that may have spread.

TREATMENT WITH CHEMOTHERAPY

AND RADIATION

CASE 94-3, QUESTION 4: M.W. begins therapy with intravenous cisplatin on day 1 combined with etoposide on days

1 to 3 given in a 21-day cycle. Four to six cycles are planned,

2221Lung Cancer Chapter 94

and she will also receive concurrent radiation.78,79 For M.W.,

what is the goal of therapy? What objective baseline data

should be acquired prior to starting treatment? What monitoring parameters should be utilized?

The goal of therapy for a patient with limited stage disease

such as M.W. would be to increase overall survival and achieve

a potential cure. In patients with limited stage disease, response

rates of 70% to 90% are expected after a regimen such as the

one M.W. is receiving, whereas response rates of 60% to 70%

are expected for patients with extensive stage disease.57 If M.W.

had been diagnosed with extensive stage disease, then the goals

would have been to increase overall survival and for palliation.

Given the complications that can arise as a result of SCLC, treatment could be used to minimize these adverse events. For example, radiotherapy is often used in treating patients with SVCS,

because it would reduce tumor size and enable resumption of

more normal blood flow. Therefore, if a patient has acceptable

performance status (e.g., 0–2) and minimal to no comorbidites,

then treatment such as the one that M.W. is receiving is the best

course of action.

A treatment regimen such as cisplatin and etoposide plus

radiation is tolerated by most patients, especially because the

number of cycles is usually limited to six. However, administration of these cytotoxic agents is associated with several adverse

effects, some of which can be life-threatening. Hence, the clinician is expected to anticipate these events, and plan treatment

accordingly to minimize complications. The patient is receiving

cisplatin, which causes several different adverse effects such as

renal insufficiency, sensory neuropathy, ototoxicity, and is considered highly emetogenic (refer to Chapter 90, Adverse Effects

of Chemotherapy and Targeted Agents). Hydration and diuresis

are required with cisplatin doses greater than 40 mg/m2 to maintain a urine output of 100 to 150 mL/hour before administration

of the drug. Mannitol is frequently added to cisplatin in order

to force dieuresis. The intravenous fluids are supplemented with

KCl and MgSO4. Monitoring of serum creatinine, electrolytes

including magnesium and calcium is performed usually before

each infusion of chemotherapeutics. An appropriate antiemetic

regimen must be implemented to prevent both acute and delayed

nausea and vomiting. For etoposide, neutropenia is usually the

dose-limiting toxicity. Therefore, monitoring of absolute neutrophil count is important and if the counts do not recover in a

timely manner (i.e., before the next dose) then delays in treatment or dosage reductions occur. In phase III clinical trials for

this regimen, grade 4 leukopenia occurred in approximately 35%

to 40% of patients, and any grade fever and infection in greater

than 20%.68,69 Therefore, consideration must be given toward

the use of colony stimulating factors to manage this latter event,

usually after radiation is completed (refer to Chapter 90, Adverse

Effects of Chemotherapy and Targeted Agents).

In conclusion, the goal of M.W.’s therapy is a potential

cure. Hydration with fluids supplemented with KCl and MgSO4

must be initiated prior to cisplatin therapy to prevent cisplatininduced renal toxicity. During therapy, clinicians must observe

for decreased ANC due to etoposide, and may need to implement

delays in therapy or use of a colony stimulating factor (e.g., granulocyte colony-stimulating factor). Supportive care such as antiemetics during therapy to prevent or manage cisplatin-associated

acute and delayed phase nausea and vomiting will also be

essential.

CASE 94-3, QUESTION 5: M.W. tolerated therapy very well,

with mild esophagitis and cough during treatment. She

did not experience any vomiting due to good aggressive

antiemetic use, nor did she exhibit any neuropathy or hearing loss. What adverse conditions that M.W. experienced

are associated with her treatment?

Both esophagitis and cough are likely attributable to radiation

effects. If esophagitis worsens to grade 3 or more, patients can

lose the ability to swallow and may require a feeding tube. During

therapy, cough can develop and patients can become concerned

that it is a sign of worsening of the disease. Radiation-induced

pneumonitis, acute (in first 3 months) and chronic (4–12 months),

can be a frequent cause of the new onset of cough, which can be

ameliorated with corticosteroid treatment.

CASE 94-3, QUESTION 6: After two cycles of chemotherapy

with concurrent radiotherapy, CT scan indicates a partial

response. Therefore, an additional four cycles of cisplatin

and etoposide were planned. How is the course of M.W.’s

disease likely to proceed?

