Drug Therapy by Design ……… Level II
Learning Objectives
After completing this case study, the reader should be able to:

Identify common symptoms associated with colon cancer at presentation and with disease
progression.

Describe the treatment goals associated with early and advanced stages of colon cancer.

Design an appropriate chemotherapy regimen for colon cancer based on patient-specific
data.

Formulate a monitoring plan for a patient receiving a prescribed chemotherapy regimen for
colon cancer based on patient-specific information.

Recommend alterations in a drug therapy plan for a patient with colon cancer based on
patient-specific information.

Use pharmacogenetic test results to design an appropriate drug therapy plan for a patient
with colorectal cancer.

Educate patients on the anticipated side effects of irinotecan, capecitabine, fluorouracil,
oxaliplatin, bevacizumab, ziv-aflibercept, regorafenib, and epidermal growth factor receptor
inhibitors.
Patient Presentation
Chief Complaint
“The pain below my right ribs is getting worse. Also, I'm having more numbness, cramping, and
burning sensations in my hands and feet, especially when I'm working a lot. I don't think I can
tolerate it much longer.”
HPI
Peter Robinson is a 56-year-old man who presents with worsening pain in his hands and feet
and increasing RUQ pain. He was diagnosed with stage IV colon cancer 11 months ago after
presenting with abdominal pain, bloating and distention, a history of intermittent BRBPR, and no
BM within the prior 4 days. He presented to the ED where a barium enema revealed an “apple
core” lesion in his descending colon that was suggestive of malignancy (Fig. 150-1). An FDGPET/CT scan showed a complete bowel obstruction and several areas of focal intense uptake in
the liver, consistent with metastases. His preoperative CEA was 5.6 ng/mL. He subsequently
underwent a laparotomy with a left hemicolectomy and lymphadenectomy. The pathology
revealed a moderately differentiated adenocarcinoma with extension through the bowel wall to
the serosal surface. The tumor was KRAS gene wild-type. Ten of 13 lymph nodes were positive
for tumor. Biopsy of a liver lesion confirmed hepatic metastases. A CT scan of the chest showed
no evidence of lung metastases. Seven weeks later, chemotherapy was initiated with
capecitabine, oxaliplatin (CapeOx), and bevacizumab. Except for occasional nausea, he
generally tolerated the chemotherapy well. However, over the past 2 months he has been
experiencing worsening redness and pain on the palms of his hands with numbness and tingling
in his fingers and toes. Six days ago he received his 19th cycle of
chemotherapy. UGT1A1 testing showed that he was homozygous for the UGT1A1*28 allele.
FIGURE 150-1.
Annular, constricting adenocarcinoma of the descending colon. This radiographic appearance is referred to as an
“apple-core” lesion and is always highly suggestive of malignancy. (Reprinted with permission from Mayer RJ.
Gastrointestinal tract cancer. In: Fauci AS, Kasper DL, Longo DL, et al., eds. Harrison's Principles of Internal
Medicine, 17th ed. New York, McGraw-Hill, 2008:577.)
PMH
Type 2 diabetes mellitus × 9 years
Hypertriglyceridemia × 5 years
FH
The patient is the oldest of three brothers; both siblings are alive and well. He has been married
for 26 years and has one daughter who is 20 years old. Both his mother and father are in good
health. His paternal grandfather died in his 60s from colon cancer, and his mother died in her
60s from ovarian cancer; he is aware of no other family history of malignancy.
SH
Self-employed as a graphic designer. He smoked cigarettes, one pack per day, since age 19
but quit 10 years ago. He does not drink alcohol and has never tried illicit drugs.
Meds
Morphine sustained-release 60 mg po twice daily
Bisacodyl 5 mg po daily as needed
Metformin 750 mg po once daily
Fenofibrate 120 mg po once daily
All
NKDA
ROS
The patient reports diffuse abdominal pain that is continuous with a “grabbing, gnawing”
sensation and painful redness and swelling on the palms of his hands. He rates the abdominal
pain severity as 5–6 out of 10. The numbness, tingling, cramping, and burning sensations in his
hands and feet have worsened in frequency and severity over the past 2 months and have not
responded well to morphine. He rates the severity of the tingling and burning pain as 6/10. He
denies fever, headaches, shortness of breath, cough, nausea, vomiting, or diarrhea. He reports
no lesions in his mouth or difficulty swallowing. He has been having fewer bowel movements
(about one every 3–4 days), but there is no pain or blood with passage of stool. He denies
polyuria, polydipsia, and burning on urination. He has not noticed any bleeding or excessive
bruising.
Physical Examination
Gen
Patient is a slightly overweight Caucasian man who appears fatigued.
VS
BP 164/93 mm Hg, P 79 bpm, RR 22, T 35.6°C; Wt 87 kg, Ht 5′9″
Skin
Redness and swelling of the palms of both hands and soles of feet
HEENT
PERRLA; EOMI; funduscopic exam without retinopathy; pale conjunctiva; no scleral icterus;
