eMedicine Specialties > Oncology > Carcinomas of the Gastrointestinal Tract
Colon Cancer, Adenocarcinoma: Treatment & Medication
Updated: Aug 31, 2009
- Overview
- Differential Diagnoses & Workup
- Treatment & Medication
- Follow-up
- Multimedia
Treatment
Medical Care
Systemic chemotherapy
5-Fluorouracil remains the backbone of chemotherapy regimens for colon cancer, both in the adjuvant and metastatic setting. In the past 10 years, it was established that combination regimens provide improved efficacy and prolonged progression-free survival in patients with metastatic colon cancer. In addition to 5-fluorouracil, oral fluoropyrimidines such as capecitabine (Xeloda) and tegafur are increasingly used as monotherapy or in combination with oxaliplatin (Eloxatin) and irinotecan (Camptosar). Some of the standard combination regimens employ prolonged continuous infusion of fluorouracil (FOLFIRI, FOLFOX)14 or capecitabine (CAPOX, XELOX, XELIRI). Availability of new classes of active drugs and biologics for colorectal cancer pushed the expected survival for patients with metastatic disease from 12 months 2 decades ago to about 22 months currently.
A meta-analysis of 6 randomized phase II and II trials examined the efficacy of capecitabine with oxaliplatin (CAP/OX) compared with fluorouracil with oxaliplatin (FU/OX) in metastatic colorectal cancer. CAP/OX resulted in a lower response rate but overall progression-free survival and overall survival were not affected and were similar in both treatment regimens. Characteristic toxicity occurred in the FU schedules and thrombocytopenia and hand-foot syndrome were more prominent in the CAP regimens.15
In a phase III multicenter trial, Kim et al compared overall survival of second-line therapy for patients with advanced colorectal carcinoma refractory to fluorouracil. Fluorouracil, leucovorin, and oxaliplatin (FOLFOX4) (n=246) versus irinotecan (n=245) was compared (crossover to the other treatment was mandated if disease progression occurred). Overall survival did not significantly differ between FOLFOX4 and irinotecan; however, FOLFOX 4 improved response rate (RR) and time to progression (TTP) compared with irinotecan (P=0.0009 for each RR and TTP). FOLFOX4 was associated with more neutropenia and paresthesias.16
Key clinical questions relate to the most advantageous selection of drug combination and the sequence of different treatment options in individual patients with colorectal cancer. This information is to be derived from information on tumor biology, patient performance status, organ function, and pharmacogenomics testing.
Adjuvant (postoperative) chemotherapy
The standard therapy for patients with stage III and some patients with stage II colon cancer for the last 2 decades consisted of fluorouracil in combination with adjuncts such as levamisole and leucovorin.17,18,19 This approach has been tested in several large randomized trials and has been shown to reduce individual 5-year risk of cancer recurrence and death by about 30%.
Two recent large randomized trials (MOSAIC and NASBP-C06) investigated the addition of oxaliplatin to fluorouracil (FOLFOX4 and FLOX, respectively) and demonstrated a significant improvement in 3-year disease-free survival for patients with stage III colon cancer. The addition of irinotecan to fluorouracil in the same patient population provided no benefit based on the results from two large randomized trials (CALGB 89803 and PETACC 3). Another randomized study, XACT, demonstrated noninferiority of capecitabine (Xeloda) compared to 5-FU/leucovorin as adjuvant therapy for patients with stage III colon cancer. A large trial comparing capecitabine plus oxaliplatin (XELOX) versus FOLFOX has completed accrual, but survival data have not yet been reported.
The role of adjuvant chemotherapy for stage II colon cancer is controversial. A large European trial (QUASAR) demonstrated small but significant benefit (3.6%) in terms of absolute 5-year survival rate for those patients who received 5-fluorouracil/leucovorin versus those in the control group. Ongoing adjuvant trials are investigating additional risk stratification of stage II colon cancer based on clinicopathological and molecular markers (ECOG 5202 trial).
Though information on results of adjuvant therapy in stage II and III colon cancer is limited, a data set assembled by the Adjuvant Colon Cancer Endpoints group with fluorouracil-based adjuvant therapy was recently analyzed. The authors concluded that adjuvant chemotherapy provides significant disease-free survival benefit because it reduces the recurrence rate particularly within the first 2 years of adjuvant therapy but with some benefit in years 3-4.20
Biologic agents
Bevacizumab (Avastin) was the first anti-angiogenesis drug to be approved in clinical practice and the first indication was for metastatic colorectal cancer. This is a humanized monoclonal antibody to vascular endothelial growth factor (VEGF) and a pivotal trial demonstrated improved progression-free and overall survival when bevacizumab was added to chemotherapy (IFL, fluorouracil plus irinotecan).
