Chapter 12: Gastric Cancer

Adjuvant Regimen: Adjuvant Capecitabine and Oxaliplatin for Gastric Cancer after D2 Gastrectomy

Bang Y-J et al. Lancet 2012;379:315–321

Capecitabine 1000 mg/m² per dose; administer orally twice daily for 14 consecutive days, on days 1–14, every 3 weeks for 8 cycles (total dosage/cycle = 28,000 mg/m²), plus:

Oxaliplatin 130 mg/m²; administer intravenously in 250–500 mL 5% dextrose injection over 2 hours on day 1, every 3 weeks, for 8 cycles (total dosage/cycle = 130 mg/m²)

Supportive Care

Antiemetic prophylaxis

Emetogenic potential on Day 1 is MODERATE

Emetogenic potential on days with capecitabine alone is MINIMAL–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:

• Antibacterial—not indicated

• Antifungal—not indicated

• Antiviral—not indicated, unless patient previously had an episode of HSV

See Chapter 47 for more information

Hand-foot reaction (palmar-plantar erythrodysesthesia, PPE)

For patients who develop a hand-foot reaction, use topical emollients (eg, Aquaphor^®), topical or orally administered steroids, antihistamine agents (H₁-receptor antagonists), or pyridoxine

  Pyridoxine may provide relief for discomfort/pain associated with PPE, although the mechanism through which this occurs remains unclear

• The suggested pyridoxine starting dose is 50 mg/day, which may be increased to a maximum of 200 mg/day

Diarrhea management

  Loperamide 4 mg; administer orally initially after the first loose or liquid stool, then

  Loperamide 2 mg; administer orally every 2 hours during waking hours, plus

  Loperamide 4 mg; administerorally 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 two tablets four 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 two 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

Rothenberg ML et al. J Clin Oncol 2001;19:3801–3807

Wadler S et al. J Clin Oncol 1998;16:3169–3178

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

  • Do not use mouthwashes that contain alcohols

  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

Treatment Modifications

Efficacy

Toxicity

Treatment Monitoring

1. Before each cycle: Physical examination with attention to clinical toxicities, CBC with differential, serum magnesium, and LFTs

2. Efficacy Assessments: Every two cycles

Patient Population Studied

Advanced Disease Regimen: Epirubicin + Cisplatin + Fluorouracil (ECF)

Webb A et al. J Clin Oncol 1997;15:261–267

Epirubicin 50 mg/m²; administer by intravenous injection over 3-20 minutes on day 1, every 3 weeks, for a maximum of 8 cycles (total dosage/3-week cycle = 50 mg/m²)

Hydration before cisplatin: ≥1000 mL 0.9% sodium chloride injection (0.9% NS); administer intravenously over a minimum of 3-4 hours. Monitor and replace magnesium/electrolytes as needed

Mannitol diuresis: Mannitol may be given to patients who have received adequate hydration. A bolus dose of 12.5 g mannitol can be administered as an intravenous injection before starting cisplatin or in the same container as cisplatin. Continued hydration is essential

Cisplatin 60 mg/m²; administer intravenously in 100–500 mL of 0.9% NS over 30–60 minutes on day 1, every 3 weeks, for a maximum of 8 cycles (total dosage/3-week cycle = 60 mg/m²)

Hydration after cisplatin: ≥1000 mL 0.9% NS; administer intravenously over a minimum of 3–4 hours. Also, encourage increased oral intake of non-alcoholic fluids. Goal is to achieve a urine output of ≥100 mL/hour

Fluorouracil 200 mg/m² by continuous intravenous infusion in 50–1000 mL 0.9% NS, or 5% dextrose injection over 24 hours, starting on cycle 1, day 1, continuously for a maximum duration of 6 months (total dosage/3-week cycle = 4200 mg/m²)

Supportive Care

Antiemetic prophylaxis

Emetogenic potential on day 1 is HIGH. Potential for delayed emetic symptoms

Emetogenic potential on days 2–21 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:

• Antibacterial—not indicated

• Antifungal—not indicated

• Antiviral—not indicated unless patient previously had an episode of HSV

See Chapter 47 for more information

Diarrhea management

Latent or delayed-onset diarrhea^✫:

  Loperamide 4 mg; administer orally initially after the first loose or liquid stool, then

  Loperamide 2 mg; administer orally every 2 hours during waking hours, plus

  Loperamide 4 mg; administer 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 two tablets four 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 two 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