moist mucous membranes; no lesions in oral cavity
Neck/Lymph Nodes
Supple neck; no lymphadenopathy
Lungs/Thorax
Symmetric chest expansion with respiratory effort; clear to A & P; regular breath sounds
CV
Normal heart sounds; regular rate and rhythm; no MRG
Abd
Well-healed scar on left upper abdomen; diffuse abdominal tenderness to palpation; no rebound
tenderness; decreased bowel sounds
Genit/Rect
Prostate normal size; no masses palpated; stool heme negative
MS/Ext
Full ROM in all four extremities
Neuro
A & O × 3; cranial nerves II–XII grossly intact; reduced DTRs bilaterally; reduced feet sensitivity
to light touch and pinprick bilaterally in stocking-glove distribution; vibration sensation reduced in
distal legs
Labs
Na 137 mEq/L
K 4.4 mEq/L
Cl 98 mEq/L
CO2 26 mEq/L
BUN 17 mg/dL
SCr 1.0 mg/dL
Glu 117 mg/dL
Hgb 9.6 g/dL
Hct 29%
Plt 252 × 103/mm3
MCV 87 μm3
MCHC 33 g/dL
WBC 8.1 × 103/mm3
Neutros 40%
Bands 3%
Eos 4%
Lymphs 45%
Monos 8%
AST 52 IU/L
ALT 45 IU/L
Alk phos 109 IU/L
LDH 370 IU/L
T. bili 1.2 mg/dL
T. chol 199 mg/dL
CEA 7.9 ng/mL
Ca 8.7 mg/dL
Phos 3.4 mg/dL
Mg 2.3 mg/dL
Urinalysis
1+ glucose, (−) ketones, 1+ protein, (−) leukocyte esterase and nitrites; (−) RBC; 2–3 WBC/hpf
Abdominal CT
Multiple liver metastases, increased approximately 30% in diameter compared to prior scan;
multiple new lesions present in both lobes of the liver
Chest CT
No evidence of pulmonary metastases
Assessment
Unresectable stage IV colon cancer, with disease progression on CapeOx plus bevacizumab
chemotherapy
Clinical Pearl
There is no available test, including presence of tumor tissue epidermal growth factor receptor
expression, that predicts response to cetuximab or panitumumab. However, tumors can be
tested for the presence of KRAS mutations that are predictive of lack of response to these
agents. Patients with tumors that are KRAS mutant are not appropriate candidates for treatment
regimens that contain cetuximab or panitumumab.
Questions
Problem Identification
Identify all of the patient's drug therapy problems.
What clinical, laboratory, and other information is consistent with colon cancer?
Desired Outcome
What are the goals of pharmacotherapy for this patient?
Therapeutic Alternatives
What chemotherapeutic options are appropriate for this patient?
What treatment modifications are appropriate to address escalating oxaliplatin-induced
neuropathy?
Optimal Plan
What drugs, dosage forms, treatment schedule, and duration of therapy are best for treating this
patient's colon cancer?
What additional drug treatment interventions should be considered for this patient?
Outcome Evaluation
How is the response to the treatment regimen for the colon cancer assessed?
What acute adverse effects are anticipated with the chemotherapy regimen, and what
parameters should be monitored?
What pharmacologic measures can be instituted to prevent or manage the acute toxicities
associated with the chemotherapy regimen?
What are the potential late-onset toxicities of the chemotherapy regimen, and how can they be
detected and prevented?
Patient Education
What information should you provide to the patient to enhance compliance, ensure successful
therapy, and minimize adverse effects?
Clinical Course
His hypertension resolved after two cycles of the chemotherapy regimen you recommended,
and his neuropathic symptoms diminished over time and with drug therapy. He received PRBC
transfusions when his hemoglobin dropped below 9 g/dL. His sustained-release morphine dose
was increased to 120 mg po every 12 hours, and oral immediate-release morphine sulfate 30
mg, every 4 hours as needed for pain was started. A scheduled regimen of docusate sodium
100 mg orally plus two senna tablets daily maintained a regular pattern of bowel movements.
After seven more cycles of chemotherapy, he presented with worsening abdominal pain,
fatigue, and new-onset dyspnea. An abdominal CT scan showed the liver lesions increased in
size, and a chest CT showed multiple bilateral pulmonary nodules consistent with pulmonary
metastases. His ALT and AST increased to five times the upper limit of normal.
Follow-Up Question
What treatment options would be appropriate to consider at this time?
Additional Case Questions
What is the role of UGT1A1 genotyping in the treatment of colon cancer?
What is the role of KRAS tumor gene testing in the treatment of colon cancer?
How should a patient who develops a thrombotic event during bevacizumab therapy be
managed?
Clinical Course
The patient expressed interest in receiving further treatment for his colon cancer. After
considering limited treatment options with his oncologist, he agreed to participate in a clinical
trial. His analgesic therapy was modified, and his pain control was acceptable. His metastatic
lesions remained stable (by clinical symptoms and CT scans) for 2 months.
Self-Study Assignments
1. Develop an algorithm for treatment of colon cancer chemotherapy-induced diarrhea.
2. Develop patient-specific education materials regarding management of cutaneous toxicities
of agents used in colon cancer treatment.