A pooled analysis of cohorts of older patients (aged 65 years or older) from 2 randomized clinical trials examined the benefit of bevacizumab plus fluorouracil-based chemotherapy in first-line treatment of metastatic colorectal cancer. The study concluded that adding bevacizumab to fluorouracil-based chemotherapy improved overall survival and progression-free survival in older patients as it does in younger patients, without increased risks of treatment in the older age group.21
Two other biologic agents approved for colorectal cancer are epidermal growth factor receptor (EGFR)-targeted monoclonal antibodies. Cetuximab (Erbitux) is a chimeric monoclonal antibody approved as monotherapy or in combination with irinotecan (Camptosar) in patients with metastatic colorectal cancer refractory to fluoropyrimidine and oxaliplatin therapy.22
Panitumumab (Vectibix) is fully human monoclonal antibody and the current indication as a monotherapy for patients with colorectal cancer in whom combination chemotherapy failed or was not tolerated. A recent trial by Hecht et al evaluated panitumumab added to bevacizumab and chemotherapy (oxaliplatin- and irinotecan-based) as first-line treatment of metastatic colorectal cancer and concluded that the addition of panitumumab resulted in increased toxicity and decreased progression-free survival.23
Intratumoral KRAS gene mutation can predict sensitivity to anti-EGFR antibodies.24 Investigators from a large international trial exploring the benefit of adding cetuximab to first-line chemotherapy with FOLFIRI (CRYSTAL Trial) reported that only patients with wild-type KRAS derived clinical benefit from cetuximab. Patients with mutant KRAS had no clinical benefit from adding cetuximab to chemotherapy and experienced only unnecessary toxicity. KRAS mutations are present in about 40% of colon adenocarcinomas. Based on these results, testing for KRAS mutation has been already added to cetuximab indication by European regulatory agency (EMEA) and is expected to be added to United States indication by the FDA as well.
Bokemeyer et al examined the overall response rate when combining cetuximab with oxaliplatin, leucovorin, and fluorouracil (FOLFOX-4), as opposed to the regimen without cetuximab, for first-line treatment of metastatic colorectal cancer in a randomized study. They also examined the influence of the KRAS mutation status. They concluded that the overall response rate for cetuximab plus FOLFOX-4 was higher than with FOLFOX-4 alone though a statistically significant increase in odds for a response with the addition of cetuximab could not be established, except in patients with KRAS wild-type tumors, for whom the addition of cetuximab increased chance of response and lowered risk of disease progression.25
Other mutations that involve some of the kinases downstream from KRAS (such as BRAF and PI3K) are being investigated and may result in even more selective methods to identify patients that may benefit from EGFR inhibition.
Radiation therapy
While radiation therapy remains a standard modality for patients with rectal cancer, the role of radiation therapy is limited in colon cancer. It does not have a role in the adjuvant setting, and in metastatic settings, it is limited to palliative therapy for selected metastatic sites such as bone or brain metastases. Newer, more selective ways of administering radiation therapy such as stereotactic radiotherapy (CyberKnife) and tomotherapy are currently being investigated and may extend indications for radiotherapy in the management of colon cancer in the future.
Surgical Care
Surgery is the only curative modality for localized colon cancer (stage I-III) and potentially provides the only curative option for patients with limited metastatic disease in liver and/or lung (stage IV disease). The general principles for all operations include removal of the primary tumor with adequate margins including areas of lymphatic drainage.
- For lesions in the cecum and right colon, a right hemicolectomy is indicated. During a right hemicolectomy, the ileocolic, right colic, and right branch of the middle colic vessels are divided and removed. Care must be taken to identify the right ureter, the ovarian or testicular vessels, and the duodenum. If the omentum is attached to the tumor, it should be removed en bloc with the specimen.
- For lesions in the proximal or middle transverse colon, an extended right hemicolectomy can be performed where the ileocolic, right colic, and middle colic vessels are divided and the specimen is removed with its mesentery.
