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Pharm D, Department of Pharmacy Practice Bharat School of Pharmacy, Mangalpally, Hyderabad.
Colorectal cancer is a common gastrointestinal cancer that starts in the colonic epithelium and is brought on by genetic defects that lead to unregulated development and reduced apoptosis. The CAPOX regimen, which includes Capecitabine and Oxaliplatin, is frequently used to treat it. While Capecitabine stops DNA synthesis, Oxaliplatin encourages DNA cross-linking, which destroys tumour cells. However, treatment is associated with toxicities include Peripheral Neuropathy, Myelosuppression, Gastrointestinal issues, and Hand-Foot Syndrome. Accurate diagnosis, risk assessment, and monitoring are essential to optimizing therapeutic outcomes.
One of the most prevalent Gastrointestinal cancers is Colorectal cancer, which develops from the epithelial lining of the colon and rectum. “It usually arises from precursor lesions and shows consistent patterns of metastasis and local invasion. The location of the tumour affects the therapy strategy and clinical presentation. Prognosis is significantly influenced by histopathological categorization.
ETIOLOGICAL FACTORS:
There are various factors that contribute to the development of colorectal cancer. The most common factor includes gene mutations like APC gene mutations, adenomatous polyps and the other factors involved are smoking, alcohol consumption, obesity, long term inflammatory bowel disease, Crohn’s disease. [1]
EPIDEMOLOGY:
Globally, colorectal cancer (CRC) is a prevalent cancer and a leading cause of mortality. With 64,863 cases and 38,367 fatalities in 2022, it is the fourth most common cancer in India for both sexes. India's CRC survival rate is significantly lower than that of wealthy nations because to its high death rate. With 40,430 cases in males and 24,433 cases in females in 2022, the colorectum is one of the most prevalent cancer locations in India. Males are more likely than females to experience this. Over 4% of cancer cases and deaths in India are caused by colorectal cancer (CRC). Within India, there is a noticeable geographical variation in occurrence. According to histology, adenocarcinomas accounted for around 93% of CRCs observed in Indian hospitals. 55% of rectal cancers and more than 45% of colon cancers were identified at the locoregional disease stage.[2]
PATHOGENESIS:
SIGNS & SYMPTOMS: [4]
The common symptoms which are experienced by colorectal patients include
• Blood in stool
• Abdominal pain
• Iron deficiency anaemia
• Unexplained weight loss
• Diarrhoea or constipation
• Incomplete bowel movement
• Weakness
• Fatigue
RISK FACTORS:
The risk factors of colorectal cancer are age above 50 years, diet, obesity, physical inactivity, Crohn’s disease, smoking, alcohol consumption, previous history of colorectal polyps. [5]
DIAGNOSIS:
Colonoscopy: Colonoscopy is a very precise test for colorectal cancer. During a colonoscopy, masses are biopsied for a pathologic diagnosis and polyps are removed. Adenomatous polyps can develop early colon cancer, making it challenging to differentiate them from non - malignant adenomatous polyps by colonoscopy.
CT Scan: CT Scan has been the standard procedure to get the abdominal images of the colorectal cancer patients. The test is most sensitive for diagnosis of large tumours than small tumours.
Faecal occult blood tests: The peroxidase present in heme of blood in faeces is identified. Sometimes it may also produce false results due to the peroxidase present in food.
PET Scan: This scan mainly helps to identify the stage of tumour, lymph nodes and provides imaging of the tumours.
Faeces immunohistochemical test: The monoclonal antibody reaction or specific polyclonal antibody reaction occur against human albumin, haemoglobin, or other factors present in blood. [6-7]
TREATMENT:
PHARMACOLOGICAL THERAPY
General chemotherapy regimens used in colorectal cancer include:
Dosing schedule:
These regimens are used in adjuvant and metastatic colorectal cancer, depending on disease stage and patient condition. [8]
NON - PHARMACOLOGICAL THERAPY:
Non-pharmacological management of colorectal cancer includes:
1. Surgery
2. Radiation Therapy
3. Concurrent Chemoradiotherapy
4. Palliative Care
DRUG INFORMATION:
CAPOX
COMPOSITION - Capecitabine and Oxaliplatin
BRAND NAME - XELOX
CATEGORY - Capecitabine - Antimetabolite agent
Oxaliplatin - Platinum containing antineoplastic agent
STRUCTURE:
Oxaliplatin Capecitabine
MECHANISM OF ACTION:
Capectabine: The prodrug form of 5-Flurouracil is Capecitabine. It activates and get metabolized to form FdUMP, FUTP. FdUMP inhibits thymidylate synthase which is involved in DNA replication and FUTP will compete with UTP and leads to miscorporation into RNA and inhibits RNA replication.
