I apologize for the late update; it's been relatively uneventful with minor changes day-to-day, which I shall list below.
During my mother's inpatient stay, she first had a reaction to the dexamethasone as it made her extremely emotional, because it is a glucocorticoid steroid. She had been on prednisone previously, but since dexamethasone is 4-5 times more potent, the prednisone was discontinued. I visited her one morning as she laid weeping, simultaneously assuring me that she truly wasn't upset or depressed.
The cyclophosphamide and concurrent infusions had her urinating at least hourly the first three days, so she slept very little. This subsided later in the week, as the cyclophosphamide was discontinued and she started doxorubicin.
Her PICC line became useless as a clot formed at the site of entry in her upper arm; fortunately, this happened soon after her last infusions. She, however, had to have PIVs (peripheral intraveneous lines) placed for her outpatient infusions the following week.
Finally, having arrived Monday afternoon, my mother went home late Sunday evening, for a total length of 6 nights. The next cycle is scheduled for 03/03 and will be hopefully only for 3 nights.
Her erythrocyte and leukocyte counts kept dropping, instead of remaining stable, so she started a granulocyte growth factor, which unfortunately causes bone pain. Around the house, she is mostly relaxing in whatever position might be comfortable, articipating in intermittent spurts of activity. The familiar environment and chance to do some walking has been beneficial, though, as she reports more energy and comfort. Finally, this last weekend, her counts began rising again.
The week following her inpatient treatment, she had her first infusion of rituximab. Evidently this drug costs thousands of dollars per dose, and it has a high risk of contraindications and complications. The standard procedure, therefore, is for the pharmacy to order a test dose (at a lower cost) and have the patient receive this test dose before ordering the rest of the prescribed amount. Luckily, my mom withstood the test dose, excepting an acute pain response (that was controlled with possibly Benadryl), and had the rest infused.
A few days later, she complained of scalp pain, but didn't lose any hair. Yesterday morning, almost three weeks into chemotherapy treatment, she stepped into the shower, and as she washed, clumps fell to the ground. So she headed to the hairdresser, and now my mother is a beautiful shaven hairless woman.
28 February, 2008
11 February, 2008
Day One
This evening's nurse is currently prepping my mother's PICC line for the very first bag of sodium chloride (for hydration) which, in another hour, will be followed by the first treatment of cytoxan (cyclophosphamide).
She just explained how cytoxan causes mouth sores and dryness, so my mom has to do saline rinses every few hours at least. She also shared she needed to test the pH of my mom's urine to make sure the chemotherapy drugs will not crystalize in her urine and potentially block her urinary system.
In order to shorten the day here on the cancer care floor, my mother had her PICC line inserted just before elsewhere. A PICC is a peripherally inserted central catheter -- this means there is a catheter with IV access on her inside upper arm and the cathether actually treads her brachial vein within an inch of her heart. Unfortunately, she's experiencing intermittent pain with the new line, which is likely venous spasm. Usually warm pads will help relieve this, though.
The orders this time around include (but are not limited to):
1st.) Cyclophosphamide (Cytoxan) -- 550 mg, 300 mg/M^2, given over 3 hours, every twelve hours for a total of 6 doses
2nd.) Mesna -- 1100 mg, 600 mg/M^2 every 24 hours, beginning 1 hour befor cyclophosphamide and continuing for 12 hours after; this is to protect the bladder from the damaging effects of cytoxan
3rd.) Dexamethasone -- 40 mg, given intravenously, scheduled before cyclophosphamide; it moderates the body's reaction to cyclophosphamide
4th.) Doxorubicin -- 31 mg, 16.7 mg/M^2, given over 72 hours, beginning 12 hours post cyclophosphamide; this is a light-sensitive chemotherapy drug, and has to be kept inside a shielding bag
5th.) Rituximab -- test dose before full dose; given on an outpatient basis next week
6th.) Vincristine -- 2 mg, 1.4 mg/M^2, , given twice, on an outpatient basis next week
She is also getting continuous infusions of sodium chloride and 5% dextrose for hydration and electrolyte maintenance, as well as ativan to help neutralize nausea.
Ultimately, this is just a strange sensation for the two of us. My mom is an active, self-sufficient woman, and here she is waiting for others to do things to her and tell her what she needs to know to survive this. Also, while watching every nurse and CNA or staffperson perform their duties, I'm simply sitting at the bedside, observing something I normally do or assist several times a week.
Another insight I'm making: I do not want to be a hospitalist; while I admire the job and the range of conditions that position oversees, it seems too process-oriented and dependent on the admissions and a quick bedside evaluation. Of course, this could all change...