- For lesions in the splenic flexure and left colon, a left hemicolectomy is indicated. The left branch of the middle colic vessels, the inferior mesenteric vein, and the left colic vessels along with their mesenteries are included with the specimen.
- For sigmoid colon lesions, a sigmoid colectomy is appropriate. The inferior mesenteric artery is divided at its origin, and dissection proceeds toward the pelvis until adequate margins are obtained. Care must be taken during dissection to identify the left ureter and the left ovarian or testicular vessels.
- Total abdominal colectomy with ileorectal anastomosis may be required for patients who have been diagnosed with HNPCC, attenuated familial adenomatous polyposis, and metachronous cancers in separate colon segments or at times in acute malignant colon obstructions with unknown status of the proximal bowel.
The advent of laparoscopy has revolutionized the surgical approach of colonic resections for cancers. The same oncologic principles are respected. Large prospective randomized trials have demonstrated that there are no significant differences with regard to intraoperative or postoperative complications, perioperative mortality rates, readmission or reoperation rates, or rate of surgical wound recurrence. At a median follow-up of 7 years, no significant differences existed in the 5-year disease-free survival rate (69% versus 68% in the laparoscopy-assisted colectomy [LAC] and open colectomy groups, respectively) or overall survival (76% versus 75%). Overall laparoscopic colectomy provides comparable oncologic outcomes (cause-specific survival, disease recurrence, number of lymph nodes harvested) to those achieved with an open approach.26,27,28,29,30,31
Standard management of patients with metastatic disease is systemic chemotherapy. The proper use of elective colon/rectal resections in nonobstructed patients with stage IV disease is a source of continuing debate. Medical oncologists properly note the major drawbacks to palliative resection, such as loss of performance status and risks of surgical complications that potentially lead to delay in chemotherapy. However, surgeons understand that elective operations have lower morbidity than emergent operations on patients who are receiving chemotherapy. Only randomized prospective data could eventually demonstrate the survival benefit of palliative resection for patients with stage IV colon cancer. Data presented at the American Society of Clinical Oncology 45th Annual Meeting in 2009 indicated that patients with asymptomatic surgically incurable colorectal cancer do not require immediate surgery for primary tumor removal.32During the past decade, colonic stents have introduced an effective method of palliation for obstruction in patients with unresectable liver metastasis.
Curative intent resections of liver metastases have significantly improved long-term survival with acceptable postoperative morbidity. A multivariate analysis of 1001 patients who underwent potentially curative resection of liver metastases identified 5 factors as independent predictors of worse outcome: size greater than 5 cm, disease-free interval of less than a year, more than one tumor, primary lymph-node positivity, and CEA greater than 200 ng/mL.33
Although resection is the only potentially curative treatment for patients with colon metastases, other therapeutic options, for those who are not surgical candidates, include thermal ablation techniques. Cryotherapy uses probes to freeze tumors and surrounding hepatic parenchyma. It requires laparotomy and can potentially have significant morbidity including liver cracking, thrombocytopenia, and disseminated intravascular coagulation (DIC). Radiofrequency ablation (RFA) uses probes that heat liver tumors and the surrounding margin of tissue to create coagulation necrosis. RFA can be performed percutaneously, laparoscopically, or through an open approach. Although RFA has minimal morbidity, local recurrence is a significant problem and is correlated with tumor size. Hepatic arterial infusion (HAI) of chemotherapeutic agents such as FUDR is a consideration following partial hepatectomy.
Standard colectomies for adenocarcinoma of the colon are depicted in the image below.
Standard colectomies for adenocarcinoma of the colon.
Consultations
- Surgical consultation
- Colorectal cancer, especially early stage disease, can be cured surgically. Following diagnosis and staging, obtaining surgical consultation for the possibility of resection may be appropriate. After surgery, the stage of the tumor may be advanced depending on the operative findings (eg, lymph node involvement, palpable liver masses, peritoneal spread).
- In the care of patients with colorectal cancer and isolated liver metastases, consider surgical consultation for possible resection. In some cases, resection of previously unresectable liver metastases may become feasible after cytoreduction with neoadjuvant chemotherapy. Therefore, ongoing involvement of the surgical oncologist is very important in patient care, even if the tumor is not considered resectable at the time of diagnosis.
- In advanced disease, surgical intervention may be helpful in palliative care of bleeding or obstruction.
