nach oben

Erschienen in:

01.07.2014 | Original Article

A phase III randomized, placebo-controlled study of topical amitriptyline and ketamine for chemotherapy-induced peripheral neuropathy (CIPN): a University of Rochester CCOP study of 462 cancer survivors

verfasst von: Jennifer S. Gewandter, Supriya G. Mohile, Charles E. Heckler, Julie L. Ryan, Jeffrey J. Kirshner, Patrick J. Flynn, Judith O. Hopkins, Gary R. Morrow

Erschienen in: Supportive Care in Cancer | Ausgabe 7/2014

Einloggen, um Zugang zu erhalten

Abstract

Purpose

Chemotherapy-induced peripheral neuropathy (CIPN) occurs in as high as 70 % of patients receiving certain types of chemotherapy agents. The FDA has yet to approve a therapy for CIPN. The aim of this multicenter, phase III, randomized, double-blind, placebo-controlled trial was to investigate the efficacy of 2 % ketamine plus 4 % amitriptyline (KA) cream for reducing CIPN.

Methods

Cancer survivors who completed chemotherapy at least 1 month prior and had CIPN (>4 out of 10) were enrolled (N = 462). CIPN was assessed using average scores from a 7-day daily diary that asks patients to rate the average “pain, numbness, or tingling in [their] hands and feet over the past 24 h” on an 11-point numeric rating scale at baseline and 6 weeks post intervention. ANCOVA was used to measure differences in 6-week CIPN with effects including baseline CIPN, KA treatment arm, and previous taxane therapy (Y/N).

Results

The KA treatment showed no effect on 6-week CIPN scores (adjusted mean difference = −0.17, p = 0.363).

Conclusions

This study suggests that KA cream does not decrease CIPN symptoms in cancer survivors.

Ocean AJ, Vahdat LT (2004) Chemotherapy-induced peripheral neuropathy: pathogenesis and emerging therapies. Support Care Cancer 12(9):619–625. doi:10.1007/s00520-004-0657-7 PubMed

Argyriou AA, Koltzenburg M, Polychronopoulos P, Papapetropoulos S, Kalofonos HP (2008) Peripheral nerve damage associated with administration of taxanes in patients with cancer. Crit Rev Oncol Hematol 66(3):218–228. doi:10.1016/j.critrevonc.2008.01.008 PubMedCrossRef

Kautio AL, Haanpaa M, Kautiainen H, Kalso E, Saarto T (2010) Burden of chemotherapy-induced neuropathy—a cross-sectional study. Support Care Cancer 19 (12). doi:10.1007/s00520-010-1043-2

Smith EM, Pang H, Cirrincione C, Fleishman S, Paskett ED, Ahles T, Bressler LR, Fadul CE, Knox C, Le-Lindqwister N, Gilman PB, Shapiro CL (2013) Effect of duloxetine on pain, function, and quality of life among patients with chemotherapy-induced painful peripheral neuropathy: a randomized clinical trial. JAMA 309(13):1359–1367. doi:10.1001/jama.2013.2813 PubMedCentralPubMedCrossRef

Jorge LL, Feres CC, Teles VE (2011) Topical preparations for pain relief: efficacy and patient adherence. J Pain Res 4:11–24. doi:10.2147/JPR.S9492 PubMedCentral

Stillman M (2006) Clinical approach to patients with neuropathic pain. Cleve Clin J Med 73(8):726–728, 729-730, 733-726PubMedCrossRef

Gilron I, Bailey JM, Tu D, Holden RR, Jackson AC, Houlden RL (2009) Nortriptyline and gabapentin, alone and in combination for neuropathic pain: a double-blind, randomised controlled crossover trial. Lancet 374(9697):1252–1261. doi:10.1016/S0140-6736(09)61081-3 PubMedCrossRef

Gilron I, Bailey JM, Tu D, Holden RR, Weaver DF, Houlden RL (2005) Morphine, gabapentin, or their combination for neuropathic pain. N Engl J Med 352(13):1324–1334. doi:10.1056/NEJMoa042580 PubMedCrossRef

Hanna M, O’Brien C, Wilson MC (2008) Prolonged-release oxycodone enhances the effects of existing gabapentin therapy in painful diabetic neuropathy patients. Eur J Pain 12(6):804–813. doi:10.1016/j.ejpain.2007.12.010 PubMedCrossRef

10.

