First December 2008

Mal's Musings

Malcolm A Traill

IN  THE  PUBLIC  INTEREST
First 8/12/2008

 

 

YOUR CANCER

&

LITHIUM TREATMENT

 

  Click to E-mail me with concerns about  CANCER, RHEUMATOID ARTHRITIS,
                                                                                    LUPUS ERYTHEMATOSUS,

                                                                                    MULTIPLE SCLEROSIS,
                                                                                    SARCOIDOSIS, HEPATITIS C, etc

                                                                                                          also
                                                                                    INVESTIGATIONS, DIAGNOSIS & TREATMENT

 

 

Your personal physician (General Practitioner) need not be a Specialist Oncologist. Using the protocol outlined here, your personal physician and you can follow, step by step, how you can play a pivotal role in the treatment of your cancer with the oral medication, Lithium.

 

Lithium tablets are cheap and readily obtainable. However, you need a prescription within Australia (and other places). Most doctors would be expected to be cooperative if a clear protocol is put before them and their supervisory role is made clear. They will also need to arrange the pathology tests and the imaging that are required for scientific-based treatment and monitoring.

 

Indications. The typical patients who would probably consider the Lithium treatment protocol for their cancer would have :

 

Your preparation. To put things on a scientific basis and for your protection, you should have some baseline assessments/tests to ensure that undesirable side effects do not develop and apply some measures for the effectiveness of the treatment :

 

a)      Absolutely essential :

                      i            Serum creatinine. Creatinine is a breakdown product of muscles and is excreted by the kidneys. If your kidneys decline in function, the creatinine level rises. It is a standard measure of kidney function. Lithium is largely eliminated by the kidneys, so that, if your kidney function is poor, Lithium can build us in the body and produce undesirable side effects, or toxic effects if it rises too high (see later to Lithium Toxicity).

The upper limit for serum creatinine that is usually quoted is ~120 μmol/L (= 0.12 mmol/L) – (some laboratories may vary).

From this, most laboratories in Australia now calculate an estimated glomerular filtration rate (eGFR), which falls as the kidney function falls. It takes into consideration the patient’s age, and may reveal that, despite a “normal” serum creatinine, the kidney function may, in fact, be reduced or impaired.

                    ii            Serum Calcium. Normally, the serum level of Calcium is tightly controlled. Some tumours cause the serum Calcium to rise, through complex mechanisms, and this can result in a medical emergency in order to bring the Calcium back under control. Lithium can also cause the serum Calcium to rise. So, it is important to know its value in advance, to see if there could be problems.

Serum Calcium is usually in the range of 2.1 - 2.6 mmol/L (some laboratories may vary), and a “corrected” Calcium is usually expressed for greater relevance. It is calculated using the level of Serum Albumin, which must be measured as well; it usually has the same reference (normal) range as the straight serum Calcium.

The basic tests that your doctor needs to order for you are :

ü      Serum Creatinine

ü      Serum Calcium

ü      Serum Albumin

Additional tests for treatment assessment. As a general principle, you should attempt to have measures of treatment responsiveness. These may require Specialist interpretation, and are largely informative. Tests that may be considered are :

ü      Serum tumour marker. If you are considered incurable, you should be aware of any tumour marker that has been elevated to date. A baseline reading of this/these should be taken. It may rise temporarily, if there is appreciable tumour breakdown, then to fall later, reflecting the reduced tumour mass.

ü      Serum Uric acid (= urate). This is a measure of the breakdown products from cell nuclei (in particular). It will rise if there is tumour breakdown

ü      Serum Lactate Dehydrogenase (= LH). This is a sensitive measure of cell wall integrity. When tumour cells break down, the Serum level rises.

ü      There may be others indicated for particular patients (ask)

“Intellectual” tests.

ü      Lymphocyte surface markers, including NK (natural killer) cells. These give an indication of changes in the cellular immune tumour-rejecting machinery. They are more expensive than the other tests, so are best reserved for special indication (ask)

ü      “Spot” Urine Tests. Changes in the serum levels may be subtle, whereas breakdown products of degenerating tumour cells excreted in the urine may be more sensitive. A “spot” urine is one that is not collected over a timed interval. In order to obtain meaningful, comparable results, the usual practice is to express the result of the substance under consideration against the urine creatinine level. Two substances seem to have information value :

Ø      “Spot” Uric acid:creatinine. This may provide a sensitive indicator that tumour cell nuclei are breaking down,

Ø      “Spot” Calcium:creatinine. The explanation of this is less clear, but initially, it probably reflects the release of Calcium from the tumour cells that are breaking down. Later it probably reflects bone metabolism (particularly breakdown).

Tests for particular organs.

                 The main ones of concern if there is tumour involvement are the liver and bone marrow. The state of the liver is usually monitored with a battery of tests known as "Liver Function Tests." The state of the marrow is usually monitored by the Haemoglobin, White Cell Count (with differential count) and Platelet Count, with the biochemical tests ALP and Calcium (see above). Discuss with your personal physician whether these, or other tests may be useful (ask).

 

b)     Imaging studies. You must try to have a very recent image of your tumour, wherever it is. X-rays are generally too crude (although those of the lung may be useful). A CT scan should be sought. An MRI is required for the brain. This will provide a baseline against which all future scans can be compared. Without a convincing image change, no-one will believe you.

 

Obtain you Lithium tablets. There a two forms of Lithium available in Australia – a simple form of Lithium Carbonate (“Lithicarb” 250 mg x 200), and the “slow release” form (“Quilonum” 450 mg x 100). For this protocol, only use the quick-release Lithicarb form – the rapid rise and fall of the blood Lithium level is probably important. (The slow release form is possibly better in Psychiatry). Lithicarb is classified as S4, meaning that a Doctor’s prescription is required. In discussions with your doctor, the indications for the usage, (including that Lithium is an immune stimulant and assists fighting infections), should assist. Your doctor will need to order the baseline tests and imaging, and then the ongoing monitoring, so that he/she will be in the picture as your treatment progresses.

