Q & A Session with Friends of Max Volunteer
Adyar Cancer Institute, Chennai
22nd May 2010, Saturday
The Medical Panel of experts
Dr. M B Agarwal – Mumbai
Dr. T G Sagar – Adayar Cancer Institute, Chennai
Dr. Raghunadha Rao – NIMS Hyderabad
Dr. G Ramanan – Apollo Specialty, Chennai
Dr. R Rajendranath – Adayar Cancer Institute, Chennai
Dr. G Prasanth – Adayar Cancer Institute, Chennai
Q1. Are there any specific treatment for side effects like muscular cramps (esp. in the calf muscle), skin patches and freckles? How to manage such issues?
Ans: In general, any drug will have its side effect while trying to cure a larger problem. Patients have to understand that there’s no foolproof system of medication/ treatment. Cramps, skin patches & freckles are the most common side effects of Glivec.
As far as cramps are concerned, patients are generally advised to tolerate and accept the symptoms as long as it is bearable and are strictly advised not to break the treatment/ decrease the dosage/ avoid medicine. However, if the effects are unbearable, minor complaints could be managed with the help of some painkillers. In some cases, Calcium replacement, Vitamin D replacement also helps.
During the course of treatment the pigment in the skin is lost and hence the skin patches and freckles. Again, there is no specific treatment for skin patches. Patients are advised to value the benefits of the medicine and accept the side effects as long as it is bearable and always keep the doctor in loop.
Q2. Can the patient take twice the dosage the following day if he/she misses the dosage for the day? Similarly, if the patient takes 2 dosages the same day, should he/she skip the dosage for the following day?
Ans: If the patient forgets to have the medicine that day, he should not have double dosage the following day. Similarly, if he/she consumes twice the same day forgetfully, should not miss the dosage the next day. In short, stick to the daily dosage pattern.
Q3. When a patient suffers from fever and common cold, should he consult hematologist or general physician? What if the patient has to travel a very long distance to meet the hematologist?
Ans: If the patient cannot travel a long distance, they can reach out to their hospital/ physician through the helpline numbers. The first step is to check the blood count. If the count is more than 4000, it is okay to get in touch with your general physician for first hand aid. However, if either the physician or the patient is unsatisfied with the aid, it is advised to immediately get in touch with the treating physician directly or through helpline initially.
If the patient is advised Glivec recently (< 3 or 6 months), the fluctuation in the blood count would be more, it is advised that the patient gets in touch with the treating oncologist instead of general physician.
Q4. Can Glivec be had along with paracetamol tablet during fever / cold?
Ans: Though in medical literature, patients are advised not to combine paracetamol and Glivec, one/ restricted dose of paracetamol can be had along with Glivec.
Q5: (a.)Can the day’s dosage be split for morning & evening?
(b.)Is there any difference between 100 mg tablet & 400 mg tablet?
(a.) In order to ensure complete effect, medicine should be had as a single dosage only and NOT to split.
(b.) Except for the dosage, there is no difference between the two in terms of medicinal value and effect. If the patient is advised 400 mg per day, he can have Four 100 mg medicines / One 400 mg medicine. Both have the same effect only.
Q6: Can a female Glivec recipient on complete cytogenetic response plan for a baby? Can Glivec be taken during pregnancy? Is breast-feeding safe on Imatinib?
Ans: The general recommendation is, once the patient decides to have a baby, she has to go off Glivec throughout the pregnancy and during breast-feeding period. The negative factor is, even if the patient has achieved a complete cytogenetic / molecular response, and is off Glivec, some of the patients would lose their control. However, when Glivec is resumed, most of the patients achieve that response back. Though there are cases where patients continued Glivec during pregnancy giving birth to baby without any congenital disease/ malfunction, there are also recorded cases of babies born with congenital defects. In such cases the defects are higher not because of CML but of Glivec. Whatever the case may be, medical recommendation is to stop Glivec during pregnancy and nursing period.