McCleane G (2000) Topical application of doxepin hydrochloride, capsaicin and a combination of both produces analgesia in chronic human neuropathic pain: a randomized, double-blind, placebo-controlled study. Br J Clin Pharmacol 49(6):574–579PubMedCentralPubMedCrossRef

11.

Lynch ME, Clark AJ, Sawynok J, Sullivan MJ (2005) Topical amitriptyline and ketamine in neuropathic pain syndromes: an open-label study. J Pain 6(10):644–649. doi:10.1016/j.jpain.2005.04.008 PubMedCrossRef

12.

Lynch ME, Clark AJ, Sawynok J (2003) A pilot study examining topical amitriptyline, ketamine, and a combination of both in the treatment of neuropathic pain. Clin J Pain 19(5):323–328PubMedCrossRef

13.

Smith DJ, Pekoe GM, Martin LL, Coalgate B (1980) The interaction of ketamine with the opiate receptor. Life Sci 26(10):789–795PubMedCrossRef

14.

Davies SN, Alford ST, Coan EJ, Lester RA, Collingridge GL (1988) Ketamine blocks an NMDA receptor-mediated component of synaptic transmission in rat hippocampus in a voltage-dependent manner. Neurosci Lett 92(2):213–217PubMedCrossRef

15.

Tatsumi M, Groshan K, Blakely RD, Richelson E (1997) Pharmacological profile of antidepressants and related compounds at human monoamine transporters. Eur J Pharmacol 340(2–3):249–258PubMedCrossRef

16.

Pancrazio JJ, Kamatchi GL, Roscoe AK, Lynch C 3rd (1998) Inhibition of neuronal Na+ channels by antidepressant drugs. J Pharmacol Exp Ther 284(1):208–214PubMed

17.

Dworkin RH, Turk DC, Peirce-Sandner S, Burke LB, Farrar JT, Gilron I, Jensen MP, Katz NP, Raja SN, Rappaport BA, Rowbotham MC, Backonja MM, Baron R, Bellamy N, Bhagwagar Z, Costello A, Cowan P, Fang WC, Hertz S, Jay GW, Junor R, Kerns RD, Kerwin R, Kopecky EA, Lissin D, Malamut R, Markman JD, McDermott MP, Munera C, Porter L, Rauschkolb C, Rice AS, Sampaio C, Skljarevski V, Sommerville K, Stacey BR, Steigerwald I, Tobias J, Trentacosti AM, Wasan AD, Wells GA, Williams J, Witter J, Ziegler D (2012) Considerations for improving assay sensitivity in chronic pain clinical trials: IMMPACT recommendations. Pain 153(6):1148–1158PubMedCrossRef

18.

Cleeland CS, Mendoza TR, Wang XS, Chou C, Harle MT, Morrissey M, Engstrom MC (2000) Assessing symptom distress in cancer patients: the M.D. Anderson Symptom Inventory. Cancer 89(7):1634–1646PubMedCrossRef

19.

Molenberghs GKM (2007) Missing data in clinical studies. Wiley, West SussexCrossRef

20.

Dworkin RH, Corbin AE, Young JP Jr, Sharma U, LaMoreaux L, Bockbrader H, Garofalo EA, Poole RM (2003) Pregabalin for the treatment of postherpetic neuralgia: a randomized, placebo-controlled trial. Neurology 60(8):1274–1283PubMedCrossRef

21.

Gamelin L, Boisdron-Celle M, Delva R, Guerin-Meyer V, Ifrah N, Morel A, Gamelin E (2004) Prevention of oxaliplatin-related neurotoxicity by calcium and magnesium infusions: a retrospective study of 161 patients receiving oxaliplatin combined with 5-Fluorouracil and leucovorin for advanced colorectal cancer. Clin Cancer Res 10(12 Pt 1):4055–4061. doi:10.1158/1078-0432.CCR-03-0666 PubMedCrossRef

22.

