Current aproach to cancer pain management: Availability and implications of different treatment options

Figures & data

Figure 1 The World Health Organization cancer pain treatment step ladder.

Figure 2 Modified analgesic ladder for the treatment of cancer pain.

Table 1 Most commonly used nonopioid analgesics in United States

Drug	Preparation	Dose	Maximum	Comments
Acetaminophen	tablets – 325, 500, 650 mg suspension – 160, 325 mg/5 ml suppository – 80, 120, 125, 200, 300, 325, 600, 650 mg	325–1000 mg PO q4–6h PRN	4000 mg/day	No anti-inflammatory effect. Hepatotoxic if overdosed
Aspirin	tablets – 81, 162, 325, 500, 650, 975 mg suppository – 60, 120, 200, 300, 600 mg	325–650 mg PO q4h PRN	4000 mg/day	Bleeding risk is the most significant concern
Diclofenac	tablets – 50 mg delayed-release – 25, 50, 75, 100 mg SR	50 mg PO BID-TID	150 mg/day	Alt dose for SR form is 100 mg PO daily
Etodolac	tablets – 400, 500 mg extended-release – 400, 500, 600 mg SR capsules – 200, 300 mg	200–400 mg PO q6–8h	1200 mg/day	The dose for SR is 400–1000 mg once daily
Ibuprofen	tablets – 100, 200, 400, 600, 800 mg suspension – 40 mg/ml, 100 mg/5 ml	400–600 mg PO q4–6h PRN	3200 mg/day	Use with caution in patients with history of peptic ulcer
Indomethacin	capsules – 25, 50 mg extended-release – 75 mg SR suspension – 25 mg/5 ml suppository – 50 mg	25–50 mg PO TID	200 mg/day	Use with caution in patients with history of peptic ulcer
Ketoprofen	tablets – 12.5 mg capsules – 25, 50, 75 mg extended-release – 100, 150, 200 mg SR	25–50 mg PO q6h–q8h	300 mg/day	Maximum dose for SR form is 200 mg/day
Ketorolac	tablets – 10 mg parenteral – 15 mg/ml, 30 mg/ml	10 mg PO q4–6h PRN or 30 mg IV/IM q6h	40 mg/day PO or 120 mg/day IV/IM	IV therapy should not exceed 5 days
Meclofenamate	capsules – 50, 100 mg	50–100 mg PO q4–6h PRN	400 mg/day
Mefenamic acid	capsules – 250 mg	250 mg PO q4–6 PRN	For therapy ≤ 1 wk in duration	Recommended first dose is 500 mg PO
Meloxicam	tablets – 7.5, 15 mg suspension – 7.5 mg/5 mL	7.5–15 mg PO once daily	15 mg/day	COX-2 preferential NSAID
Nabumetone	tablets – 500, 750 mg 2000 mg/day	100–2000 mg once daily		May divide daily dose to BID
Naproxen	tablets – 250, 375, 500 mg SR – 375, 500 mg suspension – 125 mg/5 ml	250–500 mg PO BID	1500 mg/day for 3–5days	Maintenance dose is maximum 1000 mg/d for 6 months
Oxaprozin	tablets – 600mg	1200 mg PO once daily	1800 mg/day
Piroxicam	capsules – 10, 20 mg	20 mg PO once daily	20 mg/day	May divide daily dose BID
Sulindac	tablets – 150, 200 mg	150–200 mg PO BID	400 mg/day
Tolmetin	capsules – 400 mg tablets – 200, 600 mg	200–600 mg PO BID-TID	1800 mg/day
Tramadol	Tablets – 50 mg extended-release – 100, 200, 300 mg SR	50–100 mg PO q4–6h PRN; 100– 300 mg QD for SR	400 mg/day	Maximum dose for SR form is 300 mg/day
Celecoxib	capsules – 100, 200, 400 mg	200 mg PO BID	400 mg/day	COX-2 inhibitor
Rofecoxib*	tablets – 12.5, 25, 50 mg suspension – 12.5 mg/5 ml,	50 mg PO daily for 5 days, then 25 mg PO 25 mg/5 ml daily	Withdrawn from the market in 2004
Valdecoxib*	tablets – 10, 20 mg	10-20 mg PO BID	Withdrawn from the market in 2005

Abbreviations: PO, oral; IM, intramuscular; IV, intravenous; PRN, as needed; BID, twice daily; TID, three times daily; NSAID, nonsteroidal anti-inflammatory drug; SR, sustained release.

* Note: COX-2 inhibitors Rofecoxib (Vioxx) and Valdecoxib (Bextra) were removed from the market due to increased cardiovascular and dermatological risks.