- Gastroenterology consultation
- Gastroenterology consultation is critical for screening of high-risk individuals (ie, people with family history of colorectal cancer or polyposis syndromes) and those individuals who are found to be inappropriately iron deficient or to have occult blood on screening fecal examination. A colonoscopy or sigmoidoscopy is necessary to visualize the colon endoscopically, to obtain biopsies, or to resect polyps. GI consultation may be necessary in the management of advanced disease. Recent advent of colorectal stents allows a nonsurgical management of impending obstruction in patients who present with unresectable, metastatic disease.
- GI consultation is necessary in the follow-up of patients after surgical resection and adjuvant chemotherapy. Patients must be screened for recurrent disease in the colon by colonoscopic examination at 1 year after surgery and then every 3 years.
Diet
Abundant epidemiological literature suggests association of risk for developing colorectal cancer with dietary habits, environmental exposures, and level of physical activity. Less is known about effect of diet and physical activity on the recurrence of colon cancer. A prospective observational study involving patients from the CALGB 89803 adjuvant trial demonstrated adverse effect with regards to risk for recurrence and increased mortality for patients following a "Western" diet (high intake of red meat, refined grains, fat, and sweets) compared to patients with a "prudent" diet (high intake of fruits and vegetables, poultry, and fish).
In another observational study from the same cohort of patients, patients were prospectively monitored and physical activity was recorded. The study concluded that physical activity reduces the risk of recurrence and mortality in patients with resected stage III colon cancer.
These interesting and important observations pave the way for future interventional studies involving diet and physical activity in patients with stage II and III colon cancer.
Activity
See Diet.
Medication
Commonly used combination regimens
Adjuvant therapy
- 5-Fluorouracil + leucovorin (weekly schedule, low dose leucovorin)
- 5-Fluorouracil: 500 mg/m2 IV weekly for 6 weeks
- Leucovorin: 20 mg/m2 IV weekly for 6 weeks, administered before 5-fluorouracil
- Repeat cycle every 8 weeks for a total of 24 weeks.
- LV5FU2 (de Gramont regimen)
- 5-Fluorouracil: 400 mg/m2 IV bolus, followed by 600 mg/m2 IV continuous infusion for 22 hours on days 1 and 2
- Leucovorin: 200 mg/m2 IV on days 1 and 2 as a 2-hour infusion before 5-fluorouracil
- Repeat cycle every 2 weeks for a total of 12 cycles.
- Oxaliplatin + 5-fluorouracil + leucovorin (FOLFOX4)
- Oxaliplatin: 85 mg/m2 IV on day 1
- 5-Fluorouracil: 400 mg/m2 IV bolus, followed by 600 mg/m2 IV continuous infusion for 22 hours on days 1 and 2
- Leucovorin: 200 mg/m2 IV on days 1 and 2 as a 2-hour infusion before 5-fluorouracil
- Repeat cycle every 2 weeks for a total of 12 cycles.
- Irinotecan + 5-fluorouracil + leucovorin (FOLFIRI regimen)
- Irinotecan: 180 mg/m2 IV on day 1
- 5-Fluorouracil: 400 mg/m2 IV bolus on day 1, followed by 2400 mg/m2 IV continuous infusion for 46 hours
- Leucovorin: 400 mg/m2 IV on day 1 as a 2-hour infusion, prior to 5-fluorouracil
- Repeat cycle every 2 weeks.
- Oxaliplatin + 5-fluorouracil + leucovorin (FOLFOX6)
- Oxaliplatin: 100 mg/m2 IV on day 1
- 5-Fluorouracil: 400 mg/m2 IV bolus on day 1, followed by 2400 mg/m2 IV continuous infusion for 46 hours
- Leucovorin: 400 mg/m2 IV on day 1 as a 2-hour infusion, before 5-fluorouracil
- Repeat cycle every 2 weeks.
- Oxaliplatin + 5-fluorouracil + leucovorin (mFOLFOX7)
- Oxaliplatin: 100 mg/m2 IV on day 1
- 5-Fluorouracil: 3000 mg/m2 IV continuous infusion on day 1 for 46 hours
- Leucovorin: 400 mg/m2 IV on day 1 as a 2-hour infusion, before 5-fluorouracil
- Repeat cycle every 2 weeks.
- Capecitabine + oxaliplatin (XELOX)
- Capecitabine: 850-1000 mg/m2 PO bid on days 1-14
- Oxaliplatin: 100-130 mg/m2 IV on day 1
- Repeat cycle every 21 days.
