Assessing an Old Male With Metastatic Colorectal Cancer

Colorectal malignant neoplastic disease is the 3rd most common malignant neoplastic disease in the United Kingdom.1 Colorectal malignant neoplastic disease includes cancerous growings in the colon, rectum and appendix. Colorectal malignant neoplastic disease is more prevailing among older people. The incidence in people between the ages of 45 and 49 old ages is 20 per 100,000 as compared to 300 per 100,000 for work forces and 200 per 100,000 for adult females amongst those over 75 old ages of age.

The malignant neoplastic disease can distribute to the lymph nodes and other distant sites. This is known as metastasic colorectal malignant neoplastic disease. When the malignant neoplastic disease spreads beyond extent of lymph nodes, the patient is diagnosed of Stage IV metastatic colorectal malignant neoplastic disease. Metastatic colorectal malignant neoplastic disease may be present as a new disease or develop even after patient undergoes surgery for colorectal malignant neoplastic disease. A survey shows that 50 % of patients who have undergone surgery for colorectal malignant neoplastic disease will develop distant metastases. The 5 twelvemonth endurance rate for metastatic colorectal malignant neoplastic disease without intervention is 12 % 1.

The most common site where the metastatic colorectal malignant neoplastic disease spread to is the liver. 50 % of patients with metastatic colorectal disease demo up with liver as the lone site of metastasis1. 10 % of patients with metastatic colorectal malignant neoplastic disease have pneumonic metastates4. Patients who have liver metastases may endure from icterus and abdominal puffiness. Patients with metastatic colorectal malignant neoplastic disease will besides see hurting in the organ that the malignant neoplastic disease has spread to. As an illustration, patients who have metastatic colorectal malignant neoplastic disease in the bone may see uninterrupted, terrible and localised hurting in the rib or the dorsum.

Metastates in the encephalon may take to jobs with memory, concentration, balance or motion. Lung metastates will ensue in cough and shortness of breath.

As metastatic colorectal malignant neoplastic disease is an advanced disease, it requires a combination of intervention including chemotherapy, alleviative surgery, radiation, physiological support and symptom control to better the continuance and quality of the patient ‘s staying life. The intervention of metastatic colorectal malignant neoplastic disease depends upon the site and extent of metastates. Normally, surgery will be the first pick for patients who have resectable metastates because the as surgery is the lone option for long term endurance. For others, chemotherapy is the first option. Chemotherapy can non bring around the disease but it can better symptoms and may render unresectable tumor resectable.

Merely about 10 % of patients with metastatic colorectal malignant neoplastic disease have potentially resectable liver metastates while another 14 % may be able to undergo surgery after having chemotherapy1. Surgical resection increases the life anticipation of patients. Several recent big series on resection for colorectal liver metastases ( CRLM ) have reported five twelvemonth endurance runing from 25 % to 44 % . However, there is besides a hazard with surgical resection with operative mortality between 0- 6.6 % 2. Poor predictive factors for patients with liver metastases are multiple metastases, metastates larger than 5 centimeter in diameter, synchronal presentation of metastates and high tumor marker levels14. Liver resection might besides take to hepatic failure depending on the extent of resection and presence of liver disease. Complications such as bleeding, bile leak, intra-abdominal sepsis, and cardiorespiratory disfunction can besides take to post-operative liver failure2. There is besides a hazard of return after undergoing liver metastates resection. 60 % of patients experient tumour return after liver surgery for colorectal metastates3. Besides liver metastates, surgical resection is besides usually the first pick for intervention of pneumonic metastates4. In a research conducted among 58 patients who have undergone pneumonic resection, there was no operative morbidity. The 5 and 10 twelvemonth endurance was 29 % and 20 % severally. In add-on, all the 10 twelvemonth subsisters who are still alive now did non see any recurrences4. However, this survey is comparatively little and can non stand for the whole population.

The type of intervention given to the patient besides depends on the general wellness of the patient. Patients who are sufficiently fit with a WHO public presentation position 2 or better are treated with first or 2nd line active chemotherapy1. The common first line chemotherapies include FOLFOX, FOLFIRI and XELOX regimen. FOLFIRI, FOLFOX and XELOX are known as conventional chemotherapy as they attack quickly spliting cells which non merely includes malignant neoplastic disease cells but besides liner of GI piece of land, bone marrow and hair.