On the other hand, fathering a child is safe while the patient is on Glivec, except that the patient needs frequent monitoring and prospective mother needs proper obstetrics care.
Q7: Can CML patients avail railway/ airway subsidies on travel for treatment visits?
Ans: The Govt. instituted rail travel subsidies for Cancer patients in the year 1969. Patient can avail 100% and attendant can avail 75% concession in the lower class and in upper class patient can avail 75% & attendants can avail 50% concession. In case of air travel, only patients get 50% concession.
Q8: Medical insurance companies deny insurance on air travel for CML patients. How can one avail? Can Cancer Institute help?
Ans: In India, insurance companies treat CML case as any other Cancer case. Hence there are no special considerations given to CML patients. However, if the patient must travel, he/she as an individual case, can carry specific letter about their health condition from their treating physician and request the Insurance company to look through the case as any other chronic cases like diabetes / hyper tension.
Q9: Should a patient reveal his/her health condition to the organization he/she is employed? What are the implications in either case?
Ans: On the face of it, most CML patients under proper medical guidance do well health-wise. However, regular health checkups and treatment will demand the patient to take time off from work time to time. Hence, it is best to inform & clarify the organization before joining. At the same time, there are companies apprehensive of the employee’s health condition (as they consider all cancers to be the same) and may be reluctant to offer benefits offered otherwise. In such cases, it is best that the patient carries a very detailed letter about their health condition from their treating physician assuring that the employer will not face any adverse situations in matters concerned to their employee’s heath condition.
Q10. A patient on Glivec is also on treatment for heart condition, diabetes and Hypertension. Will consumption of Glivec aggravate /affect heart condition?
Ans: Glivec per se will not affect the heart condition. However, the side effects like swelling of legs (leg edema), puffiness near eyes etc might give a false indication to the patient and the physician. In certain accelerated/acute cases of CML there are possibilities of swelling near heart, whereas in CML there is no proven case that indicates any adverse effect of Glivec on heart condition. Ideally, the cardiologist should be well updated about patient’s CML condition and the effects of Glivec prior to treatment.
Q11. Is there any precautionary measure to be taken if the patient has to undergo cataract surgery or dental extraction?
Ans: First step, prior to any surgery, inform your treating oncologist and get their inputs. In general, in Chronic cases, minor treatments like cataract/ dental extraction can be done without much worry. It is again best to carry a letter from the treating oncologist about the health / fitness condition before proceeding for any surgery in order to help the other surgeon for further treatment.
Q12. Is there any significant difference between generic Imatinib and Glivec medically? Is the efficacy of generic Imatinib is equivalent to Glivec?
Ans: If Glivec is available, then it is highly recommended as Glivec is the original molecule. However, in India there are other bio-equivalent Imatinib alternatives available which is equally effective. It is best for the oncologists to decide after thorough evaluation of various factors. As far as the side effects are concerned, there is not much difference between the generic drug & Glivec and the treatment profile is also similar.
Q13. A specific case where a patient’s BCR/ABL was Nil (negative) for the last few years. In a recent test done it was revealed that BCR/ABL was 10% and is advised mutation studies. How to interpret the molecular value and its implications and what are the options available in such cases?
Ans: The BCR/ABL value / molecular control is interpreted on ‘log’ basis. The base molecular value is assumed as 100%. If BCR/ABL count at any given time is between 100-10%, then it is 1-log, if it is 10-1% then its 2-log, if its 1-0.1% then its 3-log and if it is 0.01% then it is 4-log. The goal is to achieve negative or at least 3 to 4-log reduction.
In this specific case, if the patient has lost the molecular control adversely, the first step is to monitor that medicine is taken regularly as advised and the test is re done. It is advised that test is taken only at oncologist recommended lab/ reliable lab. If the test taken again confirms that the patient has lost molecular control, then it indicates that the patient had developed resistance to the drug.
The following option can be looked at this stage:
Option1: To increase the dosage for a period of time, then check BCR/ABL value. But ensure that WBC does not drop drastically.