- FOLFOX4 + bevacizumab
- Oxaliplatin: 85 mg/m2 IV on day 1
- 5-Fluorouracil: 400 mg/m2 IV bolus, followed by 600 mg/m2 IV continuous infusion on days 1 and 2
- Leucovorin: 200 mg/m2 IV on days 1 and 2 as a 2-hour infusion before 5-fluorouracil
- Bevacizumab: 10 mg/kg IV every 2 weeks
- Repeat cycle every 2 weeks.
Antineoplastic Agent, Antimetabolite (pyrimidine)
5-Fluorouracil (5-FU, Adrucil, Efudex)
Fluoropyrimidine analog. Cell cycle-specific with activity in the S-phase as single agent and has for many years been combined with biochemical modulator leucovorin. Mainstay of medical chemotherapy for colorectal cancer for patients for more than 40 y. Has activity as single agent that inhibits DNA replication and transcription. Cytotoxicity is cell-cycle nonspecific. Shown to be effective in adjuvant setting. Classic antimetabolite anticancer drug with chemical structure similar to endogenous intermediates or building blocks of DNA or RNA synthesis. 5-FU inhibits tumor cell growth through at least 3 different mechanisms that ultimately disrupt DNA synthesis or cellular viability. These effects depend on intracellular conversion of 5-FU into 5-FdUMP, 5-FUTP, and 5-FdUTP. 5-FdUMP inhibits thymidylate synthase (key enzyme in DNA synthesis), which leads to accumulation of dUMP, which then gets misincorporated into the DNA in the form of 5-FdUTP resulting in inhibition of DNA synthesis and function with cytotoxic DNA strandbreaks. 5-FUTP is incorporated into RNA and interferes with RNA processing. Current standard adjuvant therapy for colon cancer involves combination 5-FU/LV chemotherapy. Saltz regimen (5-FU/LV/CPT11) now standard first-line therapy for metastatic colon cancer. Because of toxicity, maximum of 400 mg/m2 of 5-FU and 100 mg/m2 of CPT11 can be used as starting dose. Levamisole is no longer an appropriate component of adjuvant therapy.
Adult
Bolus schedule: 425–600 mg/m2 weekly, with or without leucovorin
Protracted (pump) infusion: 200-300 mg/m2/24 h continuously
46 hour infusion (pump): 2400–3000 mg/m2/46 h, repeat every 14 days
Standard therapy: 500 mg/m2 IV weekly for 4 wk q6wk
Adjuvant therapy
Mayo Clinic regimen: 425 mg/m2/d IV bolus on days 1-5 after LV for 5 d every 4 wk; 6 mo of therapy is current practice
Roswell Park regimen: Continuous infusion weekly for 6 wk; 2 wk off
Pediatric
Not established
Increased risk of bleeding with anticoagulants, NSAIDs, platelet inhibitors, thrombolytic agents; enhanced bone marrow toxicity with other immunosuppressive agents
Documented hypersensitivity, bone marrow suppression, serious infection, topical administration contraindicated in pregnancy
Pregnancy
D - Fetal risk shown in humans; use only if benefits outweigh risk to fetus
Precautions
Nausea, oral and GI ulcers, depression of immune system, and hemopoiesis failure (bone marrow suppression) may occur; adjust dosage in renal impairment
Toxic effects include diarrhea, mucositis, myelosuppression, hand-foot syndrome (palmar-plantar erythrodysesthesia), dry skin, hyperpigmentation, neurological toxicity (cerebellar ataxia), cardiac toxicity
Capecitabine (Xeloda)
Fluoropyrimidine carbamate prodrug from of 5-fluorouracil (5-FU). Capecitabine itself is inactive. Undergoes hydrolysis in liver and tissues to form the active moiety (fluorouracil), inhibiting thymidylate synthetase, which in turn blocks methylation of deoxyuridylic acid to thymidylic acid. This step interferes with DNA and to a lesser degree with RNA synthesis.
