willing to continue with the shots. If not, I'd prefer switching to rivaroxaban (Xaralto).
In the 2009 book, Coagulation and Cancer, by G.F. Pineo and R.D. Hall, the authors write, "Some LMWH compounds were effective in the suppression of tumor cell growth, metastases (nandroparin, tinzaparin, enoxoparin), and antiogenesis (tinzaparin, dalteparin, and enoxoparin), whereas fondaparinux (as selective factor Xa inhibitor) was not." Id. at 266, endnotes omitted. Elsewhere in the chapter, the authors cite other studies that support the idea that LMWHs may inhibit tumor growth. Id. at 261. The authors conclude:
Duly prepared, I met with Dr. Aragon-Ching. She said that the evidence that Lovenox can inhibit metastatic activity is very limited. She said that she would not give much weight to that possibility in making the decision of whether to continue using Lovenox, or switching to Xaralto. She acknowledged that Xaralto was a relatively new drug for DVT and PE, but was satisfied that Xaralto was as effective as Lovenox. She said that NIH would recommend that I stay on Lovenox, because they do clinical trials for a living, and Lovenox is well-known for its lack of interactions with most drugs. Because Xaralto is a newer drug, there is not as much evidence about its lack of interactions, although she said that it should be as safe and effective as Lovenox. She recommended that I have the Lovenox injections for 4 weeks, then switch over to Xaralto, unless I was to enter a clinical trial. She added that, if I went on Xaralto and then later entered a clinical trial, I could switch back to Lovenox with no problems.
Dr. Aragon-Ching also said that I should not go on coumadin. It doesn't work as well, has too many side effects, and is too diet-dependent. It's simply an older drug that has been superseded by newer drugs.
Prior to my meeting with her, I did some research on whether Lovenox can help suppress growth of my cancer. Along the way, I got an education on the use of low molecular weight heparins (LMWHs) to combat venous thromboembolism (VTE). VTE includes deep vein thrombosis (DVT) and pulmonary embolism (PE). Patients with cancer -- especially metastatic cancer, and who have had chemotherapy -- are at increased risk for VTE. A good overview of VTE, and the emerging use of oral anticoagulants, is available here.
The question I was looking into is whether LMWHs such as Lovenox can help inhibit the growth of my metastatic bladder cancer. Lovenox is an injected form of LMWH, with the generic name of enoxaparin sodium. I'm currently injecting myself with 120 mg of Lovenox twice a day. If there is evidence that enoxaparin can help slow the spread of my cancer, then I'm willing to continue with the shots. If not, I'd prefer switching to rivaroxaban (Xaralto).
In the 2009 book, Coagulation and Cancer, by G.F. Pineo and R.D. Hall, the authors write, "Some LMWH compounds were effective in the suppression of tumor cell growth, metastases (nandroparin, tinzaparin, enoxoparin), and antiogenesis (tinzaparin, dalteparin, and enoxoparin), whereas fondaparinux (as selective factor Xa inhibitor) was not." Id. at 266, endnotes omitted. Elsewhere in the chapter, the authors cite other studies that support the idea that LMWHs may inhibit tumor growth. Id. at 261. The authors conclude:
Over the years it has become increasingly evident that the thrombotic process plays a vital role in cancer cell development, proliferation, migration and metastasis leading to the hope that suppression of the coagulation cascade could have a beneficial effect on the cancer. Data from clinical trials initially aimed at the treatment of venous thromboembolism in cancer patients and later directly in cancer patients who did not have thrombosis provided evidence that LMWH could improve survival in the patients who had a wide variety of primary tumor sites . . . .Id. at 270. Unfortunately, the excepts of the book that I was able to pull up on Google books omitted the pages with the critical endnotes, so I could not readily locate the studies cited for those propositions.
Duly prepared, I met with Dr. Aragon-Ching. She said that the evidence that Lovenox can inhibit metastatic activity is very limited. She said that she would not give much weight to that possibility in making the decision of whether to continue using Lovenox, or switching to Xaralto. She acknowledged that Xaralto was a relatively new drug for DVT and PE, but was satisfied that Xaralto was as effective as Lovenox. She said that NIH would recommend that I stay on Lovenox, because they do clinical trials for a living, and Lovenox is well-known for its lack of interactions with most drugs. Because Xaralto is a newer drug, there is not as much evidence about its lack of interactions, although she said that it should be as safe and effective as Lovenox. She recommended that I have the Lovenox injections for 4 weeks, then switch over to Xaralto, unless I was to enter a clinical trial. She added that, if I went on Xaralto and then later entered a clinical trial, I could switch back to Lovenox with no problems.