Grothey A, Nikcevich DA, Sloan JA, Kugler JW, Silberstein PT, Dentchev T, Wender DB, Novotny PJ, Chitaley U, Alberts SR, Loprinzi CL (2011) Intravenous calcium and magnesium for oxaliplatin-induced sensory neurotoxicity in adjuvant colon cancer: NCCTG N04C7. J Clin Oncol 29(4):421–427. doi:10.1200/JCO.2010.31.5911 PubMedCentralPubMedCrossRef

23.

Colombo N, Bini S, Miceli D, Bogliun G, Marzorati L, Cavaletti G, Parmigiani F, Venturino P, Tedeschi M, Frattola L, Buratti C, Mangioni C (1995) Weekly cisplatin +/− glutathione in relapsed ovarian carcinoma. Int J Gynecol Cancer 5(2):81–86PubMedCrossRef

24.

Smyth JF, Bowman A, Perren T, Wilkinson P, Prescott RJ, Quinn KJ, Tedeschi M (1997) Glutathione reduces the toxicity and improves quality of life of women diagnosed with ovarian cancer treated with cisplatin: results of a double-blind, randomised trial. Ann Oncol 8(6):569–573PubMedCrossRef

25.

Milla P, Airoldi M, Weber G, Drescher A, Jaehde U, Cattel L (2009) Administration of reduced glutathione in FOLFOX4 adjuvant treatment for colorectal cancer: effect on oxaliplatin pharmacokinetics, Pt-DNA adduct formation, and neurotoxicity. Anticancer Drugs 20(5):396–402. doi:10.1097/CAD.0b013e32832a2dc1 PubMedCrossRef

26.

Durand JP, Alexandre J, Guillevin L, Goldwasser F (2005) Clinical activity of venlafaxine and topiramate against oxaliplatin-induced disabling permanent neuropathy. Anticancer Drugs 16(5):587–591PubMedCrossRef

27.

Durand JP, Deplanque G, Montheil V, Gornet JM, Scotte F, Mir O, Cessot A, Coriat R, Raymond E, Mitry E, Herait P, Yataghene Y, Goldwasser F (2011) Efficacy of venlafaxine for the prevention and relief of oxaliplatin-induced acute neurotoxicity: results of EFFOX, a randomized, double-blind, placebo-controlled phase III trial. Ann Oncol 23(1):200–205. doi:10.1093/annonc/mdr045 PubMedCrossRef

28.

Saif MW, Syrigos K, Kaley K, Isufi I (2010) Role of pregabalin in treatment of oxaliplatin-induced sensory neuropathy. Anticancer Res 30(7):2927–2933PubMed

29.

Gedlicka C, Kornek GV, Schmid K, Scheithauer W (2003) Amelioration of docetaxel/cisplatin induced polyneuropathy by alpha-lipoic acid. Ann Oncol 14(2):339–340PubMedCrossRef

30.

Gedlicka C, Scheithauer W, Schull B, Kornek GV (2002) Effective treatment of oxaliplatin-induced cumulative polyneuropathy with alpha-lipoic acid. J Clin Oncol 20(15):3359–3361PubMedCrossRef

31.

Maestri A, De Pasquale Ceratti A, Cundari S, Zanna C, Cortesi E, Crino L (2005) A pilot study on the effect of acetyl-L-carnitine in paclitaxel- and cisplatin-induced peripheral neuropathy. Tumori 91(2):135–138PubMed

32.

Hershman DL, Unger JM, Crew KD, Minasian LM, Awad D, Moinpour CM, Hansen L, Lew DL, Greenlee H, Fehrenbacher L, Wade JL, Wong SF, Hortobagyi GN, Meyskens FL, Albain KS (2013) Randomized placebo-controlled trial of acetyl-L-carnitine for the prevention of taxane-induced neuropathy in women undergoing adjuvant breast cancer therapy. J Clin Oncol 31(20):2627–2633PubMedCrossRef

33.