Adult
1250 mg/m2 PO q12h pc for 2 wk followed by 1 wk of rest period; administer as 3-wk cycle
Pediatric
Not established
Aluminum/magnesium hydroxide antacids or meals increase drug absorption; increased risk of bleeding with anticoagulants (monitor INR and PT frequently), NSAIDs, platelet inhibitors, thrombolytic agents; enhanced bone marrow toxicity with other immunosuppressive agents; coadministration with leucovorin may cause diarrhea, dehydration, and death from severe enterocolitis; may increase phenytoin levels
Documented hypersensitivity to drug or related products; severe renal impairment (CrCl <30 mL/min); dihydropyrimidine dihydrogenase (DPD) deficiency
Pregnancy
D - Fetal risk shown in humans; use only if benefits outweigh risk to fetus
Precautions
Adjust dose in moderate renal impairment (CrCl 30-50 mL/min); discontinue drug if intractable diarrhea, bone marrow suppression, myocardial ischemia, or stomatitis develop; caution in patients that have received extensive pelvic radiation or alkylating therapy; hand and foot syndrome characterized by numbness, dysesthesia/paresthesia, tingling, erythema, blistering, severe pain, desquamation, and painless or painful swelling may occur
Toxic effects include diarrhea, hand-foot syndrome, nausea and vomiting, elevations in bilirubin and transaminases, myelosuppression, neurologic syndrome (cerebellar ataxia), cardiac toxicity
Antidote, Folic Acid Antagonist
Leucovorin (Folinic acid, Citrovorum Factor)
Reduced form of folic acid that does not require enzymatic reduction reaction for activation. Allows for purine and pyrimidine synthesis, both of which are needed for normal erythropoiesis. Current standard therapy for colon cancer involves combination chemotherapy. Binds to and stabilizes ternary complex of FdUTP (intracellular active metabolite of fluoropyrimidines) and thymidylate synthetase (TS), augmenting cytotoxic effects of 5-fluorouracil. Used as an adjunct to fluorouracil.
Adult
20-400 mg/m2 IV in combination with 5-fluorouracil
Standard therapy: 20 mg/m2 IV every wk for 4 wk q6wk
Adjuvant therapy: 20 mg/m2 IV before 5-FU on days 1-5 for 5 d q4wk (Mayo Clinic regimen); 6 mo of therapy is current practice
Pediatric
Not established
Decreases effect of methotrexate, phenytoin, phenobarbital, sulfamethoxazole and trimethoprim combinations; increases toxicity of fluorouracil
Documented hypersensitivity; pernicious anemia or vitamin deficient megaloblastic anemias
Pregnancy
C - Fetal risk revealed in studies in animals but not established or not studied in humans; may use if benefits outweigh risk to fetus
Precautions
Do not administer intrathecally or intraventricularly
Toxic effects include skin rash, pruritus, facial flushing, and nausea and vomiting
Antineoplastic Agent, Miscellaneous
Irinotecan is a topoisomerase I inhibitor.
Irinotecan (Camptosar, CPT-11)
Semisynthetic derivative of camptothecin, an alkaloid extract from the Camptotheca acuminate tree. Inactive in its parent form. Converted by the carboxylesterase enzyme to its active metabolite from, SN-38.
SN-38 binds to and stabilizes the topoisomerase I-DNA complex and prevents the relegation of DNA after it has been cleaved by topoisomerase I, inhibiting DNA replication. Effective in treatment of colorectal cancer. Current standard therapy for metastatic colon cancer involves combination of 5-FU/LV/CPT11 chemotherapy (see Standard Therapy).
Because of toxicity problems associated with Saltz regimen (5-FU/LV/CPT11), now standard first-line therapy for metastatic colon cancer, maximum of 400 mg/m2 of 5-FU and 100 mg/m2 of CPT11 can be used as starting dose.
Adult
Monotherapy:
125 mg/m2 IV over 90 min weekly for 4 wk, followed by a 2-wk rest; schedule can be modified to 2 wk followed by a 1-wk rest
300-350 mg/m2 IV on an every-3-wk schedule
180 mg/m2 IV as monotherapy or in combination with infusional 5-FU/LV on an every-2-wk schedule
Pediatric
Not established
Concomitant administration with other antineoplastics may result in prolonged neutropenia and thrombocytopenia in addition to increased morbidity/mortality
Documented hypersensitivity, severe diarrhea, febrile neutropenia, unresponsive or progressive adenocarcinoma, and pregnancy
Pregnancy
C - Fetal risk revealed in studies in animals but not established or not studied in humans; may use if benefits outweigh risk to fetus
Precautions
Adverse effects include myelosuppression, alopecia, nausea, vomiting, and diarrhea (early and late), and elevations in transaminases and bilirubin; monitor bone marrow function
Antineoplastic Agent, Alkylating Agent
Oxaliplatin is a platinum analog.