FOLFOX involves the use of oxaliplatin, infusional 5-fluorouracil and leucovarin. Leucovarin which is a Ca folinate may be substituted by folinic acid. The usage of folinic acid together with 5-fluorouracil will increase plasma concentration of 5-fluorouracil. The usage of infusional 5-fluorouracil and leucovarin entirely can increase endurance to about 10-12 month. Oxaliplatin, a Pt based alkylating agent is usually given by endovenous infusion8. Oxaliplatin is known for its neurotoxic side effects such as centripetal peripheral neuropathy but its neurotoxicity is dose restricting. A clinical survey has proven the efficaciousness and safety of FOLFOX regimen in patients with terrible hepatic disfunction secondary to liver metastates. The drugs were good tolerated and the patients ‘s liver map trials show an improvement7. However, the sample size studied is little as they merely involved 3 patients. Alternatively of utilizing infusional 5-fluorouracil, there are unwritten parallels of fluorouracil which are available such as tegafur. Tegafur with U have been proven to possess similar efficaciousness as fluorouracil and folinic acid for metastatic colorectal malignant neoplastic disease.

FOLFIRI comprises of Irinotecan, infusional 5-Fluorouracil and leucovarin6. Irinotecan inhibits topoimerase I, an enzyme involved in DNA reproduction. Irinotecan is given by extract. Besides being incorporated into the FOLFIRI regimen, Irinotecan can besides be used as a monotherapy when intervention incorporating fluorouracil has failed8. However, patients with unnatural glucuronidation of hematoidin such as those with Gilbert ‘s syndrome may be at higher hazard of myelosuppression when taking irinotecan11. The most common side consequence associated with FOLFIRI is diarrhoea.

XELOX regimen utilises oxaliplatin and capecitabine. Capecitabine is metabolised to fluorouracil8. Both XELOX and FOLFOX have similar efficaciousness but XELOX offers benefits in footings of clinical safety and convenience over FOLFOX10. There is a lower incidence of anemia, neutropenia, all class neuropathy, alopecia among those taking XELOX although the patients taking XELOX might be more prone to hand-to-foot syndrome and diarrhoea10.

Besides the conventional chemotherapy, there is a different type of intervention available to handle metastatic colorectal malignant neoplastic disease which is known as targeted therapy. Targeted therapy utilizes antibodies to adhere to specific protein that are indispensable for growing of malignant neoplastic disease cells6. The three types of drugs used in targeted therapy are cetuximab, bevacizumab and panitumumab. Harmonizing to the NCCN guidelines, patients who are subjected to targeted therapy should hold their biopsy sample from the tumor tested to find the position for KRAS tumor marker5. Patients who have mutated KRAS cistron should non be given a EGRF inhibitor.

Bevacizumab is a monoclonal antibody that inhibits vascular endothelial growing factor, which is responsible of exciting new blood vas formation in the tumour8. Benvacizumab is non effectual by itself6. However, the NICE counsel besides do non urge the usage of bevacizumab with fluorouracil plus folinic acid with or without irinotecan as the first line intervention of metastatic colorectal malignant neoplastic disease. The add-on of bevacizumab to conventional chemotherapy improved the patient ‘s status in footings of increased overall endurance, increased patterned advance free period and decrease of tumor size1. However, bevacizumab is responsible for higher incidences of class 3 or 4 high blood pressure among patients taking the combination therapy compared to those taking chemotherapy merely. Bevacizumab besides increases hazard of arterial thromboembolism particularly in those with anterior arterial thromboembolic event or 65 old ages old or older1.

Cetuximab is a recombinant monoclonal antibody that inhibits the proliferation of cells by barricading the human cuticular growing factor receptor ( EGFR ) . However, it is merely active against EGFR-expressing tumor. Cetuximab can be used in combination with Irinotecan for intervention of EGFR-expressing metastatic colorectal malignant neoplastic disease but this combination is non recommended as a 2nd line or subsequent intervention after failure of chemotherapy that has included irinotecan8. Patients must be given an antihistamine before having the first extract of cetuximab. Harmonizing to maker ‘s entry, the response to cetuximab is linked to an acne-like roseola. A randomised controlled test observed increased life anticipation among patients with grade3 roseola compared to those with grade 2 or 1 roseola.

Panitumumab is a monoclonal antibody that binds to the EGRF. Panitumumab is indicated as a monotherapy for intervention of EGFR-expressing metastatic colorectal malignant neoplastic disease with non-mutated KRAS cistron that do non react to fluoropyrimidine, oxaliplatin and irrotecan incorporating chemotherapy regimens. A survey compared panitumumab with best supportive attention in the intervention of metastatic colorectal malignant neoplastic disease in patients who have failed standard chemotherapy. Best supportive attention excludes use of active chemotherapy. Panitumumab was found to diminish tumour patterned advance rate by 46 % and significantly better disease control compared to outdo supportive care12.

