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Colorectal Cancer is described as the third most common cancer in the UK. The statistics states that about 40,000 cases of colon cancer are registered each year. Among those patients, about half of them survive for not more than 5 years.(Cancer Research UK).
Although, the aetiology of the CRC is not clearly understood, it is believed that 85% - 90% of CRC cases are because of genetic, environmental and diet factors (Campos et al., 2005). Advancing age is considered as one of the greatest risk factor favoring the development of CRC (Nelson et al., 1997). CRC is mainly seen in the people above 50 years or older. However, 15% of colorectal cancers found in people who are less than 45 years old. But still, the highest rate of colorectal cancer occurs among those aged between 65 and 84. (Byrne, 2008).
According to Dr. Jemal, men are more susceptible to develop colorectal cancer than women. The conclusion of her statement can be clarified by viewing here article named 'Cancer Statistics, 2008'.According to this article, the rate of colorectal cancer between 2000 and 2004 was 69.2 per 100,000 population among men and 45.8 per 100,000 population among women. Apart from this, the article also describes that in USA, when compared to other races, the African Americans have the highest rate of colorectal cancer. (Jemal et al., 2008).
Adjuvant folinic acid/5-fluorouracil chemotherapy:
In case of Mrs RP, old-age factor is likely to be responsible for the Dukes (stage 3 ) colon cancer. After her surgery, Mrs RP received adjuvant folinic acid/5-fluorouracil chemotherapy for six months. 5-FU has been a prime drug for the metastatic colon cancer treatment since the last 45 years. 5-FU inhibits thymidyate synthase (TS) and integrates with DNA and RNA which leads to cytotoxic action inside cells (clasina et al., 1995). Several regimens have been tested and investigated along with this prime drug. One of this regimen includes combination of 5-FU with modulators such as folinic acid, which can be used as continous infusion schedules (Thierry et al., 2007) .
If the extensive co-morbidities of Mrs RP (especially CVD and Advanced age) and the key principles of chemotherapy are taken into consideration, it seems appropriate to consider the use of folinic acid/ 5-FU rather than including the combination of chemotherapeutic drugs.
Carcinoembryonic antigen (CEA) and recurrence:
The most useful application of CEA (which was found to be at a rising level in patient) is in the detection of metastasis from colorectal malignancy (Michael J. Duffy, 2001). No doubt, that oral formulations of 5-FU allows a protracted exposure. It is also true that it does not need a central venous catheter, or the high cost fusion pump. However, the absorption of 5-FU from the Gastro Intestinal tract, in its original form, is very unreliable. Thus, there's a possibility for the errors in bioavailability of this drug. (Hoff et al., 2001)
This might be a strong possibility of the occurrence of this condition in the case of Mrs RP. Moreover, Mrs RP takes a potent laxative, co-danthramer. Co-danthramer is a combination of poloxamer 118 and co-danthrusate and is considered as a carcinogenic in nature.( Siegers et al.,1993) Considering the initial complications of Mrs RP, there's a slight possibility, that it may have been a reason for the recurrence of the cancer, and the metastasis. Nausea, loss of weight and anorexia are frequent symptoms linked with recurrence of the cancer. The abdominal pain and loss of appetite are side effects because of 5-FU, while flatulence and abdominal pain might be due to liver metastasis.(Leconte,1999)
Mechanisms Of Resistance Of Neoplasm:
The following figure shows many ways responsible for the mechanisms of resistance of neoplasm. (Michael M. Gottesman, 2002)
Laboratory Results Justification:
Turning the attention towards laboratory results, the lab results of Mrs RP are normal and uneventful, apart from the rise of potassium levels. It clearly indicates the sign of hyperkalamia, which initially shifts the attention towards the renal impairment. But the renal function deteriorates with the advancement in the age. In order to come to an appropriate conclusion regarding the normal critical clearance, it is compulsory to co-relate it with the age of the patient. This comparison can be carried out by Cockcroft-Gault formula which is stated as under.
Creatinine clearance (mL/min) = X Ã- (140 - age) Ã- weight (kg)
Serum creatinine (micromol/L)
where X = 1.04 for females and 1.23 for males. (Graham et al., 2003)
So, adding the values to the above equation,
Creatinine clearance = 1.04 Ã- (140 - 74) Ã- 51
Creatinine clearance = 74 mL/min
This value represents a normal renal function. Thus the chances of increase in serum in potassium level due to renal impairment are very negligible. However, having a close look at the daily medications of Mrs RP states that there is a wide possibility that the patients' hyperkalamia might be drug- induced. Ramiprill, a potent ACE inhibitor, can cause potassium retention with co-amidifurose (a combination diuretic), which might result in increase in serum potassium levels.(Davies et al,. 2000) It would be practical to advise the clinician of consider this standpoint and if possible, replace the combination diuretic with a potassium sparing diuretic like furosemide. In the same manner, the patient must be advised to exclude the potassium containing victuals from her diet.
Details Regarding Patients Current Medications:
Mrs. RP has an extensive past medical history, because of which she is on some medications. A brief information of the medications is given in the table below:
Medications as per Prescription
Mechanism Of Action
Co-amilofruse 5/40 one tablet p.o. daily
Used to treat Oedema, which is caused by heart failure, kidney problems and liver diseases.
Ramipril 5 mg p.o. daily
Prevents vasoconstriction by inhibiting ACE and thus helps to prevent angiotensin 1 and 2,causing decrease in the blood pressure & decrease in aldosterone secretion.
Digoxin 125 Âµg p.o. daily
Used to treat heart failure and arrhythmias
Co-danthramer 10 mL p.o. nocte
Faecal softeners/stimulant laxatives
(poloxamer 188 + dantron)
Increases the water content in the stool making them easier to pass. (Dantron laxative works by stimulating the nerve endings in the walls of the intestines causing muscles to contract more to alleviate the abdominal pain.)