Oxaliplatin (Eloxatin, Diaminocyclohexane platinum, DACH-platinum)
Third-generation platinum-based antineoplastic agent used in combination with an infusion of 5-fluorouracil (5-FU) and leucovorin for treatment of metastatic colorectal cancer in patients with recurrence or progression following initial treatment with irinotecan, 5-FU, and leucovorin. Also indicated for previously untreated advanced colorectal cancer in combination with 5-FU and leucovorin. Covalently binds to DNA with preferential binding to the N-7 position of guanine and adenine. DNA mismatch repair enzymes are unable to recognize oxaliplatin-DNA adducts in contrast with other platinum-DNA adducts as a result of their bulkier size. Forms interstrand and intrastrand Pt-DNA crosslinks that inhibit DNA replication and transcription. Cytotoxicity is cell-cycle nonspecific with activity in all phases of the cell cycle.
Adult
Day 1: 85 mg/m2 IV over 2 h; administer simultaneously with leucovorin 200 mg/m2; followed by 5-FU 400 mg/m2 IV bolus over 2-4 min, then 5-FU 600 mg/m2 IV continuous infusion in 500 mL D5W over 22 h
Day 2: Leucovorin 200 mg/m2 IV over 2 h, followed by 5-FU 400 mg/m2 IV bolus over 2-4 min, then 5-FU 600 mg/m2 IV as a continuous infusion in 500 mL D5W over 22 h
Oxaliplatin can also be administered at 130 mg/m2 IV on a q3wk schedule
Pediatric
Not established
May increase 5-FU serum concentration by approximately 20%
Documented hypersensitivity to oxaliplatin or other platinum compounds (allergic reactions may present with facial flushing and rash, pneumonitis)
Pregnancy
D - Fetal risk shown in humans; use only if benefits outweigh risk to fetus
Precautions
Anaphylaxis may occur within minutes of administration; may cause neurotoxicity with acute and chronic forms (acute toxicity seen in 80-85% of all patients and is characterized by a peripheral sensory neuropathy with distal paresthesias, visual and voice changes, often triggered or exacerbated by exposure to cold), pulmonary fibrosis, bone marrow suppression, GI tract symptoms (eg, nausea, vomiting, diarrhea, stomatitis), renal or hepatic toxicity (decrease dose), or thromboembolism, myelosuppression; dilute IV only in dextrose-containing solution
Antineoplastic Agent, Monoclonal Antibody
Cetuximab (Erbitux)
Recombinant, human/mouse chimeric monoclonal antibody that specifically binds to the extracellular domain of human epidermal growth factor receptors (EGFR, HER1, c-ErbB-1). Cetuximab-bound EGF receptor inhibits activation of receptor-associated kinases, resulting in inhibition of cell growth, induction of apoptosis, and decreased production of matrix metalloproteinase and vascular endothelial growth factor.
Indicated for treating irinotecan-refractory, EGFR-expressed, metastatic colorectal carcinoma. Treatment is preferably combined with irinotecan. May be administered as monotherapy if irinotecan is not tolerated.
Adult
First dose: 400 mg/m2 IV infused over 2 h
Weekly maintenance doses: 250 mg/m2 IV infused over 1 h
Not to exceed infusion rate of 10 mg/min (ie, 5 mL/min);
must administer with low-protein–binding 0.22 m m in-line filter; premedication with an H1 antagonist (eg, diphenhydramine 50 mg IV) recommended
Pediatric
Not established
Limited data exist; none reported
None for metastatic colorectal carcinoma
Pregnancy
C - Fetal risk revealed in studies in animals but not established or not studied in humans; may use if benefits outweigh risk to fetus
Precautions
Caution with documented hypersensitivity, including allergy to murine proteins; may cause infusion-related hypotension and airway distress (eg, bronchospasm, stridor, hoarseness), particularly with the first infusion (90%); premedicate with diphenhydramine 50 mg IV; decrease dose with mild or moderate (grade 1 or 2) infusion reaction and immediately and permanently discontinue with severe (grade 3 or 4) infusion reactions; common adverse effects include acnelike rash, dry skin, pruritus, tiredness or weakness, fever, diarrhea, constipation, abdominal pain, hypomagnesemia, infusion reaction, paronychia, hypertrichia; may rarely cause interstitial lung disease; do not shake or dilute solution; sunlight can exacerbate any skin reactions
Bevacizumab (Avastin)
Indicated in combination with a fluoropyrimidine-based chemotherapy as a first-line or second-line treatment for metastatic colorectal cancer. Murine derived monoclonal antibody that inhibits angiogenesis by targeting and inhibiting vascular endothelial growth factor (VEGF). Inhibiting new blood vessel formation denies blood, oxygen, and other nutrients needed for tumor growth. Used in combination with standard chemotherapy.