Oxaliplatin: The platinum containing compound will cause intrastrands in DNA causing DNA unwinding and inhibits replication of DNA ultimately causing apoptosis of tumour cells. [13]
PHARMACOKINETICS:
CAPECITABINE:
ABSORPTION: It is rapidly and extensively absorbed from the gastrointestinal tract with a time to reach a peak concentration T max of 2 hours and peak plasma drug concentration C max of 3-4 mg/L. The bioavailability is 100%
DISTRIBUTION: In vitro human plasma studies have determined that plasma protein binding of capecitabine and its metabolites is less than 60% and is not concentration dependent. Capecitabine was primarily bound to human albumin.
METABOLISM: The liver is the primary site of capecitabine metabolism, which produces 5-DFCR (5- Deoxy 5- fluorocytidine) and 5′-DFUR(5- Deoxy 5- Fluorouridine) through a series of enzymatic processes. Due to increased thymidine phosphorylase activity, final activation to 5-Fluorouracil mostly occurs in tumour tissues. Dihydro pyrimidine dehydrogenase then breaks down 5-FU into inactive metabolites that are eliminated in urine.
ELIMINATION: The predominant route of elimination is renal, and dosage reduction of 75% is recommended in patients with creatinine clearance (CrCl) of 30 to 50 mL/min.
OXALIPLATIN:
ABSORPTION: Oxaliplatin is rapidly and extensively absorbed after infusion. The bioavailability is 100%, the time taken to reach a peak concentration T max is 2 hours.
DISTRIBUTION: Oxaliplatin is rapidly distributed. In blood platinum binds irreversibly to plasma proteins (predominantly serum albumin) and erythrocytes.
METABOLISM: It rapidly and widely undergoes non-enzymatic biotransformation in the circulation by displacing its oxalate ligand, producing several reactive platinum-containing species. These species circulate with a range of inert conjugates that eventually bind to proteins and DNA, some of which are harmful.
ELIMINATION: Oxaliplatin is mainly eliminated through renal route. About 30–50% of the platinum dose is recovered in urine within 2–5 days; renal clearance of ultra filterable platinum correlates with glomerular filtration rate (GFR).
PHARMACODYNAMICS:
CAPECITABINE: Capecitabine does not bind to any receptor in body. It is a prodrug that is activated by tumours. Due to increased thymidine phosphorylase activity in tumour tissues, it is converted to active chemotherapy agent 5-fluorouracil (5-FU). Once generated, 5-FU metabolites are integrated into DNA and RNA, impairing nucleic acid activity and causing cell death. They also inhibit thymidylate synthase, preventing thymidine synthesis and DNA replication.
OXALIPLATIN: Oxaliplatin enters cancer cells and is activated non-enzymatically into reactive platinum species that covalently bind to DNA bases (mostly at the N7 sites of guanine and adenine). Intrastrand and interstrand DNA cross-links and bulky adducts are created as a result, distorting the DNA helix, preventing transcription and DNA replication, inducing DNA damage responses, and ultimately causing cell cycle arrest and apoptosis in tumour cells. [14]
DOSE:
ADULTS
|
Oxaliplatin |
130 mg/m2 |
Over 2-6 hours on day-1 |
IV |
|
Capecitabine |
1000 mg/m2 |
On days 1- 14 |
Oral |
CLINICAL INDICATIONS:
Colon Cancer - Stage 2 (high risk), stage – 3 and stage - 4
Rectal Cancer – Adjuvant, metastatic cancer. [15]
ADVERSE EFFECTS:
Gastrointestinal Toxicity - Diarrhoea, nausea, vomiting, stomatitis, abdominal pain
Haematological Toxicity – Neutropenia, Thrombocytopenia, Anaemia
Peripheral Neuropathy - Paraesthesia, Dysesthesia, cold – induced neuropathy, sensory impairment
Hand–Foot Syndrome – Redness, pain, swelling of palms and soles, skin peeling
Hypersensitivity Reactions – Rash, fever, bronchospasm, anaphylaxis in severe cases
Hepatic and Metabolic Effects – Elevated liver enzymes, hyperbilirubinemia. [16]
CONTRAINDICATIONS:
CAPOX is contraindicated in patients with renal impairment, hepatic impairment, severe myelosuppression, pregnancy and breast-feeding women. [17]
DRUG INTERACTIONS:
Potentially fatal increased toxicity of fluorouracil, the active metabolite of Capecitabine, due to reduced clearance. Atleast 4 weeks gap should be maintained between end of Brivudine therapy to Capecitabine therapy.