Table 2 Most commonly used opioid analgesics in United States

Drug name	Formulation	Duration of action (hours)	Recommended analgesic dose
Morphine sulfate	Tablets (IR): 15 and 30 mg	2–4	10–30 mg q3–4h
	Rectal suppositories: 5, 10, 20, and 30 mg		10–20 mg q4h
	Parenteral (SC, IM, IV): 2, 4 and 20 mg/ml		2.5–10 mg q2–6h1
	Epidural		3–5 mg once, then 0.1–0.7 mg/hr
	Intrathecal		Start 100:1 IT-to-IV, then titrate to pain
MS Contin^®	Tablets (CR): 15, 30, 60, 100, 200 mg	8–12	15–30 mg q8–12h
Oramorph^®SR	Tablets (SR): 15, 30, 60, 100 mg	8–12	15–30 mg q8–12h
Kadian^®	Capsules (ER): 20, 30, 50, 60, 100 mg	24	20 mg q24h, may increase by 20 mg increments every other day
Avinza^®	Capsules (ER): 30, 60, 90, 120 mg	24	30 mg q24h, may increase by 30 mg increments q4days (max 1600 mg/d)
Codeine	Tablets: 15, 30, 60 mg Oral solution: 15 mg/5 ml, 30 mg/5 ml	2–4	15–60 mg q4–6h (max 60 mg/d)
Dilaudid^® (hydromorphone)	Tablets (IR): 2, 4, 8 mg; Oral solution: 5 mg/5 mL; Suppositories: 3 mg	2–4	2–8 mg q3-4h for PO and PR
	Parenteral (SC, IM, IV): 1, 2, 4, 8 mg/ml;		1–4 mg q4–6h2
	Intrathecal		Start 100:1 IT-to-IV, then titrate to pain
Palladone^®	Capsules (ER): 12, 16, 24, 32 mg	24	Withdrawn from the market in 2005
Roxycodone^® (oxycodone)	Tablets (IR3): 5, 15, 30 mg, capsules: 5 mg; Oral solution: 5 mg/5 ml, 20 mg/ml	2–4	5–30 mg q4h
OxyContin^®	Tablets (SR): 10, 20, 40, 80, 160 mg	12	10–160 mg q12h4
Opana^® (oxymorphone)	Tablets (IR) 5, 10 mg	4-8	5–10 mg q4–6h
Opana^®ER	Tablets (ER) 5, 10, 20, 40 mg	12	5–40 mg q12h
Propoxyphene HCl	Capsules: 65 mg5	2–4	65 mg q4h (max 390 mg/24h)
Methadone	Oral solution: 5 mg/5 ml, 10 mg/5 ml, 10 mg/ml; Tablets: 5, 10, 40 mg	4–8	2.5–10 mg q3-6h Has very long half-life (8–60 hours)
Meperidine (Demerol^®)	Oral solution: 50 mg/5 ml Tablets: 50, 100 mg	2–4	50–150 mg q3–4h (decrease dose if given IV, administer slow or via PCA).
	Parenteral (SC, IM, IV): 10 mg/ml		Not recommended for chronic use.
Fentanyl	Parenteral (IM, IV)	1–3	25–100 mcg q1–2h 0.5–1.5 mcg/kg/hr IV infusion via PCA
Actiq^®	Oral transmucosal lozenge: 200, 400, 600, 800, 1200, 1600 mcg	2–4	Start with 200 mcg for breakthrough pain episodes6, then titrate to pain
Duragesic^®	Transdermal patch: 25, 50, 75, 100 mcg/hr	72	25 mcg/h q72hr, may increase q3–6days

Abbreviations: IR, immediate release; CR, controlled release; SR, sustained release; ER, extended release.

1 Notes: Alternative dose for IV morphine: 0.1 mg/kg IV once, then 1-10mg/hr via IV PCA.

2 Start 0.2-0.6 mg q2-3h (IV), 0.8-1 mg q4-6h (SC/IM) in opiate-naive patients

3 Oxycodone is also available as OxyIR (5 mg immediate release tablets); doses are similar to Roxycodone

4 80 mg and 160 mg formulations of Oxycontin should be used in opiate-tolerant patients only

5 65 mg propoxyphene hydrochloride (Darvon^®) = 100 mg propoxyphene napsylate (Darvon-N)

6 Can be also used IM or SC at 2.5-10 mg q8-12h, but generally PO is recommended for chronic pain

7 For use only in opiate tolerant patients, recommended maximum dose is 4 units per day