Dr. Aragon-Ching also said that I should not go on coumadin. It doesn't work as well, has too many side effects, and is too diet-dependent. It's simply an older drug that has been superseded by newer drugs.
On the subject of clinical trials, Dr. Aragon-Ching said that the key issue was whether my nodes were large enough to meet the clinical trial threshold. I learned that the standards for lymph node sizes in clinical trials are set forth in
a document called "Response Evaluation Criteria in Solid Tumors" (RECIST). The 2009 version of the RECIST standards -- version 1.1 -- requires that lymph nodes be at least 15 mm on their short axis before they can be considered a "target lesion" for purposes of a clinical trial. As stated in an article summarizing the new guidelines:
Lymph nodes with a short axis of ≥15 mm are considered measurable and assessable as target lesions, and the short-axis measurement should be included in the sum of target lesion measurements in the calculation of tumor response as opposed to the longest axis used for measurements of other target lesions. Lymph nodes with a short axis of < 10 mm are defined as “nonpathologic” (Fig. 8A). All other pathologic nodes—that is, those with a short axis of ≥10 mm but <15 mm—should be considered nontarget lesions.
Since all US clinical trials follow the RECIST 1.1 guidelines, until my nodes are of sufficient size, I'm not eligible. Which is fine: I'd much rather have my nodes stay small and not enter a trial, than have them growing and then enter a trial.
Nevertheless, as Dr. Aragon-Ching and I discussed, it's highly likely that my cancer is going to progress. If and when that happens, then she recommended that I enter an immunotherapy clinical trial relating to PD-L1. She didn't think it mattered which PD-L1 trial it was -- either the Hoffman-LaRoche MPDL-3280A trial, or the soon-to-open NIH study which I'll learn more about tomorrow when I meet with Dr. Apolo.
Wednesday, October 8, 2014
Mets Day 910: Discharge and game plan
This morning I had a V/Q study, which is a type of lung ventilation/perfusion scan, to measure my lung capacity. It showed that I was at about 70% of expected perfusion capacity, which confirms that my PE is impacting the ability of my lungs to oxygenate my blood. After I'm on the blood thinner medication for 6-8 weeks, I'll have a follow-up V/Q scan to make sure that the issues relating to my PE have been addressed.
I then was instructed on how to inject myself with Lovenox. Last night, Jennifer received instruction and successfully injected me. This morning I successfully showed that I could shoot myself, so to speak. I was told that I would be discharged later today with 56 syringes, sufficient for four weeks of twice daily injections. I'll be reassessed at that time to determine wither I can drop to a once daily injection. Perhaps eventually I might be able to switch to an oral blood thinner, such as rivaroxaban (Xarelto), although I was warned that Xarelto has only been recently approved for DVT and PE, and there is limited data on using it with mets cancer patients. In addition, Xarelto has not been as well-studied for drug interactions, so if I ever enter a clinical trial and was on Xeralto, I'd probably have to go back onto Lovenox. Plus, if ever I was badly bleeding and needed to reverse the effects of the blood thinner I was taking, Lovenox can be reversed, while Xeralto cannot, and would have to metabolize out. The question is, how much of a pain it be to inject myself daily or twice daily, both in terms of the hassle of doing it, and the ongoing bruising and tenderness in the injection sites, versus the possible risks from Xeralto? Eh, I'll cross that bridge later.
I also had a consult with NIH's hematology department - the fellow showed up 90 minutes after the scheduled time, and the attending doctor wandered by a half hours thereafter. Oh that I could bill doctors my regular lawyer billing rate for all the time that I've spent waiting for doctors. Anyway, I was questioned in depth by the fellow on possible symptoms, causes, and family history of DVT and PE. Aside from my brother having had DVT and PE last year for unexplained reasons, there is no immediate family history to my knowledge. Hematology will have my blood run through various tests and possibly a broader genetic sequencing for further insight, but the fellow guessed that my PE is a simple case of metastatic cancer and chemo causing my blood to turn into sludge. Interestingly, the attending said that there was limited evidence suggesting the Lovenox might inhibit the growth of certain types of malignancies, so he suggested that I stay on that instead of shifting to Xeralto. Note to self: do some follow-up research on that.