The continuum of attention construct is applied to intervention of metastatic colorectal malignant neoplastic disease. Each intervention is individualized. Specific chemotherapy drugs may be given, stopped and restarted harmonizing to the demand of the patient. There may besides be a “ care period ” which gives the patients a interruption from the active chemotherapy to hold a better quality of life. The patient ‘s response to chemotherapy is monitored with periodic x-ray surveies ( such as CT scans ) every six to eight hebdomads during therapy. In add-on, blood degrees of a tumour marker called carcinoembryonic antigen ( CEA ) are by and large measured every one to three months during therapy. If the CEA degrees are lifting invariably, the disease might be come oning and there is a demand for a alteration in therapy.

In this clinical scenario, the patient is 67 old ages old and may be classified as an aged. The issues that are frequently linked to malignant neoplastic disease intervention in aged patients are physiological alterations associated with aging, load of coexisting unwellnesss, altered drug pharmacokinetics and functional damage. Therefore, the aged are frequently non given the optimal intervention due to fear of toxicity. For that ground, a comprehensive geriatric appraisal that incorporates assorted facets of functionality and wellness, including mental position, emotional status/depression, activities of day-to-day life ( ADLs ) , instrumental ADLs, place environment, societal support, comorbidity, nutrition, and polypharmacy should be conducted before doing any intervention decision20.

In my sentiment, this patient should be given consecutive therapy of FOLFIRI regimen followed by FOLFOX regimen. In this instance, planned consecutive therapy is more suited than aggressive combination therapy as tolerability and quality of life is the cardinal issue. The FOLFIRI and FOLFOX government are less affected by the age of the patient. One pharmacokinetics survey found no difference in plasma values of irinotecan or its primary metabolite between patients aged 65 old ages and younger topics. This shows that nephritic or hepatic damage does non by and large require any alteration to irinotecan dose, with the exclusion of a hematoidin degree & gt ; 2 mg/dl, in which it is recommended non to be used20. Dose strength besides did non differ between patients aged & amp ; lt ; 70 and 70 for either oxaliplatin or 5-Fluorouracil /Leucovarin, proposing that progressing age did non affect drug bringing for oxaliplatin,5-fluorouracil and leucovarin.

A Phase II clinical test supported the usage of FOLFIRI as first line intervention in aged patients as it is an active regimen with manageable toxicity 15. FOLFIRI was besides found to better quality of life among the aged as shown by a stage III survey. A pooled safety and efficaciousness analysis of FOLFOX in aged has besides maintained same efficacy/toxicity ratio as in younger patients.9 Irinotecan which is included in FOLFIRI was shown to better survival independent of patient ‘s age13.

The FOLFIRI/ FOLFOX therapy is more advantageous over FOLFOX/FOLFIRI. Patients who receive FOLFIRI regimen foremost followed by FOLFOX have higher average endurance of 21.5 months compared to 20.6 months in patients allocated to the latter ( P = .99 ) . As a first-line therapy, FOLFIRI achieved higher response rate compared to FOLFOX ( 56 % vs 54 % ) ( P = .26 ) . Second-line FOLFIRI achieved 4 % RR while FOLFOX achieved 15 % RR. In first-line therapy, FOLFOX besides result in more terrible side effects compared to FOLFIRI. Rate 3/4 mucositis, sickness and emesis, and grade 2 alopecia were more frequent with FOLFIRI while grade 3/4 neutropenia and neurosensory toxicity were more frequent with FOLFOX. The findings of this survey was non statistically important as ( P & gt ; 0.05 ) in most cases16. However, this survey showed that aged patients ( those older than 65 old ages ) did non see increased toxicity in first-line and 2nd line therapy as compared with younger topics.

Another survey on 5-fluoropyrimidine based chemotherapy found that patients aged older than 65 old ages might be more prone to diarrhoea, stomatis and infection. This is shown by the higher rates of diarrhoea ( 21 % vs. 16 % ) , stomatitis ( 17 % vs. 13 % ) , and infection ( 4 % vs. 2 % ) in those older than6518.

The guidelines recommend Atropine 0.25-1mg to be given to patients under FOLFIRI government to minimise cholinergic inauspicious effects unless contraindicated. Loperamide can be given at the oncoming of diarrheoa which is frequently associated with irinotecan17.

The consecutive government of FOLFIRI followed by FOLFOX has the lowest cost-effectiveness ratio compared to FOLFOX or other consecutive governments which include cetuximab or bevacizumab. The cost was calculated in dollars while the effectivity is assessed in life anticipation in footings of hebdomads for a 70 twelvemonth old male19.