She just explained how cytoxan causes mouth sores and dryness, so my mom has to do saline rinses every few hours at least. She also shared she needed to test the pH of my mom's urine to make sure the chemotherapy drugs will not crystalize in her urine and potentially block her urinary system.In order to shorten the day here on the cancer care floor, my mother had her PICC line inserted just before elsewhere. A PICC is a peripherally inserted central catheter -- this means there is a catheter with IV access on her inside upper arm and the cathether actually treads her brachial vein within an inch of her heart. Unfortunately, she's experiencing intermittent pain with the new line, which is likely venous spasm. Usually warm pads will help relieve this, though.
The orders this time around include (but are not limited to):
1st.) Cyclophosphamide (Cytoxan) -- 550 mg, 300 mg/M^2, given over 3 hours, every twelve hours for a total of 6 doses
2nd.) Mesna -- 1100 mg, 600 mg/M^2 every 24 hours, beginning 1 hour befor cyclophosphamide and continuing for 12 hours after; this is to protect the bladder from the damaging effects of cytoxan
3rd.) Dexamethasone -- 40 mg, given intravenously, scheduled before cyclophosphamide; it moderates the body's reaction to cyclophosphamide
4th.) Doxorubicin -- 31 mg, 16.7 mg/M^2, given over 72 hours, beginning 12 hours post cyclophosphamide; this is a light-sensitive chemotherapy drug, and has to be kept inside a shielding bag
5th.) Rituximab -- test dose before full dose; given on an outpatient basis next week
6th.) Vincristine -- 2 mg, 1.4 mg/M^2, , given twice, on an outpatient basis next week
She is also getting continuous infusions of sodium chloride and 5% dextrose for hydration and electrolyte maintenance, as well as ativan to help neutralize nausea.
Ultimately, this is just a strange sensation for the two of us. My mom is an active, self-sufficient woman, and here she is waiting for others to do things to her and tell her what she needs to know to survive this. Also, while watching every nurse and CNA or staffperson perform their duties, I'm simply sitting at the bedside, observing something I normally do or assist several times a week.
Another insight I'm making: I do not want to be a hospitalist; while I admire the job and the range of conditions that position oversees, it seems too process-oriented and dependent on the admissions and a quick bedside evaluation. Of course, this could all change...
08 February, 2008
The Plan
I realized I haven't clearly delineated my mother's plan of attack, so I thought I'd briefly list what she's decided.
First, she will undergo four cycles of R-hyperCVAD + MTX-Ara-C. These drugs are rituximab, hyperfractionated cyclophosphamide, vincristine, doxorubicin (Adriamycin), dexamethasone, methotrexate, and cytarabine (cytosine arabinoside or "ara-c").
Traditionally, most lymphomas are first treated with R-CHOP (rituximab, cyclophosphamide, doxorubicin, vincristine, and prednisone), but MCL is poorly responsive to R-CHOP; it either does not respond well or responds but without going into a prolonged remission. Therefore, my mother is undergoing a much harsher combination of chemotherapy and steroidal drugs. These drugs require that she be hospitalized for approximately 5-6 days with each cycle. Additionally, she will be neutropenic (lymphopenic, eosinopenic, etc.) which specifically means she'll have essentially little to no immune response; she cannot have sick visitors, I cannot have my dogs visit her, she cannot receive fresh flowers, she cannot eat fresh food, and she cannot travel, among other forbidden delacicies.
After approximately the third cycle, she will then have a procedure to extract healthy stem cells, which will be preserved. Finally, hopefully after the fourth cycle, my mother will undergo either full-body radiation or radiolabeled immunoglobulin therapy to completely kill off her entire body, quite bluntly. Afterwards, in a three-week stay in the hospital, she will receive her own healthy stem cells in what is known as an "autologous stem cell transplant" (allogenic would be from a foreign donor). This has a much lower complications rate than an allogenic stem cell transplant.
The hope is that the ASCT in conjunction with her highly aggressive chemotherapy regimen will actually be curative, so far as we can deem complete remission a cure. There may be, after all, a way to beat this nasty thing called MCL!
First, she will undergo four cycles of R-hyperCVAD + MTX-Ara-C. These drugs are rituximab, hyperfractionated cyclophosphamide, vincristine, doxorubicin (Adriamycin), dexamethasone, methotrexate, and cytarabine (cytosine arabinoside or "ara-c").