I also met again with Drs. Wood and Apolo. They are going to coordinate my follow-up care with Dr. Aragon-Ching, who will see me next Monday. I will come back to visit with Dr. Apolo next Tuesday, to further explore whether any clinical trials are currently available to me, and if so, whether now is an appropriate time to do one. Dr. Apolo said that, although my supraclavicular nodes are not increasing in size, Monday's CT scan was able to detect that I have a cluster of supraclavicular nodes that are larger than normal: two are about 1 cm across on the short axis, and others are smaller than 1 cm, but still larger normal. Dr. Wood compared those nodes to a cluster of Hershey's kisses that have started to melt. They were still distinct, but the borders were beginning to become less distinct. While Dr. Wood's HER2 clinical trial required a single tumor at least 2 cm in size, Dr. Apolo said that, for the PD-L1 trials that she had in mind, it might be possible to consider the aggregate of those cluster of nodes to meet the minimum size. She said that later today she was going to sit down with the radiologist who initially read Monday's CT scan, and do a closer evaluation of my CT scan. We'll discuss next week her thoughts on possible clinical trials.
I'm not of the mind that I should jump into any clinical trial that might be open to me. For example, Dr. Wood's Phase 1 HER2 study seems too unproven for me at this point. If I had advanced tumors in my liver or lungs, and there were no other therapies available to me, then I might consider it. But I currently have a relatively light metastatic cancer burden, and know that, in all likelihood, my cancer is likely to progress in time. Each treatment is like a single bullet: I'll likely be able to use each therapy only once. There is no expectation that any therapy will cure me, since there is no known cure for metastatic bladder cancer, and none on the immediate horizon. Instead, each of these experimental therapies are intended to slow the growth of cancer, and prolong my life. The question for any future is therapy will be a balance of my current condition against the wisdom of waiting; the likelihood that the therapy would work on my mets BC; and the potential side effects. I'll be making that decision after in-depth consultations with my doctors.
I've essentially abandoned the idea of having my metastatic nodes removed. I questioned both Drs. Wood and Apolo about that idea, and they firmly rejected it, for three reasons: First, there is no evidence that a lymphanadectomy would help me. The studies on lymphanadectomies on patients with metastatic cancer differentiate between those nodes located in the abdomen (where there is some evidence that removal of additional nodes can help, which is why I had 61 nodes removed at the time of my radical cystectomy), and nodes in the chest, where there is virtually no evidence of any beneficial effect. Second, a lymphanadectomy would not be curative, or even therapeutic, because my bladder cancer is systemic throughout my lymph node system, and is not confined to my enlarged nodes. As Dr. Apolo said, "you have a systemic disease. It needs a systemic treatment." Third, the risks to having a lymphanadectomy of those supraclavicular nodes are significant, especially nerve damage to the shoulder, left arm, or even the heart, as well as potential damage to the veins and arteries lacing that region. On balance, the risks of a lymphanadectomy outweigh the benefits.
I then was instructed on how to inject myself with Lovenox. Last night, Jennifer received instruction and successfully injected me. This morning I successfully showed that I could shoot myself, so to speak. I was told that I would be discharged later today with 56 syringes, sufficient for four weeks of twice daily injections. I'll be reassessed at that time to determine wither I can drop to a once daily injection. Perhaps eventually I might be able to switch to an oral blood thinner, such as rivaroxaban (Xarelto), although I was warned that Xarelto has only been recently approved for DVT and PE, and there is limited data on using it with mets cancer patients. In addition, Xarelto has not been as well-studied for drug interactions, so if I ever enter a clinical trial and was on Xeralto, I'd probably have to go back onto Lovenox. Plus, if ever I was badly bleeding and needed to reverse the effects of the blood thinner I was taking, Lovenox can be reversed, while Xeralto cannot, and would have to metabolize out. The question is, how much of a pain it be to inject myself daily or twice daily, both in terms of the hassle of doing it, and the ongoing bruising and tenderness in the injection sites, versus the possible risks from Xeralto? Eh, I'll cross that bridge later.
