Skip to main content
Key Specialties
Cardiology Diabetology Endocrinology Gastroenterology Geriatrics and Gerontology Gynecology and Obstetrics Hematology Infectious Disease Internal Medicine Nephrology Neurology Oncology Pediatrics Respiratory Medicine Rheumatology Surgery
Congress Coverage
2024 ACC Congress 2023 ESMO Congress 2023 EASD Congress 2023 ERS Congress 2023 ESC Congress
Clinical Collections
Advances in Alzheimer’s

At a glance: The ONWARDS insulin icodec trials

A round-up of the ONWARDS phase 3 clinical trials evaluating the novel weekly insulin icodec in people with diabetes.
ADVANCED SEARCH
Log in
Top
Supportive Care in Cancer
Published in: Supportive Care in Cancer 6/2011

01-06-2011 | Original Article

A double-blind, placebo-controlled trial of a topical treatment for chemotherapy-induced peripheral neuropathy: NCCTG trial N06CA

Authors: Debra L. Barton, Edward J. Wos, Rui Qin, Bassam I. Mattar, Nathan Benjamin Green, Keith S. Lanier, James Dewitt Bearden III, John W. Kugler, Kay L. Hoff, Pavan S. Reddy, Kendrith M. Rowland Jr, Mike Riepl, Bradley Christensen, Charles L. Loprinzi

Published in: Supportive Care in Cancer | Issue 6/2011

Login to get access

Abstract

Background

Chemotherapy-induced peripheral neuropathy (CIPN) is a troublesome chronic symptom that has no proven pharmacologic treatment. The purpose of this double-blind randomized placebo-controlled trial was to evaluate a novel compounded topical gel for this problem.

Methods

Patients with CIPN were randomized to baclofen 10 mg, amitriptyline HCL 40 mg, and ketamine 20 mg in a pluronic lecithin organogel (BAK-PLO) versus placebo (PLO) to determine its effect on numbness, tingling, pain, and function. The primary endpoint was the baseline-adjusted sensory subscale of the EORTC QLQ-CIPN20, at 4 weeks.

Results

Data in 208 patients reveal a trend for improvement that is greater in the BAK-PLO arm over placebo in both the sensory (p = 0.053) and motor subscales (p = 0.021). The greatest improvements were related to the symptoms of tingling, cramping, and shooting/burning pain in the hands as well as difficulty in holding a pen. There were no undesirable toxicities associated with the BAK-PLO and no evidence of systemic toxicity.