Sertraline 50 mg p.o. daily
Works by inhibiting CNS neuronal uptake of serotonin, leading to an increase in the level of serotonin in the CNS.
Warfarin - variable dose according to INR (currently 4 mg alternating with 5 mg daily).
Works by slowing the production of this vitamin K by the body
Oral chemotherapeutic drugs-Laws and Documentations:
The optimum position, to which the oral chemotherapeutic drugs might be dispensed, is gaining a lot of importance these days as these drugs are available to a wide range of tumours. A statement on "the safe practice and pharmaceutical care of patients receiving oral anti-cancer chemotherapy" was presented in 2004 by 'The British Oncology Pharmacy Association' (BOPA).This document consists of the principles, on which the the clinicians well as oncologist must cling to while dealing with anti cancer drugs and the patients. These norms were also reinforced by Depatment of health publication (2004) in an article named ''Building a safer NHS for patients: improving medication safety''.
Following the progress in chronological order, in the year 2008, a rapid response report based on 'Incorrect dosing of oral anti-cancer medicines' was issued by National Patient Safety Agency. The purpose of this report was to give a 'heads up' to the healthcare staff related to the cycle of prescribing and dispensing potential drugs to the patients. If viewed closely, almost all the main principles stated in these documents go parallel with each other.
Single-agent Oral Capecitabine Chemotherapy:
Focusing o the single-agent oral capecitabine chemotherapy, according to the 'summary of product characteristics 2008', the dosage of capacetabine are only needed to be reduced, if creatinine clearance is between 30 and 50 ml/min, and that to 75%. However, in this case, as we saw it earlier, the creatinine clearance, is 74mL/min. Thus, there is no harm in providing capecitabine to the patient. According to Mrs RP's body surface area, she is prescribed capecitabine 1800 mg p.o.b.d. for 14 days.
Warfarin Medication Cautiousness:
It can also be observed that Mrs. RP is currently on warfarin (coumarin derivative, anticoagulant) to prevent the recurrence of thromboembolism as she was diagnosed for deep vein thrombosis that was 1 month ago. There have been reports and cases regarding altered coagulation and bleeding signs in the patient taking capecitabine concomitantly with anticoagulants like warfarin. According to the present condition of Mrs RP, it is likely possible that she might be continuing her warfarin medication for at least two more months. Hence it becomes necessary to take some defensive measures in order to manage this drug interaction. A couple of them are as follows:
The oncologist responsible for the treatment should be warned regarding the interaction an if possible, close monitoring IR of the patien during treatment with capacitabine.
Suggesting Mrs RP regarding the possible effect an make her more cautious about monitoring the clotting aand adjustment in warfarin dosage.
It is very necessary for the patients to observe and manage the side effects of the oral chemotherapy appropriately, so that the patients can keep the track of the intensity of these side effects and thus take the necessary precautions or in some cases, urgently report to the clinician. In case of Mrs RP, there's a great possibility that her diarrhoe might be a side effect of capacetabine. At the end of the day, capacetabine is a prodrug of 5-FU and thus, can show many side effects similar to 5-FU(Walko et al., 2005). These drugs are cytotoxic agents which can cause gastrointestinal toxicity which may result into diarrhoe.
However, diarrhoe is one of the most common side effects of the drugs. Thus, it becomes very important to co-relate different conditions along with the other disorders faced by the patient. Therefore, before reaching to the conclusion, it would be a better option to ask Mrs. RP regarding an episode of any medical condition like gastroenteritis, a very common condition, which causes diahoerrea. She should be also questioned about her consistency in taking the codanthramer liquid (Faecal softeners/stimulant laxatives), which was noted on her prescription and whether she had stopped taking the drug during the occurrence of diarrhea.
Based on the side effects experienced by Mrs.RP, it might be a better option to reconsider dosage of capecitabine for her second cycle. Perhaps it would be a better option if Mrs. RP is counseled for the use of anti-diarhoerials if there is re-occurrence of diarrhea.
Thus, summing up all the deduced information and combining it with the current conditions of the patient, a special care plan for Mrs RP must be prepared in co-ordination and under the advice of the clinician, based on:
The present wants of treatment, which includes minimizing the symptoms
Appropriate measures in order to satisfy the needs of the treatment,which includes evaluation of treatments ans consideration of the alternative agents (if possible)
Determining the ultimate goal of the treatments which includes maintaining the serum potassium level and controlling the malignancy.
In order to have proper information of the situation and to understand the overall objective of the treatment, patient counseling is very essential. In this case, Mrs. RP should be counseled about the the medications that she is going to administer and the exact reasons for why she is intended to have those drugs. It will also be necessary to inform Mrs RP of the need to monitor the side-effects rather carefully.
Use Of Radiotherapy:
The use of radiotherapy might be considered as a good option. Radiotherapy is painless and it kills the cancer cells by using high-energy rays, without causing more harm to the normal cells(Cancer Research UK). In case of Mrs RP palliative radiotherapy would also be a good option inorder to take care of symptoms of cancer, or to manage the expansion of the tumor(BBC Health).
Use Of Carbon Nanotubes (CNTs)- A Novel Therapy:
Ever, since discovery of CNTs by Iijima, an extensive research has been carried on on CNTs.(Hassan et al., CNTs can be defined as the cylindrical molecules that made completely by carbon atoms.Recently, CNTs have been presented as a novel carrier system of therapeutic molecules.According to Yang and co-workers, the CNTs might be used for targeting the cancer at the lymph nodes. (Yang et al.,2008).