Pharmacologic Treatment of Cancer Pain

Analgesic Ladder

World Health Organization (WHO) developed guidelines for treatment of cancer pain (World Health Organization 1990, Zech 1995). It includes three-step "analgesic ladder" for pharmacologic management ofcancer pain.

Application of the World Health Organization (WHO) analgesic ladder helps provide adequate analgesia in the majority of cases (Fig. 28.1) (Jacox et al. 1994, Miguel 2000, Patt 1993). The steps in the analgesic ladder are designed to treat mild, moderate and severe cancer pain:

• Mild pain: Non-opioid analgesics including non-steroidal anti-inflammatory drugs (NSAIDS; +/-) used in adjuvant therapy such as anticonvulsants and acetaminophen.

• Mild to moderate pain: Opioids and non-opioid analgesics and adjuvant therapy.

• Moderate to severe pain: Strong opioids such as long-acting opioids in addition to short-acting opioids and/or adjuvant therapy.

Figure 28.1 World Health Organization (WHO) Analgesic Ladder 1990.

Modified Analgesic Ladder

If the pain is persistent despite increasing doses of opioids, interventional treatment is warranted. Interventional procedures are demonstrated as Step 4 in the modified analgesic ladder below (Fig. 28.2). Interventional procedures are should be considered in cases of severe to intractable pain.

Figure 28.2 Modified World Health Organization (WHO) analgesic ladder for cancer pain, including interventional management. Adapted from Miguel (2000).

Non-opioid Analgesics

The first line of treatment includes non-opioid analgesics. Table 28.1 describes the commonly used non-opioid analgesics, their usual doses, route of administration, and possible side effects of each drug.

Opioid Therapy in the Treatment of Cancer Pain

When non-opioid analgesic fails to control the patient pain, opioid therapy plays an important role in treatment of cancer pain. Table 28.2 explains the difference in opioid peak onset based on route of administration (Fukshansky et al. 2005). Table 28.3 shows different opioids, available doses, route of administration, duration of action, and equi-analgesic doses (Burton 2004a). The characteristics of each drug, including side effects are discussed in different chapters in this book.

Combining short- and long-acting opioids in moderate to severe pain can be effective if the pain is not well-controlled and if the patient is already on PRN short-acting opioids.

Modified Who Analgesic Ladder

Figure 28.2 Modified World Health Organization (WHO) analgesic ladder for cancer pain, including interventional management. Adapted from Miguel (2000).

Table 28.1 Commonly used non-opioid analgesics in cancer pain.

Route of

Possible side

Drug

Usual dosage

administration

effects

Other considerations

Acetaminophen

325-1500 mg

PO or suppository

Hepatotoxic on high dose

Do not exceed 4000 mg/day

Aspirin

81-325 mg/day

PO or suppository

Bleeding ulcers

Ibuprofen

200-2400 mg/day

PO or suppository

Bleeding ulcers

Caution with renal patients

Ketorolac

10 mg PO q 4-6 h or 30 mg IV/IM q 6 h

Oral, IV, or IM

Bleeding ulcers

IV dose should not exceed 3-4 days

Naproxen

250-500 mg PO BID

Oral

Bleeding ulcers

Do not exceed a dose of

1000 mg/day for more than 6 months

Tramadol

50-100 mg PO q 6 h

Oral

Higher risk of seizures if used with antidepressants

Centrally acting non-opiate analgesic with low affinity for ^-opioid receptors

Tramadol-

100-300 mg/day

Oral

Same as above

Same as above

sustained release sustained release

PO=per os.

Table 28.2 Opioid peak onset based on route of administration.

Route

Peak onset

Oral

60-90 min

Subcutaneous

30 min

Intravenous

15-20 min

In case of moderate to severe pain that is persistent throughout the 24-h period, combining long-acting opioids and short-acting opioids in cancer pain is often ideal. This can be done by adding a small dose of long-acting opioid to the already administered PRN short-acting opioid. Then, increase the dose of long-acting opioids gradually (every 1 to 2 weeks) until the dose of PRN short-acting opioids constitutes 15-20% of the total daily dose of patient's requirement of opioids. Figure 28.3 shows ideal treatment with long and short-acting opioids. It shows around the clock medication used long-acting opioids for persistent pain. Breakthrough pain is usually treated with breakthrough medication, which is a short-acting medication. Prescribing physician should be aware of the potential for overmedication, as shown in Fig. 28.3. If the patient is not using any short-acting or breakthrough medications, he/she may be approaching the overmedication line. Evaluation of the patient on a regular basis for signs of overmedication, such as sedation or drowsiness, is necessary.

Table 28.3 Routes and equianalgesic doses of selected opioids.

Equi-analgesic dose to

Drug

Available names and dosage

Duration of action

30 mg PO morphine perday

Route of administration

Morphine Sulfate

. PO 15, 30 mg Rectal 5,10, 20, and

IV 1-10 mg dosage

3-4 h

30 mg PO is equivalent to

PO, Rectal, IV, epidural, or intrathecal

instant release (MSIR)

* 30 mg

10 mg IV

(only FDA approved opioid for intrathecal use in PF form)

Morphine

MS contin ® 15, 30, 60, 100, 200 mg

8 h

30 mg PO morphine

Oral (tablet should not be broken or

sulfate-sustained

Ormamorph SR® 15, 30, 60,100 mg

12 h

dissolved)

release

Kadian® 20,30,50,60,100 mg Avinza® 30, 60, 90, 120 mg

24 h 24 h

Hydromorphone

Oral 2, 4, 8 mg Parenteral 1, 2, 4,

Suppository 3 mg

3 h

IV or Oral 5 mg

Oral, IV, or suppository

(Dilaudid®)

8 mg

suppository 2 mg

Codeine

15, 30, 60 mg Oral

2-4 h

90 mg orally

Oral

Propoxyphene

Darvon 65 mg Darvon N 100 100 mg

3-4 h

200 mg orally

oral

Percocet 5/325, 7.5/500, and 10/650

3-4 h

20 mg orally

Oral or suspension

Oxycodone-sustained

Oxycontin® 10, 20, 40, 80,160 mg

12 h

20 mg

Oral (tablet should not be broken or

release

dissolved)

Oxymorphone

Opana® 5, 10 mg

4 h

20 mg

Methadone

5, 10, 40 mg P0

6-8 h

30 mg

Oral tablets or suspension

Fentanyl

• Transdermal patches (Duragesic®) 12, 25, 50, 75, or 100 mcgm/hr Q

72 h

100 mcgm

IV, transdermal, or transmucosal

48-72 h

2-4 h

. Transbuccal lozenge (Actiq®) 200, 400, 600,1200, or 1800 mcgm

FDA=Food and Drug Administration; IV=intravenous; PO=peros.

FDA=Food and Drug Administration; IV=intravenous; PO=peros.

Figure 28.3 Ideal treatment of cancer pain with opioids using short- and long-acting agents. Long-acting opioids are used to help with the persistent pain, while short-acting opioids are used for the breakthrough pain. Please note the line for overmedication.

Patient-Controlled Analgesia in Cancer Pain

Patient with cancer pain who has intravenous (IV) access, unable to tolerate per os (PO) opioids, and prefers to have control over their pain management may benefit from patient-controlled analgesia (PCA). The patient can carry PCA machine in a backpack and deliver opioids through intermittent boluses controlled by the patient, and/or have a basal infusion of medications. Patient-controlled analgesia is described in detail in other chapters.

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