Rao RD, Michalak JC, Sloan JA, Loprinzi CL, Soori GS, Nikcevich DA, Warner DO, Novotny P, Kutteh LA, Wong GY (2007) Efficacy of gabapentin in the management of chemotherapy-induced peripheral neuropathy: a phase 3 randomized, double-blind, placebo-controlled, crossover trial (N00C3). Cancer 110(9):2110–2118. doi:10.1002/cncr.23008 PubMedCrossRef

34.

Hammack JE, Michalak JC, Loprinzi CL, Sloan JA, Novotny PJ, Soori GS, Tirona MT, Rowland KM Jr, Stella PJ, Johnson JA (2002) Phase III evaluation of nortriptyline for alleviation of symptoms of cis-platinum-induced peripheral neuropathy. Pain 98(1–2):195–203PubMedCrossRef

35.

Kautio AL, Haanpaa M, Saarto T, Kalso E (2008) Amitriptyline in the treatment of chemotherapy-induced neuropathic symptoms. J Pain Symptom Manage 35(1):31–39. doi:10.1016/j.jpainsymman.2007.02.043 PubMedCrossRef

36.

Kautio AL, Haanpaa M, Leminen A, Kalso E, Kautiainen H, Saarto T (2009) Amitriptyline in the prevention of chemotherapy-induced neuropathic symptoms. Anticancer Res 29(7):2601–2606PubMed

37.

Rao RD, Flynn PJ, Sloan JA, Wong GY, Novotny P, Johnson DB, Gross HM, Renno SI, Nashawaty M, Loprinzi CL (2008) Efficacy of lamotrigine in the management of chemotherapy-induced peripheral neuropathy: a phase 3 randomized, double-blind, placebo-controlled trial, N01C3. Cancer 112(12):2802–2808. doi:10.1002/cncr.23482 PubMedCrossRef

38.

Quasthoff S, Hartung HP (2002) Chemotherapy-induced peripheral neuropathy. J Neurol 249(1):9–17PubMedCrossRef

39.

Windebank AJ, Grisold W (2008) Chemotherapy-induced neuropathy. J Peripher Nerv Syst 13(1):27–46. doi:10.1111/j.1529-8027.2008.00156.x PubMedCrossRef

40.

Barton DL, Wos EJ, Qin R, Mattar BI, Green NB, Lanier KS, Bearden JD 3rd, Kugler JW, Hoff KL, Reddy PS, Rowland KM Jr, Riepl M, Christensen B, Loprinzi CL (2011) A double-blind, placebo-controlled trial of a topical treatment for chemotherapy-induced peripheral neuropathy: NCCTG trial N06CA. Support Care Cancer 19(6):833–841. doi:10.1007/s00520-010-0911-0 PubMedCentralPubMedCrossRef

Titel: A phase III randomized, placebo-controlled study of topical amitriptyline and ketamine for chemotherapy-induced peripheral neuropathy (CIPN): a University of Rochester CCOP study of 462 cancer survivors
verfasst von: Jennifer S. Gewandter
Supriya G. Mohile
Charles E. Heckler
Julie L. Ryan
Jeffrey J. Kirshner
Patrick J. Flynn
Judith O. Hopkins
Gary R. Morrow
Publikationsdatum: 01.07.2014
Verlag: Springer Berlin Heidelberg
Erschienen in: Supportive Care in Cancer / Ausgabe 7/2014
Print ISSN: 0941-4355
Elektronische ISSN: 1433-7339
DOI: https://doi.org/10.1007/s00520-014-2158-7

Update Onkologie

Bestellen Sie unseren Fach-Newsletter und bleiben Sie gut informiert.

Newsletter bestellen

Live-Webinar "Urologie und Sexualmedizin in der Praxis"

Springer Medizin

A phase III randomized, placebo-controlled study of topical amitriptyline and ketamine for chemotherapy-induced peripheral neuropathy (CIPN): a University of Rochester CCOP study of 462 cancer survivors