Oral care

Prophylaxis and treatment for mucositis/stomatitis

  General advice:

• Encourage patients to maintain intake of non-alcoholic fluids

  If mucositis or stomatitis is present:

• 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

Hand-foot reaction (palmar-plantar erythrodysesthesia, PPE)

For patients who develop a hand-foot reaction, use topical emollients (eg, Aquaphor^®), topical or orally administered steroids, antihistamine agents (H₁-receptor antagonists), or pyridoxine

  Pyridoxine may provide relief; starting dose is 50 mg/day, which may be increased to a maximum of 200 mg/day

Efficacy (N = 111-126)

Patient Population Studied

A trial of 274 patients with previously untreated advanced esophagogastric cancer randomized to receive epirubicin, cisplatin, and fluorouracil (ECF; N = 137) compared with fluorouracil, doxorubicin, and methotrexate (FAMTX; N = 137). The ECF regimen resulted in a survival and response advantage, tolerable toxicity, and better quality of life, and cost-effectiveness

Treatment Modifications

Toxicity

Therapy Monitoring

1. Before each cycle: Physical examination with attention to clinical toxicities, CBC with differential, serum sodium, potassium, magnesium, creatinine, BUN, and LFTs

2. Before repeated cisplatin treatments: Monitor serum creatinine with estimated creatinine clearance (CrCl), or measure CrCl with either a 12- or a 24-hour urine collection

Note: Prior to starting chemotherapy: In patients with a history of ischemic heart disease, measure left ventricular ejection fraction by multiple gated acquisition (MUGA) scanning or echocardiography. Omit epirubicin if the left ventricular ejection fraction is <50%

Advanced Disease Regimen: Docetaxel + Cisplatin + Fluorouracil (DCF)

van Cutsem E et al. J Clin Oncol 2006;24:4991–4997

Docetaxel 75 mg/m²; administer intravenously diluted in a volume of 0.9% sodium chloride injection (0.9% NS) or 5% dextrose injection (D5W) sufficient to produce a docetaxel concentration within the range 0.3–0.74 mg/mL over 60 minutes on day 1, every 3 weeks (total dosage/cycle = 75 mg/m²)

Hydration before cisplatin: ≥1000 mL 0.9% NS; administer intravenously over a minimum of 3 hours

Mannitol 12.5–25 g; administer by intravenous injection or infusion over 5–15 minutes before starting cisplatin. Mannitol may be given to patients who have received adequate hydration. Continued intravenous hydration is essential to insure diuresis. Mannitol may be prepared as an admixture (in the same container) with cisplatin

Cisplatin 75 mg/m²; administer intravenously in 100–250 mL 0.9% NS over 1–3 hours on day 1, every 3 weeks (total dosage/cycle = 75 mg/m²)

Hydration after cisplatin: ≥1000 mL 0.9% NS; administer intravenously over a minimum of 3 hours. Encourage increased oral intake of non-alcoholic fluids. Goal is to achieve a urine output of ≥100 mL/hour. Monitor and replace magnesium and other electrolytes as needed

Fluorouracil 750 mg/m² per day; administer by continuous intravenous infusion in 50–1000 mL 0.9% NS or D5W over 24 hours for 5 consecutive days, on days 1–5, every 3 weeks (total dosage/cycle = 3750 mg/m²)

Supportive Care

Antiemetic prophylaxis

Emetogenic potential on day 1 is HIGH. Potential for delayed emetic symptoms

Emetogenic potential on days 2–5 is LOW

See Chapter 39 for antiemetic recommendations

Hematopoietic growth factor (CSF) prophylaxis

Primary prophylaxis is indicated with one of the following:

  Filgrastim (G-CSF) 5 mcg/kg per day by subcutaneous injection, or

  Pegfilgrastim (pegylated filgrastim) 6 mg/0.6 mL by subcutaneous injection for 1 dose

• Begin use from 24–72 hours after myelosuppressive chemotherapy is completed

See Chapter 43 for more information

Antimicrobial prophylaxis

Risk of fever and neutropenia is LOW

  Antimicrobial primary prophylaxis to be considered:

• Antibacterial—not indicated

• Antifungal—not indicated

• Antiviral—not indicated unless patient previously had an episode of HSV

See Chapter 47 for more information

Diarrhea management

Latent or delayed-onset diarrhea^✫:

  Loperamide 4 mg; administer orally initially after the first loose or liquid stool, then

  Loperamide 2 mg; administer orally every 2 hours during waking hours, plus

  Loperamide 4 mg; administer 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 two tablets four 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 two 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

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

  • Do not use mouthwashes that contain alcohols

  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

Treatment Modifications

Efficacy

Patient Population Studied

A trial of 445 evaluable patients with metastatic or locally recurrent, unresectable gastric carcinoma randomly assigned to receive DCF or cisplatin and fluorouracil (CF). The DCF regimen resulted in a significantly longer time to progression, survival and higher response rate than CF, but G3/4 adverse events were significant in both arms

Toxicity (N = 221)

Therapy Monitoring

1. Before each cycle: Physical examination, CBC with differential, serum electrolytes, magnesium, calcium, creatinine, BUN, and LFTs

2. Response evaluation: Every 2 cycles

Advanced Disease Regimens: Epirubicin (E), Cisplatin (C), Fluorouracil (F), Oxaliplatin (O), Capecitabine (X): ECF, ECX, EOF, and EOX

Cunningham D et al. N Engl J Med 2008;358:36–46. Comment in: N Engl J Med 2008;358:1965, Nat Clin Pract

Gastroenterol Hepatol 2008;5:414–415, N Engl J Med 2010;362:858–859

REAL-2 study conclusion: Capecitabine and oxaliplatin are as effective as fluorouracil and cisplatin, respectively, in patients with previously untreated esophagogastric cancer

ECF Regimen

Epirubicin 50 mg/m²; administer intravenously over 3–20 minutes on day 1 before cisplatin, every 3 weeks, for a maximum of 8 cycles (total dosage/cycle = 50 mg/m²)

Hydration before cisplatin: ≥1000 mL 0.9% sodium chloride injection (0.9% NS); administer intravenously over a minimum of 3 hours

Cisplatin 60 mg/m²; administer intravenously in 100–500 mL 0.9% NS over 30–60 minutes on day 1, every 3 weeks, for a maximum of 8 cycles (total dosage/cycle = 60 mg/m²)

Hydration after cisplatin: ≥1000 mL 0.9% NS; administer intravenously over a minimum of 3 hours. Encourage increased oral fluid intake. Goal is to achieve a urine output ≥100 mL/hour. Monitor and replace magnesium and other electrolytes as needed

Fluorouracil 200 mg/m² per day; administer by continuous intravenous infusion over 24 hours in 50–1000 mL 0.9% NS or 5% dextrose injection (D5W) for 21 consecutive days, on days 1–21, every 3 weeks, for a maximum of 8 cycles (total dosage/cycle = 4200 mg/m²)

ECX Regimen

Epirubicin 50 mg/m²; administer intravenously over 3–20 minutes on day 1 before cisplatin, every 3 weeks, for a maximum of 8 cycles (total dosage/cycle = 50 mg/m²)

Hydration before cisplatin: ≥1000 mL 0.9% NS; administer intravenously over a minimum of 3 hours

Cisplatin 60 mg/m²; administer intravenously in 100–500 mL 0.9% NS over 30–60 minutes on day 1, every 3 weeks, for a maximum of 8 cycles (total dosage/cycle = 60 mg/m²)

Hydration after cisplatin: ≥1000 mL 0.9% NS; administer intravenously over a minimum of 3 hours. Encourage increased oral fluid intake. Goal is to achieve a urine output ≥100 mL/hour. Monitor and replace magnesium and other electrolytes as needed

Capecitabine 625 mg/m² per dose; administer orally, twice daily for 21 consecutive days, on days 1–21, every 3 weeks, for a maximum of 8 cycles (total dosage/cycle = 26,250 mg/m²)

• The first 80 patients received capecitabine 500 mg/m² per dose, twice daily

EOF Regimen

Epirubicin 50 mg/m²; administer intravenously over 3–20 minutes on day 1 before oxaliplatin, every 3 weeks, for a maximum of 8 cycles (total dosage/cycle = 50 mg/m²)

Oxaliplatin 130 mg/m²; administer intravenously in 250 mL D5W over 2 hours on day 1, every 3 weeks, for a maximum of 8 cycles (total dosage/cycle = 130 mg/m²)