I also had a consult with NIH's hematology department - the fellow showed up 90 minutes after the scheduled time, and the attending doctor wandered by a half hours thereafter. Oh that I could bill doctors my regular lawyer billing rate for all the time that I've spent waiting for doctors. Anyway, I was questioned in depth by the fellow on possible symptoms, causes, and family history of DVT and PE. Aside from my brother having had DVT and PE last year for unexplained reasons, there is no immediate family history to my knowledge. Hematology will have my blood run through various tests and possibly a broader genetic sequencing for further insight, but the fellow guessed that my PE is a simple case of metastatic cancer and chemo causing my blood to turn into sludge. Interestingly, the attending said that there was limited evidence suggesting the Lovenox might inhibit the growth of certain types of malignancies, so he suggested that I stay on that instead of shifting to Xeralto. Note to self: do some follow-up research on that.
I also met again with Drs. Wood and Apolo. They are going to coordinate my follow-up care with Dr. Aragon-Ching, who will see me next Monday. I will come back to visit with Dr. Apolo next Tuesday, to further explore whether any clinical trials are currently available to me, and if so, whether now is an appropriate time to do one. Dr. Apolo said that, although my supraclavicular nodes are not increasing in size, Monday's CT scan was able to detect that I have a cluster of supraclavicular nodes that are larger than normal: two are about 1 cm across on the short axis, and others are smaller than 1 cm, but still larger normal. Dr. Wood compared those nodes to a cluster of Hershey's kisses that have started to melt. They were still distinct, but the borders were beginning to become less distinct. While Dr. Wood's HER2 clinical trial required a single tumor at least 2 cm in size, Dr. Apolo said that, for the PD-L1 trials that she had in mind, it might be possible to consider the aggregate of those cluster of nodes to meet the minimum size. She said that later today she was going to sit down with the radiologist who initially read Monday's CT scan, and do a closer evaluation of my CT scan. We'll discuss next week her thoughts on possible clinical trials.
I'm not of the mind that I should jump into any clinical trial that might be open to me. For example, Dr. Wood's Phase 1 HER2 study seems too unproven for me at this point. If I had advanced tumors in my liver or lungs, and there were no other therapies available to me, then I might consider it. But I currently have a relatively light metastatic cancer burden, and know that, in all likelihood, my cancer is likely to progress in time. Each treatment is like a single bullet: I'll likely be able to use each therapy only once. There is no expectation that any therapy will cure me, since there is no known cure for metastatic bladder cancer, and none on the immediate horizon. Instead, each of these experimental therapies are intended to slow the growth of cancer, and prolong my life. The question for any future is therapy will be a balance of my current condition against the wisdom of waiting; the likelihood that the therapy would work on my mets BC; and the potential side effects. I'll be making that decision after in-depth consultations with my doctors.
I've essentially abandoned the idea of having my metastatic nodes removed. I questioned both Drs. Wood and Apolo about that idea, and they firmly rejected it, for three reasons: First, there is no evidence that a lymphanadectomy would help me. The studies on lymphanadectomies on patients with metastatic cancer differentiate between those nodes located in the abdomen (where there is some evidence that removal of additional nodes can help, which is why I had 61 nodes removed at the time of my radical cystectomy), and nodes in the chest, where there is virtually no evidence of any beneficial effect. Second, a lymphanadectomy would not be curative, or even therapeutic, because my bladder cancer is systemic throughout my lymph node system, and is not confined to my enlarged nodes. As Dr. Apolo said, "you have a systemic disease. It needs a systemic treatment." Third, the risks to having a lymphanadectomy of those supraclavicular nodes are significant, especially nerve damage to the shoulder, left arm, or even the heart, as well as potential damage to the veins and arteries lacing that region. On balance, the risks of a lymphanadectomy outweigh the benefits.
Tuesday, October 7, 2014
Mets Day 909: PE, CT, happy me
I'm still in the NIH hospital. They'll keep me here until tomorrow, since they want to confirm that I am getting the right dosage of Lovenox to break up my pulmonary embolism (PE). I've been getting 120 mg of Lovenox twice a day. Tonight the nurse will teach Jennifer and I how to do self-injections. Tomorrow morning I'll prove that I can do it, and then I'll be discharged after another set of labs confirm that everything is ok.