The chances for long-term survival greater than 5 years is very

low, even for the patient with no other comorbidities and limited

stage disease such as M.W. At the completion of chemotherapy, M.W. should be offered therapy with prophylactic cranial

irradiation because brain metastases occur in greater than 50%

of patients with SCLC. Prophylactic cranial irradiation not only

reduces the incidence of metastatic disease but also increases

overall survival. Within a year of completing therapy, most

patients experience progressive or relapsed disease. The duration of the remission is the single largest predictor of outcome,

and patients are classified as having either sensitive or refractory

disease, depending on length of this duration. Approximately

half of those tumors that are deemed sensitive in this setting

respond to second-line therapy. Therefore, most SCLC tumors

become resistant to therapy either during first-line or salvage

therapy. Patients can also exhibit second primary tumors, especially NSCLC, during the course of the disease.

KEY REFERENCES AND WEBSITES

A full list of references for this chapter can be found at

http://thepoint.lww.com/AT10e. Below are the key references

and websites for this chapter, with the corresponding reference

number in this chapter found in parentheses after the reference.

Key References

DeVita VT et al, eds. DeVita, Hellman, and Rosenberg’s Cancer:

Principles and Practice of Oncology. 8th ed. Philadelphia, PA:

Lippincott Williams & Wilkins; 2008. (1)

Doll R et al. Mortality in relation to smoking: 50 years’ observations on male British doctors. BMJ. 2004;328:1519. (12)

Jemal A et al. Cancer statistics, 2010. CA Cancer J Clin. 2010;60:277.

(3)

Langer CJ et al. The evolving role of histology in the management of advanced non-small-cell lung cancer. J Clin Oncol. 2010;

28:5311. (36)

Peto R et al. Smoking, smoking cessation, and lung cancer in

the UK since 1950: combination of national statistics with two

case-control studies. BMJ. 2000;321:323. (11)

Socinski MA, Bogart JA. Limited-stage small-cell lung cancer:

the current status of combined-modality therapy. J Clin Oncol.

2007;25:4137. (79)

2222Section 17 Neoplastic Disorders

Subramanian J, Govindan R. Lung cancer in never smokers: a

review. J Clin Oncol. 2007;25:561. (13)

Key Websites

National Cancer Comprehensive Network. Small cell lung cancer. NCCN guidelines for the treatment of SCLC. http://www.

nccn.org/professionals/physician gls/f guidelines.asp. Accessed January 4, 2011. (58)

National Cancer Comprehensive Network. Non–small cell lung

cancer. NCCN guidelines for the treatment of SCLC. http://

www.nccn.org/professionals/physician gls/f guidelines.asp.

Accessed January 4, 2011. (22)

National Cancer Institute. New Surgeon General’s report outlines how tobacco smoke causes disease. http://www.cancer.

gov/ncicancerbulletin/121410/page2. Accessed November 4,

2010.

Colorectal Cancer 95

Sachin R. Shah and Julian Hoyt Slade, III

CORE PRINCIPLES

CHAPTER CASES

1 Family history, patient-specific factors, and environmental factors are identified as

risk factors for colorectal cancer. Environmental factors could be modified to

reduce the risk of colorectal cancer.

Case 95-1 (Question 1)

2 Early detection of colorectal cancer through screening reduces cancer-related

mortality. Most patients at low risk of colorectal cancer are recommended to begin

screening at the age of 50 years.

Case 95-1 (Question 2)

3 Patients may be asymptomatic at diagnosis or have nonspecific symptoms.

Carcinoembryonic antigen (CEA) may be elevated in patients with colorectal

cancer, but it cannot be used alone for diagnosis.

Case 95-2 (Questions 1, 2)

4 Adjuvant combination chemotherapy with 5

-fluorouracil (5

-FU) and oxaliplatin is

currently considered the standard of care for patients with stage III colorectal

cancer after surgery with curative intent.

Case 95-2 (Question 3)

5 All patients diagnosed with localized colorectal cancer should undergo routine

surveillance visits with their oncologist for a period of 5 years after completion of

their definitive therapy.

Case 95-2 (Question 6)

6 During the last decade newer chemotherapy agents (oxaliplatin, irinotecan) and

targeted therapies (bevacizumab, cetuximab, panitumumab) have doubled the

overall survival of patients with metastatic colorectal cancer. Fluoropyrimidine

(5

-FU or capecitabine) remains the key agent in the first-line treatment of

advanced cancer. The right combination and sequencing of these agents is vital to

improving the care of patients with colorectal cancer.

Case 95-3 (Question 1)

7 Utilization of specific predictive markers helps maximize the desired outcome in

colorectal cancer. Patients with tumor expressing wild-type-KRAS gene receive

significant survival benefit from anti–epidermal growth factor receptor (EGFR)

monoclonal antibody therapy.