Note: Oxaliplatin must not be mixed with sodium chloride solutions

Fluorouracil 200 mg/m² per day; administer by continuous intravenous infusion in 50–1000 mL 0.9% NS or D5W over 24 hours for 21 consecutive days, on days 1–21, for a maximum of 8 cycles (total dosage/cycle = 4200 mg/m²)

EOX Regimen

Epirubicin 50 mg/m²; administer intravenously over 3–20 minutes on day 1 before oxaliplatin, every 3 weeks, for a maximum of 8 cycles (total dosage/cycle = 50 mg/m²)

Oxaliplatin 130 mg/m²; administer intravenously in 250 mL D5W over 2 hours on day 1, every 3 weeks, for a maximum of 8 cycles (total dosage/cycle = 130 mg/m²)

Note: Oxaliplatin must not be mixed with sodium chloride solutions

Capecitabine 625 mg/m² per dose; administer orally, twice daily for 21 consecutive days, on days 1–21, every 3 weeks, for a maximum of 8 cycles (total dosage/cycle = 26,250 mg/m²)

• The first 80 patients received capecitabine 500 mg/m² per dose, twice daily

Supportive Care

Antiemetic prophylaxis for ECF and ECX regimens

Emetogenic potential on day 1 is HIGH. Potential for delayed emetic symptoms

Emetogenic potential on days 2–21 is LOW

Antiemetic prophylaxis for ECF and ECX regimens

Emetogenic potential on day 1 is MODERATE

Emetogenic potential on days 2–21 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

See Chapter 47 for more information

Diarrhea management

Latent or delayed-onset diarrhea^✫:

  Loperamide 4 mg; administer orally initially after the first loose or liquid stool, then

  Loperamide 2 mg; administer orally every 2 hours during waking hours, plus

  Loperamide 4 mg; administer 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 two tablets four 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 two tablets daily

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

  If mucositis or stomatitis is present:

• 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

Hand-foot reaction (palmar-plantar erythrodysesthesia, PPE)

For patients who develop a hand-foot reaction, use topical emollients (eg, Aquaphor^®), topical or orally administered steroids, antihistamine agents (H₁-receptor antagonists), or pyridoxine

  Pyridoxine may provide relief; starting dose is 50 mg/day, which may be increased to a maximum of 200 mg/day

Treatment Modifications

Treatment Modifications (Per Protocol-Patients)

Efficacy

Toxicities

Patient Population Studied

The REAL-2 study was a trial of 1002 patients with previously untreated advanced esophagogastric cancer who were randomly assigned to 1 of 4 combination chemotherapy regimens, including epirubicin, cisplatin, and fluorouracil (ECF; N = 263); epirubicin, cisplatin, and capecitabine (ECX; N = 250); epirubicin, oxaliplatin, and fluorouracil (EOF; N = 245); and epirubicin, oxaliplatin, and capecitabine (EOX; N = 244). The primary endpoint was noninferiority in overall survival for the triplet therapies containing capecitabine or fluorouracil, and for those containing oxaliplatin or cisplatin. Progression-free survival and response rates did not differ significantly among the regimens. Adverse effects associated with capecitabine and fluorouracil were similar. In comparison with cisplatin, oxaliplatin-containing regimens had less associated G3 or G4 neutropenia, alopecia, renal toxicity, and thromboembolism but higher rates of G3 or G4 diarrhea and peripheral neuropathy. The investigators concluded capecitabine and oxaliplatin are as effective as fluorouracil and cisplatin, respectively, in patients with previously untreated esophagogastric cancer

Therapy Monitoring

1. Before each cycle: Physical examination, CBC and differential counts, clotting analysis, LFTs, serum creatinine and (estimated or measured) creatinine clearance

2. In patients with a history of ischemic heart disease, measure left ventricular ejection fraction by MUGA scanning or echocardiography prior to starting therapy and at intervals thereafter

3. Baseline chest radiography and computed tomography of the chest, abdomen, and pelvis, with or without upper gastrointestinal endoscopy within 28 days before treatment commences

Note: Prior to starting therapy: In patients with a history of ischemic heart disease, measure left ventricular ejection fraction by multiple gated acquisition (MUGA) scanning or echocardiography. Omit epirubicin if the left ventricular ejection fraction is <50%

Advanced Disease Regimen: Irinotecan + Cisplatin

Ajani JA et al. Cancer 2002;94:641–646

Irinotecan 65 mg/m²; administer intravenously by intravenous infusion diluted in 5% dextrose injection (D5W) to a concentration within the range 0.12-2.8 mg/mL over 90 minutes every week for 4 consecutive weeks, weeks 1-4, every 6 weeks (total dosage/cycle = 260 mg/m²)