I'll have to keep up with the Lovenox injections twice daily for at least 4 weeks. The doctors want to be sure that all of my clots and deep vein thrombosis (DVT) has been addressed. After 4 weeks, I might shift to once daily shots, which could go for 6 months, or it could last as long as I have bladder cancer. We'll see. Since mets cancer is a known risk factor for DVT and PE, her thinking is that I should probably stay on the Lovenox for the rest of my life. Neither Dr. Apolo nor Dr. Wood recommended that I go on coumadin, because it is so hard to regulate and can be rather unpredictable. I'm not excited about daily shots into perpetuity, but it's better than dying from a stroke. (A few minutes ago, I spoke with Dr. Aragon-Ching, who said that it may be possible after 30 days or so to transition me from Lovenox to oral Xarelto. I will meet with her on Monday to get her views on my follow-up care.)
Dr. Wood gave me a copy of my CT scan. It showed "redemonstrated right lower lobe calcified granuloma", as well as "new, well-defined, linear low-density filling defect within the central aspect of the main portal vein, extending from the portohepatis to the confluence of the SMV" and "an additional filling defect is noted in the central left portal vein." In other words, I've got a bunch of blood clots in my lung and portal veins in my liver. The results of this scan were what caused Dr. Wood to order me back to the hospital last night. Reading it, I can understand why. Compared to my scans of 9/2/14, 7/15/14, and 3/25/14, these clots are new and dramatic. All of the medical professionals that have attended me - the doctors, PA's, nurses - have repeatedly told me how lucky I am that I just happened to have a scan that detected the PE before I had any symptoms.
The CT scan also reported on the size of my enlarged lymph nodes under my left clavicle. The radiologist reports "mild interval decrease in the size of the superior left supraclavicular lymph node, measuring approximately 1.0 cm in the short axis dimension, previously measuring 1.3 cm." My other nodes in the area are stable in size, the largest about 1.0 cm across. This finding that my largest lymph node as decreased in size is somewhat surprising, since I have not had any therapy since my last scan. It could be due to how the CT scan sliced the node, although the radiologist was definitive in his conclusion of "stable and interval decrease in size, respectively, of the two prominent supraclavicular lymph nodes."
Aside from the PE, there are two other immediate takeaways from this CT scan:
1) My cancer seems to have stopped growing for now, and is in fact receding. This is a surprise, and so far, no one has been able to explain it. I'm grateful that it has, and give thanks to God for this news.
2) The smaller size of my nodes mean that I do not qualify for the HER2/neu trial that triggered this latest round of fun and games. The minimum tumor size has to be 2 cm. I also likely will not qualify for any of the PD-L1 trials at this time either. Dr. Apolo told me this morning that she was going to personally measure the node size when she reviewed my CT scan images, but I have not heard back from her. This means that I'm back to watchful waiting - the same place I was prior to about 11 am yesterday morning. Ooch, whiplash.
I'll have to keep up with the Lovenox injections twice daily for at least 4 weeks. The doctors want to be sure that all of my clots and deep vein thrombosis (DVT) has been addressed. After 4 weeks, I might shift to once daily shots, which could go for 6 months, or it could last as long as I have bladder cancer. We'll see. Since mets cancer is a known risk factor for DVT and PE, her thinking is that I should probably stay on the Lovenox for the rest of my life. Neither Dr. Apolo nor Dr. Wood recommended that I go on coumadin, because it is so hard to regulate and can be rather unpredictable. I'm not excited about daily shots into perpetuity, but it's better than dying from a stroke. (A few minutes ago, I spoke with Dr. Aragon-Ching, who said that it may be possible after 30 days or so to transition me from Lovenox to oral Xarelto. I will meet with her on Monday to get her views on my follow-up care.)
Dr. Wood gave me a copy of my CT scan. It showed "redemonstrated right lower lobe calcified granuloma", as well as "new, well-defined, linear low-density filling defect within the central aspect of the main portal vein, extending from the portohepatis to the confluence of the SMV" and "an additional filling defect is noted in the central left portal vein." In other words, I've got a bunch of blood clots in my lung and portal veins in my liver. The results of this scan were what caused Dr. Wood to order me back to the hospital last night. Reading it, I can understand why. Compared to my scans of 9/2/14, 7/15/14, and 3/25/14, these clots are new and dramatic. All of the medical professionals that have attended me - the doctors, PA's, nurses - have repeatedly told me how lucky I am that I just happened to have a scan that detected the PE before I had any symptoms.