 

The Lithium Treatment. If your Serum creatinine/eGFR and Serum Calcium (corrected) are acceptable, and you have all the other appropriate baseline tests/images, you can start Lithium treatment. (If your kidney function is mildly reduced, you may also be able to start, but with a reduced Lithium dosage and more frequent pathology checks  – ask.)

Lithium Rx protocol. This is outlined in the Chapter “Prostate Cancer and Lithium – a Therapeutic Renaissance,” to which you should refer. ( Click here for site Home Page ) Each treatment cycle is over two days (tip: use odd or even dates to remember the first day of the cycle) :

 

            Day One: Set a convenient time 20-30 min. before a meal, such a 12:00 h (midday). On an empty stomach, take 2 (two Lithicarb x 250 mg, = 500 mg) of the 250 mg tablets with a glass of water. An occasional patient may experience nausea, in which case have the tablets with a sandwich or a banana/etc.

At close to 6 h later (6 pm; = 18:00 h) take another 2 (two Lithicarb x 250 mg, = 500 mg) tablets with a glass of water (having a meal more than 20 min later). If you are like most people, you will forget the timing. It is important with this protocol to set an alarm clock (eg mobile ‘phone) for the next dose time – or you will lapse !

 

            Day Two: Have NO Lithium tablets; but make sure that you have a good fluid input. Aim for at least 3 L/day, because water washes the Lithium out through the kidneys and helps attain a lower blood level before the next Lithium Rx day. [If you, in error, continue taking the Lithicarb 250 mg x 2 = 500mg) every day, you may rapidly run into lithium toxicity (see later)].

 

          After the baseline tests/images :-

Start (Day 1)

Midday: Lithicarb 250 mg x 2 (= 500 mg) + water

 

6 PM (18:00 h): Lithicarb 250 mg x 2 (= 500 mg) + water

Day 2

NONE

 

Day 3

Midday: Lithicarb 250 mg x 2 (= 500 mg) + water

 

6 PM (18:00 h): Lithicarb 250 mg x 2 (= 500 mg) + water

Day 4

NONE

 

Day 5

Blood test for Serum Lithium level (in the morning)

 

Midday: Lithicarb 250 mg x 2 (= 500 mg) + water

 

6 PM (18:00 h): Lithicarb 250 mg x 2 (= 500 mg) + water

Day 6

NONE

 

Day 7

Midday: Lithicarb 250 mg x 2 (= 500 mg) + water

 

6 PM (18:00 h): Lithicarb 250 mg x 2 (= 500 mg) + water

         and so on . . . . . .

 

If you are likely to be forgetful, have someone with you to remind you, and check the dosages off on a calendar.

 

Lithium Monitoring. You must have a check of your Serum Lithium level after 2 (two) Lithium treatment cycles : If you took your first two doses on day 1 (start, 1st day taking Rx), then the second two doses on day 3, then you should have blood for a serum Lithium level taken in the morning before the Lithium Rx on day 5, when the serum Lithium level should be at the lowest point in the cycle (see table above). If this Serum Lithium level is, or above 0.5 mmol/L, there should be a dose reduction (ask). If it is much higher, the Lithium Rx should be halted until the situation can be understood (ask). If there is any doubt, simply stop the treatment and reassess the situation (ask).

 

Ongoing Monitoring. This may require individual variation (ask). In general, all the baseline pathology tests, including serum Lithium, should be measured at about 10 -14 days. These, and imaging, can be performed at one month from the start of Lithium Rx. There is a latent period, which may vary between 30 days for faster growing tumours, to 2-3 months for slow growing tumours, before any appreciable diminution of the tumour may be identified, although there may be early changes shown in spot urine tests or blood tests.

 

Lithium side effects and toxicity. Lithium is not metabolized by the body; what goes in, comes out, principally in the urine. It has a relatively narrow “therapeutic window,” meaning that there is not much margin between having a desirable effect, and starting to produce undesirable side effects, and then toxic symptoms. That is why there is the importance in checking kidney function, maintaining good fluid intake, and checking serum lithium levels frequently. Even in the upper therapeutic range, certain side effects may be noted : increased urine output, loose bowels, abdominal discomfort. At higher levels and extending into the toxic range : slurred speech, unsteady gait, coarse tremor, unclear thought (a bit like alcohol). The more severe toxic symptoms of confusion, delirium, unable to stand, vomiting and diarrhoea, are mentioned here, but these should never occur if good care is taken and accurate records kept. Those living with you should be advised, so they may spot the early changes of lithium side effects/toxicity easily.

 

Lithium toxicity – treatment. If Lithium toxicity is suspected and the patient can still walk, talk, and is not vomiting, simply cease all Lithium doses and push fluids and the Lithium will slowly be washed out in the urine. If the patient is unable to walk, communicate sensibly, and/or is vomiting, urgent medical attention is indicated. Try to ascertain why the toxicity developed (eg worsening renal function, dehydration, or confused tablet taking).

 

Feedback will be welcome

 

  Click to E-mail me with concerns about  CANCER, RHEUMATOID ARTHRITIS,
                                                                                    LUPUS ERYTHEMATOSUS,

                                                                                    MULTIPLE SCLEROSIS,
                                                                                    SARCOIDOSIS, HEPATITIS C, etc

                                                                                                          also
                                                                                    INVESTIGATIONS, DIAGNOSIS & TREATMENT

 

 

Malcolm Adams Traill

 

Copyright © MA Traill December 2008