Hydration before cisplatin: ≥1000 mL 0.9% sodium chloride injection (0.9% NS); administer intravenously over a minimum of 3 hours

Cisplatin 30 mg/m²; administer intravenously in 100–500 mL 0.9% NS over 60 minutes, every week after irinotecan for 4 consecutive weeks, weeks 1–4, every 6 weeks (total dosage/cycle = 120 mg/m²)

Hydration after cisplatin: ≥1000 mL 0.9% NS; administer intravenously over a minimum of 3 hours. Encourage increased oral fluid intake. Goal is to achieve a urine output of ≥100 mL/hour. Monitor and replace magnesium and other electrolytes as needed

Note: Irinotecan and cisplatin are administered weekly for 4 consecutive weeks followed by a recovery period of 2 weeks without treatment

Supportive Care

Antiemetic prophylaxis

Emetogenic potential: HIGH. Potential for delayed emetic symptoms

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:

• Antibacterial—not indicated

• Antifungal—not indicated

• Antiviral—not indicated unless patient previously had an episode of HSV

See Chapter 47 for more information

Diarrhea management

Latent or delayed-onset diarrhea^✫:

  Loperamide 4 mg orally initially, then 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

• If diarrhea persists ≤48 hours despite loperamide, stop loperamide and hospitalize patient for IV hydration

Persistent diarrhea:

  Octreotide 100–150 mcg subcutaneously 3 times daily. Maximum total daily dose = 1500 mcg

Antibiotic therapy during latent or delayed onset diarrhea:

  Ciprofloxacin 500 mg orally every 12 hours if absolute neutrophil count <500/mm³ with or without accompanying fever in association with diarrhea

• Antibiotics should also be administered if patient is hospitalized with prolonged diarrhea and should be continued until diarrhea resolves

Acute cholinergic syndrome

Atropine sulfate 0.25–1 mg subcutaneously

• If symptoms are severe, add as primary prophylaxis during subsequent cycles

• For irinotecan, acute cholinergic syndrome is characterized by abdominal cramps, diarrhea, diaphoresis, hypotension, bradycardia, rhinitis, increased salivation, visual disturbances, and lacrimation

Patient Population Studied

A phase II trial of 36 evaluable patients with advanced untreated gastric or gastroesophageal junction carcinoma

Efficacy (N = 36)

Toxicity (N = 36)

Treatment Modifications

Therapy Monitoring

1. Cycle 1: CBC with differential, serum electrolytes, magnesium, calcium, creatinine, BUN, and LFTs on days 1 and 22

2. Before repeated cycles: Physical examination, CBC with differential, serum electrolytes, magnesium, calcium, creatinine, BUN, and LFTs

Advanced Disease Regimen: Cisplatin + Fluorouracil (FUP)

Vanhoefer U et al. J Clin Oncol 2000;18:2648–2657

Fluorouracil 1000 mg/m²; administer by continuous intravenous infusion in 50-1000 mL 0.9% sodium chloride injection (0.9% NS) or 5% dextrose injection (D5W) over 24 hours for 5 consecutive days, on days 1–5, every 28 days (total dosage/cycle = 5000 mg/m²)

Hydration before cisplatin: ≥1000 mL 0.9% NS; administer intravenously over a minimum of 3 hours

Optional mannitol diuresis: Mannitol 12.5–25 g; administer by intravenous injection or infusion over 5–15 minutes before starting cisplatin

• Mannitol may be given to patients who have received adequate hydration

• Mannitol may be prepared as an admixture (in the same container) with cisplatin

Cisplatin 100 mg/m²; administer intravenously in 100–500 mL of 0.9% NS over 1 hour on day 2, every 28 days (total dosage/cycle = 100 mg/m²)

Hydration after cisplatin: ≥1000 mL 0.9% NS; administer intravenously over a minimum of 3 hours. Encourage increased oral fluid intake. Goal is to achieve a urine output of ≥100 mL/hour. Monitor and replace magnesium and other electrolytes as needed

Optional mannitol diuresis: Mannitol 20–50 g; administer intravenously over 2–5 hours after cisplatin

• Administer through a hydrophilic inline filter with pore size ≤5 μm to prevent infusion of mannitol crystals