Traditionally, most lymphomas are first treated with R-CHOP (rituximab, cyclophosphamide, doxorubicin, vincristine, and prednisone), but MCL is poorly responsive to R-CHOP; it either does not respond well or responds but without going into a prolonged remission. Therefore, my mother is undergoing a much harsher combination of chemotherapy and steroidal drugs. These drugs require that she be hospitalized for approximately 5-6 days with each cycle. Additionally, she will be neutropenic (lymphopenic, eosinopenic, etc.) which specifically means she'll have essentially little to no immune response; she cannot have sick visitors, I cannot have my dogs visit her, she cannot receive fresh flowers, she cannot eat fresh food, and she cannot travel, among other forbidden delacicies.
After approximately the third cycle, she will then have a procedure to extract healthy stem cells, which will be preserved. Finally, hopefully after the fourth cycle, my mother will undergo either full-body radiation or radiolabeled immunoglobulin therapy to completely kill off her entire body, quite bluntly. Afterwards, in a three-week stay in the hospital, she will receive her own healthy stem cells in what is known as an "autologous stem cell transplant" (allogenic would be from a foreign donor). This has a much lower complications rate than an allogenic stem cell transplant.
The hope is that the ASCT in conjunction with her highly aggressive chemotherapy regimen will actually be curative, so far as we can deem complete remission a cure. There may be, after all, a way to beat this nasty thing called MCL!
05 February, 2008
Vincristine
Chemotherapy drugs are often toxic, and before treatment, it's wise to educate oneself about what possible side effects and toxicities might be experienced as well as to understand its basic pharmacology. Part of the R-hyperCVAD + MTX-Ara-C is "V"incristine, one of the older known drugs in this powerful combination.Vincristine's formal name is 22-oxovincaleukoblastine, and its formula is C46H56N4O10 with a molar mass of 824.96 g/mole. It is an antineoplastic antitumor alkaloid, now biosynthesized, but originally isolated from Vinca rosea Linn. It has a melting point of 218-220 degrees C, but is in liquid form during intravenous administration. It must not be administered intrathecally as this is fatal; 55 cases have been reported since 1968 of accidental spinal route injection. Once administered, it distributes through rapid, extensive, and reversible tissue binding. Excess will be excreted in the bile and feces, so take care in handling any waste products separately. Vincristine is used specifically to treat leukemias and lymphomas, including mantle-cell lymphoma.
Vincristine is a antimitotic that inhibits mitosis in the metaphase stage, by binding to tubulin, preventing the formation of spindles and thus the transition to telephase. Vincristine also appears to interfere with the ability by the cell to synthesise DNA and RNA. As one can see in the structure above, it is a large molecule with many polar oxygens; these enable its binding to the tubulin. It is also related to several other compounds, listed at http://biotech.icmb.utexas.edu/botany/vvv.html.
Unfortunately, vincristine is known for its severe toxicity. It is teratogenic, carciogenic, and fetotoxic. Side effects include myelosuppression, irritation at the injection site, and neurotoxicities, including peripheral neuropathy. However, this is due to neural tissue distribution in the body, as vincristine does not readily cross the blood-brain barrier (CSF:plasma ratio of 5%). For this reason, persons with demyelinating disorders cannot take vincristine. An extensive list of possible adverse effects can be found at http://www.cancercare.on.ca/pdfdrugs/vincrist.pdf.
In 2006, a study was performed on rats in which one group received a fixed dose of vincristine while another group received an increasing dose with each weekly treatment. At the end of 5 and 19 weeks, both groups exhibited peripheral sensory-motor neuropathy, while the fixed-dose group exhibited more long-term histological and electrophysiological signs of neuropathy. Signs included axonal degeneration with relative demyelination as well as a significant decrease in the amplitude of the sensory nerve action potential and compound muscle action potential in tested nerves. However, encouragingly, after discontinuation (at 14 weeks), both groups exhibited lesser number of fibers with axonal and myelin lesions, so there is an expectation that a normal rat should exhibit improvement of electrophysiological and histological changes even after vincristine treatment. The rat has been considered a viable model for human physiology, so a patient being treated with intravenous R-hyperVCAD should not expect vincristine to be fatal or experienced neuropathy to persist at identical levels after treatment ends.
04 February, 2008
Rashes
Yesterday I visited my mother at her home to find a note that she'd gone to the emergency department. While not exactly the news one would want to hear, I still found it exciting. This was an opportunity for me to partially, unofficially, shadow the role of a physician in a setting I found personally interesting and I could also support my mom, who was probably sitting there alone. I turned around and ran out the door.