Increased effects/toxicity of these drugs possible due to inhibition of CYP2C9 by Capecitabine and/or its metabolites resulting in reduced clearance. The combination need to avoided or monitor the increased INR levels.
This combination will lead to reduced efficacy of Capecitabine due to its reduced conversion to its active metabolites. This combination should be monitored closely or the combination need to be avoided.
Oxaliplatin when combined with nephrotoxic drugs will cause increased nephrotoxicity. Try to avoid this combination or need to monitor closely.
This combination will lead to additive neurotoxicity. This combination need close monitoring. [18]
CASE DISCUSSION:
CASE STUDY – 1
A 69 years old male patient was admitted in the Oncology department with chief complaints of on routine check up patient was found to have anemia further evaluated gave blood transfusions and evaluated. Patient had a history of blood in stools. The past medical history of the patient includes K/C/O HTN, DM and CAD S/P CABG.
Upon further investigation the patient was diagnosed with carcinoma colon with anemia (PT3pN2a). Patient underwent a surgical procedure of DL + Right radical hemicolectomy on 15/7/2025. Later patient was advised for chemotherapy cycles. On examination patient condition was BP- 120/80 mm hg, PR- 88 bpm, RR- 20/min, Temp- 97.4F
CT BRAIN: Gliosis with encephalomalacia changes in left frontoparietal and right inferior regions due to chronic infarcts. Hypodense areas in bilateral periventricular white matter regions- S/0 small vessel ischemic changes.
X Ray CHEST: Patch areas of increased marking in bilateral perihilar and upper zones. Mild blunting of right costophrenic angle.
INTRA OP Findings: Bulky ulcero infiltrative growth involving caecum with bulky mesenteric lymph nodes. No free fluid or peritoneal or liver deposits.
Colonoscopy: Caecal ulcero proliferative growth? malignant
Histopathology: Features are suggestive of moderately differentiated adenocarcinoma with Lymph node metastasis
PET CT: FDG avid enhancing irregular mural thickening involving caecum, ileocaecal junction, likely primary neoplastic etiology- suggested histopathological correlation.
Based upon the laboratory investigations the patient was diagnosed with Colon carcinoma. The patient was advised for chemotherapy along with the pre medications including Inj. PALNOX 0.25mg+ Inj. DEXA 8 mg) in 100ml NS over 15 minutes and (Inj. MgSO4 1amp + Inj. Calcium gluconate 1 amp) in 100ml NS over 30 minutes for hydration.
On 7/8/2025 – WEEK 1 chemotherapy Inj. OXALIPLATIN 180mg in 1 unit 5% dextrose over 3 hours infused slowly. Tab. CAPECITABINE 500mg Oral
On 28/8/2025 – WEEK 2 chemotherapy Inj. OXALIPLATIN 180mg in 1 unit 5% dextrose over 3 hours infused slowly. Tab. CAPECITABINE 500mg Oral
The laboratory investigations were found to be normal in Cycle 1 and Cycle 2 of chemotherapy.
On 20/09/2025 – WEEK 3 chemotherapy Inj. OXALIPLATIN 180mg in 1 unit 5% dextrose over 3 hours infused slowly. Tab. CAPECITABINE 500mg Oral
Few laboratory parameters were found to be abnormal, like Hb – 9 mg/dL, RBC- 3.3 million/cu mm, Urea – 33 mg/dl
CASE STUDY – 2
A 55 years old male patient was admitted in the Oncology department with chief complaints of bleeding, constipation, heart burn. The patient had past medical history of DM on T. GLYCOMET GP BD, T. ISTAMET 50/500mg BD, T. DAPAVEL 5mg and HTN on T.MET XL 12.5 mg HS and CAD on T. CLOPITAB 75mg, T. ROSUVAS 40mg HS. The patient was diagnosed with carcinoma of 1/3rd rectum. The diagnosis was done based on the following investigations.
Upper GI Endoscopy: Prominent esophageal veins for further evaluation. Small hiatus hernia.
Colonoscopy: Rectal growth? Neoplastic. Sigmoid polyp.
Colonoscopy biopsy: Invasive adenocarcinoma.
PET CT: FDG avid illdefined enhancing mural thickening involving mid rectum, likely primary neoplastic etiology, suggested histopathological correlation.
MRI Pelvis with contrast: It reveals semicircular infiltrating polypoidal soft tissue mass lesion along anterior wall of upper rectum.
Based on examination and PET CT, MRI Pelvis the patient was diagnosed with CA MID 1/3rd RECTUM cT2N1M0. The patient was advised for chemotherapy post NACT/RT.