Conclusion

Topical treatment with BAK-PLO appears to somewhat improve symptoms of CIPN. This topical gel was well tolerated, without evident systemic toxicity. Further research is needed with increased doses to better clarify the clinical role of this treatment in CIPN.
Literature
1.
Cavaletti G, Bogliun G, Marzorati L et al (1995) Peripheral neurotoxicity of Taxol in patients previously treated with cisplatin. Cancer 75:1141–1150PubMedCrossRef
2.
Cavaletti G, Fabbrica D, Minoia C et al (1998) Carboplatin toxic effects on the peripheral nervous system of the rat. Ann Oncol 9:443–447PubMedCrossRef
3.
Ocean JA, Vahdat LT (2004) Chemotherapy-induced peripheral neuropathy: pathogenesis and emerging therapies. Support Care Cancer 12:619–625PubMed
4.
Pace A, Bove L, Aloe A et al (1997) Paclitaxel neurotoxicity: clinical and neurophysiological study of 23 patients. Ital J Neurol Sci 18:73–79PubMedCrossRef
5.
Rowinsky EK, Chaudry V, Cornblath DR et al (1993) Neurotoxicity of taxol. J Natl Cancer Inst Monogr 15:107–115PubMed
6.
Verstappen C, Heimans JJ, Hockman K et al (2003) Neurotoxic complications of chemotherapy in patients with cancer. Drugs 63(15):1549–1563PubMedCrossRef
7.
Windebank AJ (1999) Chemotherapeutic neuropathy. Curr Opin Neurol 5:565–571CrossRef
8.
Campana WM, Eskeland N, Calcutt NA et al (1998) Prosaptide prevents paclitaxel neurotoxicity. Neurotoxicology 19:237–244PubMed
9.
Cliffer KD, Siuciak JA, Carson SR et al (1998) Physiological characterization of taxol-induced large-fiber sensory neuropathy in the rat. Ann Neurol 43:46–55PubMedCrossRef
10.
Guastalla JP, Pujade-Lauraine E, Weber B (1998) Efficacy and safety of paclitaxel and carboplatin combination in patients with previously treated advanced ovarian carcinoma. Ann Oncol 9(9):37–43PubMedCrossRef
11.
12.
Pujude-Lauraine E, Guastalla JP, Weber B et al (1997) Efficacy and safety of the combination of paclitaxel/carboplatin in patients with previously treated advanced ovarian carcinoma: a multicenter French Groupe des investigateurs Nationauz pour l'etude des cancers ovariens phase II study. Semin Oncol 24:S15-30–S15-35
13.
14.
Envig AI, Wiernik PH, Wadler S et al (1998) Phase I study of paclitaxel (taxol) and granulocyte colony stimulating factor (g-csf) in patients with unresectable malignany. Invest New Drugs 16:29–36CrossRef
15.
LoMonaco M, Milone M, Batocchi AP et al (1992) Cisplatin neuropathy: clinical course and neurophysiologic findings. J Neurol 239:199PubMedCrossRef
16.
Nikcevich DA, Grothey A, Sloan JA, Kugler JW, Silberstein PT, Dentchev T, Wender DB, Novotny PJ, Windschitl HE, Loprinzi CL (2008) Effect of intravenous calcium and magnesium (IV CaMg) on oxaliplatin-induced sensory neurotoxicity (sNT) in adjuvant colon cancer: results of the phase III placebo-controlled, double-blind NCCTG trial N04C7. J Clin Oncol 26:(abstr 4009)
17.
Ahmad M, Goucke CR (2002) Management strategies for the treatment of neuropathic pain in the elderly. Drugs Aging 19(12):929–945PubMedCrossRef
18.
Argoff CE, Katz N, Backonja M (2004) Treatment of postherpetic neuralgia:a review of therapeutic options. J Pain Symptom Manage 28(4):396–411PubMedCrossRef
19.
Jensen PG, Larson JR (2001) Management of painful diabetic neuropathy. Drugs Aging 18(10):737–749PubMedCrossRef
20.
Hammack JE et al (2002) Phase III evaluation of nortriptyline for alleviation of symptoms of cis-platinum-induced peripheral neuropathy. Pain 98(1–2):195–203PubMedCrossRef
21.
Rao RD, Michalak JC, Sloan JA et al (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):2110–2118PubMedCrossRef
22.
Rao RD, Flynn PJ, Sloan J et al (2008) Efficacy of lamotrigine in the management of chemotherapy-induced peripheral neuropathy: a phase 3 randomized, double blind, placebo controlled NCCTG trial, N01C3. Cancer 112(21):2802–2808PubMedCrossRef
23.
Moore DH, Donnelly J, McGuire WP et al (2003) Limited access trial using amifostine for protection against cisplatin- and three-hour paclitaxel-induced neurotoxicity: a phase ii study of the Gynecologic Oncology Group. J Clin Oncol 21(22):4207–4213PubMedCrossRef
24.
Vahdat L, Papadopoulos K, Lange D et al (2001) Reduction of paclitaxel-induced peripheral neuropathy with glutamine. Clin Cancer Res 7:1192–1197PubMed
25.
Baron (2006) Mechanisms of disease: neuropathic pain, a clinical perspective. Nat Clin Pract Neurol 2(2):95–106PubMedCrossRef
26.
Jones M (2000) Chronic neuropathic pain: pharmacological interventions in the new millennium. Int J Pharm Comp 4(1):6–15
27.
28.
29.
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 19:323–328PubMedCrossRef
30.
Lynch ME, Clark AJ, Sawynok J, Sullivan MJL (2005) Topical 2% amitriptyline and 1% ketamine in neuropathic pain syndromes. Anesthesiology 103(1):140–146PubMedCrossRef
31.
Lynch ME, Clark AJ, Sawynok J, Sullivan MJ (2005) Topical amitriptyline and ketamine in neurotopical amitriptyline and ketamine in neuropathic pain syndromes: an open label study. J Pain 6(10):644–649PubMedCrossRef
32.
Lockhart E (2004) Topical combination of amitriptyline and ketamine for post herpetic neuralgia. J Pain 5:S182CrossRef
33.
Everton D, Bhagwat D, Damask M (2007) An open-label pharmacokinetic study in humans of a 4% amitriptyline, 2% ketamine topical cream. J Pain 8(4 suppl 1):S48CrossRef
34.
Ceschel G, Bergamante V, Maffei P et al (2005) Solubility and transdermal permeation properties of dehydroepiandrosterone cyclodextrin complex from hydrophilic and lipophilic vehicles. Drug Delivery 12:275–280PubMedCrossRef
35.
Franek M, Vaculin S, Rokyta R (2004) GABAB receptor agonist baclofen has non-specific antinociceptive effect in the model of peripheral neuropathy in the rat. Pysiol Res 53:351–355
36.
Smith GD, Harrison SM, Birch PJ et al (1994) Increased sensitivity to the antinociceptive activity of ± baclofen in an animal model of chronic neuropathic, but not chronic inflammatory hyperalgesia. Neuropharmacology 33:1103–1108PubMedCrossRef
37.
Gammaitoni A, Gallagher RM, Welz-Bosna M (2000) Topical ketamine gel: possible role in treating neuropathic pain. Pain Medicine 1(1):97–100PubMedCrossRef
38.
Pocock SJ, Simon R (1975) Sequential treatment assignment with balancing for prognostic factors in the controlled clinical trial. Biometrics 31:103–115PubMedCrossRef
39.
Postma TJ, Aaronson NK, Heimans JJ, EORTC Quality of Life Group et al (2005) The development of an EORTC quality of life questionnaire to assess chemotherapy-induced peripheral neuropathy: the QLQ-CIPN20. Eur J Cancer 41(8):1135–1139PubMedCrossRef
40.
McNair DM, Loor M, Droppleman LF (2003) Profile of mood states manual. Multi-Health Systems, New York
41.
Cleeland CS, Ryan KM (1994) Pain assessment: global use of the brief pain inventory. Ann Acad Med Singapore 23(2):129–138PubMed
42.
Sloan JA, O'Fallon JR, Suman VJ et al (1998) Incorporating quality of life measurement into oncology clinical trials. Proc Am Stat Assoc 1998:282–287
43.
Grunberg SM, Groshen S, Steingass S (1996) Comparison of conditional quality of life terminology and visual analogue scale measurements. Qual Life Res 5:65–72PubMedCrossRef
44.
Gudex C, Dolan P, Kind P (1996) Health state valuations from the general public using the visual analogue scale. Qual Life Res 5:521–531PubMedCrossRef
Metadata
Title
A double-blind, placebo-controlled trial of a topical treatment for chemotherapy-induced peripheral neuropathy: NCCTG trial N06CA
Authors
Debra L. Barton
Edward J. Wos
Rui Qin
Bassam I. Mattar
Nathan Benjamin Green
Keith S. Lanier
James Dewitt Bearden III
John W. Kugler
Kay L. Hoff
Pavan S. Reddy
Kendrith M. Rowland Jr
Mike Riepl
Bradley Christensen
Charles L. Loprinzi
Publication date
01-06-2011
Publisher
Springer-Verlag
Published in
Supportive Care in Cancer / Issue 6/2011
Print ISSN: 0941-4355
Electronic ISSN: 1433-7339
DOI
https://doi.org/10.1007/s00520-010-0911-0