Case 95-3 (Question 4)

8 Myelosuppression, diarrhea, and peripheral neuropathy are potential dose-limiting

toxicities associated with chemotherapy agents used in the treatment of colon and

rectal cancers. Prevention strategies, diligent monitoring, and adequate

supportive-care measures are vital to effective toxicity management and should be

used to maintain patient safety and enhance quality of life.

Case 95-2 (Questions 4, 5),

Case 95-3 (Question 3)

9 Severe, life-threatening adverse effects are uncommon, but potential hazards are

associated with targeted colorectal cancer therapies and avoiding their use is

warranted in patients at increased risk of experiencing these complications.

Prevention and treatment strategies are available for common adverse effects such

as hypertension associated with bevacizumab use or EGFR inhibitor–induced

dermatologic toxicity.

Case 95-3 (Questions 3, 5,

6)

10 Certain genetic variants of key enzymes involved in the catabolism of 5

-FU and

irinotecan are associated with increased toxicity from these agents. The clinical

utility of identifying these variants in an effort to avoid or manage these toxicities

continues to be elucidated.

Case 95-3 (Question 2)

2223

visuospatial, bowel/bladder function, and ability to get dressed.

There were no differences noted in the neuropsychiatric inventory for behavioral issues associated with dementia.49 A 23-mg

dose of donepezil was recently approved for patients in the moderate to severe stages of AD. Small improvements were seen in

TABLE 103-7 U.S. Food and Drug Administration–Approved Drugs for Alzheimer Disease (AD) Generic Drug (Brand Name) and Mechanism Dosage Form and Dosage Indication and Effect Adverse Effects Other Donepezil HCl (Aricept) Reversibly inhibits AChE, primarily in CNS Aricept – Tablets 5 mg – Tablets 10 mg – Tablets 23 mg Aricept RDT – Tablets, orally disintegrating 5 mg – Tablets, orally disintegrating 10 mg Mild to moderate Alzheimer disease: Adults: PO: 5 mg once daily; may increase to 10 mg once daily after 4 to 6 weeks. Severe Alzheimer Disease: Adults: PO: Start with 5 mg once daily. Increase to 10 mg once daily after 4 to 6 weeks. A dosage of 23 mg once daily may be given after the patient has been on 10 mg once daily for at least 3 months. General Dosing Information:  Orally disintegrating tablets are bioequivalent to tablets.  Administer in the evening, just before bedtime.  May be taken without respect to food.  Allow the oral disintegrating tablet to dissolve on the tongue and follow with water. Treatment of mild to severe dementia of the Alzheimer type. Small improvements in cognition and function occur within 12–24 weeks; benefits may last for at least 2 years. Cholinergic effects, particularly affecting the GI tract (nausea, anorexia, diarrhea); headache; bradycardia may occur. Completely bioavailable and may be given as a single daily dose owing to long half-life (70 hours). Metabolized by CYP3A4 isoenzymes. Galantamine HBr (Razadyne and Razadyne ER) Reversibly inhibits AChE, primarily in CNS; also stimulates nicotinic receptors at a site distinct from that of acetylcholine Razadyne – Tablets 4 mg (as base) – Tablets 8 mg (as base) – Tablets 12 mg (as base) – Oral Solution 4 mg/mL Razadyne ER – Capsules, extended-release 8 mg (as base) – Capsules, extended-release 16 mg (as base) – Capsules, extended-release 24 mg (as base) Immediate-Release Tablets and Oral Solution: Adults: PO: 4 mg twice daily. May increase to 8 mg twice daily after 4 weeks. A further increase to 12 mg twice daily may be attempted after minimum of 4 weeks at previous dose. Extended-Release Capsules: Adults: PO: 8 mg/d. Increase to 16 mg/d after min 4 weeks. A further increase to 24 mg/d may be attempted after minimum of 4 weeks at previous dose. General Dosing Information:  Administer immediate-release tablets and oral solution twice daily, preferably with morning and evening meal.  Administer extended-release tablets once daily in the morning, preferably with food. Renal/Hepatic Function Impairment: In patients with moderately impaired hepatic function (Child-Turcotte-Pugh score 7–9) and those with moderate renal function impairment, the dose should not exceed 16 mg/d. Not recommended for patients with severe renal (CrCl less than 9 mL/min) or severe hepatic function impairment (Child-Turcotte-Pugh score 10–15). Treatment of mild to moderate dementia of the Alzheimer type. Small improvements in cognition and function occur within 12–24 weeks. Benefits may last for more than 1 year. Cholinergic effects, particularly affecting the GI tract (nausea, anorexia, diarrhea); headache; bradycardia may occur. Highly bioavailable. Initial dose is not therapeutic; slow titration increases tolerability. Metabolized by CYP2D6 and CYP3A4 isoenzymes.

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