Option 2: To advise 2nd generation drug alternative, Tyrosine Kinase Inhibitor (TKI) like DASATINIB or NILOTINIB, which is now available in India. The only drawback is that these drugs are expensive and is not covered by any program like that of GIPAP. Similarly, trials are going on still for another 2nd generation drug called BOSATINIB, which is available in market, expensive again.
Option 3: If the patient is young, financially sound and has identified a matching donor, can opt for Bone Marrow Transplant.
Option 4: Combination therapy- If all the above options (tried exclusively) do not work then a combination of drugs like Imatinib and Interferon or other alternate sources can be tried to achieve desired result.
Additional point: If the BCR/ABL value fluctuates between the 3-log & 4-log values, then there’s not much cause for worry. On the other hand, if the fluctuation is drastic then the options have to be tried in consultation with the treating oncologist.
Q14. What is FISH test? How is the value interpreted? How is it different from BCR/ABL or molecular test?
Ans: FISH test is another alternate to BCR/ABL, but slightly inferior in technology. Few lab centres that do not have facility to perform BCR/ABL test, carry FISH test. Unlike BCR/ABL the drawback of FISH test is that, it may reveal what is called ‘false positivism’ i.e. if your FISH test value is < 10%, then the most likely chance is that BCR/ABL value is Negative / Nil. Any value <10% in FISH test is acceptable. If the cytogenetic shows no ph chromosome, yet FISH test gives a positive value, it is better to follow up with BCR/ABL (and bone marrow cardio typing in worst case scenario) to get a genuine picture of molecular control.
Q15. What are the adversities of Bone Marrow Transplantation?
Ans: If bone marrow is the only option available, then the failure rate is 30%. The outcomes are as follows:
(a.) The procedure is unsuccessful and the patient might die in the process
(b.) The disease may not disappear or may resume anytime.
(c.) The patient might develop certain serious complications from the procedure.
In total, the failure rate can be 30%. Other factors that determines the success / failure is the competence of the centres, treating options, age & fitness of the patients etc.
Q16. Can a CML patient on sustained molecular remission a.) Stop the medicine? b.) Reduce the dosage of medicine? c.) Reduce the frequency of medicine?
Ans: The solution is based on the tolerance level of the patient. If the patient tolerates the treatment well, though on molecular control for a very long period, the ideal medical advice would be to neither stop /reduce the dosage at any given time. In case of intolerance, it is better to increase the interval rather than stopping the medicine. The treating physician is the one to decide on this.
Q17. What is the difference between ‘Glivec intolerance’ and ‘Glivec not working’ on a patient?
Ans: Any drug administered on patient will have an effect, either positive or adverse. From a medical view, if the effect of Imatinib is adverse, leading to intolerable side effects or complications like body ache, swelling etc. it is referred to as ‘intolerance’. In such cases the probable chances are that patient will respond to the 2nd line of TKI’s. If the medicine is not working on the patient, there would be no OPTIMAL symptom of cure / positive effect on the patient which can be interpreted through tests like BCR/ABL or FISH.
Q18. Can Bone Marrow test be done in a less painful manner? What does Bone Marrow test reveal that BCR/ABL does not? Is there an alternate procedure?
Ans: As per the literature, if a cytogenetic response is achieved then there is no need to perform a Bone Marrow test. However, there are certain parameters, which the blood test/ molecular test alone cannot reveal, in such cases a cytogenetic scan or other modes of test including Bone marrow is performed on the patient. The solution to a lesser painful Bone Marrow test is in the hands of the physician. The treating physician should take optimum care to counsel the patient, provide ideal ambience, sedative and time instead of rushing the procedure thereby ensuring a more or less painless experience.
Q19. Is CML hereditary?