The CT scan also reported on the size of my enlarged lymph nodes under my left clavicle. The radiologist reports "mild interval decrease in the size of the superior left supraclavicular lymph node, measuring approximately 1.0 cm in the short axis dimension, previously measuring 1.3 cm." My other nodes in the area are stable in size, the largest about 1.0 cm across. This finding that my largest lymph node as decreased in size is somewhat surprising, since I have not had any therapy since my last scan. It could be due to how the CT scan sliced the node, although the radiologist was definitive in his conclusion of "stable and interval decrease in size, respectively, of the two prominent supraclavicular lymph nodes."
Aside from the PE, there are two other immediate takeaways from this CT scan:
1) My cancer seems to have stopped growing for now, and is in fact receding. This is a surprise, and so far, no one has been able to explain it. I'm grateful that it has, and give thanks to God for this news.
2) The smaller size of my nodes mean that I do not qualify for the HER2/neu trial that triggered this latest round of fun and games. The minimum tumor size has to be 2 cm. I also likely will not qualify for any of the PD-L1 trials at this time either. Dr. Apolo told me this morning that she was going to personally measure the node size when she reviewed my CT scan images, but I have not heard back from her. This means that I'm back to watchful waiting - the same place I was prior to about 11 am yesterday morning. Ooch, whiplash.
Monday, October 6, 2014
Mets Day 908: From clinical trial inquiry to hospitalization
This morning I received a call from Brenda Robinson, the clinical trial coordinator
for Dr. Lauren Wood at NIH. Ms. Robinson told me that she was interested in getting me to participate in a clinical trial relating to a customized immunotherapy the used the fact that my cancer had HER2/neu overexpression. She said that she had an immediate slot available for me, and asked if I could come in that afternoon for a CT screening. Although I did not have enough information to determine whether I wanted to participate in that particular trial, I agreed to go in for the scan and get more information.
Two hours later, I was at NIH. I went to phlebotomy for the blood draw and urine test, then went to radiology for the CT scan. The receptionist said that she did not yet have my orders from the doctor, so I went upstairs to the clinic to find Ms. Robinson. She quickly appeared and was surprised that the orders were not yet entered. She went to the computer and got everything set up, and returned with an 11 page disclosure about the clinical trial. It was NIH NCI Study No. 13-C-0016: Phase 1 study of adenoviral transduced autologous dendritic cell vaccine expressing human HER2/neu ECTM in adults with tumors with 1-3+ HER2/neu expression. I started reading through the disclosures when Ms. Robinson said that Dr. Wood was available to meet with me and explain a bit more about the trial.
Dr. Wood was joined by a team of 5: a fellow, two medical students, and two nurses. She enthusiastically explained the intent of the trial. I learned that this was a first-in-human trial for a new type of customized immunotherapy. She explained how my cancer had tested positive for HER2 overexpression (the test results were plus 3). The HER2 protein sends signals to tumor cells to make them grow and preventing the tumor from dying. HER2 overexpression has been studied extensively in connection with breast cancer, where it is present in 25-30% of cases. The HER2 genome is responsive to several medicines, including trastuzumab (Herceptin), pertuzumab (Perjerta), and ado-trastuzumab emansine (Kadcyla), which are monoclonal antibodies that recognize and inhibit distinct portions of the HER2 protein. The drugs have to be administered repeatedly to have an effect, and they don't necessarily work on all HER2 cancers.
The clinical trial involves the creation of a AdHER2 DC vaccine to induce the patient's own immune system to make multiple, different types of antibodies to HER2, called polyclonal antibodies. Mammalian studies have shown that a AdHER2 DC vaccine has caused significant regression and shrinkage of large established tumors. A YouTube video of this trial is available here. The objective of the trial is to see if the vaccine that works in mammalian studies can be translated to humans. Because monoclonal antibodies such as trastuzumab can adversely affect cardiac function in some patients, the FDA is requiring this trial to closely monitor cardiac function.