My mother was falling victim to a rash that had slowly been spreading across her skin, even welding into one large red welt on her back. It wasn't necessarily painful, she said. There was a slight burning sensation, but little else, almost surely due to the inflammatory response. She'd first noticed it Thursday, but by Sunday morning, it'd crept onto her face and she needed to go to the ED. There were plans to get a port ("portacath") this morning, and if the rash was in the way, she surely needed to delay those plans.
The port is a catheter installed beneath her skin near her heart (on the chest); it serves essentially the same function as an peripheral IV (IV in the hands or forearms or other distant point from the heart). However, PIVs have two main problems that a port solves: (1) the veins on the hands and forearms are less structurally stable and unable to withstand the toxicity of many drugs, including chemotherapy drugs; (2) PIVs (and PICCs) have to be removed and reinserted after a specific period of time -- if needed, a port can be essentially permanent. The skin will just regrow over the port and when needed, my mom will go to the hospital and have the port repunctured by a Huber point needle, and the port will be useable.
At the ED, my mom and I suffered 1/3rd of the waiting people probably typically endure (we were in a small, slow ED, so waiting times were fairly short), but it was still enough that my mother kept peeking out the door and staring down the long empty hallway.
Of course the emergency physician had no idea what she had, although he was very polite, and I managed to see how little time a physician really spends with his patient -- even when it's slow. First he ran the standard blood labs, which all came back normal. He then contacted the dermatologist on-call for a consult. He came in and performed a skin biopsy, which was fascinating to watch. They brought in a sterile laceration kit, and he numbed her up with some local anesthetic. Next, he snipped away a 2 mm by 5 mm piece, and dropped it in a cup of formaldehyde, then proceeded to suture her up. His conclusion: the lab results today hopefully told more, but he suspected that it was related to her lymphoma, either directly or due to a partially compromised immune system. If not that, perhaps it was a drug reaction. His tentative diagnosis was some form of erythema, and should clear up within two weeks of initial onset. (This didn't comfort my mother later that evening when the burning pain worsened.)
Time in: 10:30 AM. Time out: 1:15 PM.
Conclusion A: Port appointment postponed until Thursday.
Conclusion B: Emergency medicine is often unfinished.
Edit 02/05/08, 9:39 AM: The biopsy results are "nonspecific reaction." The rash is still progressing on my mom's body.
My mother was falling victim to a rash that had slowly been spreading across her skin, even welding into one large red welt on her back. It wasn't necessarily painful, she said. There was a slight burning sensation, but little else, almost surely due to the inflammatory response. She'd first noticed it Thursday, but by Sunday morning, it'd crept onto her face and she needed to go to the ED. There were plans to get a port ("portacath") this morning, and if the rash was in the way, she surely needed to delay those plans.
The port is a catheter installed beneath her skin near her heart (on the chest); it serves essentially the same function as an peripheral IV (IV in the hands or forearms or other distant point from the heart). However, PIVs have two main problems that a port solves: (1) the veins on the hands and forearms are less structurally stable and unable to withstand the toxicity of many drugs, including chemotherapy drugs; (2) PIVs (and PICCs) have to be removed and reinserted after a specific period of time -- if needed, a port can be essentially permanent. The skin will just regrow over the port and when needed, my mom will go to the hospital and have the port repunctured by a Huber point needle, and the port will be useable.
At the ED, my mom and I suffered 1/3rd of the waiting people probably typically endure (we were in a small, slow ED, so waiting times were fairly short), but it was still enough that my mother kept peeking out the door and staring down the long empty hallway.
Of course the emergency physician had no idea what she had, although he was very polite, and I managed to see how little time a physician really spends with his patient -- even when it's slow. First he ran the standard blood labs, which all came back normal. He then contacted the dermatologist on-call for a consult. He came in and performed a skin biopsy, which was fascinating to watch. They brought in a sterile laceration kit, and he numbed her up with some local anesthetic. Next, he snipped away a 2 mm by 5 mm piece, and dropped it in a cup of formaldehyde, then proceeded to suture her up. His conclusion: the lab results today hopefully told more, but he suspected that it was related to her lymphoma, either directly or due to a partially compromised immune system. If not that, perhaps it was a drug reaction. His tentative diagnosis was some form of erythema, and should clear up within two weeks of initial onset. (This didn't comfort my mother later that evening when the burning pain worsened.)
Time in: 10:30 AM. Time out: 1:15 PM.
Conclusion A: Port appointment postponed until Thursday.
Conclusion B: Emergency medicine is often unfinished.
Edit 02/05/08, 9:39 AM: The biopsy results are "nonspecific reaction." The rash is still progressing on my mom's body.
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