Second-Line Colorectal Cancer Regimens: Bevacizumab after First Progression Bevacizumab + FOLFIRI
Bevacizumab 5 mg/kg; administer intravenously in 100 mL 0.9% sodium chloride Injection (0.9% NS) every 2 weeks (total dosage/cycle = 5 mg/kg)
Note: Administration duration for the initial dose is 90 minutes. If administration is well tolerated, the administration duration may be decreased stepwise during subsequent administrations to 60 minutes and, finally, to a minimum duration of 30 minutes
FOLFIRI (Tournigand C et al. J Clin Oncol 2004;22:229–237):
Irinotecan 180 mg/m2; administer intravenously over 90 minutes in 500 mL 5% dextrose injection (D5W) on day 1, every 2 weeks (total dosage/cycle = 180 mg/m2), plus:
Either: (racemic) leucovorin calcium 400 mg/m2 or levoleucovorin calcium 200 mg/m2; administer intravenously over 2 hours in 25–500 mL 0.9% NS or D5W on day 1, every 2 weeks (total dosage/cycle for racemic leucovorin = 400 mg/m2, for levoleucovorin = 200 mg/m2), followed by:
Fluorouracil 400 mg/m2; administer by intravenous injection over 1–2 minutes after leucovorin on day 1, every 2 weeks, followed by:
Fluorouracil 2400 mg/m2; administer by continuous intravenous infusion over 46 hours in 100–1000 mL 0.9% NS or D5W, starting on day 1, every 2 weeks (total dosage/cycle = 2800 mg/m2)
Supportive Care
Antiemetic prophylaxis
Emetogenic potential on day 1 is MODERATE
Emetogenic potential on day 2 is LOW
See Chapter 39 for antiemetic recommendations
Hematopoietic growth factor (CSF) prophylaxis
Primary prophylaxis is NOT indicated
See Chapter 43 for more information
Antimicrobial prophylaxis
Risk of fever and neutropenia is LOW
Antimicrobial primary prophylaxis to be considered:
See Chapter 47 for more information
Acute cholinergic syndrome
Atropine sulfate 0.25–1 mg subcutaneously or intravenously if abdominal cramping or diarrhea develop during or within 1 hour after irinotecan administration
If symptoms are severe, add as primary prophylaxis at least 30 minutes before irinotecan during subsequent cycles
For irinotecan, acute cholinergic syndrome may be characterized by: abdominal cramping, diarrhea, diaphoresis, hypotension, flushing, bradycardia, rhinitis, increased salivation, meiosis, and lacrimation
Diarrhea management
Latent or delayed onset diarrhea✫:
Loperamide 4 mg orally initially after the first loose or liquid stool, then
Loperamide 2 mg orally every 2 hours during waking hours, plus
Loperamide 4 mg orally every 4 hours during hours of sleep
Continue for at least 12 hours after diarrhea resolves
Recurrent diarrhea after a 12-hour diarrhea-free interval is treated as a new episode
Rehydrate orally with fluids and electrolytes during a diarrheal episode
If diarrhea persists >48 hours despite loperamide, stop loperamide and hospitalize the patient for IV hydration
Persistent diarrhea:
Octreotide 100–150 mcg subcutaneously 3 times daily. Maximum total daily dose is 1500 mcg
Antibiotic therapy during latent or delayed onset diarrhea:
A fluoroquinolone (eg, Ciprofloxacin 500 mg orally every 12 hours) if absolute neutrophil count <500/mm3 with or without accompanying fever in association with diarrhea
BEVACIZUMAB + FOLFOX-4
Bevacizumab 5 mg/kg; administer intravenously in 100 mL 0.9% sodium chloride Injection (0.9% NS) every 2 weeks (total dosage/cycle = 15 mg/kg)
Note: Administration duration for the initial dose is 90 minutes. If administration is well tolerated, the administration duration may be decreased stepwise during subsequent administrations to 60 minutes and, finally, to a minimum duration of 30 minutes
FOLFOX-4 (de Gramont A et al. J Clin Oncol 2000;18:2938–2947):
Oxaliplatin 85 mg/m2; administer intravenously in 250 mL 5% dextrose injection (D5W) over 2 hours concurrently with leucovorin administration, on day 1, every 2 weeks, (total dosage/cycle = 85 mg/m2)
Note: Oxaliplatin must not be mixed with sodium chloride injection. Therefore, when leucovorin and oxaliplatin are given concurrently via a Y-connector, both drugs must be administered in D5W
Leucovorin calcium 200 mg/m2 per dose; administer intravenously in 25–500 mL D5W over 2 hours on 2 consecutive days, on days 1 and 2, every 2 weeks (total dosage/cycle = 400 mg/m2), followed by:
Fluorouracil 400 mg/m2 per dose; administer by intravenous injection over 1–2 minutes after leucovorin on 2 consecutive days, on days 1 and 2, every 2 weeks, followed by:
Fluorouracil 600 mg/m2 per dose; administer by continuous intravenous infusion in 100–1000 mL 0.9% NS or D5W over 22 hours on 2 consecutive days, on days 1 and 2, every 2 weeks (total dosage/cycle = 2000 mg/m2)
Note: Fluorouracil boluses (400 mg/m2 by intravenous injection) may be omitted for better hematologic tolerance
Supportive Care
Antiemetic prophylaxis
Emetogenic potential on days with cetuximab is MINIMAL
Emetogenic potential on days with oxaliplatin is MODERATE
Emetogenic potential on days with fluorouracil and leucovorin is LOW
See Chapter 39 for antiemetic recommendations
Hematopoietic growth factor (CSF) prophylaxis
Primary prophylaxis may be indicated
See Chapter 43 for more information
Antimicrobial prophylaxis
Risk of fever and neutropenia is LOW
Antimicrobial primary prophylaxis to be considered:
See Chapter 47 for more information
Diarrhea management
Latent or delayed onset diarrhea✫:
Loperamide 4 mg orally initially after the first loose or liquid stool, then
Loperamide 2 mg orally every 2 hours during waking hours, plus
Loperamide 4 mg orally every 4 hours during hours of sleep
Continue for at least 12 hours after diarrhea resolves
Recurrent diarrhea after a 12-hour diarrhea-free interval is treated as a new episode
Rehydrate orally with fluids and electrolytes during a diarrheal episode
If a patient develops blood or mucus in stool, dehydration, or hemodynamic instability, or if diarrhea persists >48 hours despite loperamide, stop loperamide and hospitalize the patient for IV hydration
Alternatively, a trial of Diphenoxylate hydrochloride 2.5 mg with Atropine sulfate 0.025 mg (eg, Lomotil)
Initial adult dose is 2 tablets 4 times daily until control has been achieved, after which the dose may be reduced to meet individual requirements. Control may often be maintained with as little as 2 tablets daily
Clinical improvement of acute diarrhea is usually observed within 48 hours. If improvement of chronic diarrhea after treatment with a maximum daily dose of 8 tablets is not observed within 10 days, control is unlikely with further administration
Persistent diarrhea:
Octreotide 100–150 mcg subcutaneously 3 times daily. Maximum total daily dose is 1500 mcg
Antibiotic therapy during latent or delayed onset diarrhea:
A fluoroquinolone (eg, Ciprofloxacin 500 mg orally every 12 hours) if absolute neutrophil count <500/mm3 with or without accompanying fever in association with diarrhea
Oral care
Prophylaxis and treatment for mucositis/stomatitis
General advice:
Encourage patients to maintain intake of non-alcoholic fluids
Evaluate patients for oral pain and provide analgesic medications
Consider histamine (H2-subtype) receptor antagonists (eg, ranitidine, famotidine), or a proton pump inhibitor for epigastric pain
Lactobacillus sp.-containing probiotics may be beneficial in preventing diarrhea
Patients with intact oral mucosa:
Clean the mouth, tongue, and gums by brushing after every meal and at bedtime with an ultra-soft toothbrush with fluoride toothpaste
Floss teeth gently every day unless contraindicated. If gums bleed and hurt, avoid bleeding or sore areas, but floss other teeth
Patients may use saline or commercial bland, non-alcoholic rinses
If mucositis or stomatitis is present:
Keep the mouth moist utilizing water, ice chips, sugarless gum, sugar-free hard candies, or a saliva substitute
Rinse mouth several times a day to remove debris
Use a solution of ¼ teaspoon (1.25 g) each of baking soda and table salt (sodium chloride) in one quart (~950 mL) of warm water. Follow with a plain water rinse
Do not use mouthwashes that contain alcohols
Foam-tipped swabs (eg, Toothettes®) are useful in moisturizing oral mucosa, but ineffective for cleansing teeth and removing plaque
Advise patients who develop mucositis to:
Choose foods that are easy to chew and swallow
Take small bites of food, chew slowly, and sip liquids with meals
Encourage soft, moist foods such as cooked cereals, mashed potatoes, and scrambled eggs
For trouble swallowing, soften food with gravies, sauces, broths, yogurt, or other bland liquids
Avoid sharp, crunchy foods; hot, spicy or highly acidic foods (eg, citrus fruits and juices); sugary foods; toothpicks; tobacco products; alcoholic drinks