I was told that the trial would consist of the removal of certain types of my blood cells through a process called apheresis, where my blood is drawn, run through a cell separator machine to take out my circulating cells (including lymphocytes and monocytes), and the plasma and red cells returned to my body. The circulating cells are then used to custom make a vaccine. Enough circulating cells are removed during apheresis to make 5 or 6 batches of vaccine, using my own dendritic immune cells. Those dendritic cells are derived from the monocytes in my circulating cells. The NIH doctors would mix in a combination of trastuzumab, pertuzumab, and ado-trastuzumab emansine into that vaccine, then would inject it transdermally (under my skin). The protocol calls for 5 rounds of injections: weeks 0, 4, 8, 16, and 24, as well as two years of monitoring.
After trying to digest all of this information, I went back downstairs for the CT scan. The tech was unable to get a return blood draw from my port, suggesting that there was a clot or other type of blockage around the tip of my port. She was able to inject heparin into my port, however, so we used it for the injection of the contrast during the CT scan. While waiting for my CT scan, I sent an email to Dr. Apolo, asking for her input on whether she thought that I should enter this particular clinical trial. After summarizing the trial, I wrote:
Five minutes after I got home, I was called by Dr. Wood. She said that she had just reviewed the results of my CT scan. She said that it showed a large clot in a vein in my liver, and multiple clots in the lower lobe of my right lung -- a serious case of pulmonary embolism, or PE. She asked me to immediately return to the NIH hospital for administration of blood thinners. She said that I likely would be in the hospital for a day or two. I briefed Jennifer, jumped back in the Audi and went back to NIH. After I was admitted, I met with Dr. Wood, who had waited for my return. She explained that mets cancer patients were at increased risk for PE. She said that the best treatment would be for me to have two subcutaneously injections daily of enoxaparin (Lovenox). She said that this was more effective in patients with a cancer burden than IV-administered unfractionated low molecular weight heparin.
So now I'm reclining in my hospital bed watching the Deadskins get thumped by the Seahawks. At around halftime, the nurse came if to inject the Lovenox into my abdomen. She admired my love handles, and said that they were perfect for the injections. I smiled with the knowledge that the decades of preparation for this day has finally paid off. I'll get another injection tomorrow morning, and then probably will get trained on injecting myself. I'll have to do the injections twice a day for the next month or so, then may be able to shift to oral therapy. Whether by serendipity or a bit of divine intervention, I'm grateful that the PE was detected without my suffering any harm. It was (ahem) a stroke of good luck.
Two hours later, I was at NIH. I went to phlebotomy for the blood draw and urine test, then went to radiology for the CT scan. The receptionist said that she did not yet have my orders from the doctor, so I went upstairs to the clinic to find Ms. Robinson. She quickly appeared and was surprised that the orders were not yet entered. She went to the computer and got everything set up, and returned with an 11 page disclosure about the clinical trial. It was NIH NCI Study No. 13-C-0016: Phase 1 study of adenoviral transduced autologous dendritic cell vaccine expressing human HER2/neu ECTM in adults with tumors with 1-3+ HER2/neu expression. I started reading through the disclosures when Ms. Robinson said that Dr. Wood was available to meet with me and explain a bit more about the trial.
Dr. Wood was joined by a team of 5: a fellow, two medical students, and two nurses. She enthusiastically explained the intent of the trial. I learned that this was a first-in-human trial for a new type of customized immunotherapy. She explained how my cancer had tested positive for HER2 overexpression (the test results were plus 3). The HER2 protein sends signals to tumor cells to make them grow and preventing the tumor from dying. HER2 overexpression has been studied extensively in connection with breast cancer, where it is present in 25-30% of cases. The HER2 genome is responsive to several medicines, including trastuzumab (Herceptin), pertuzumab (Perjerta), and ado-trastuzumab emansine (Kadcyla), which are monoclonal antibodies that recognize and inhibit distinct portions of the HER2 protein. The drugs have to be administered repeatedly to have an effect, and they don't necessarily work on all HER2 cancers.
The clinical trial involves the creation of a AdHER2 DC vaccine to induce the patient's own immune system to make multiple, different types of antibodies to HER2, called polyclonal antibodies. Mammalian studies have shown that a AdHER2 DC vaccine has caused significant regression and shrinkage of large established tumors. A YouTube video of this trial is available here. The objective of the trial is to see if the vaccine that works in mammalian studies can be translated to humans. Because monoclonal antibodies such as trastuzumab can adversely affect cardiac function in some patients, the FDA is requiring this trial to closely monitor cardiac function.