• Continuing intravenous administration of fluids is essential for effective diuresis, particularly if mannitol is administered before, during, or after cisplatin

Supportive Care

Antiemetic prophylaxis

Emetogenic potential on days 1 and 3–5 is LOW

Emetogenic potential on day 2 is HIGH. Potential for delayed emetic symptoms

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:

• Antibacterial—not indicated

• Antifungal—not indicated

• Antiviral—not indicated unless patient previously had an episode of HSV

See Chapter 47 for more information

Diarrhea management

Latent or delayed-onset diarrhea^✫:

  Loperamide 4 mg; administer orally initially after the first loose or liquid stool, then

  Loperamide 2 mg; administer orally every 2 hours during waking hours, plus

  Loperamide 4 mg; administer 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 two tablets four 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 two 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

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

  • Do not use mouthwashes that contain alcohols

  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

Efficacy

Toxicity (N = 127)

Patient Population

The EORTC trial 40902 of 245 eligible patients with advanced adenocarcinoma of the stomach randomized to receive sequential high-dose methotrexate, fluorouracil, and doxorubicin (FAMTX) versus etoposide, leucovorin, and fluorouracil (ELF) versus infusional fluorouracil and cisplatin (FUP). The overall response rate in patients with measurable disease was 12% (FAMTX), 9% (ELF), and 20% (FUP)

Therapy Monitoring

1. Before each cycle: Physical examination, CBC with differential, serum electrolytes, magnesium, calcium, creatinine, BUN, and LFTs

2. Response evaluation: Every 2 cycles

Treatment Modifications

Advanced Disease Regimens: Cisplatin + Fluorouracil (CF) Irinotecan + Fluorouracil (IF)

Dank M et al. Ann Oncol 2008;19:1450–1457

Cisplatin + Fluorouracil (CF):

Hydration before cisplatin: ≥1000 mL 0.9% sodium chloride injection (0.9% NS); administer intravenously over a minimum of 3 hours

Optional mannitol diuresis: Mannitol 12.5–25 g; administer by intravenous injection or infusion over 5–15 minutes before starting cisplatin

• Mannitol may be given to patients who have received adequate hydration

• Mannitol may be prepared as an admixture (in the same container) with cisplatin

Cisplatin 100 mg/m²; administer intravenously in 100–500 mL 0.9% NS over 1–3 hours on day 1, every 28 days (total dosage/cycle = 100 mg/m²)

Hydration after cisplatin: ≥1000 mL 0.9% NS; administer intravenously over a minimum of 3 hours. Encourage increased oral fluid intake. Goal is to achieve a urine output of ≥100 mL/hour. Monitor and replace magnesium and other electrolytes as needed

Optional mannitol diuresis: Mannitol 20–50 g; administer intravenously over 2–5 hours after cisplatin

• Administer through a hydrophilic inline filter with pore size ≤5 μm to prevent infusion of mannitol crystals

• Continuing intravenous fluid administration is essential for effective diuresis, particularly if mannitol is administered before, during, or after cisplatin

Fluorouracil 1000 mg/m² per day; administer by continuous intravenous infusion in 50–1000 mL 0.9% NS or 5% dextrose injection over 24 hours for 5 consecutive days, on days 1–5, every 28 days (total dosage/cycle = 5000 mg/m²)

Supportive Care

Antiemetic prophylaxis

Emetogenic potential on day 1 is HIGH. Potential for delayed emetic symptoms

Emetogenic potential on days 2–5 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:

• Antibacterial—not indicated

• Antifungal—not indicated

• Antiviral—not indicated unless patient previously had an episode of HSV

See Chapter 47 for more information

Irinotecan + Fluorouracil (IF):

Note: IF provides a platinum-free frontline treatment alternative for metastatic gastric cancer

Irinotecan 80 mg/m² per dose; administer intravenously diluted in D5W to a concentration within the range 0.12–2.8 mg/mL over 30 minutes, weekly, for 6 consecutive weeks followed by a 1-week rest (total dosage/7-week cycle = 480 mg/m²), followed by:

Leucovorin 500 mg/m² per dose; administer intravenously in 25–250 mL 0.9% NS or D5W over 2 hours, weekly, for 6 consecutive weeks followed by a 1-week rest (total dosage/7-week cycle = 3000 mg/m²), followed by:

Fluorouracil 2000 mg/m² per dose; administer intravenously in 50–1000 mL 0.9% NS or D5W over 22 hours, weekly, for 6 consecutive weeks followed by a 1-week rest (total dosage/7-week cycle = 12,000 mg/m²)

Supportive Care

Antiemetic prophylaxis

Emetogenic potential: MODERATE

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:

• Antibacterial—not indicated

• Antifungal—not indicated

• Antiviral—not indicated unless patient previously had an episode of HSV

See Chapter 47 for more information

Acute cholinergic syndrome associated with irinotecan

Atropine sulfate 0.25–1 mg subcutaneously

• If symptoms are severe, add as primary prophylaxis during subsequent cycles

• For irinotecan, acute cholinergic syndrome is characterized by: abdominal cramps, diarrhea, diaphoresis, hypotension, bradycardia, rhinitis, increased salivation, visual disturbances, and lacrimation

Supportive Care for both CF and IF regimens:

Diarrhea management

Latent or delayed-onset diarrhea^✫:

  Loperamide 4 mg; administer orally initially after the first loose or liquid stool, then

  Loperamide 2 mg; administer orally every 2 hours during waking hours, plus

  Loperamide 4 mg; administer 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 two tablets four 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 two 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 acetate (solution) 100–150 mcg; administer 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

• Antibiotics should also be administered if patient is hospitalized with prolonged diarrhea and should be continued until diarrhea resolves

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

  • Do not use mouthwashes that contain alcohols

  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

Hand-foot reaction (palmar-plantar erythrodysesthesia, PPE)

For patients who develop a hand-foot reaction, use topical emollients (eg, Aquaphor^®), topical or orally administered steroids, antihistamine agents (H₁-receptor antagonists), or pyridoxine

  Pyridoxine may provide relief for discomfort/pain associated with PPE, although the mechanism through which this occurs remains unclear

• The suggested pyridoxine starting dose is 50 mg/day, which may be increased to a maximum of 200 mg/day

Efficacy (N = 333)

Toxicity

Patient Population

A trial of 333 patients with advanced adenocarcinoma of the stomach or esophagogastric junction randomized to receive irinotecan and fluorouracil (IF arm, 170 patients) versus cisplatin and fluorouracil (CF arm, 163 patients). The overall response rate in patients with measurable disease was 31.8% (IF) versus 25.8% (CF)

Monitoring

1. Before each cycle: Physical examination, CBC with differential, serum electrolytes, magnesium, calcium, creatinine, BUN, and LFTs

2. Response evaluation: Every 8 weeks

Treatment Modifications

Advanced Disease Regimen: Her2-Positive Advanced Gastric Cancer Cisplatin + Trastuzumab with Capecitabine or Fluorouracil

Bang Y-J et al. Lancet 2010;376:687–697

Either:

Capecitabine 1000 mg/m² per dose; administer orally twice daily for 14 consecutive days, on days 1–14 (28 doses), every 3 weeks for 6 cycles, (total dosage/cycle = 28,000 mg/m²)

OR

Fluorouracil 800 mg/m² per day; administer by continuous intravenous infusion in 50–1000 mL 0.9% sodium chloride injection (0.9% NS) or 5% dextrose injection over 24 hours for 5 consecutive days, on days 1–5, every 3 weeks, for 6 cycles (total dosage/cycle = 4000 mg/m²)

With:

Hydration before cisplatin: 1000 mL 0.9% NS; administer intravenously over a minimum of 1 hour before commencing cisplatin administration

(optional) Mannitol 12.5–25 g; administer by intravenous injection or intravenous infusion over 5–15 minutes before starting cisplatin

• Mannitol may be given to patients who have received adequate hydration. Continued hydration is essential to ensure diuresis

• Mannitol may be prepared as an admixture (in the same container) with cisplatin

Cisplatin 80 mg/m²; administer intravenously in 50–500 mL 0.9% NS over 30–60 minutes on day 1, every 3 weeks, for 6 cycles (total dosage/cycle = 80 mg/m²)

Hydration after cisplatin: ≥1000 mL 0.9% NS; administer intravenously over a minimum of 2 hours. Monitor and replace magnesium and other electrolytes as needed. Encourage patients to increase their intake of non-alcoholic fluids

Trastuzumab: Administer intravenously in 250 mL 0.9% NS every 3 weeks for 6 cycles