Ans: CML is caused due to abnormality in the chromosome. The abnormality happens after birth, in specific cells that are in the bone marrow and not in the cells that are responsible for reproduction, or cells that transfer the gene pool to the next generation. CML is an acquired condition due to an unknown reason where there’s a mutation or abnormality in the chromosome, which converts a blood cell into a cancerous cell in the Bone Marrow thereby producing abnormal amount of WBC leading to leukemia. Hence CML it is not hereditary and does not affect the cells responsible for reproduction and not genetically transmitted to the next generation.
Also, there is no identified genetic risk factor, which would predispose a person to develop CML.
Q20. In case of Japan, after the bomb blast in Hiroshima & Nagasaki, the generations of children were found to have leukemia due to the mutation in the chromosome. Is there any specific cause for CML in general all over the world? Is there any possible preventive measure identified?
Ans: As far as Japan’s case is concerned, research studies have proved that the radiations play a major role in the mutation of chromosome. Whereas in case of CML, the studies done and the ongoing research reveal only a limited information that CML is caused due to mutation in a specific chromosome and NOT the actual cause / reason for such abnormality. In other cancers like cervical, breast, etc the possible cause is identified and hence the treatment available at a large scale. Unfortunately, for CML there is no literature on possibilities for such abnormality /preventive measure and it is relatively a rare type of Cancer unlike the others.
Q21. Is it acceptable for patients on Glivec to consume liquor on social occasion? What are the passive effects on smoking on CML?
Ans: There is no data, which prevents the patient on Glivec from social drinking or getting a little exposed to passive smoking. Only the patient should know his or her limit, otherwise can lead a normal life.
Q22. How is the treatment monitored for a patient who is advised Glivec newly?
Ans: The initial step is clinical examination, then a complete blood count or peripheral smear followed by a bone marrow to check for the Philadelphia chromosome. Once the treatment is initiated and drug administered, the first few months are very crucial period for there could be huge fluctuation in the blood count and even patient might experience certain discomforts. Hence, at this stage a frequent and periodic monitoring and blood test is done. Once the treatment stabilizes, physician looks for cytogenetic response / molecular response and hence BCR/ABL test is done once in a quarter and sometimes infrequently as required. To summarize, the test would be a complete blood picture (which would be the recurring theme) occasional bone marrow test (preferably in the early stage), then BCR/ABL performed once in 3-6 months.
Q23. Given the fact that there is some amount of toxicity with Glivec, what is the need to fix the minimum dosage as 600 mg in most cases?
Ans: In TKI (2nd line drugs), there are plans to advise one-size-fits-all dosage. The goal is to inhibit the enzyme all over the body. There is a similar dosage-response relationship w.r.t. Imatinib too. Studies have shown that maximum inhibition occurs between 600 – 800mg dosage and the response is also maximum and quicker. It is also a fact, higher the dosage, higher is the toxicity. If the trade off is between the response and dose, given the toxicity level, the preferred minimum dosage is 400mg. However, for some reason, on a case-to-case basis if the response is better in higher dosage and if the patient tolerates, then there is no reason not to fix the minimum dosage as 600mg given the fact, whatever the dosage be, there is going to be a certain amount of toxicity.
Q24. If a patient on higher dosage of Imatinib achieves molecular control of 3 to 4-log reduction, can the dosage be reduced to 400 mg?
Ans: The standard dosage, in literature, for Chronic phase is 400mg. Studies and tests over a decade has convinced physicians all over that 400 mg is good enough for CML. But for some reason on a case-to-case basis if the patient is advised a higher dosage and has achieved a response, then it is advised to persist with the advised higher dosage. If the patient is unable to tolerate, medically or on financial grounds and if all factors permit, the physician can advise 400 mg itself. From medical point of view, once resistance is developed at a lower dose, physician tries to achieve a response through increase in dose. Once the response is achieved and if the patient tolerates the shift then they persist with increased dose. It is recommended to do all necessary evaluations before moving from lower to higher dosage and vice-versa.
Q25. Can a patient on ‘Sprycel’ currently (who was earlier on Imatinib) shift back to Glivec once remission is achieved through Spricel?