I was told that the trial would consist of the removal of certain types of my blood cells through a process called apheresis, where my blood is drawn, run through a cell separator machine to take out my circulating cells (including lymphocytes and monocytes), and the plasma and red cells returned to my body. The circulating cells are then used to custom make a vaccine. Enough circulating cells are removed during apheresis to make 5 or 6 batches of vaccine, using my own dendritic immune cells. Those dendritic cells are derived from the monocytes in my circulating cells. The NIH doctors would mix in a combination of trastuzumab, pertuzumab, and ado-trastuzumab emansine into that vaccine, then would inject it transdermally (under my skin). The protocol calls for 5 rounds of injections: weeks 0, 4, 8, 16, and 24, as well as two years of monitoring.
After trying to digest all of this information, I went back downstairs for the CT scan. The tech was unable to get a return blood draw from my port, suggesting that there was a clot or other type of blockage around the tip of my port. She was able to inject heparin into my port, however, so we used it for the injection of the contrast during the CT scan. While waiting for my CT scan, I sent an email to Dr. Apolo, asking for her input on whether she thought that I should enter this particular clinical trial. After summarizing the trial, I wrote:
I am most interested in your thoughts on whether I should participate in this study, or instead enroll in either your PD-L1 study, or the MPDL3280A study, or some of the other trials that we had discussed. My initial impression is that, because the HER2 study is a first-in-human phase 1 trial and the therapeutic effect is unknown, it might be better for me to enroll in a PD-L1 trial instead. Or should I take a stab at this, then do the PD-L1 trial later? Or vice-versa?I left for home after the scan. I was told that I should plan on coming back to NIH tomorrow for a bone scan, echocardiogram, and further discussion of the trial protocol. I stopped at Chipotle on the way home, as I had not eaten since the night before. While walking into Chipotle, Dr. Apolo called me. She said that she had told Dr. Wood about me back in August, but expected that Dr. Wood would have spoken with her before contacting me. She recalled that we had decided to wait until my next scan on November 18 before deciding what course of treatment, if any, and seemed surprised that her colleagues had initiated contact with me about a trial. While praising Dr. Wood's innovative research with the AdHER2 DC vaccine, Dr. Apolo noted that it was a first-ever Phase 1 trial, and there was no evidence that it would work in humans. By contrast, the PD-L1 trials had shown significant response in more than 50% of study participants. She said that, while it was nice to have choices on trials, she would recommend that, if I was to choose to enter a trial, she would recommend that I participate in a PD-L1 trial. She proposed that I defer for at least a week my decision on whether to enter Dr. Wood's HER2 trial, and in the meantime Dr. Apolo would review the results of today's CT scan, and meet with me on Tuesday, October 14. That sounded sensible to me.
Five minutes after I got home, I was called by Dr. Wood. She said that she had just reviewed the results of my CT scan. She said that it showed a large clot in a vein in my liver, and multiple clots in the lower lobe of my right lung -- a serious case of pulmonary embolism, or PE. She asked me to immediately return to the NIH hospital for administration of blood thinners. She said that I likely would be in the hospital for a day or two. I briefed Jennifer, jumped back in the Audi and went back to NIH. After I was admitted, I met with Dr. Wood, who had waited for my return. She explained that mets cancer patients were at increased risk for PE. She said that the best treatment would be for me to have two subcutaneously injections daily of enoxaparin (Lovenox). She said that this was more effective in patients with a cancer burden than IV-administered unfractionated low molecular weight heparin.
So now I'm reclining in my hospital bed watching the Deadskins get thumped by the Seahawks. At around halftime, the nurse came if to inject the Lovenox into my abdomen. She admired my love handles, and said that they were perfect for the injections. I smiled with the knowledge that the decades of preparation for this day has finally paid off. I'll get another injection tomorrow morning, and then probably will get trained on injecting myself. I'll have to do the injections twice a day for the next month or so, then may be able to shift to oral therapy. Whether by serendipity or a bit of divine intervention, I'm grateful that the PE was detected without my suffering any harm. It was (ahem) a stroke of good luck.
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