Loading Dose: Trastuzumab 8 mg/kg; administer over 90 minutes as a loading dose on cycle 1, day 1 only (total dosage during the 1st cycle = 8 mg/kg), then:

Maintenance Doses: Trastuzumab 6 mg/kg; administer over 30 minutes on day 1, every 21 days for 5 cycles (total dosage/cycle = 6 mg/kg)

Note: Assess left ventricular ejection fraction (LVEF) prior to initiating trastuzumab and at regular intervals during treatment

Crossover to trastuzumab at the time of disease progression was not allowed

Supportive Care

Antiemetic prophylaxis

Emetogenic potential on days with cisplatin is HIGH. Potential for delayed emetic symptoms

Emetogenic potential on days with capecitabine or fluorouracil is LOW

Emetogenic potential on days with trastuzumab alone is MINIMAL–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:

• Antibacterial—not indicated

• Antifungal—not indicated

• Antiviral—not indicated, unless patient previously had an episode of HSV

See Chapter 47 for more information

Diarrhea management

Latent or delayed-onset diarrhea^✫:

  Loperamide 4 mg; administer orally initially after the first loose or liquid stool, then

  Loperamide 2 mg; administer orally every 2 hours during waking hours, plus

  Loperamide 4 mg; administer 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 two tablets four 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 two 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

Trastuzumab infusion reactions

• A symptom complex most commonly consisting of chills and/or fever may occur in as many as 40% of patients during the first infusion of trastuzumab. These symptoms occur infrequently with subsequent trastuzumab infusions. Other signs and/or symptoms may include nausea, vomiting, pain (in some cases at tumor sites), rigors, headache, dizziness, dyspnea, hypotension, rash, and asthenia. Although the symptoms are usually mild to moderate in severity, infrequently, trastuzumab may need to be discontinued

• When such a symptom complex is observed, it can be treated with or without reduction in the rate of trastuzumab infusion, and:

  • Acetaminophen 650 mg; administer orally

  • Diphenhydramine 25–50 mg administer orally or by intravenous injection, and

  • Meperidine 12.5–25 mg; administer by intravenous injection every 10 minutes if needed for shaking chills (generally, cumulative doses >50 mg are not needed; use with caution in persons with moderate or more severely impaired renal function)

Hand-foot reaction (palmar-plantar erythrodysesthesia, PPE)

For patients who develop a hand-foot reaction, use topical emollients (eg, Aquaphor^®), topical or orally administered steroids, antihistamine agents (H₁-receptor antagonists), or pyridoxine

  Pyridoxine may provide relief for discomfort/pain associated with PPE, although the mechanism through which this occurs remains unclear

• The suggested pyridoxine starting dose is 50 mg/day, which may be increased to a maximum of 200 mg/day

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

  • Do not use mouthwashes that contain alcohols

  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

Treatment Modifications

Patient Population Studied

Efficacy

Toxicity

Treatment Monitoring

1. CBC with differential, serum electrolytes, magnesium and calcium, BUN, and creatinine before the start of a new cycle

2. Tumor assessment every two cycles

3. LVEF assessment (MUGA or echocardiography) every 3 months in patients receiving trastuzumab

Advanced Disease Regimens: Single-Agent Docetaxel or Single-Agent Irinotecan in Second Line

Kang JH et al. J Clin Oncol 2012;30:1513–1518

Docetaxel 60 mg/m²; administer intravenously in a volume of 0.9% sodium chloride injection or 5% dextrose injection (D5W) sufficient to produce a docetaxel concentration within the range 0.3–0.74 mg/mL over 60 minutes on day 1, every 3 weeks (total dosage/cycle = 60 mg/m²)

OR

Irinotecan 150 mg/m²; administer intravenously in 500 mL D5W over 90 minutes on day 1, every 2 weeks (total dosage/cycle = 150 mg/m²)

Supportive Care

Antiemetic prophylaxis

Emetogenic potential with docetaxel is LOW

Emetogenic potential with irinotecan is MODERATE

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:

• Antibacterial—not indicated

• Antifungal—not indicated

• Antiviral—not indicated, unless patient previously had an episode of HSV

See Chapter 47 for more information

Acute cholinergic syndrome

Atropine sulfate 0.25–1 mg; administer subcutaneously or intravenously if abdominal cramping or diarrhea develops during or within 1 hour after irinotecan administration

• If symptoms are severe, add as primary prophylaxis at least 30 min 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