Ans: If there are ‘n’ mutant cells in the body, not all the mutant cells show sensitivity to a particular drug, there could also be cells that are resistant to that drug. Similar is the case for Glivec and Sprycel, which are 2 different drugs with same efficacy on CML. It is to be understood that, Sprycel is administered to cure CML mutant cell in general and not just on Imatinib resistant cells alone. Medically, if a patient is administered Spricel on account of resistance developed on Glivec, it is ideal to persist with Sprycel.
Q26. When Glivec is not tolerated, hemoglobin, WBC and platelet levels drop. Can blood/WBC/platelet transfusion be done depending on the case?
Ans: When RBC/ platelet levels drop to a very low range, RBC (blood) transfusion or platelet transfusion can be done. For lower WBC level, WBC transfusion cannot be done as it only lasts for a few hours in the body and also risk factors are more. Instead, if WBC is consistently low, to keep the neutrophil up, ‘GCSF’ injection is administered along with Glivec. It is an expensive modality though. If the platelets drop to a dangerously low level, then Glivec is suspended temporarily and transfusion is done. In case of drop in hemoglobin to a very low count, ‘Erithropoitin’ is injected to improve the RBC count and the patient is advised to continue with Glivec.
Q27. From an awareness/ knowledge perspective, what are the possible side effects that a patient on Glivec for more than 5 years should look out for?
Ans: Most of the fluctuation / perturbations in the body or counts appear in the initial phase of administering with Glivec. Once the patient tolerates and responds well to the drug and the disease is in remission, it is unlikely to have any critical side effects so way down the line. Having said that, since the drug literature is available only for a decade, not many critical side effects or after effects are identified as of yet. Researches and studies are going on to identify newer problems of long-term consumption of drug. In a very small percentage of patients on long term Imatinib medication, bone issues due to toxicity and vision disturbances have been found exact cause for which is unknown. Secondly, recent analysis have identified that an isolated central nervous system relapse might occur, i.e. CML might grow in the brain. However, substantial data is unavailable to support any of the above.
Similarly, there are pediatric CML cases on Glivec identified with bone issues, but the literature and factual data on pediatric CML is very limited as the population is very small.
Q28: Is there any age restriction form Bone Marrow Transplantation?
Ans: Worldwide BMT is done on patients up to 50-60 years. The success rate is better on younger patients if all other factors are normal. However, from the medical angle, BMT is NOT recommended if patient responds well with 1st / 2nd generation drugs, if BCR/ABL is in desired range, if there’s no significant toxicity. BMT as an option should be considered only if other options of treatment fail.
Q29. How should a CML patient respond to a question on their health condition to another person – whether ‘cured’ or ‘in control’?
Ans: In India and across the world, literature on CML and many types of cancer were made available only from 1999. It is still a very early stage to call oneself ‘completely cured’ unless medical experts confirm on a patient that there is no evidence of disease. Once molecular control is achieved, patient can address the condition as ‘in good control’ or ‘in sustained molecular remission’. Medically, it would be ideal to describe the condition as ‘in control’ of the disease.
Q30. Should I reveal my CML condition to others at all?
Ans: It is very subjective and depends on how one perceives his/ her medical condition. CML per se is a chronic disease like that of diabetes, hypertension etc. Years before, there were apprehensions about diseases like diabetes, hypertension, etc., but today it’s has become a very common name in our household. Similar will be the case with CML or leukemia down the line but as of today very limited literature is available to general public. However, thanks to medical efforts and studies globally the perception on disease and one’s illness has changed for good. The focus / goal of the Medical and social fraternity is to identify methods of medication and cure for any type of disease. Hence from a medical community’s point of view, as long as the patient could provide a moral support to oneself or to a similar person there is no harm in revealing the medical condition. In addition to that, it is a must that the patient’s primary care giver, say family general physician or dental physician or the one’s from whom the patient seeks medical advise apart from oncologist / hematologist should be very well aware of the condition in order to provide ideal medical care.
Reported by Supraja Sriram