Upon completion of examination, the chemotherapy was initiated with pre medications like Inj. ONDEM – 8mg, Inj DEXA 8mg in 100ml NS over 30 minutes, Inj. Calcium Gluconate 1amp, Inj. Magnesium Sulphate 1amp in 100ml NS over 30 minutes.
On 30/10/2025 – WEEK 1 chemotherapy of T. CAPECITABINE 500mg 3 tabs BD for 14 days. Inj. Oxaliplatin 220mg in 500ml 5%Dextrose over 120 minutes. The laboratory parameters were found to be normal.
On 20/11/2025 – WEEK 2 chemotherapy of T. CAPECITABINE 500mg 3 tabs BD for 14 days. Inj. Oxaliplatin 220mg in 500ml 5%Dextrose over 120 minutes. All the parameters were normal.
On 11/12/2025 – WEEK 3 chemotherapy of T. CAPECITABINE 500mg 3 tabs BD for 14 days. Inj. Oxaliplatin 220mg in 500ml 5%Dextrose over 120 minutes. The abnormalities were Hb –8.8mg/dL, SGOT – 52U/L, SGPT – 58U/L, TOTAL BILIRUBIN – 1.5 mg/dL, ALKALINE PHOSPHATASE – 148.0U/L. The abnormalities were found after Cycle 2.
CASE STUDY – 3
A 74 years old male patient was admitted in Oncology department with chief complaints of fever with chills and generalised weakness. The patient was diagnosed with Adenocarcinoma of colon. These were the few investigations performed to diagnose the adenocarcinoma of colon.
HISTOPATHOLOGY – Feature are suggestive of low grade spindle cell lesion.
PET CT– Large FDG avid enhancing exophytic lesion arising from antropyloric region of stomach and proximal duodenum with extensions as described.
COLONOSCOPY – Descending colon polyp proctitis.
ENDOSCOPY: Gastric sub mucosal mass.
The patient was a case of ca colon post hemicolectomy. The patient was advised for 12 cycles of FOLFOX but defaulted after 5 cycles and now presented within exophytic mass arising from pyloric region. The patient was evaluated for biopsy and suggestive of spindle cell neoplasm in outside hospital. The patient underwent exploratory laparotomy and found tumor was inoperable and gastrojejunostomy was done. On reevaulation patient was diagnosed with adenocarcinoma in colon and planned foe Cycle 1 XELOX Chemotherapy. The
On 2/05/2025 – WEEK 1 chemotherapy of Inj. OXALIPLATIN 180mg in 500ml 5% Dextrose over 2 hours, T. CAPECITABINE 500mg, 3tabs in the morning.
Along with few premedications Inj. PAN 40mg, INJ.DEXA 8mg + Inj. ZOFER 8mg in 100ml NS, (Inj. Calcium Gluconate +INJ.MGSO4 1amp) in 100ml NS over 30 minutes.
On 7/6/2025 – WEEK 2 chemotherapy of Inj. OXALIPLATIN 180mg in 500ml 5% Dextrose over 2 hours, T. CAPECITABINE 500mg, 3tabs in the morning. The patient was found to have decreased WBC count of 2500 cells/cu mm and was given Inj. GCSF 300mcg STAT. Patient was also presented with fever, cough, restlessness, difficulty in breathing, giddiness. The patient was advised for decrease in Oxaliplatin dose to 160mg.
CASE STUDY – 4
A 59 years old male patient was admitted in the Oncology department with the chief complaints of generalised weakness, abdominal pain. The patient was diagnosed with metastatic colon carcinoma- stage 4. The diagnosis was made based on below laboratory investigations:
COLONOSCOPY: ? Ca sigmoid colon – biopsy taken.
PET CT – PET CT findings are suggestive of generalised thickening in sigmoid colon appears to be primary non neoplastic lesion, significantly decreased in size.
HISTOPATHOLOGY: Feature are consistent with moderately differentiated adenocarcinoma.
ULTRASOUND – No sonographic abnormality detected.
Upon examination, patient was advised for chemotherapy with CAPOX along with premedications like Inj. AVIL – 1 amp STAT, Inj. AKYNZEO 235/0.25 IV in 100ml NS over 30 minutes, Inj. DEXA 4mg IV, STAT, Inj. RANTAC 50mg IV STAT, Inj. Calcium Gluconate 10ml+Inj.MGSO4 2 gm IV in 100ml NS over 30 minutes.
On 3/10/2025 – WEEK 1 chemotherapy of Capecitabine – 500mg (3tabs) Oral on days 1-14, Oxaliplatin 230mg in 1 unit 5% Dextrose over 2 hours. No noted abnormalities.