Adult
5-10 mg/kg IV over 60 min q2wk until disease progression detected
Pediatric
Not established
Coadministration with 5-fluorouracil increases incidence (2-fold) of serious and fatal arterial thromboembolic events (ie, CVA, MI, TIAs, angina)
Documented hypersensitivity
Pregnancy
C - Fetal risk revealed in studies in animals but not established or not studied in humans; may use if benefits outweigh risk to fetus
Precautions
Common adverse effects include hypertension, epistaxis, fatigue, thrombosis, increased risk of bleeding, diarrhea, leukopenia, proteinuria, nephritic syndrome, headache, anorexia, and stomatitis; may cause serious or fatal, but rare events including gastrointestinal perforation, intra-abdominal infections, impaired wound healing, hemoptysis (particularly with lung cancers), reversible posterior leukoencephalopathy syndrome (RPLS), nasal septum perforation, and internal bleeding; increases risk of serious and fatal arterial thrombotic events with 5-fluorouracil
Do not initiate treatment for at least 28 days following major surgery, the surgical incision should be fully healed; breastfeeding should be discontinued during and for at least 20 d following treatment with bevacizumab
Panitumumab (Vectibix)
Recombinant human IgG2 kappa monoclonal antibody that binds to human epidermal growth factor receptor (EGFR). Indicated to treat colorectal cancer that has metastasized following standard chemotherapy.
Adult
6 mg/kg IV infused over 60 min q2wk
Pediatric
Not established
Data limited; none reported
None known
Pregnancy
C - Fetal risk revealed in studies in animals but not established or not studied in humans; may use if benefits outweigh risk to fetus
Precautions
Common adverse effects include rash (acneiform), paronychia, hypomagnesemia, fatigue, abdominal pain, nausea, and diarrhea, pneumonitis; serious adverse effects include pulmonary fibrosis, severe rash complicated by infections, infusion reactions (for grade I or II reaction, reduce infusion rate by 50%; for grade III or IV reaction, immediately discontinue permanently), ocular toxicity, abdominal pain, vomiting, and constipation; administer using low-protein–binding filter
More on Colon Cancer, Adenocarcinoma |
| Overview: Colon Cancer, Adenocarcinoma |
| Differential Diagnoses & Workup: Colon Cancer, Adenocarcinoma |
 Treatment & Medication: Colon Cancer, Adenocarcinoma |
| Follow-up: Colon Cancer, Adenocarcinoma |
| Multimedia: Colon Cancer, Adenocarcinoma |
| References |
| Further Reading |
| « Previous Page | Next Page » |
References
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Further Reading
Related eMedicine topic
Colon, Adenocarcinoma (Radiology)
Clinical studies
Fluorouracil and Leucovorin Plus Either Irinotecan or Oxaliplatin With or Without Cetuximab in Treating Patients With Previously Untreated Metastatic Adenocarcinoma of the Colon or Rectum
Celecoxib Combined With Fluorouracil and Leucovorin in Treating Patients With Resected Stage III Adenocarcinoma (Cancer) of the Colon
Trial for Microarray Analysis of Colon Cancer Outcome-A (MACCO-A)
Keywords
colon cancer, colorectal cancer, adenocarcinoma, gastrointestinal cancer, colorectal malignancy, colon cancer prevention, colon cancer treatment, colon cancer medications, colon cancer detection, colon cancer screening, colon cancer diagnosis, colorectal adenoma, adenomatous polyp, colon polyp, colorectal polyp, adenomatous polyposis, hereditary nonpolyposis colon cancer syndrome, HNPCC, Lynch syndrome, familial adenomatous polyposis, FAP, inflammatory bowel disease, IBD, colitis, Crohn’s disease, Crohn disease