Other articles of this Issue 6/2011

Supportive Care in Cancer 6/2011 Go to the issue

Original Article

Evaluation of risk factors predictive of nausea and vomiting with current standard-of-care antiemetic treatment: analysis of phase 3 trial of aprepitant in patients receiving adriamycin–cyclophosphamide-based chemotherapy

Short Communication

A pilot phase II trial of magnesium supplements to reduce menopausal hot flashes in breast cancer patients

Short Communication

Body mass index and breast cancer treatment-related lymphedema

Original Article

Impact on daily functioning and indirect/direct costs associated with chemotherapy-induced nausea and vomiting (CINV) in a US population

Original Article

Music’s relevance for pediatric cancer patients: a constructivist and mosaic research approach

Original Article

Issues of “life” and “death” for patients receiving palliative care—comments when confronted with a research tool
Webinar | 19-02-2024 | 17:30 (CET)

Keynote webinar | Spotlight on antibody–drug conjugates in cancer

Watch now

Antibody–drug conjugates (ADCs) are novel agents that have shown promise across multiple tumor types. Explore the current landscape of ADCs in breast and lung cancer with our experts, and gain insights into the mechanism of action, key clinical trials data, existing challenges, and future directions.

Dr. Véronique Diéras
Prof. Fabrice Barlesi
Developed by: Springer Medicine
Image Credits