On 7/11/2025 – WEEK 2 chemotherapy of Capecitabine – 500mg (3tabs) Oral on days 1-14, Oxaliplatin 230mg in 1 unit 5% Dextrose over 2 hours. There were no known abnormalities.
On 3/12/2025 – WEEK 3 chemotherapy of Capecitabine – 500mg (3tabs) Oral on days 1-14, Oxaliplatin 230mg in 1 unit 5% Dextrose over 2 hours. The abnormal parameters were noted including WBC – 3370 cells/cu mm, PLATELETS – 1.25 lakhs cells, Indirect Bilirubin- 0.19 mg/dl. These are identified after 3rd cycle of CAPOX.
CASE STUDY – 5
A patient of 47 years old male was admitted in Oncology department with chief complaints of abdominal pain, decreased appetite. The patient was diagnosed with Ca of Rectum lower 1/3rd post NACTRT. Patient had a medical history of T2DM and on regular medication. Certain investigations are performed to diagnose the disease which include:
MRI PELVIS: Well defined T2 hypointense intramural polypoidal soft tissue lesion noted in rectum. S/O Neoplastic etiology stage T2.
HISTOPATHOLOGY: Feature are suggestive of Adenocarcinoma
SIGMOIDOSCOPY: A small rectal ulcer? Residual disease.
COLONOSCOPY: Sessile rectal polyp.
Patient was diagnosed with Ca of Rectum lower 1/3rd post NACTRT and advised for chemotherapy of CAPOX with pre medications like Inj. DEXA 8mg in 100ml NS over 30 minutes, T. NYKRON 1 tab STAT, Inj. PAN 40mg + Inj. AVIL 1amp IV STAT.
On 12/06/2025 WEEK 1 chemotherapy of Inj. OXALIPLATIN 240mg in 1 unit 5% Dextrose, Cap. CAPABEL – DT 1000mg. Parameters were found to be normal.
On 3/7/2025- WEEK 2 chemotherapy of Inj. OXALIPLATIN 240mg in 1 unit 5% Dextrose, Cap. CAPABEL – DT 1000mg. Parameters were found to be abnormal including Hb - 10.1, WBC – 3500cells/cu mm, Platelets- 80000 cells, Creatinine- 0.6mg/dl, ALP – 123U/L. The abnormality was identified after cycle 2 of CAPOX.
CONCLUSION
CAPOX and FOLFOX are the first line treatment for Gastrointestinal cancers. The regimens are widely used for treatment of gastrointestinal cancers and tolerance was good during initial cycles. The toxicities occurred among the patients from Cycle- 3 to 4. The toxicities were managed using supportive medications. The toxicities caused by the regimens include myelosuppression (anemia, neutropenia, thrombocytopenia), hepatotoxicity, neurotoxicity, nephrotoxicity which requires close monitoring and adjustment in doses along with supportive and palliative care. This early identification of the toxicities will lead to increase in survival rate of patients.
CASE STUDY – 1; 69 years old, male with Colon cancer tolerated 2 cycles of CAPOX, after cycle 3 patient developed anaemia, hepatotoxicity.
CASE STUDY – 2; 55 years old male with Ca mid 1/3rd Rectum treated with CAPOX developed toxicities like anaemia, hepatotoxicity after cycle 3.
CASE STUDY – 3; 74 years old male diagnosed with adenocarcinoma colon tolerated 2 cycles of CAPOX then developed leukopenia required GCSF, along with fever, cough, giddiness, restlessness, difficulty in breathing required the dose adjustment.
CASE STUDY – 4; 59 years old male with Colon cancer Stage 4 developed leukopenia, thrombocytopenia and abnormality in indirect bilirubin levels after the administration of CAPOX regimen.
CASE STUDY – 5; 47 years old male diagnosed with Ca of Rectum lower 1/3rd post NACTRT was treated with CAPOX developed myelosuppression, nephrotoxicity, altered ALP levels after cycle 2.
ACKNOWLEDGMENTS
The authors would like to acknowledge the facilities provided by Bharat Institutions – Pharmacy in executing this article.
REFERENCES
Nermetla Mahesh, Oddi Sahithi, Mogilicharla Archana, Jarupla Mahika, Dornala Manoj, Dr. Swathi Boddupally Toxicological Evaluation of Capox Regimen in Colorectal Cancer Therapy, Int. J. of Pharm. Sci., 2026, Vol 4, Issue 7, 5137-5146, https://doi.org/10.5281/zenodo.21623099
10.5281/zenodo.21623099